The Immune System 4th Edition By Parham – Test Bank

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The Immune System 4th Edition By Parham – Test Bank
SAMPLE QUESTIONS

 

THE IMMUNE SYSTEM, FOURTH EDITION

CHAPTER 2: INNATE IMMUNITY: THE IMMEDIATE RESPONSE TO INFECTION

© 2015 Garland Science

 

2–1      Soluble effector molecules are effective when encountering pathogens in/on _____. (Select all that apply.)

  1. extracellular spaces
  2. cytoplasm
  3. epithelial surfaces
  4. interstitial spaces
  5. vesicular compartments
  6. lymph.

 

2–2      Which of the three complement pathways becomes activated soonest after an initial infection?

  1. the classical pathway
  2. the lectin pathway
  3. the alternative pathway.

 

2–3      Identify the incorrectly paired molecular association.

  1. iC3: factor B
  2. CR4: iC3b
  3. properdin: C3bBb
  4. membrane cofactor protein: C3b2Bb
  5. decay-accelerating factor: C3bBb.

 

2–4      All of the following complement proteins help form a pore in the pathogen’s membrane except _____.

  1. C3b
  2. C5b
  3. C6
  4. C7
  5. C8
  6. C9.

 

2–5      The importance of CD59 (also known as protectin) is to _____.

  1. promote the speed of complement activation by protecting C3 convertase C3bBb from proteolytic degradation
  2. prevent the recruitment of C9
  3. dissociate the components of the alternative C3 convertase
  4. prevent the attachment of C3b to host cell surfaces
  5. inhibit the anchoring of C5b, C6, and C7 to host cell surfaces.

 

2–6      _____ are soluble complement fragments that mediate localized and systemic inflammatory responses.

  1. cryptdins
  2. defensins
  3. anaphylatoxins
  4. selectins
  5. C-reactive proteins.

 

2–7      All of the following statements are correct regarding \alpha2-macroglobulin except _____.

  1. it binds covalently to its target via a thioester bond
  2. it possesses a bait region to lure its target
  3. it undergoes a conformational change that enables it to enshroud the target
  4. when bound to its target it is cleared from the circulation by hepatocytes, fibroblasts, and macrophages bearing receptors specific for the complex
  5. its target is the membrane-attack complex on human cells.

 

2–8      Although activation of the three different pathways of complement involves different components, the three pathways converge on a common enzymatic reaction referred to as complement fixation.

  1. Describe this reaction.
  2. Describe the enzyme responsible for this reaction in the alternative pathway.
  3. Identify the three effector mechanisms of complement that are enabled by this common pathway.

 

2–9      Which of the following is the soluble form of C3 convertase of the alternative pathway of complement activation?

  1. iC3
  2. iC3b
  3. C3b
  4. iC3Bb
  5. C3bBb.

 

2–10    Explain the steps that take place when a bacterium is opsonized via C3b:CR1 interaction between the bacterium and a resident macrophage in tissues.

 

2–11    In the early stages of the alternative pathway of complement activation there are complement control proteins that are soluble (factors H and I) and associated with the cell surface (DAF and MCP). Identify the (i) soluble and (ii) cell surface-associated complement control proteins that operate in the terminal stages of the alternative pathway of complement activation, and describe their activities.

 

2–12

  1. Review the differences between the three pathways of complement (alternative, lectin, and classical) in terms of how they are activated.
  2. Distinguish which pathway(s) are considered part of an adaptive immune response and which are considered part of innate immunity, and say why.

 

2–13    Which of the following does not accurately describe complement components?

  1. soluble proteins
  2. made by the spleen
  3. located in extracellular spaces
  4. some function as proteases once activated
  5. activated by a cascade of enzymatic reactions.

 

2–14    Explain why a genetic deficiency of C3 leads to a type of immunodeficiency characterized by recurrent and severe infections.

 

2–15    Which of the following is the membrane-bound form of C3 convertase of the alternative pathway of complement activation?

  1. iC3
  2. C3a
  3. C3b
  4. iC3Bb
  5. C3bBb.

 

2–16    Explain how the alternative C3 convertase on pathogen cell surfaces is (A) formed and (B) stabilized.

 

2–17    Why is it important to expose the hydrophobic sites of C7 and C8 during the formation of the membrane-attack complex?

 

2–18    The plasma proteins that counteract the activity of factor P by inactivating C3 convertase through the cleavage of C3b are _____.

  1. factor B and factor H
  2. factor H and factor I
  3. factor B and factor I
  4. decay-accelerating factor and factor H
  5. decay-accelerating factor and membrane cofactor protein.

 

2–19    The membrane-bound proteins on human cells that dissociate and inactivate alternative C3 convertase to avoid complement activation are _____.

  1. factor B and factor H
  2. factor H and factor I
  3. factor B and factor I
  4. decay-accelerating factor and factor H
  5. decay-accelerating factor and membrane cofactor protein.

 

2–20    Explain the similarities between membrane cofactor protein, factor H, and complement receptor 1 in terms of their complement control properties.

 

2–21    Explain how the anaphylatoxins C3a and C5a contribute physiologically to inflammation during complement activation.

 

2–22    Which of the following complement components is an opsonin that binds to complement receptor 1 (CR1) on macrophages?

  1. C3b
  2. C3a
  3. Bb
  4. Ba
  5. C3bBb.

 

2–23    Which of the following polymerizes to form a transmembrane channel that compromises the integrity of cell membranes?

  1. C5
  2. C6
  3. C7
  4. C8
  5. C9.

 

2–24    Which of the following are important in anchoring the membrane-attack complex to the membrane?

  1. C3 and C5
  2. C5 and C6
  3. C6 and C7
  4. C7 and C8
  5. C8 and C9.

 

2–25    Which of the following does not contain a glycosylphosphatidylinositol (GPI) lipid tail?

  1. decay-accelerating factor (DAF)
  2. homologous restriction factor (HRF)
  3. membrane cofactor protein (MCP)
  4. protectin (CD59)
  5. all of the above contain a GPI tail.

 

2–26    The ligand for CR3 and CR4 formed by the cleavage of C3b by the combined action of factors H and I is called _____.

  1. C3bBb
  2. C3a
  3. C3b2Bb
  4. iC3b
  5. C5b.

 

2–27    Which of the following does not describe the actions of the coagulation system?

  1. blood clot formation
  2. enhancement of dissemination of microbes into lymphatics and bloodstream
  3. decrease in blood loss and fluid into interstitial spaces in tissues
  4. release of inflammatory mediators by platelets
  5. wound healing.

 

2–28    Damage to tissues triggers a cascade of plasma proteins involving bradykinin and is known as _____.

  1. the alternative pathway of complement
  2. the coagulation system
  3. the kinin system
  4. receptor-mediated endocytosis
  5. the acute-phase response.

 

2–29    Which of the following does not describe defensins?

  1. highly conserved with few variants
  2. contain a large proportion of arginine residues
  3. contain three intra-chain disulfide bonds
  4. amphipathic, with hydrophobic and hydrophilic regions
  5. disrupt pathogen membranes by penetrating them and disrupting their integrity.THE IMMUNE SYSTEM, FOURTH EDITION

    CHAPTER 4: ANTIBODY STRUCTURE AND THE GENERATION OF B-CELL DIVERSITY

    © 2015 Garland Science

     

     

    4–1

    The five classes (isotypes) of immunoglobulins comprise

    1. IgA, IgD, IgE, IgG, IgM
    2. IgA, IgC, IgD, IgE, IgG
    3. IgA, IgD, IgE, IgH, IgM
    4. IgA, IgD, IgE, IgG, IgK
    5. IgA, IgD, IgE, IgG, IgS.

     

    4–2

    The name given to a fully activated and differentiated B cell that secretes antibody is

    1. T cell
    2. antigen-presenting cell
    3. hematopoietic cell
    4. secretory cell
    5. plasma cell.

     

    4–3      Describe the structure of an antibody molecule and how this structure enables it to bind to a specific antigen. Include the following terms in your description: heavy chain (H chain), light chain (L chain), variable region, constant region, Fab, Fc, antigen-binding site, hypervariable region, and framework region.

     

    4–4      Match the antibody term in Column A with its correct description in Column B.

     

    Column A Column B
    ___a. hinge region 1. the stem that carries out effector function of antibodies through interaction with cell-bound receptors and serum proteins
    ___b. κ 2. provides flexibility to permit binding to different antigenic arrangements
    ___c. Fab 3. a heavy-chain isotype
    ___d. α 4. the arms of the antibody that bind antigen
    ___e. Fc 5. a light-chain isotype

     

     

    4–5      All of the following comprise heavy-chain isotypes of immunoglobulin except

    1. α
    2. β
    3. γ
    4. δ
    5. ε

     

    4–6      Which of the following statements regarding immunoglobulin light chains is correct?

    1. κ associates with only particular heavy-chain isotypes.
    2. There is no functional difference between κ and λ.
    3. A given antibody may contain just κ, or just λ, or both.
    4. Most antibodies in humans contain λ light chains.
    5. Light chains possess only framework regions, not hypervariable regions.

     

    4–7

    _____, _____, and _____ are the three most abundant antibodies in blood:

    1. IgA, IgD, and IgE
    2. IgA, IgE, and IgG
    3. IgA, IgG, and IgM
    4. IgE, IgG, and IgM
    5. IgD, IgE, and IgM.

     

    4–8

    The five isotypes of immunoglobulin differ from each other in their _____:

    1. light-chain constant regions
    2. heavy-chain constant regions
    3. light-chain variable regions
    4. heavy-chain variable regions
    5. heavy-chain variable and constant regions.

     

    4–9      Which one of the following features renders all IgG antibodies less susceptible to proteolysis than the other antibody classes?

    1. length of the hinge region
    2. ability to exchange chains with other IgG antibodies
    3. presence of additional disulfide bonds
    4. capacity to activate complement
    5. degree of accessibility for binding to C1.

     

    4–10    Which of the following is mismatched?

    1. 100–110-amino-acid motif: immunoglobulin domain
    2. discontinuous epitope: amino acids that are separated in the protein chain but come together in the folded protein
    3. heavy-chain classes: IgG, IgA, IgM, IgE, IgD
    4. multivalent antigen: antigen that carries several epitopes of the same or different specificity
    5. four C domains: IgM and IgD.

     

    4–11

    The _______ contribute to antigen specificity of immunoglobulins, and _______ make up the more conservative flanking regions.

    1. hypervariable loops; framework regions
    2. constant domains; variable domains
    3. heavy chains; light chains
    4. variable gene segments; joining gene segments
    5. antigenic determinants; complementarity determining regions.

     

    4–12    The immunoglobulin heavy-chain gene consists of _______ segments, whereas the immunoglobulin light-chain gene consists of _______ segments.

    1. κ; λ
    2. VDJ; VJ
    3. VJ; VDJ
    4. P; N
    5. RAG-1; RAG-2.

     

    4–13    On the heavy-chain immunoglobulin gene locus, recombination signal sequences flank _______ of the V segment, _______ of the D segment, and _______ of the J segment.

    1. the 5′ side; both sides; the 3′ side
    2. the 5′ side; the 5′ side, the 5′ side
    3. the 3′ side; both sides; the 3′ side
    4. both sides; both sides; both sides
    5. the 3′ side; both sides; the 5′ side.

     

    4–14    Which of the following describes two recombination signal sequences required for a permitted somatic recombination event?

    1. VH 7-12-9::9-23-7 JH
    2. Vλ7-23-9::9-23-7 Jλ
    3. DH 7-12-9::9-23-7 JH
    4. Vκ7-12-9::7-23-9 Jκ
    5. VH 9-23-7::7-12-9 DH.

     

    4–15    The enzyme responsible for recombining V, D, and J segments during somatic recombination is called

    1. V(D)J recombinase
    2. terminal deoxynucleotidyl transferase
    3. exonuclease
    4. DNA polymerase
    5. DNA ligase.

     

    4–16    Which of the following is not a component of V(D)J recombinase?

    1. Artemis
    2. Terminal deoxynucleotidyl transferase
    3. RAG-1/RAG-2
    4. DNA ligase IV
    5. DNA-dependent protein kinase and the associated Ku protein.

     

    4–17    Which of the following corresponds to the antigen-binding site of immunoglobulins?

    1. VH:CH
    2. VH:VL
    3. VL:CL
    4. CH:CL
    5. VH:CL.

     

    4–18    Another term commonly used to describe hypervariable loops is

    1. multivalency
    2. framework regions
    3. hinge region
    4. complementarity-determining regions
    5. signal joint.

     

    4–19    Which of the following is not a term used to describe the molecules or components of molecules to which antibodies bind? (Select all that apply.)

    1. CDR loops
    2. antigen
    3. hypervariable region
    4. antigenic determinant
    5. conformational epitope.

     

    4–20    All of the following are utilized in the binding of antibodies to antigens except

    1. interchain disulfide bonds
    2. hydrogen bonding
    3. hydrophobic interactions
    4. electrostatic forces (salt bridges)
    5. van der Waals interactions.

     

    4–21

    1. What is an epitope?
    2. Define the term multivalent antigen.
    3. How does a linear epitope differ from a conformational epitope?
    4. Do antibodies bind their antigens via noncovalent bonding or via covalent bonding?

     

    4–22

    1. What is the basic structural difference between the immunoglobulins produced by B cells and their descendants before antigen encounter and after antigen encounter?
    2. Say which cell type(s) produce each form.
    3. In which way do these different molecular forms resemble each other?

     

    4–23    A _____ antibody is one that facilitates a chemical reaction involving the antigen to which it binds and interacts.

    1. conformational
    2. multivalent
    3. catalytic
    4. hypervariable
    5. monoclonal.

     

    4–24

    1. Explain why catalytic antibodies are attracting attention in the medical field.
    2. Provide two potential examples.

     

    4–25    Match the term in Column A with its description in Column B.

     

    Column A Column B
    ___a. hybridoma

     

    1. derived from blood following vaccination with an antigen
    ___b. myeloma

     

    2. a pure type of antibody synthesized by a single clone of cells
    ___c. monoclonal antibody

     

    3. immortalized cell line generated by fusing a B cell with a tumor cell
    ___d. antiserum 4. a tumor of plasma cells
    ___e. chimeric monoclonal antibody

     

    5. engineered antibody containing mouse V regions and human C regions

     

     

    4–26    Production by the patient of antibodies against therapeutic mouse monoclonal antibodies is the major limitation for their use in humans. These human anti-antibodies are directed against the _____ of the mouse antibody.

    1. V regions
    2. D regions
    3. C regions
    4. J regions
    5. MC regions.

     

    4–27    Identify the incorrect statement regarding flow cytometry.

    1. Samples must be incubated with fluorescent molecules (such as fluorescent antibodies) before analysis.
    2. It is possible to label samples with two fluorescent tags and determine whether cells are negative or positive for either one tag or the other, or both.
    3. A one-dimensional histogram measures the amount of fluorescence versus cell number.
    4. Samples must consist of a single cell type and not be composed of multiple cell types.
    5. A laser is used to detect labeled cells.
    6. A stream of cells in single file is generated by a nozzle.

     

    4–28    With the exception of B cells, all other cells of the body have the immunoglobulin genes in the

    1. germline configuration
    2. monoclonal form
    3. recombined configuration
    4. expressed configuration
    5. chimeric form.

     

    4–29    Indicate which of the following statements is false. (Select all that apply.)

    1. Immunoglobulin heavy- and light-chain loci are encoded on the same chromosome.
    2. Light chains contain V and J segments, whereas heavy chains contain V, D, and J segments.
    3. The Vκ gene segments are duplicated in about 50% of the human population.
    4. All immunoglobulin loci include a leader sequence.
    5. On the heavy-chain locus, V rearranges to D first, and then J joins the combined VD sequence.
    6. Immunoglobulin heavy-chain loci undergo two rounds of somatic recombination, whereas light-chain loci undergo only one.

     

    4–30    Which of the following statements is correct concerning membrane-coding (MC) exons of immunoglobulin genes?

    1. MC exons are located upstream (5′) of the constant-domain exons.
    2. MC exons code for amino acids that anchor and stabilize the light chain to the membrane of B cells.
    3. MC exons specify transmembrane hydrophobic amino acids that associate with the B-cell membrane.
    4. MC exons are removed from primary RNA transcripts as a consequence of alternative mRNA splicing when secreted antibodies are produced by plasma cells.
    5. Somatic hypermutation causes alteration in the coding sequence of MC exons.

     

    4–31    In what way does the κ light chain differ from the λ light chain?

    1. κ performs a different function from λ when bound to the immunoglobulin heavy chain.
    2. κ, but not λ, is encoded on the same chromosome as the heavy-chain locus.
    3. κ contains a VJ region, whereas λ contains a VDJ region.
    4. The κ locus encodes a single C segment, whereas the λ locus has more than one.
    5. κ contains a transmembrane domain but lambda does not.

     

    4–32    In contrast with leader peptides and the C regions, the V regions in immunoglobulin heavy-chain genes

    1. encode hydrophobic amino acids that anchor the immunoglobulin chains to B-cell membranes
    2. comprise the smallest number of gene segments in the human immunoglobulin loci
    3. are composed of V, D, and J gene segments that must undergo gene rearrangement to generate a transcribable exon
    4. do not undergo somatic hypermutation
    5. are not subject to allelic exclusion.

     

    4–33    Which of the following is matched incorrectly?

    1. κ light-chain locus: chromosome 2
    2. coding joint: nonhomologous end-joining of V and J gene segments
    3. λ light-chain locus: four or five C gene segments
    4. affinity maturation: addition of P and N nucleotides
    5. recombination signal sequence: heptamer–spacer–nonamer.

     

    4–34    The enzyme responsible for adding N nucleotides is

    1. V(D)J recombinase
    2. terminal deoxynucleotidyl transferase
    3. uracil-DNA-glycosylase (UNG)
    4. DNA ligase
    5. activation-induced cytidine deaminase (AID).

     

    4–35    Which of the following enzymes facilitates the process of affinity maturation?

    1. DNA ligase
    2. V(D)J recombinase
    3. terminal deoxynucleotidyl transferase
    4. activation-induced cytidine deaminase (AID)
    5. exonuclease.

     

    4–36    The process of gene rearrangement in immunoglobulin and T-cell receptor genes is called

    1. somatic hypermutation
    2. isotype switching
    3. somatic recombination
    4. apoptosis
    5. clonal selection.

     

    4–37

    1. Explain briefly how a vast number of immunoglobulins of different antigen specificities can be produced from the relatively small number of immunoglobulin genes present in the genome. Include the following terms in your explanation: somatic recombination; germline configuration; V, D, and J segments.
    2. What is the final arrangement of gene segments in the rearranged immunoglobulin heavy-chain gene V region, and in what order do these gene segment rearrangements occur?
    3. In what order do the various immunoglobulin loci rearrange?

     

    4–38    Junctional diversity during gene rearrangement results from the addition of

    1. switch region nucleotides
    2. P and N nucleotides
    3. V, D, and J nucleotides
    4. recombination signal sequences
    5. mutations in complementarity-determining regions.

     

    4–39    What would be the effect of a genetic defect that resulted in a lack of somatic recombination between V, D, and J segments?

     

    3–40

    A circulating B cell that has never before encountered antigen expresses _____ on the cell surface:

    1. IgM and IgD
    2. IgM
    3. IgD
    4. IgM and IgG
    5. IgG
    6. IgE.

     

    4–41    All of the following processes occur in mature B cells after antigen encounter except

    1. alternative splicing
    2. affinity maturation
    3. proliferation
    4. somatic recombination
    5. isotype switching.

     

    4–42

    How do recombination signal sequences ensure that gene segment rearrangement occurs in the right order?

     

    4–43    How is additional diversity introduced into the variable region by the molecular mechanism of somatic recombination? Include the following terms in your answer: junctional diversity, P nucleotides, N nucleotides, terminal deoxynucleotidyl transferase (TdT).

     

    4–44    The third hypervariable region (CDR3) is the most variable site in an immunoglobulin V region. It differs in its composition between the light-chain and heavy-chain V regions. Explain what this difference is and how the diversity in CDR3 is generated.

     

    4–45    Identify the correct order of gene segments in a rearranged heavy-chain gene in a naive B cell.

    1. L–VDJ–Cμ–Cδ
    2. VDJ–Cμ–Cδ–L
    3. L–VDJ–Cδ–Cμ
    4. VDJ–L–Cμ–Cα1
    5. L–VDJ–Cμ–Cα1.

     

    4–46    Which of the following does not describe B-cell receptors?

    1. B-cell receptors are membrane-bound and secreted.
    2. B-cell receptors consist of a variable region and a constant region.
    3. B-cell receptors lack specificity and can bind to a number of different antigens.
    4. B-cell receptors possess specificity and can therefore bind only to unique epitopes.
    5. B cell receptors undergo affinity maturation as a consequence of somatic hypermutation.

     

    4–47    Explain how mature, naive B cells co-express IgM and IgD.

     

    4–48    Describe the process responsible for altering the expression of membrane-bound immunoglobulin to secreted antibody.

     

    4–49    Which of the following determines the isotype of an immunoglobulin?

    1. the composition of the hypervariable regions
    2. whether the immunoglobulin is membrane-bound or secreted
    3. its light chain
    4. its heavy chain
    5. the composition of the cytoplasmic tails of Igα and Igβ

     

    4–50    Naive B cells are recognized by their expression of

    1. no immunoglobulins on the cell surface because somatic recombination has not yet commenced
    2. both membrane-bound and secreted forms of immunoglobulin
    3. both IgM and IgD on the cell surface
    4. V(D)J recombinase
    5. uracil-DNA-glycosylase (UNG).

     

    4–51    Which of the following statements regarding Igα and Igβ proteins are correct? (Select all that apply.)

    1. They associate with all isotypes of antibodies on the cell membrane.
    2. They are not required to form the fully functional B-cell receptor.
    3. They facilitate signal transduction through their long cytoplasmic tails.
    4. They are linked to one another by disulfide linkages.
    5. They are made by somatic rearrangement.

     

    4–52

    1. What are the functions of the Igα and Igβ proteins?
    2. Explain why it is desirable that they do not vary in sequence from cell to cell in the same way that immunoglobulins do.

     

    4–53    The highest degree of diversity resulting from somatic recombination is concentrated ____________ of the VH and VL domains, whereas the point mutations caused by somatic hypermutation are found ____________.

    1. in CDR3; throughout the V region
    2. in CDR3; in CDR1 and CDR2 of VH and VL domains
    3. in CDR1 and CDR2; in CDR3
    4. in CDR1 and CDR2; throughout the V region
    5. in all three CDRs; in C regions.

     

    4–54    As an adaptive immune response progresses, the production of variant antibodies that compete more effectively for antigen occurs, and B cells producing these antibodies are preferentially selected on the basis of their improved binding to antigen. This phenomenon is referred to as _______.

    1. isotype switching
    2. neutralization
    3. allelic exclusion
    4. affinity maturation
    5. somatic rearrangement.

     

    4–55    All of the following are required for isotype switching except

    1. switch-region recombination
    2. J chain
    3. activation-induced cytidine deaminase (AID)
    4. B-cell proliferation
    5. uracil-DNA glycosylase (UNG).

     

    4–56    Which of the following does not activate complement? (Select all that apply.)

    1. IgG1
    2. IgG2
    3. IgG3
    4. IgG4
    5. IgA
    6. IgE
    7. IgM
    8. IgD.

     

    4–57    Which of the following can be found in serum in a monovalent form?

    1. IgG4
    2. IgD
    3. IgA1
    4. antibodies made up of four C domains
    5. IgG3.

     

    4–58    Neutralizing antibodies

    1. interfere with antigen degradation
    2. facilitate uptake of antigen through Fc regions
    3. stimulate complement activation
    4. inhibit interaction of antigen with human cell surfaces
    5. sensitize mast cells and basophils.

     

    4–59    Which of the following statements regarding immunoglobulins is correct?

    1. Immunoglobulins make up five classes (or isotypes) called IgA, IgD, IgE, IgG, and IgM.
    2. Regardless of their isotype, immunoglobulins all have the same effector function.
    3. Antibodies consist of four identical heavy chains and four identical light chains.
    4. Peptide bonds hold the heavy and light chains together.
    5. The constant regions make up the antigen-binding site.

     

    4–60    Indicate which of the following statements are true (T) or and which are false (F) with reference to immunoglobulin structure.

    1. __The antibody secreted by a plasma cell has a different specificity for antigen than the immunoglobulin expressed by its B-cell precursor.
    2. __The amino-terminal regions of heavy and light chains of different immunoglobulins all differ in amino acid sequence.
    3. __A flexible hinge region holds the heavy chain and light chain together.
    4. __The heavy-chain constant region is responsible for the effector function of immunoglobulins.
    5. __λ and κ light chains have different functions.

     

    4–61    Which of the following is mismatched?

    1. surface immunoglobulin: B-cell antigen receptor
    2. affinity maturation: isotype switching
    3. constant region of antibodies: binding to complement proteins
    4. activation-induced cytidine deaminase: somatic hypermutation
    5. switch sequences: class switching.

     

    4–62    Which of the following statements about the production and use of monoclonal antibodies is incorrect?

    1. Production of monoclonal antibodies requires a purified form of antigen.
    2. A monoclonal antibody has specificity for only one epitope of an antigen.
    3. B cells are fused with a tumor cell called a myeloma, to immortalize the resulting hybridoma.
    4. Monoclonal antibodies made in mice have limited therapeutic potential.
    5. Humanized monoclonal antibodies reduce complications associated with using mouse monoclonal antibodies.

     

    4–63    The mutational mechanism that results in the production of antibodies that bind antigen with higher affinity is called _____:

    1. somatic recombination
    2. isotype switching
    3. somatic hypermutation
    4. clonal selection
    5. antigen processing.

     

    4–64    The process of _____ results in change in the constant region of the heavy-chain of antibodies, causing a change in the effector function and transport properties of antibodies:

    1. complement fixation
    2. neutralization
    3. isotype switching
    4. somatic hypermutation
    5. somatic recombination.

     

    4–65    The process used to produce either surface or secreted forms of the immunoglobulin heavy chain is called

    1. alternative RNA processing
    2. isotype switching
    3. somatic recombination
    4. somatic hypermutation
    5. opsonization.

     

    4–66

    1. What is affinity maturation and what molecular process enables it to occur?
    2. Describe this process and its consequences.

     

    4–67

    1. What is isotype switching?
    2. Explain the molecular mechanism of isotype switching.
    3. Why is isotype switching important?

     

    4–68    Which immunoglobulin isotypes (out of IgM, IgG1, IgG2, IgG3, IgG4, IgA, IgE, and IgD) participate in (a) neutralization; (b) opsonization; (c) sensitization for killing by NK cells; (d) sensitization of mast cells; (e) activation of complement? Which isotypes (f) are transported across epithelium; (g) are transported across the placenta; (h) diffuse into extravascular sites?

     

    4–69    Isotype switching and immunoglobulin gene rearrangement by somatic recombination are both recombinational processes but have very different outcomes. Give four ways in which they differ from each other.

     

    4–70    Monoclonal antibodies are used for a wide range of applications including serological assays and diagnostics probes in the laboratory, and as therapeutic reagents in the clinic. Discuss why ‘humanizing’ monoclonal antibodies is necessary for use as therapeutic reagents but is not necessary when monoclonal antibodies are used as serological or diagnostic reagents.

     

    4–71    What would be the effect of a genetic defect that resulted in a lack of recombination between the switch regions in the immunoglobulin C-region genes?

     

    4–72    Influenza virus contains two proteins, called hemagglutinin and neuraminidase, exposed on the surface of the virion. Two additional proteins, located on the interior of the virion, are called matrix protein and nucleoprotein. Which of these four proteins will generate a better antibody response and why?

     

    4–73

    1. Identify the four types of antibody used for therapeutic purposes.
    2. How is each produced?
    3. (i) Which is most desirable for the treatment of chronic conditions? (ii) Why? (iii) Provide an example.

     

    4–74

    1. What is the difference between polyclonal antibodies and monoclonal antibodies?
    2. How is each produced?

     

    4–75    Match the term in Column A with its description in Column B

    Column A Column B
    ___a. monoclonal antibody production

     

    1. the rearrangement of V, D, and J segments to form an immunoglobulin

     

    ___b. isotype switching

     

    2. the derivation of antibodies from a single clone of B lymphocytes that have identical antigen specificity
    ___c. opsonization

     

    3. change of immunoglobulin class but preservation of antigen specificity
    ___d. somatic hypermutation

     

    4. nucleotide changes in variable regions of immunoglobulin genes affecting affinity for antigen
    ___e. somatic recombination.

     

    5. enhancement of receptor-mediated phagocytosis of immunoglobulin-coated antigen

     

    4–76    IgM and IgD are co-expressed on naive B cells by a process called

    1. isotype switching
    2. somatic recombination
    3. somatic hypermutation
    4. alternative mRNA splicing
    5. affinity maturation.

     

    4–77    Which immunoglobulin’s main function is to mediate sensitization of mast cells?

    1. IgA
    2. IgD
    3. IgE
    4. IgG
    5. IgM.

     

    4–78    Which immunoglobulin is transported most efficiently across mucosal epithelium?

    1. IgA
    2. IgD
    3. IgE
    4. IgG
    5. IgM.

     

    4–79    _______ forms dimers, whereas _______ forms pentamers.

    1. IgG; IgD
    2. IgE; IgM
    3. IgD; IgM
    4. IgA; IgM
    5. IgM; IgG.

     

    4–80    A newborn derives passive immunity from its mother as a result of placental transfer of _____ during pregnancy.

    1. IgA
    2. IgD
    3. IgE
    4. IgG
    5. IgM.

     

    4–81    _____ is secreted into the bloodstream, whereas _____ is secreted into mucus such as gastrointestinal fluid, colostrum, saliva, tears, and sweat.

    1. monomeric IgM: pentameric IgM
    2. monomeric IgA: dimeric IgA
    3. monomeric IgA: dimeric IgG
    4. monomeric IgA: monomeric IgM
    5. dimeric IgA: pentameric IgM.

     

    4–82    Identify which of the following is not associated with activation-induced cytidine deaminase (AID) activity.

    1. diversification of the VH domain but not the VL domain
    2. synthesized in proliferating B cells during active immune responses
    3. somatic hypermutation
    4. isotype switching
    5. conversion of cytosine to uracil.

     

    4–83    The process of _____ results in the amplification of particular B cells with specificity for antigen:

    1. germline recombination
    2. somatic recombination
    3. clonal selection
    4. antigen processing
    5. antigen presentation.

     

    4–84    The antibody transported across mucosal epithelia is _____:

    1. IgA
    2. IgD
    3. IgE
    4. IgG
    5. IgM.

    THE IMMUNE SYSTEM, FOURTH EDITION

    CHAPTER 6: THE DEVELOPMENT OF B LYMPHOCYTES

    © 2015 Garland Science

     

     

     

    6–1      Describe the six functionally distinct phases of B-cell development.

     

    6–2      Which of the following cell-surface markers differentiates hematopoietic stem cells from other cell constituents in the bone marrow?

    1. pre-B-cell receptor
    2. BAFF receptor
    3. CD34
    4. CD4
    5. membrane-bound stem-cell factor (SCF).

     

    6–3      You are going to use flow cytometry to determine the proportion of developing B cells in the bone marrow that are immature, anergic, or mature. You have three monoclonal antibodies specific for three different B-cell surface proteins. The first has specificity for the cell-surface protein CD19, which is expressed by all developing and mature B cells; the second is specific for the Fc region of IgD; and the third is specific for the Fc region of IgM. The antibodies are conjugated to three different fluorescent tags that can be detected and distinguished by the flow cytometer.

    1. Use histograms to show your analysis of CD19-positive cells and indicate which part of your histogram you would gate to analyze IgM and IgD expression. Indicate the gated population with an arrow.
    2. Using a two-dimensional dot plot, compare the expression of IgD and IgM of these gated cells, and say which of these populations represents (i) immature B cells, (ii) mature B cells, and (iii) anergic B cells.

     

    6–4      Which of the following is characteristic of a large pre-B cell?

    1. VDJ is successfully rearranged and μ heavy chain is made.
    2. V–J is rearranging at the light-chain locus.
    3. μ heavy chain and λ or κ light chain is made.
    4. V is rearranging to DJ at the heavy-chain locus.
    5. D–J is rearranging at the heavy-chain locus.

     

    6–5      Which of the following statements is correct?

    1. The κ light-chain genes rearrange before the heavy-chain genes.
    2. The κ light-chain genes rearrange before the λ light-chain genes.
    3. The λ light-chain genes rearrange before the heavy-chain genes.
    4. The λ light-chain genes rearrange before the κ light-chain genes.
    5. The μ heavy-chain genes rearrange first and then the λ light-chain genes rearrange.

     

    6–6      Immature B cells develop into B cells in the

    1. subendosteum
    2. bone marrow
    3. thymus
    4. blood
    5. secondary lymphoid organs.

     

    6–7      Place the following phases of a B cell’s life history in the correct chronological order.

    1. negative selection
    2. attacking infection
    3. finding infection
    4. searching for infection
    5. repertoire assembly
    6. positive selection.

     

    6–8      Place the following stages of B-cell development in the correct chronological order.

    1. early pro-B cell
    2. large pre-B cell
    3. immature B cell
    4. stem cell
    5. late pre-B cell
    6. small pre-B cell.

     

    6–9

    1. Discuss the importance of the bone marrow stroma for B-cell development.
    2. What would be the effect of anti-IL-7 antibodies on the development of B cells in the bone marrow, and at which stage would development be impaired? Explain your answer.

     

    6–10

    1. What are the two main checkpoints of B-cell development in the bone marrow?
    2. What is the fate of developing B cells that produce (i) functional or (ii) nonfunctional heavy and light chains?
    3. Explain how these two checkpoints correlate with the process of allelic exclusion that ensures that only one heavy-chain locus and one light-chain locus produce functional gene products.

     

    6–11    Large pre-B cells are characterized by which of the following?

    1. They do not express CD19 at the cell surface.
    2. Rearrangement of light-chain genes commences.
    3. Nonproductive rearrangement of both heavy-chain loci has already occurred.
    4. Allelic exclusion of the immunoglobulin light-chain loci has already occurred.
    5. μ is assembled with VpreBλ5.

     

    6–12    All hematopoietic stem cells express

    1. CD34
    2. CD127
    3. CD19
    4. VpreBλ5
    5. Pax-5

     

    6–13    Which of the following do not associate with one another during B-cell development?

    1. IL-7: IL-7 receptor of late pro-B cells
    2. Pax-5: CD19 gene
    3. surrogate light chain: δ heavy chain
    4. VpreB: λ5
    5. SCF: Kit
    6. pre-B-cell receptor: Igα and Igβ

     

    6–14    The latest stages of late pro-B-cell development are recognized by the association of a surrogate light chain with a μ chain. The surrogate light chain is composed of

    1. E2A and EFB
    2. Igα and Igβ
    3. VpreB and λ5
    4. RAG-1 and RAG-2
    5. Pax-5 and CD19.

     

    6–15    A genetic defect in the λ5 gene would cause which of the following consequences? (Select all that apply.)

    1. inability to produce functional μ chains
    2. inability to produce a pre-B-cell receptor
    3. inability to produce functional κ or λ chains
    4. production of different light chains owing to defects in allelic exclusion
    5. B-cell immunodeficiency
    6. chronic bacterial infections
    7. requirement for prophylactic injections of antibodies from healthy donors.

     

    6–16    What would be the consequence if terminal deoxynucleotidyl transferase (TdT) were expressed throughout the whole of small pre-B-cell development?

     

    6–17    Which of the following is not paired with its correct complement?

    1. N nucleotides: more abundant in rearranged heavy-chain genes than in rearranged light-chain genes
    2. second checkpoint in B-cell development: assembly of a functional B-cell receptor
    3. receptor editing: exchange of light chain for one that is not self-reactive
    4. first checkpoint in B-cell development: selection by the pre-B-cell receptor
    5. large pre-B-cell stage: constitutive expression of RAG-1 and RAG-2 proteins.

     

    6–18    Which of the following would occur after the production of a functional μ chain as a pre-B-cell receptor?

    1. RAG proteins are degraded.
    2. The chromatin structure of the heavy-chain locus is reorganized to prevent gene rearrangement.
    3. Transcription of the RAG1 and RAG2 genes ceases.
    4. There is allelic exclusion of a second μ chain.
    5. All of the above would occur.

     

    6–19    An important advantage of having two gene loci (κ and λ) for the light chain is

    1. that the likelihood of a successful rearrangement of light-chain genes increases.
    2. that immunoglobulins are homogeneous and not heterogeneous in mature B cells.
    3. that different effector functions are conferred by the two different light-chain loci.
    4. that surrogate light-chain transcription cannot compete with κ and λ transcription and enables B-cell development.
    5. all of the above.

     

    6–20    Which of the following is correctly matched? (Select all that apply.)

    1. early pro-B cell: VDJ rearranged
    2. pre-B-cell receptor: VpreBλ5/μu heavy chain
    3. mature B cell: IgM plus IgD
    4. small pre-B cell: VJ rearranged
    5. immature B cell: μ heavy chain plus λ or κ light chain on surface.

     

    6–21    Large pre-B cells undergo clonal expansion before the rearrangement of light-chain loci. Which of the following are beneficial consequences of clonal expansion? (Select all that apply.)

    1. Autoreactive B cells are eliminated before the expenditure of energy needed to rearrange a functional light-chain gene.
    2. The energy used to make a functional heavy chain is not wasted as a result of the inability to produce a functional light chain.
    3. RAG gene expression is decreased, which in turn signals light-chain rearrangement.
    4. A diverse population of immature B cells is generated that express the same μ chain but a distinct light chain.
    5. Approximately 85% of small pre-B cells will progress to the immature B-cell stage.

     

    6–22    When expression of _______ is turned off in small pre-B cells, the result is the presence of P nucleotides but an absence of N nucleotides in around 50% of light-chain genes.

    1. Kit
    2. CD19
    3. TdT
    4. Pax-5
    5. RAG-1 and RAG-2.

     

    6–23    A defect in which of the following proteins blocks B-cell development at the pre-B-cell stage, resulting in almost no circulating antibodies in individuals with this defect?

    1. IL-7 receptor
    2. terminal deoxynucleotidyltransferase (TdT)
    3. Pax-5
    4. Bruton’s tyrosine kinase (Btk)
    5. CD19.

     

    6–24    The consequence of allelic exclusion at the immunoglobulin loci ensures that _____. (Select all that apply.)

    1. B-cell receptors have a low-avidity binding
    2. B cells express antigen receptors of a single specificity
    3. hybrid immunoglobulins are formed
    4. all functional copies of a gene are expressed
    5. homogeneous B-cell receptors bind more effectively to antigen.

     

    6–25    A developing B cell unable to generate a productive rearrangement on any of the four light-chain loci will undergo

    1. self-renewal
    2. apoptosis
    3. allelic exclusion
    4. malignant transformation
    5. differentiation into a B-1 cell.

     

    6–26    All of the following participate in signal transduction in developing B cells except

    1. terminal deoxynucleotidyl transferase (TdT)
    2. FLT3
    3. CD19
    4. Igα and Igβ
    5. Bruton’s tyrosine kinase (Btk)
    6. CD45

     

    6–27    Negative selection of developing B cells ensures that

    1. there is not an overabundance of circulating B cells that would compete with other important cell types in the circulation
    2. only antigen-activated B cells leave the bone marrow
    3. clonal expansion of B cells does not occur in the absence of infection
    4. B-cell receptors that bind to normal constituents of the body do not emerge
    5. B cells do not leave secondary lymphoid tissues.

     

    6–28    Receptor editing occurs _____. (Select all that apply.)

    1. in the bone marrow
    2. after encounter with foreign antigen in secondary lymphoid organs
    3. in mature B cells
    4. to establish self-tolerance of the B-cell repertoire
    5. to express an excess of IgM over IgD on the surface of mature B cells.

     

    6–29    Which of the following statements about the IgD made by B cells of upper respiratory mucosa is not true?

    1. These antibodies bind to airborne bacteria such as Haemophilus influenzae.
    2. λ light chains are used almost exclusively by these IgD antibodies.
    3. Two-thirds of these IgD antibodies possess κ light chains.
    4. These IgD antibodies recruit basophils and induce the secretion of antibacterial peptides.

     

    6–30    Individuals who fail to express functional Bruton’s tyrosine kinase exhibit all of the following characteristics except

    1. B-cell development is blocked at the immature B-cell stage.
    2. They are usually male because the Btk gene is on the X chromosome.
    3. They suffer from an immune deficiency known as X-linked agammaglobulinemia (XLA).
    4. Recurrent infections with extracellular bacteria are common.
    5. They benefit from treatment with immunoglobulin infusions.

     

    6–31    All of the following are associated with the development of Burkitt’s lymphoma except

    1. The expression of Myc protein is perturbed.
    2. A chromosomal translocation involving a proto-oncogene and an immunoglobulin gene occurs.
    3. Overproduction of the Bcl-2 protein prolongs the lifetime of B-lineage cells.
    4. Cell division restraints on mutated B cells are lifted.
    5. In addition to a chromosomal translocation event, mutations elsewhere in the genome are usually involved.

     

    6–32    Which of the following is a characteristic of B-2 cells?

    1. They are sometimes referred to as CD5 B cells.
    2. They comprise only 5% of the B-cell repertoire.
    3. In adults, they are renewed by cell division in the peripheral circulation.
    4. They are located primarily in secondary lymphoid organs.
    5. They are not dependent on T helper cells for activation.

     

    6–33    Identify the mismatched pair of chemokine and the cells that secrete it.

    1. CCL19: lymph-node dendritic cells
    2. CXCL13: follicular dendritic cells
    3. CCL21: stromal cells of secondary lymphoid tissues
    4. All of the above are correctly matched.

     

    6–34    Plasma cells have all of the properties listed except

    1. they rapidly proliferate in secondary lymphoid follicles
    2. they secrete antibody
    3. they are terminally differentiated B cells
    4. they no longer express MHC class II molecules
    5. they cease expressing membrane-bound immunoglobulin
    6. they differentiate into plasma cells after migration from germinal centers to other sites in lymphoid tissue and bone marrow.

     

    6–35    All of the following events occur within germinal centers except

    1. centrocytes mature from centroblasts
    2. isotype switching
    3. centroblasts arise from activated B ells
    4. B cells are activated by CD4 helper T cells
    5. affinity maturation
    6. somatic hypermutation
    7. production of memory B cells.

     

    6–36    In which location would plasma cells not be present?

    1. bone marrow
    2. afferent lymphatic vessels
    3. medullary cords of lymph nodes
    4. lamina propria of gut-associated lymphoid tissues
    5. red pulp of spleen
    6. efferent lymphatic vessels.

     

    6–37    Match the name of the B-cell tumor in Column A with its correct description in Column B.

    Column A Column B
    ___a.   multiple myeloma 1.         most cases caused by B-1 cells
    ___b.   chronic lymphocytic leukemia (CLL) 2.         derived from lymphoid progenitor in bone marrow and rearrangement of immunoglobulin loci has not occurred
    ___c.   acute lymphoblastic leukemia (ALL) 3.         expresses VpreBλ5
    ___d.   Burkitt’s lymphoma 4.         derived from plasma cells in the bone marrow
    ___e.   pre-B-cell leukemia 5.         associated with chromosomal translocations involving the proto-oncogene MYC

     

     

    6–38    Which of the following is true of centrocytes? (Select all that apply.)

    1. Somatic hypermutation has occurred.
    2. They are large proliferating cells.
    3. Isotype switching is complete.
    4. They produce secreted forms of immunoglobulins.
    5. They lack MHC class II molecules on the cell surface.

     

     

    6–39    Immunological tolerance in the B-cell repertoire is called _______ tolerance when it develops in primary lymphoid organs, and _______ tolerance when it is induced outside the bone marrow.

    1. primary; secondary
    2. apoptotic; anergic
    3. stromal; follicular
    4. receptor-mediated; systemic
    5. central; peripheral.

     

    6–40    What is the role of primary lymphoid follicles in eliminating B cells that have antigen receptors specific for soluble self antigen?

     

    6–41    A plasma cell is characterized by which of the following features? (Select all that apply.)

    1. It differentiates in the medulla of lymph nodes and the bone marrow.
    2. It dedicates 10–20% of total protein synthesis to antibody production.
    3. Levels of MHC class II molecules are elevated.
    4. It undergoes extensive proliferation in germinal centers.
    5. It produces secreted immunoglobulin instead of the membrane-bound form.

     

    6–42

    1. Explain why immunological memory is important in acquired immunity.
    2. Describe how immunoglobulin expressed during a primary immune response differs qualitatively and quantitatively from the immunoglobulin expressed during a secondary immune response.

     

    6–43    When producing monoclonal antibodies, why is it important to use as a fusion partner a myeloma cell that is unable to produce its own immunoglobulin?

    1. to ensure that allelic exclusion of μ chain occurs normally
    2. to ensure that the antibodies are homogeneous and able to make strong bivalent attachments to multivalent antigens
    3. to ensure that the monoclonal antibodies are not autoreactive
    4. to provide a greater opportunity for making a successful rearrangement at the light-chain locus
    5. to ensure that antibodies are secreted and not membrane-bound.

     

    6–44    The proto-oncogene _______ is associated with the development of Burkitt’s lymphoma.

    1. BCL-2
    2. Myc
    3. CD5
    4. CD19
    5. BTK.

     

    6–45    Which of the following characterizes the B-1 cells that develop prenatally?

    1. They lack N nucleotides.
    2. They possess polyspecificity for bacterial polysaccharide antigens.
    3. They arise early in embryonic development preceding the development of the majority subset of B cells.
    4. They have little or no IgD on the cell surface.
    5. All of the above.

     

    6–46    Explain how B cells undergo the process of negative selection and indicate at which stage of development and at which location these events occur.

     

    6–47    What is the fate of an immature B cell that encounters and has specificity for self antigen?

    1. If further heavy-chain and light-chain gene rearrangements are possible, it undergoes apoptosis.
    2. Somatic hypermutation.
    3. Decrease in production of IgD.
    4. Continued rearrangement of heavy-chain genes.
    5. Continued rearrangement of light-chain genes.

     

    6–48    Which of the following pertains to the fate of immature B cells that have specificity for univalent self antigens? (Select all that apply.)

    1. The cells acquire a state of unresponsiveness called anergy.
    2. IgD is retained in the cytosol.
    3. IgD on the cell surface fails to activate the B cell when bound to self antigen.
    4. The cells have a much longer life-span than mature B cells.
    5. The cells die by apoptosis.

     

    6–49    The circulatory route through a lymphoid tissue for both immature B cells and mature B cells that do not encounter specific antigen is:

    1. bloodstream →HEV of lymphoid cortex → primary lymphoid follicle → efferent lymphatic vessel
    2. afferent lymphatic vessel → primary lymphoid follicle →HEV of lymphoid cortex →efferent lymphatic vessel
    3. afferent lymphatic vessel →medullary cords → primary lymphoid follicle →efferent lymphatic vessel
    4. primary lymphoid follicle →HEV of lymphoid cortex →afferent lymphatic vessel →efferent lymphatic vessel
    5. bloodstream →afferent lymphatic vessel → HEV of lymphoid cortex →efferent lymphatic vessel.

     

    6–50

    1. Give three properties that distinguish B-1 cells from B-2 cells.
    2. Do you think that B-1 cells should be categorized as participants in innate immune responses or in acquired immune responses? Explain your rationale.

     

    6–51

    1. Identify properties that are shared by anergic B cells and plasma cells.
    2. What key property is different?

     

    6–52    Indicate which of the following statements concerning memory B cells are true (T) and which are false (F):

    ___ a.  Memory B cells are derived from germinal center B cells as immune responses subside.

    ___ b.  Memory B cells have long life spans.

    ___ c.  Memory B cells possess high-affinity antigen receptors as a consequence of affinity maturation.

    ___ d.  Memory B cells have more stringent requirements for activation than naive B cells do.

    ___ e.  Memory B cells express only IgM and retain the capacity to switch to the most beneficial isotype during secondary responses.

     

    6–53    Hinda Mundy, 26 years old, grew concerned when a lump appeared in her lower neck and she had pain in her chest and a dry cough. She also told her physician that she had experienced fatigue, night sweats, unintentional weight loss, pruritis (dry, itchy skin), and intermittent fevers over the past few months. Immunohistological staining of a biopsy of the enlarged lymph node revealed the presence of large multinucleated Reed–Sternberg cells. Polymerase chain reaction (PCR) tests confirmed immunoglobulin gene rearrangements; however, B-cell antigen expression was absent. Hinda entered complete remission after treatment with four cycles of chemotherapy combined with radiotherapy. These symptoms and treatment are most consistent with a diagnosis of

    1. Hodgkin’s lymphoma
    2. multiple myeloma
    3. acute lymphoblastic leukemia (ALL)
    4. Waldenström’s magroglobulinemia
    5. chronic lymphocytic leukemia (CLL).

     

    6–54    Multiple myeloma involves the unregulated proliferation of an antibody-producing plasma cell (myeloma cell) independently of antigen stimulation or T-cell help. Myeloma cells populate multiple sites in the bone marrow, where they produce immense quantities of monoclonal immunoglobulin as well as suppressing normal marrow function. Myeloma cells also synthesize and secrete excessive amounts of free light chains (known as Bence-Jones protein), which, because of their low molecular weight (~25 kDa) are excreted as free light chains in the urine.

    In a given patient the free light chains are both monoclonal and all are of either the κ or the λ type.

    1. Explain both of these observations.
    2. Why do you think patients with multiple myeloma are more susceptible than normal to pyogenic infections, such as pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae?
  6. THE IMMUNE SYSTEM, FOURTH EDITION

    CHAPTER 6: THE DEVELOPMENT OF B LYMPHOCYTES

    © 2015 Garland Science

     

     

     

    6–1      Describe the six functionally distinct phases of B-cell development.

     

    6–2      Which of the following cell-surface markers differentiates hematopoietic stem cells from other cell constituents in the bone marrow?

    1. pre-B-cell receptor
    2. BAFF receptor
    3. CD34
    4. CD4
    5. membrane-bound stem-cell factor (SCF).

     

    6–3      You are going to use flow cytometry to determine the proportion of developing B cells in the bone marrow that are immature, anergic, or mature. You have three monoclonal antibodies specific for three different B-cell surface proteins. The first has specificity for the cell-surface protein CD19, which is expressed by all developing and mature B cells; the second is specific for the Fc region of IgD; and the third is specific for the Fc region of IgM. The antibodies are conjugated to three different fluorescent tags that can be detected and distinguished by the flow cytometer.

    1. Use histograms to show your analysis of CD19-positive cells and indicate which part of your histogram you would gate to analyze IgM and IgD expression. Indicate the gated population with an arrow.
    2. Using a two-dimensional dot plot, compare the expression of IgD and IgM of these gated cells, and say which of these populations represents (i) immature B cells, (ii) mature B cells, and (iii) anergic B cells.

     

    6–4      Which of the following is characteristic of a large pre-B cell?

    1. VDJ is successfully rearranged and μ heavy chain is made.
    2. V–J is rearranging at the light-chain locus.
    3. μ heavy chain and λ or κ light chain is made.
    4. V is rearranging to DJ at the heavy-chain locus.
    5. D–J is rearranging at the heavy-chain locus.

     

    6–5      Which of the following statements is correct?

    1. The κ light-chain genes rearrange before the heavy-chain genes.
    2. The κ light-chain genes rearrange before the λ light-chain genes.
    3. The λ light-chain genes rearrange before the heavy-chain genes.
    4. The λ light-chain genes rearrange before the κ light-chain genes.
    5. The μ heavy-chain genes rearrange first and then the λ light-chain genes rearrange.

     

    6–6      Immature B cells develop into B cells in the

    1. subendosteum
    2. bone marrow
    3. thymus
    4. blood
    5. secondary lymphoid organs.

     

    6–7      Place the following phases of a B cell’s life history in the correct chronological order.

    1. negative selection
    2. attacking infection
    3. finding infection
    4. searching for infection
    5. repertoire assembly
    6. positive selection.

     

    6–8      Place the following stages of B-cell development in the correct chronological order.

    1. early pro-B cell
    2. large pre-B cell
    3. immature B cell
    4. stem cell
    5. late pre-B cell
    6. small pre-B cell.

     

    6–9

    1. Discuss the importance of the bone marrow stroma for B-cell development.
    2. What would be the effect of anti-IL-7 antibodies on the development of B cells in the bone marrow, and at which stage would development be impaired? Explain your answer.

     

    6–10

    1. What are the two main checkpoints of B-cell development in the bone marrow?
    2. What is the fate of developing B cells that produce (i) functional or (ii) nonfunctional heavy and light chains?
    3. Explain how these two checkpoints correlate with the process of allelic exclusion that ensures that only one heavy-chain locus and one light-chain locus produce functional gene products.

     

    6–11    Large pre-B cells are characterized by which of the following?

    1. They do not express CD19 at the cell surface.
    2. Rearrangement of light-chain genes commences.
    3. Nonproductive rearrangement of both heavy-chain loci has already occurred.
    4. Allelic exclusion of the immunoglobulin light-chain loci has already occurred.
    5. μ is assembled with VpreBλ5.

     

    6–12    All hematopoietic stem cells express

    1. CD34
    2. CD127
    3. CD19
    4. VpreBλ5
    5. Pax-5

     

    6–13    Which of the following do not associate with one another during B-cell development?

    1. IL-7: IL-7 receptor of late pro-B cells
    2. Pax-5: CD19 gene
    3. surrogate light chain: δ heavy chain
    4. VpreB: λ5
    5. SCF: Kit
    6. pre-B-cell receptor: Igα and Igβ

     

    6–14    The latest stages of late pro-B-cell development are recognized by the association of a surrogate light chain with a μ chain. The surrogate light chain is composed of

    1. E2A and EFB
    2. Igα and Igβ
    3. VpreB and λ5
    4. RAG-1 and RAG-2
    5. Pax-5 and CD19.

     

    6–15    A genetic defect in the λ5 gene would cause which of the following consequences? (Select all that apply.)

    1. inability to produce functional μ chains
    2. inability to produce a pre-B-cell receptor
    3. inability to produce functional κ or λ chains
    4. production of different light chains owing to defects in allelic exclusion
    5. B-cell immunodeficiency
    6. chronic bacterial infections
    7. requirement for prophylactic injections of antibodies from healthy donors.

     

    6–16    What would be the consequence if terminal deoxynucleotidyl transferase (TdT) were expressed throughout the whole of small pre-B-cell development?

     

    6–17    Which of the following is not paired with its correct complement?

    1. N nucleotides: more abundant in rearranged heavy-chain genes than in rearranged light-chain genes
    2. second checkpoint in B-cell development: assembly of a functional B-cell receptor
    3. receptor editing: exchange of light chain for one that is not self-reactive
    4. first checkpoint in B-cell development: selection by the pre-B-cell receptor
    5. large pre-B-cell stage: constitutive expression of RAG-1 and RAG-2 proteins.

     

    6–18    Which of the following would occur after the production of a functional μ chain as a pre-B-cell receptor?

    1. RAG proteins are degraded.
    2. The chromatin structure of the heavy-chain locus is reorganized to prevent gene rearrangement.
    3. Transcription of the RAG1 and RAG2 genes ceases.
    4. There is allelic exclusion of a second μ chain.
    5. All of the above would occur.

     

    6–19    An important advantage of having two gene loci (κ and λ) for the light chain is

    1. that the likelihood of a successful rearrangement of light-chain genes increases.
    2. that immunoglobulins are homogeneous and not heterogeneous in mature B cells.
    3. that different effector functions are conferred by the two different light-chain loci.
    4. that surrogate light-chain transcription cannot compete with κ and λ transcription and enables B-cell development.
    5. all of the above.

     

    6–20    Which of the following is correctly matched? (Select all that apply.)

    1. early pro-B cell: VDJ rearranged
    2. pre-B-cell receptor: VpreBλ5/μu heavy chain
    3. mature B cell: IgM plus IgD
    4. small pre-B cell: VJ rearranged
    5. immature B cell: μ heavy chain plus λ or κ light chain on surface.

     

    6–21    Large pre-B cells undergo clonal expansion before the rearrangement of light-chain loci. Which of the following are beneficial consequences of clonal expansion? (Select all that apply.)

    1. Autoreactive B cells are eliminated before the expenditure of energy needed to rearrange a functional light-chain gene.
    2. The energy used to make a functional heavy chain is not wasted as a result of the inability to produce a functional light chain.
    3. RAG gene expression is decreased, which in turn signals light-chain rearrangement.
    4. A diverse population of immature B cells is generated that express the same μ chain but a distinct light chain.
    5. Approximately 85% of small pre-B cells will progress to the immature B-cell stage.

     

    6–22    When expression of _______ is turned off in small pre-B cells, the result is the presence of P nucleotides but an absence of N nucleotides in around 50% of light-chain genes.

    1. Kit
    2. CD19
    3. TdT
    4. Pax-5
    5. RAG-1 and RAG-2.

     

    6–23    A defect in which of the following proteins blocks B-cell development at the pre-B-cell stage, resulting in almost no circulating antibodies in individuals with this defect?

    1. IL-7 receptor
    2. terminal deoxynucleotidyltransferase (TdT)
    3. Pax-5
    4. Bruton’s tyrosine kinase (Btk)
    5. CD19.

     

    6–24    The consequence of allelic exclusion at the immunoglobulin loci ensures that _____. (Select all that apply.)

    1. B-cell receptors have a low-avidity binding
    2. B cells express antigen receptors of a single specificity
    3. hybrid immunoglobulins are formed
    4. all functional copies of a gene are expressed
    5. homogeneous B-cell receptors bind more effectively to antigen.

     

    6–25    A developing B cell unable to generate a productive rearrangement on any of the four light-chain loci will undergo

    1. self-renewal
    2. apoptosis
    3. allelic exclusion
    4. malignant transformation
    5. differentiation into a B-1 cell.

     

    6–26    All of the following participate in signal transduction in developing B cells except

    1. terminal deoxynucleotidyl transferase (TdT)
    2. FLT3
    3. CD19
    4. Igα and Igβ
    5. Bruton’s tyrosine kinase (Btk)
    6. CD45

     

    6–27    Negative selection of developing B cells ensures that

    1. there is not an overabundance of circulating B cells that would compete with other important cell types in the circulation
    2. only antigen-activated B cells leave the bone marrow
    3. clonal expansion of B cells does not occur in the absence of infection
    4. B-cell receptors that bind to normal constituents of the body do not emerge
    5. B cells do not leave secondary lymphoid tissues.

     

    6–28    Receptor editing occurs _____. (Select all that apply.)

    1. in the bone marrow
    2. after encounter with foreign antigen in secondary lymphoid organs
    3. in mature B cells
    4. to establish self-tolerance of the B-cell repertoire
    5. to express an excess of IgM over IgD on the surface of mature B cells.

     

    6–29    Which of the following statements about the IgD made by B cells of upper respiratory mucosa is not true?

    1. These antibodies bind to airborne bacteria such as Haemophilus influenzae.
    2. λ light chains are used almost exclusively by these IgD antibodies.
    3. Two-thirds of these IgD antibodies possess κ light chains.
    4. These IgD antibodies recruit basophils and induce the secretion of antibacterial peptides.

     

    6–30    Individuals who fail to express functional Bruton’s tyrosine kinase exhibit all of the following characteristics except

    1. B-cell development is blocked at the immature B-cell stage.
    2. They are usually male because the Btk gene is on the X chromosome.
    3. They suffer from an immune deficiency known as X-linked agammaglobulinemia (XLA).
    4. Recurrent infections with extracellular bacteria are common.
    5. They benefit from treatment with immunoglobulin infusions.

     

    6–31    All of the following are associated with the development of Burkitt’s lymphoma except

    1. The expression of Myc protein is perturbed.
    2. A chromosomal translocation involving a proto-oncogene and an immunoglobulin gene occurs.
    3. Overproduction of the Bcl-2 protein prolongs the lifetime of B-lineage cells.
    4. Cell division restraints on mutated B cells are lifted.
    5. In addition to a chromosomal translocation event, mutations elsewhere in the genome are usually involved.

     

    6–32    Which of the following is a characteristic of B-2 cells?

    1. They are sometimes referred to as CD5 B cells.
    2. They comprise only 5% of the B-cell repertoire.
    3. In adults, they are renewed by cell division in the peripheral circulation.
    4. They are located primarily in secondary lymphoid organs.
    5. They are not dependent on T helper cells for activation.

     

    6–33    Identify the mismatched pair of chemokine and the cells that secrete it.

    1. CCL19: lymph-node dendritic cells
    2. CXCL13: follicular dendritic cells
    3. CCL21: stromal cells of secondary lymphoid tissues
    4. All of the above are correctly matched.

     

    6–34    Plasma cells have all of the properties listed except

    1. they rapidly proliferate in secondary lymphoid follicles
    2. they secrete antibody
    3. they are terminally differentiated B cells
    4. they no longer express MHC class II molecules
    5. they cease expressing membrane-bound immunoglobulin
    6. they differentiate into plasma cells after migration from germinal centers to other sites in lymphoid tissue and bone marrow.

     

    6–35    All of the following events occur within germinal centers except

    1. centrocytes mature from centroblasts
    2. isotype switching
    3. centroblasts arise from activated B ells
    4. B cells are activated by CD4 helper T cells
    5. affinity maturation
    6. somatic hypermutation
    7. production of memory B cells.

     

    6–36    In which location would plasma cells not be present?

    1. bone marrow
    2. afferent lymphatic vessels
    3. medullary cords of lymph nodes
    4. lamina propria of gut-associated lymphoid tissues
    5. red pulp of spleen
    6. efferent lymphatic vessels.

     

    6–37    Match the name of the B-cell tumor in Column A with its correct description in Column B.

    Column A Column B
    ___a.   multiple myeloma 1.         most cases caused by B-1 cells
    ___b.   chronic lymphocytic leukemia (CLL) 2.         derived from lymphoid progenitor in bone marrow and rearrangement of immunoglobulin loci has not occurred
    ___c.   acute lymphoblastic leukemia (ALL) 3.         expresses VpreBλ5
    ___d.   Burkitt’s lymphoma 4.         derived from plasma cells in the bone marrow
    ___e.   pre-B-cell leukemia 5.         associated with chromosomal translocations involving the proto-oncogene MYC

     

     

    6–38    Which of the following is true of centrocytes? (Select all that apply.)

    1. Somatic hypermutation has occurred.
    2. They are large proliferating cells.
    3. Isotype switching is complete.
    4. They produce secreted forms of immunoglobulins.
    5. They lack MHC class II molecules on the cell surface.

     

     

    6–39    Immunological tolerance in the B-cell repertoire is called _______ tolerance when it develops in primary lymphoid organs, and _______ tolerance when it is induced outside the bone marrow.

    1. primary; secondary
    2. apoptotic; anergic
    3. stromal; follicular
    4. receptor-mediated; systemic
    5. central; peripheral.

     

    6–40    What is the role of primary lymphoid follicles in eliminating B cells that have antigen receptors specific for soluble self antigen?

     

    6–41    A plasma cell is characterized by which of the following features? (Select all that apply.)

    1. It differentiates in the medulla of lymph nodes and the bone marrow.
    2. It dedicates 10–20% of total protein synthesis to antibody production.
    3. Levels of MHC class II molecules are elevated.
    4. It undergoes extensive proliferation in germinal centers.
    5. It produces secreted immunoglobulin instead of the membrane-bound form.

     

    6–42

    1. Explain why immunological memory is important in acquired immunity.
    2. Describe how immunoglobulin expressed during a primary immune response differs qualitatively and quantitatively from the immunoglobulin expressed during a secondary immune response.

     

    6–43    When producing monoclonal antibodies, why is it important to use as a fusion partner a myeloma cell that is unable to produce its own immunoglobulin?

    1. to ensure that allelic exclusion of μ chain occurs normally
    2. to ensure that the antibodies are homogeneous and able to make strong bivalent attachments to multivalent antigens
    3. to ensure that the monoclonal antibodies are not autoreactive
    4. to provide a greater opportunity for making a successful rearrangement at the light-chain locus
    5. to ensure that antibodies are secreted and not membrane-bound.

     

    6–44    The proto-oncogene _______ is associated with the development of Burkitt’s lymphoma.

    1. BCL-2
    2. Myc
    3. CD5
    4. CD19
    5. BTK.

     

    6–45    Which of the following characterizes the B-1 cells that develop prenatally?

    1. They lack N nucleotides.
    2. They possess polyspecificity for bacterial polysaccharide antigens.
    3. They arise early in embryonic development preceding the development of the majority subset of B cells.
    4. They have little or no IgD on the cell surface.
    5. All of the above.

     

    6–46    Explain how B cells undergo the process of negative selection and indicate at which stage of development and at which location these events occur.

     

    6–47    What is the fate of an immature B cell that encounters and has specificity for self antigen?

    1. If further heavy-chain and light-chain gene rearrangements are possible, it undergoes apoptosis.
    2. Somatic hypermutation.
    3. Decrease in production of IgD.
    4. Continued rearrangement of heavy-chain genes.
    5. Continued rearrangement of light-chain genes.

     

    6–48    Which of the following pertains to the fate of immature B cells that have specificity for univalent self antigens? (Select all that apply.)

    1. The cells acquire a state of unresponsiveness called anergy.
    2. IgD is retained in the cytosol.
    3. IgD on the cell surface fails to activate the B cell when bound to self antigen.
    4. The cells have a much longer life-span than mature B cells.
    5. The cells die by apoptosis.

     

    6–49    The circulatory route through a lymphoid tissue for both immature B cells and mature B cells that do not encounter specific antigen is:

    1. bloodstream →HEV of lymphoid cortex → primary lymphoid follicle → efferent lymphatic vessel
    2. afferent lymphatic vessel → primary lymphoid follicle →HEV of lymphoid cortex →efferent lymphatic vessel
    3. afferent lymphatic vessel →medullary cords → primary lymphoid follicle →efferent lymphatic vessel
    4. primary lymphoid follicle →HEV of lymphoid cortex →afferent lymphatic vessel →efferent lymphatic vessel
    5. bloodstream →afferent lymphatic vessel → HEV of lymphoid cortex →efferent lymphatic vessel.

     

    6–50

    1. Give three properties that distinguish B-1 cells from B-2 cells.
    2. Do you think that B-1 cells should be categorized as participants in innate immune responses or in acquired immune responses? Explain your rationale.

     

    6–51

    1. Identify properties that are shared by anergic B cells and plasma cells.
    2. What key property is different?

     

    6–52    Indicate which of the following statements concerning memory B cells are true (T) and which are false (F):

    ___ a.  Memory B cells are derived from germinal center B cells as immune responses subside.

    ___ b.  Memory B cells have long life spans.

    ___ c.  Memory B cells possess high-affinity antigen receptors as a consequence of affinity maturation.

    ___ d.  Memory B cells have more stringent requirements for activation than naive B cells do.

    ___ e.  Memory B cells express only IgM and retain the capacity to switch to the most beneficial isotype during secondary responses.

     

    6–53    Hinda Mundy, 26 years old, grew concerned when a lump appeared in her lower neck and she had pain in her chest and a dry cough. She also told her physician that she had experienced fatigue, night sweats, unintentional weight loss, pruritis (dry, itchy skin), and intermittent fevers over the past few months. Immunohistological staining of a biopsy of the enlarged lymph node revealed the presence of large multinucleated Reed–Sternberg cells. Polymerase chain reaction (PCR) tests confirmed immunoglobulin gene rearrangements; however, B-cell antigen expression was absent. Hinda entered complete remission after treatment with four cycles of chemotherapy combined with radiotherapy. These symptoms and treatment are most consistent with a diagnosis of

    1. Hodgkin’s lymphoma
    2. multiple myeloma
    3. acute lymphoblastic leukemia (ALL)
    4. Waldenström’s magroglobulinemia
    5. chronic lymphocytic leukemia (CLL).

     

    6–54    Multiple myeloma involves the unregulated proliferation of an antibody-producing plasma cell (myeloma cell) independently of antigen stimulation or T-cell help. Myeloma cells populate multiple sites in the bone marrow, where they produce immense quantities of monoclonal immunoglobulin as well as suppressing normal marrow function. Myeloma cells also synthesize and secrete excessive amounts of free light chains (known as Bence-Jones protein), which, because of their low molecular weight (~25 kDa) are excreted as free light chains in the urine.

    In a given patient the free light chains are both monoclonal and all are of either the κ or the λ type.

    1. Explain both of these observations.
    2. Why do you think patients with multiple myeloma are more susceptible than normal to pyogenic infections, such as pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae?THE IMMUNE SYSTEM, FOURTH EDITION

      CHAPTER 10: PREVENTING INFECTION AT MUCOSAL SURFACES

      © Garland Science 2015

       

      10–1    Explain how secondary lymphoid tissues of the mucosa are (A) similar to and (B) different from secondary lymphoid tissues elsewhere in the body (the systemic immune system).

       

      10–2    Because the mucosae _____, this tissue is predisposed to infection.

      1. constitute thin, permeable barriers
      2. secrete a continuous layer of mucus
      3. generate enzymes and proteoglycans
      4. are associated with secretory IgA production
      5. are not connected to the lymphatics.

       

      10–3    Identify which of the following is not a property of secreted mucins.

      1. contain glycosylated cysteine residues
      2. contain many repetitive sequence motifs
      3. constitute a viscous matrix stabilized by disulfide bonds
      4. bind to positively charged effector molecules
      5. encoded by seven genes in humans
      6. expressed in different mucosal tissues.

       

      10–4    Unlike secreted mucins, membrane mucins _____.

      1. do not trap and kill nearby microorganisms
      2. are not cross-linked by disulfide bonds
      3. do not possess repetitive domains
      4. are not glycosylated
      5. are encoded by only one gene in humans.

       

      10–5    Commensal microorganisms in the gastrointestinal tract facilitate all of the following except _____.

      1. compete with pathogenic variants for nutrients and space
      2. convert toxic substances to benign derivatives
      3. degrade plant fibers to make their nutrients available
      4. secrete enzymes required for protein degradation
      5. synthesize essential metabolites
      6. induce the development of gut-associated lymphoid tissue.

       

      10–6    The large population of microbes that contribute to the gut microbiota and have an important role in food processing are called _____.

      1. lamina propria
      2. Peyer’s patches
      3. microfold cells
      4. commensal microorganisms
      5. opportunists.

       

      10–7    All of the following are part of Waldeyer’s ring except _____.

      1. appendix
      2. palatine tonsils
      3. lingual tonsils
      4. adenoids.

       

      10–8    Which of the following pairs is mismatched? (Select all that apply.)

      1. appendix: large intestine
      2. mesenteric lymph nodes: urogenital tract
      3. effector compartment: induction of adaptive immune responses
      4. adenoids: base of nose
      5. villi: small intestine
      6. Peyer’s patches: afferent lymphatics.

       

      10–9    At which anatomical location are Peyer’s patches?

      1. stomach
      2. small intestine
      3. cecum
      4. large intestine
      5. Waldeyer’s ring.

       

      10–10  Laboratory animals reared in gnotobiotic conditions _____.

      1. are fed probiotics to disrupt the composition of their microflora
      2. lack normal gut microbiota
      3. develop appendicitis
      4. have larger secondary lymphoid tissues than do control animals
      5. have elevated levels of SIgA in the gut lumen.

       

      10–11  _____ microorganisms are microbes that colonize mucosal surfaces but under normal circumstances do not cause disease.

      1. Opportunistic
      2. Commensal
      3. Parasitic
      4. Mesenteric
      5. Pathogenic.

       

      10–12  _____ makes up the membranes of connective tissue that help to anchor the gastrointestinal tract and hold it in place.

      1. The mesentery
      2. Peyer’s patches
      3. The lamina propria
      4. The subepithelial dome
      5. Waldeyer’s ring.

       

      10–13  Waldeyer’s ring includes which of the following? (Select all that apply.)

      1. Peyer’s patches
      2. lingual tonsils
      3. adenoids
      4. mesenteric lymph nodes
      5. palatine tonsils.

       

      10–14  Which of the following describe M cells in the gut? (Select all that apply.)

      1. They derive their name from mucus cells.
      2. They are located in the dome of a Peyer’s patch.
      3. They deliver antigens and pathogens from the lymphoid tissue to the luminal side of the gut mucosa by transcytosis.
      4. They are protected from digestive enzymes by a thick glycocalyx and a layer of mucus.
      5. They do not directly participate in antigen processing or presentation.

       

      10–15  Mucosae of a healthy intestinal tract _____. (Select all that apply.)

      1. have a large number of activated T and B cells
      2. harbor T cells bearing a very wide diversity of antigen specificities
      3. contain intraepithelial lymphocytes
      4. have large numbers of resident neutrophils
      5. are populated with both α:β and γ:δ effector T cells.

       

      10–16  Which of the following migrates from non-mucosal tissue to draining lymph nodes to facilitate the induction of adaptive immune responses?

      1. dendritic cells
      2. macrophages
      3. NK cells
      4. neutrophils
      5. commensal microorganisms.

       

      10–17  Describe two ways in which dendritic cells capture antigen from the intestine for presentation to T lymphocytes.

       

      10–18  Describe the route that a Peyer’s patch-activated T lymphocyte follows, beginning with a naive T lymphocyte in a high endothelial venule and ending with an effector T lymphocyte in the lamina propria.

       

      10–19  Identify three locations where secretory IgA can bind to antigens in mucosal tissue, and for each give the fate of the antigen upon binding to secretory IgA.

       

      10–20  Identify ways in which intestinal macrophages are (A) similar to and (B) different from macrophages in non-mucosal tissues.

       

      10–21  _____ assists in the differentiation of blood-derived monocytes into intestinal macrophages.

      1. TGF-β
      2. B7
      3. IL-12
      4. CXCL8
      5. CD14.

       

      10–22  All of the following are expressed by intestinal epithelial cells except _____.

      1. NOD receptors
      2. FcαR
      3. TLRs
      4. MHC class II
      5. NFκB.

       

      10–23  Match the term in column A with its function in column B.

      Column A

       

      Column B

       

      ___a. M cells 1. mucus secretion
      ___b. brush border 2. antimicrobial products in crypts
      ___c. FoxP3-positive T cells 3. portals for antigen transport
      ___d. Paneth cells 4. suppress immune responses to food antigen
      ___e. goblet cells 5. microvilli on enterocytes for nutrient absorption

       

      10–24  M cells, unlike dendritic cells, _____.

      1. do not secrete digestive enzymes into the lumen of the gut
      2. are not associated with Peyer’s patches
      3. do not facilitate the transport of microbes from the gut lumen to the GALT
      4. do not process and present their antigen to naive T cells.

       

      10–25  The significance of MAdCAM-1 on the endothelium of blood vessels is that it binds to _____.

      1. the integrin α4β7 on effector lymphocytes homing to mucosal tissues
      2. B cells destined to become intraepithelial lymphocytes
      3. dendritic cells, and causes the upregulation of antigen processing and presentation
      4. the chemokine CCL25, which is secreted by gut epithelia
      5. intestinal helminths, and mediates killing of these parasites.

       

      10–26  In addition to M cells, _____ can capture pathogens directly from the lumen of the gut.

      1. intraepithelial lymphocytes
      2. plasma cells
      3. Paneth cells
      4. dendritic cells
      5. macrophages.

       

      10–27  Which of the following is not associated with the process by which B cells produce secretory IgA in breast milk?

      1. J chain
      2. MAdCAM-1
      3. αE7
      4. poly-Ig receptor
      5. CCR9
      6. transcytosis.

       

      10–28  Intracytoplasmic bacteria in enterocytes of the gastrointestinal tract are detected by _____.

      1. poly-Ig receptor
      2. major basic protein
      3. MIC-A and MIC-B
      4. NOD proteins
      5. receptors for phosphoantigens.

       

      10–29  Secretory IgA binds to pathogens in all of the following locations except the _____.

      1. endosomes of an M cell
      2. lamina propria
      3. lumen of the gut
      4. blood
      5. Peyer’s patches.

       

      10–30  What is the function of the TNF-family cytokine APRIL made by epithelial cells of the colon?

      1. elevates rate of M-cell proliferation
      2. degrades IgA1
      3. mediates isotype switching from IgM to IgA2
      4. binds to J chain of dimeric IgA
      5. upregulates MAdCAM-1 production.

       

      10–31  All of the following soluble factors enhance isotype switching from IgM to IgA in B cells except _____.

      1. retinoic acid
      2. IL-9
      3. TGF-β
      4. IL-4
      5. IL-10
      6. B-cell activating factor (BAFF)
      7. APRIL.

       

      10–32  Match the term in column A with the receptor involved in its transport across mucosal epithelia in column B. Responses may be used more than once or not at all.

      Column A Column B
      ___a. IgA 1. FcRn
      ___b. IgE 2. poly-Ig receptor
      ___c. IgG 3. CD23
      ___d. IgM 4. none of the above receptors are used by this immunoglobulin for transport

       

       

      10–33  Which of the following is not an activity associated with secretory IgA and secretory IgM in mucosal secretions?

      1. toxin neutralization
      2. complement fixation
      3. binds to mucin through disulfide bonds
      4. restricts commensal microorganisms to gut lumen
      5. limits population size of commensal microorganisms.

       

      10–34  IgA proteases produced by Streptococcus pneumoniae mediate all of the following effects except _____.

      1. separation of Fab and Fc regions
      2. interference with FcαR-mediated endocytosis
      3. enhanced adherence of Fab-coated bacteria to mucosal epithelium
      4. preferential cleavage of IgA2 over IgA1.

       

      10–35  _____ compensates for the absence of secretory IgA in selective IgA deficiency because it can be secreted by mucosal tissues using the same receptor needed for transcytosis.

      1. Monomeric IgA
      2. IgD
      3. IgE
      4. IgG
      5. IgM.

       

      10–36  Match the term in column A with its correct match in column B.

      Column A Column B
      ___a. IL-13 1. stimulation of protective TH2-mediated immune responses
      ___b. αE7 integrin 2. stem-cell hyperplasia in intestinal crypts
      ___c. major basic protein 3. IgA protease activity
      ___d. helminthic infections 4. adhesion of CD8 T cells to gut epithelium
      ___e. Haemophilus influenzae 5. cytotoxic eosinophil product

       

       

      10–37  The cytokine influencing eosinophil development and function during helminth infections is _____.

      1. IL-3
      2. IL-9
      3. IL-19
      4. IL-10
      5. IL-5.

       

      10–38  Why do children who have had their tonsils or adenoids removed respond less effectively to the oral polio vaccine than children who still have these tissues?

       

      10–39  What property of the mucosal immune system enables breast milk to contain antibodies against microorganisms encountered in the gut or other mucosal tissues? Explain your answer.

       

      10–40  Explain why individuals who have the condition selective IgA deficiency do not succumb to repeated infection through mucosal surfaces.

       

      10–41  Describe four actions of effector CD4 TH2 cells that provide protection from infections by intestinal helminths and lead to expulsion of the parasites from the gastrointestinal tract.

       

      10–42  _____ is the vascular addressin found on endothelial cells of intestinal mucosa that binds to integrins of gut-homing effector lymphocytes.

      1. CCL25
      2. C-cadherin
      3. NOD1
      4. MAdCAM-1
      5. CCR9.

       

      10–43  The dominant immunoglobulin synthesized at mucosal surfaces is _____.

      1. IgA
      2. IgD
      3. IgE
      4. IgG
      5. IgM.

       

      10–44  If a B cell has been activated by antigen in the mucosa of the respiratory tract, then _____. (Select all that apply.)

      1. lactating mothers will provide antigen-specific natural IgA in breast milk
      2. secretory IgA will be synthesized in the lamina propria of all mucosae
      3. it does not enter the bloodstream but instead remains in the mucosa and differentiates into an effector B cell
      4. it will recirculate through all mucosal tissues, including respiratory and gastrointestinal mucosae
      5. monomeric IgA is secreted into the lamina propria.

       

      10–45  In which of the following tissues is IgA2 produced at approximately twice the level of IgA1?

      1. spleen
      2. mammary glands
      3. large intestine
      4. gastric mucosa
      5. upper small intestine.

       

      10–46  Secretory IgA is best described as _____.

      1. a non-inflammatory immunoglobulin that restricts the passage of antigens across mucosal surfaces
      2. a complement-activating immunoglobulin that causes destruction of invasive microflora through the membrane-attack complex
      3. an opsonizing antibody that facilitates uptake by M cells through Fc receptors
      4. an inflammatory immunoglobulin that stimulates the chemotaxis of neutrophils into mucosal surfaces
      5. a monomeric IgA that neutralizes antigen effectively at mucosal surfaces.

       

      10–47  Secretory IgA and _____ can bind to the poly-Ig receptor and be transported into the lumen of the gut or across other mucosal surfaces.

      1. IgG
      2. IgE
      3. IgD
      4. monomeric IgM
      5. pentameric IgM.

       

      10–48  Which of the following types of immune response are most beneficial in clearing helminth infections in the intestinal tract? (Select all that apply.)

      1. production of IgG2 antibodies
      2. production of IgE antibodies
      3. complement fixation
      4. eosinophil activation
      5. antibody-dependent cell-mediated cytotoxicity
      6. IFN-γ-induced production of mucus
      7. TH1-derived cytokines.

      THE IMMUNE SYSTEM, FOURTH EDITION

      CHAPTER 12: COEVOLUTION OF INNATE AND ADAPTIVE IMMUNITY

      © Garland Science 2015

       

      12–1    All of the following are characteristic of NK cells except _____.

      1. they express Toll-like receptors
      2. they are tolerant of healthy cells
      3. they circulate in a partly activated state
      4. they all express the same selection of activating and inhibitory NK-cell receptors
      5. they can be activated by FcγRIIIA (CD16a).

       

      12–2    Which of the following statements regarding NK cells is false?

      1. They express either inhibitory receptors or activating receptors, but not both.
      2. Their inhibitory receptors are necessary to prevent killing of healthy cells.
      3. They all express CD56.
      4. Because NK cells express diverse combinations of receptors, no single NK cell expresses them all.
      5. Some of their activating and inhibitory receptors use MHC class I ligands.

       

      12–3    The only single receptor that can activate NK cells without the need for a second activating receptor is _____.

      1. NKG2D
      2. CD56
      3. 2B4
      4. CD94:NKG2A
      5. CD16a.

       

      12–4    Identify which of the following would be sufficient to activate NK cells.

      1. NKG2A and CD94
      2. NKG2D and 2B4
      3. KIR2DL1 and KIR3DL1
      4. CD56 and LFA-1.

       

      12–5    Identify which of the following is not a characteristic of CD94:NKG2A.

      1. contains a C-type lectin domain
      2. is an inhibitory NK-cell receptor
      3. binds to carbohydrate ligands
      4. is a disulfide-linked heterodimer
      5. contains an immunoreceptor tyrosine-based inhibitory motif (ITIM).

       

      12–6    Explain (A) how the ligand for CD94:NKG2A serves as an indicator of non-infectious or non-malignant states of potential target cells, and (B) the consequence if ligand expression is compromised on target cells.

       

      12–7    Identify the mismatched pair:

      1. CD94:NKG2A; ITIM
      2. NKG2D; MIC proteins
      3. SHP-1; Vav1
      4. 2B4; IgG
      5. HLA-E; leader-sequence peptide.

       

      12–8    _____ has/have tyrosine phosphatase activity that interrupts the signaling pathways required for the activation of NK cells.

      1. SHP-1
      2. MIC proteins
      3. KIR ligands
      4. phosphoantigens
      5. lipid-transfer proteins.

       

      12–9    All of the following describe Vav1 except _____.

      1. guanine-nucleotide exchange factor
      2. regulated by SHP-1
      3. active when phosphorylated
      4. found on the surface of NK cells
      5. mediates signaling that promotes NK cells’ release of cytotoxic granules.

       

      12–10  All of the following contribute to the generation of functional NK cells in the bone marrow with diverse KIR phenotypes except _____.

      1. competing bi-directional promoters of KIR genes
      2. delay of KIR expression until NK cells enter the circulation
      3. closely packed KIR genes on chromosome 19
      4. establishment of a level balance between activating and inhibitory signals
      5. gene silencing by DNA methylation
      6. the number of KIR ligands brought by the HLA-A, -B, and -C tissue type.

       

      12–11  Which of the following is false regarding HLA-G?

      1. It is expressed as transmembrane or secreted forms.
      2. It binds to LILRB1 inside endosomes of NK cells.
      3. It stimulates the production of angiogenic factors by activating NK cells.
      4. It is expressed exclusively by extravillous trophoblast cells.
      5. It engages inhibitory receptors on uterine NK cells.

       

      12–12  Extravillous trophoblast cells do not express _____. (Select all that apply.)

      1. HLA-A
      2. HLA-B
      3. HLA-C
      4. HLA-E
      5. HLA-F
      6. HLA-G
      7. HLA class II.

       

      12–13  Which of the following maternal profiles is most strongly correlated with pre-eclampsia where the fetus has a C2 epitope inherited from the father?

      1. homozygous for KIR A haplotype and C1 epitope
      2. homozygous for KIR B haplotype and C1 epitope
      3. homozygous for KIR A haplotype and C2 epitope
      4. homozygous for KIR B haplotype and C2 epitope
      5. heterozygous for KIR A/B haplotypes and C1/C2 epitopes
      6. homozygous for KIR A haplotype and heterozygous for C1/C2 epitopes
      7. homozygous for KIR B haplotype and heterozygous for C1/C2 epitopes
      8. heterozygous for KIR A/B haplotypes and homozygous for C1 epitopes
      9. heterozygous for KIR A/B haplotypes and homozygous for C2 epitopes.

       

      12–14  Which of the following maternal profiles is most strongly correlated with obstructed labor where the fetus has a C2 epitope inherited from the father?

      1. homozygous for KIR A haplotype and C1 epitope
      2. homozygous for KIR B haplotype and C1 epitope
      3. homozygous for KIR A haplotype and C2 epitope
      4. homozygous for KIR B haplotype and C2 epitope
      5. heterozygous for KIR A/B haplotypes and C1/C2 epitopes
      6. homozygous for KIR A haplotype and heterozygous for C1/C2 epitopes
      7. homozygous for KIR B haplotype and heterozygous for C1/C2 epitopes
      8. heterozygous for KIR A/B haplotypes and homozygous for C1 epitopes
      9. heterozygous for KIR A/B haplotypes and homozygous for C2 epitopes.

       

      12–15  In the context of NK-cell inhibitory and activating receptors and maternal arterial invasion, explain the cause of (A) pre-eclampsia and (B) obstructed labor. Base your response on a pregnancy involving a fetus who has inherited a C2 epitope from the father but whose mother is homozygous for C1.

       

      12–16  Identify which of the following is not a characteristic of γ:δ T cells. (Select all that apply.)

      1. Some express a homodimer of the CD8 α chain.
      2. They do not express CD28.
      3. They are subject to MHC restriction.
      4. Most do not express either CD4 or CD8.
      5. Most circulating cells do not enter secondary lymphoid tissue.
      6. They undergo gene rearrangement.
      7. They originate from the same precursor cells as do α:β T cells.
      8. Their response is solely dependent on the T-cell receptor.
      9. They make up the minority of resident T cells in tissues.
      10. Circulating cells express Vγ9:Vγ2.

       

      12–17  At birth, the size of the repertoire of γ:δ T-cell receptors is _____ its size at adolescence.

      1. smaller than
      2. larger than
      3. about the same as.

       

      12–18  Match the term in column A with its description in column B.

      Column A Column B
      ___a. CCR7

       

      1. permits entry of γ:δ T cells into infected tissues
      ___b. CCR5

       

      2. expressed on central memory γ:δ T cells but not effector memory γ:δ T cells
      ___c. CD27 3. expressed on ~20% of circulating γ:δ T cells
      ___d. CD45RA 4. presents lipid antigens to γ:δ T cells
      ___e. CD1d 5. expressed on terminally differentiated γ:δ T cells

       

      12–19  Match the receptor in column A with its ligand in column B. Responses in column B may be used more than once.

      Column A

      ___a. Vα24–Jα18:Vβ11

      Column B

      1. phosphoantigens presented by BTN3A1

       

      ___b. Vγ9:Vδ2 2. lipid antigens presented by CD1d

       

      ___c. Vγ:Vδ1 3. ringed metabolites of riboflavin presented by MR1

       

      ___d. Vγ4:Vδ5 4. phospholipid antigens presented by endothelial protein C receptor (EPCR)
      ___e. Vα7.2–Jα33:Vβ2, -13, or -22.  

       

      12–20  Which of the following is not a ligand for α:β T cells?

      1. peptide antigens
      2. lipid antigen
      3. sulfatides
      4. heterocyclic organic molecules.

       

      12–21  In contrast to CD1d, CD1a, b, and c are not expressed by _____.

      1. professional antigen-presenting cells
      2. epithelial cells
      3. developing thymocytes.

       

      12–22  Match the term in column A with its complement in column B.

      Column A Column B
      ___a. saposin 1. NKT-cell development
      ___b. sulfatide

       

      2. fills up bottom of antigen-binding site to allow antigenic lipid to be accessible on the top
      ___c. scaffold lipid 3. MR1
      ___d. BTN3A 4. phosphoantigen
      ___e. lipid-transfer protein 5. CD1d
      ___f. promyelocytic leukemia zinc finger protein (PLZF) 6. CD1e

       

      ___g. second signal for NKT-cell activation 7. IL-12
      ___h. riboflavin 8. an example of a lipid-transfer molecule found in endosomes

       

       

       

      12–23  All of the following develop in the thymus except _____.

      1. α:β T cells
      2. γ:δT cells
      3. NK cells
      4. NKT cells
      5. MAIT cells.

       

      12–24  All of the following are correct regarding MAIT cells except _____. (Select all that apply.)

      1. CD8+
      2. respond to viral infection
      3. α:β T-cell receptors
      4. populate lungs, mucosal tissues, liver, and blood
      5. activated by microbiota that make riboflavin
      6. respond to antigen presented by BTN3A
      7. comprise 20–40% of lymphocytes in liver as oligoclonal populations of effector cells with memory phenotype
      8. positively selected by thymic epithelium expressing high levels of MR1.

       

      12–25  Which of the following is not a characteristic of MR1?

      1. MHC class-I-like molecule
      2. binding site is populated with large basic and aromatic amino acid residues
      3. associated with β2-microglobulin
      4. highly polymorphic in mammals
      5. encoded on chromosome 1
      6. binds to metabolites of riboflavin.

       

      12–26  Natural killer cells (NK cells) carry activating and inhibitory receptors on their surface.

      1. What property of NK cells do these receptors activate or inhibit, respectively? Explain your answer.
      2. How are NK cells thought to use these receptors to recognize and eliminate virus-infected cells?
      3. Why are the actions of NK cells categorized as innate immunity, and what do we know of their specificity for MHC class I molecules?
      4. Why do the NK cells of the recipient of an organ transplant sometimes attack the transplanted tissue?

       

      12–27  Which of the following characterize MIC-A and MIC-B proteins? (Select all that apply.)

      1. recognized by NKG2D receptors of NK cells and some CD8 T cells
      2. activate the NFkB signaling pathway
      3. activate mast cells in the intestinal wall
      4. closely related to MHC class I heavy chains
      5. bind to MHC class I molecules and activate CD8 T cells.

       

      12–28  Vγ9:Vδ2 T cells differ from α:β T cells in that they _____. (Select all that apply.)

      1. respond to phosphorylated metabolic intermediates (phosphoantigens) of isoprenoid biosynthesis pathways
      2. bind to lipid antigens presented by CD1
      3. do not carry out gene rearrangement
      4. are not subject to positive and negative selection in the thymus
      5. have limited diversity of V gene rearrangement.

       

      12–29  Which of the following are expressed by Vγ9:Vδ2 T cells? (Select all that apply.)

      1. IFN-γ
      2. MHC class I
      3. granulysin
      4. CD56
      5. CCR5
      6. IL-4
      7. CD40L
      8. CD28.

       

      12–30  _____ binds to MIC-A and MIC-B, which are synthesized in response to infection in gut epithelium. (Select all that apply.)

      1. MHC class I
      2. NKG2D
      3. Vγ:Vδ1
      4. fibroblast growth factor
      5. CD1.

       

      12–31  _____ express a limited range of diversity in their antigen receptors yet can still bind to large groups of pathogens expressing common chemical entities. (Select all that apply.)

      1. α:βT cells
      2. γ:δT cells
      3. NK cells
      4. NKT cells
      5. B-1 cells.

       

      12–32  Explain the path taken by CD1 molecules that eventually bind to pathogen-derived lipids inside endosomes of the MHC class II compartment.

       

      12–33  All NK cells express _____. (Select all that apply.)

      1. CD3
      2. MIC
      3. NKG2D
      4. KIR2DL1
      5. CD56.

       

      12–34  Which of the following describe the characteristics of CD94:NKG2A? (Select all that apply.)

      1. It is an activating receptor of NK cells.
      2. It is an inhibitory receptor of NK cells.
      3. It binds to specific allotypes of HLA-A, -B, and -C heavy chains.
      4. It binds to complexes of leader sequences of HLA-A, -B, and -C heavy chains bound to HLA-E.
      5. It is a member of the killer-cell immunoglobulin-like receptor (KIR) family.

       

      12–35  In regard to killer-cell immunoglobulin-like receptors (KIRs) indicate which of the following statements is true (T) or false (F).

      ___ a.  KIRs have a broader range of specificity for HLA class I compared with CD94:NKG2A.

      ___ b.  KIRs are activating receptors of NK cells and stimulate the release of perforin and granzyme.

      ___ c.  KIRs bind to monomorphic determinants on HLA-A, -B, and -C molecules.

      ___ d.  All HLA-C allotypes are suitable ligands for KIRs.

      ___ e.  KIRs are encoded in the leukocyte receptor complex (LRC) on chromosome 19.

      ___ f.   MIC-A and MIC-B are suitable ligands for KIRs.

       

      12–36

      Match the molecule in column A with its appropriate ligand in column B. (Answers may be used more than once.)

      Column A Column B
      ___ a. Vγ:Vδ T-cell receptor 1. HLA-A
      ___ b. CD94:NKG2A 2. FasL
      ___ c. NKG2D 3. phosphoantigen
      ___ d. LILRBI 4. HLA-E
      ___ e. FAS 5. MIC-A and MIC-B
      ___ f. Vγ:Vδ2 T-cell receptor 6. HLA-C
      ___ g. KIR2DL1 7. glycolipid antigen
      ___ h. CD1  

       

      12–37  _____ is a molecule expressed on NK cells and Vγ:Vδ1 T cells.

      1. CD3
      2. MIC-A
      3. NKG2D
      4. CD94:NKG2A
      5. killer-cell immunoglobulin-like receptor (KIR).

       

      12–38  If, during development, none of the KIRs expressed by a NK cell are able to interact with self-MHC class I molecules, then the NK cell retains expression of _____.

      1. LILRBI
      2. KIR2DL1
      3. KIR2DL2/3
      4. KIR3DL1
      5. CD94:NKG2A.

       

      12–39  CD1a, CD1b, and CD1c _____. (Select all that apply.)

      1. are highly polymorphic and bind to a variety of pathogen-specific lipids
      2. are encoded within the MHC on chromosome 6
      3. express antigen-binding sites distinct from classical MHC class I molecules
      4. are associated with β2-microglobulin at the surface of antigen-presenting cells
      5. can bind to lipids in the endoplasmic reticulum or in endocytic vesicles.

       

      12–40  CD1d differs from CD1a, CD1b, and CD1c in that _____. (Select all that apply.)

      1. CD1d does not present lipid antigens
      2. CD1d is expressed in a variety of epithelial tissues
      3. CD1d presents antigen to NK T cells
      4. strong memory responses are generated by CD1d
      5. CD1d has a restricted receptor repertoire.

       

      12–41  Charlene Cook, a 38-year-old primigravida, is 35 weeks pregnant. Until recently she has had an uneventful pregnancy. Two weeks ago, her obstetrician noted lower-extremity edema, trace protein in her urine (10–20 mg/dl), and normal blood pressure (120/80 mmHg). At today’s appointment her blood pressure is elevated at 160/100 mmHg, she has marked proteinuria (3+; 300 mg/dl), worsening of ankle swelling, facial and hand swelling, and she mentions sudden onset of headache and visual disturbance. Charlene is admitted immediately to hospital and is diagnosed with pre-eclampsia. Within hours she is induced and gives birth to a healthy baby girl. In the context of uterine NK-cell function, which of the following is inconsistent with the cause of Charlene’s pre-eclampsia?

      1. There is inadequate extravillous trophoblast invasion of the spiral arteries or the uterus.
      2. She has maternal homozygosity for the KIR A haplotype.
      3. Uterine NK cells fail to secrete adequate amount of cytokines and growth factors needed to promote angiogenesis and remodeling of the maternal arteries.
      4. The baby’s father and mother are homozygous for the C1 epitope.
      5. Insufficient activating signals were delivered to uterine NK cells.

      THE IMMUNE SYSTEM, FOURTH EDITION

      CHAPTER 14: IgE-MEDIATED IMMUNITY AND ALLERGY

      © Garland Science 2015

       

       

      14–1    Which of the following are matched correctly? (Select all that apply.)

      1. type I hypersensitivity: IgE
      2. type II hypersensitivity: IgG
      3. type III hypersensitivity: immune complexes
      4. type IV hypersensitivity: IgG
      5. type IV hypersensitivity: delayed-type hypersensitivity.

       

      14–2    Which of the following are associated with soluble antigen? (Select all that apply.)

      1. type I hypersensitivity
      2. type II hypersensitivity
      3. type III hypersensitivity
      4. type IV hypersensitivity
      5. mast-cell activation.

       

      14–3    Match the term in column A with its description in column B.

       

      Column A Column B
      ___ a. delayed-type hypersensitivity

       

      1. innocuous environmental antigen
      ___ b. hygiene hypothesis

       

      2. type IV hypersensitivity
      ___ c. allergy

       

      3. a state of hypersensitivity

       

      ___ d. immediate hypersensitivity

       

      4. type I hypersensitivity

       

      ___ e. allergen 5. epidemic of allergy

       

       

       

      14–4    Which of the following is not mediated by antibodies?

      1. type I hypersensitivity
      2. type II hypersensitivity
      3. type III hypersensitivity
      4. type IV hypersensitivity.

       

      14–5    Which of the following is associated with type III hypersensitivity?

      1. nickel
      2. recombinant human insulin
      3. plant oil
      4. mouse-derived monoclonal antibody
      5. helminth infection.

       

      14–6    _____ hypersensitivity reactions interact with soluble epitopes and not cell-surface associated epitopes.

      1. type I and II
      2. type I and III
      3. type I and IV
      4. type II and III
      5. type II and IV
      6. type III and IV.

       

      14–7    Identify four different ways in which an individual may come into contact with an allergen and provide two examples of allergens for each type of contact.

       

      14–8    A.        Describe in detail the mechanism responsible for mast-cell activation during a type I hypersensitivity reaction.

      1. What are the products of mast-cell activation?

       

      14–9    Adaptive immune responses targeted at infections by helminth worms and other parasitic multicellular animals employ all of the following except _____. (Select all that apply.)

      1. CD8 T cells
      2. IgE
      3. eosinophils
      4. mast cells
      5. CD4 TH2 cells
      6. basophils
      7. neutrophils
      8. IL-4.

       

      14–10  During a primary immune response IgM sometimes switches to IgE. Which of the following best describes the consequence of this early switch?

      1. The B cell would switch again to IgG3.
      2. The B cell would remain in the germinal center but would not differentiate into a plasma cell.
      3. The B cell would die by apoptosis.
      4. The IgE produced would have low affinity for antigen.

       

      14–11  Which of the following regarding FcεRI is false?

      1. It is expressed on the surface of mast cells and basophils.
      2. It is a low-affinity receptor involved in type I hypersensitivity reactions.
      3. It binds to IgE in the absence of antigen.
      4. It is a membrane-bound tetramer.
      5. It contains signaling components that re activated following antigen cross-linking.

       

      14–12

      1. Explain why it is essential that FcεRI and Fcε RII are not able to bind simultaneously to the same IgE molecule.
      2. Why does simultaneous binding not occur?

       

      14–13  The sheddase _____ cleaves FcεRII on the cell surface, resulting in the production of monomeric and trimeric forms of FcεRII.

      1. cathepsin G
      2. CR2
      3. eotaxin
      4. major basic protein
      5. ADAM10.

       

      14–14  All of the following are released immediately by mast cells after FcεRI cross-linking except _____.

      1. heparin
      2. eicosanoids
      3. neutral proteases
      4. histamine
      5. TNF-α.

       

      14–15  Lipid mediators produced by activated mast cells include which of the following? (Select all that apply.)

      1. platelet-activating factor
      2. cathepsin G
      3. chymase
      4. leukotrienes
      5. carboxypeptidase
      6. prostaglandins.

       

      14–16  All of the following are biological effects mediated by the products of mast cells except _____.

      1. chemotaxis of neutrophils, eosinophils, and effector T cells
      2. growth factor secretion
      3. smooth muscle contraction
      4. connective tissue remodeling
      5. All of the above are mediated by mast cells.

       

      14–17  Identify the mismatched pair.

      1. TNF-α: immediate release from mast cells
      2. mucosal mast cell production: T-cell immunodeficiencies
      3. connective tissue mast cells: chymotryptase
      4. lipid mediator: prostaglandins
      5. leukotrienes: increase vascular permeability.

       

      14–18  Prostaglandin D2 (PGD2) enhances all of the following except _____.

      1. smooth muscle contraction
      2. chemotaxis of neutrophils
      3. increased vascular permeability
      4. vasodilation.

       

      14–19  Which of the following directly inhibits the cyclooxygenase pathway by inhibiting the activity of prostaglandin synthase?

      1. ADAM10
      2. experimental anti-IgE
      3. aspirin (acetyl salicylate)
      4. chymotryptase
      5. ADAM33.

       

      14–20  _____ released by TH2 cells promotes an elevated level of eosinophils in the circulation.

      1. IL-4
      2. IL-13
      3. TNF-α
      4. FcγRII
      5. IL-5.

       

      14–21

      1. Explain the importance of allergens having protease activity in the context of antigen-specific T-cell activation.
      2. Provide a specific example of a major allergen that has protease activity.

       

      14–22  Match the physical effects of IgE-mediated mast-cell degranulation in column A with the tissue exposed to the allergen in column B.

      Column A Column B
      ___ a. decrease in blood pressure 1. respiratory tract

       

      ___ b. diarrhea

       

      2. heart and vascular system
      ___ c. swelling of tissues

       

      3. gastrointestinal tract

       

      ___ d. constriction of the throat

       

       
      ___ e. wheezing

       

       
      ___ f. vomiting

       

       
      ___ g. violent bursts of sneezing

       

       

       

       

      14–23  Explain briefly how penicillin initiates a type I hypersensitivity response.

       

      14–24

      1. Explain how erythrocytes become coated with complement component C3b during an allergic reaction to penicillin.
      2. Why is this important to the mechanism by which IgE antibodies are produced?

       

      14–25  Why are antihistamines used to treat allergic rhinitis and allergic asthma? What symptoms of each disease, respectively, do they alleviate.

       

      14–26

      1. Describe two ways in which the immunoglobulins acting as antigen receptors on the surface of a mast cell differ from the immunoglobulins acting as the antigen receptors on the surface of a B cell.
      2. What is the essential difference in response of these two cell types when antigen binds to these surface immunoglobulins.

       

      12–27  Some allergies can be treated by a procedure called desensitization.

      1. Explain two current approaches to desensitization.
      2. Explain the main disadvantage associated with each.

       

      14–28  Give three ways in which a susceptible person can help to minimize the risk of having an allergic reaction.

       

      14–29  How do mast cells contribute to innate immunity?

       

      14–30  What are the effects of histamine binding to the H1 receptor on smooth muscle, mucosal epithelia, and the endothelial cells of blood vessels.

       

      14–31  The antigens that provoke hypersensitivity reactions are referred to as

      1. T-independent antigens
      2. superantigens
      3. subunit vaccines
      4. attenuated vaccines
      5. allergens.

       

      14–32  Which of the following allergens is not likely to be encountered through inhalation?

      1. plant pollen
      2. metals
      3. animal dander
      4. mold spores
      5. house dust mite feces.

       

      14–33  _____ express FcεRI and contain granules containing inflammatory mediators. (Select all that apply.)

      1. macrophages
      2. activated eosinophils
      3. mast cells
      4. natural killer cells
      5. basophils.

       

      14–34  Match the mast cell product in column A with its biological effect in column B.

      Column A Column B
      ___ a. IL-4 1. activates endothelium
      ___ b. CCL3 2. amplifies TH2-cell response
      ___ c. TNF-α 3. increases vascular permeability
      ___ d. histamine 4. connective tissue matrix remodeling
      ___ e. tryptase 5. chemotaxis

       

      14–35  Aspirin (acetyl salicylate) inhibits prostaglandin synthesis by binding irreversibly to prostaglandin synthase, the first enzyme in the _____ pathway.

      1. cyclooxygenase
      2. carboxypeptidase
      3. metalloprotease
      4. lipooxygenase
      5. peroxidase.

       

      14–36  Which of the following is associated with eosinophilia? (Select all that apply.)

      1. IL-5-induced proliferation
      2. endocardium damage
      3. neuropathy
      4. B-cell lymphoma
      5. decreased bone marrow function.

       

      14–37  Which of the following genetic polymorphisms is associated with a predisposition to asthma? (Select all that apply.)

      1. promoter variants of IL-5
      2. structural variant of IgG receptor
      3. HLA class II allotypes
      4. β2-adrenergic receptor variant
      5. ACOX5 (5-lipoxygenase).

       

      14–38  The wheal-and-flare inflammatory reaction is an example of

      1. an immediate type I allergic response
      2. a late-phase type I allergic response
      3. a late-phase type IV allergic response
      4. an immediate type III allergic response
      5. a late-phase type III allergic response.

       

      14–39  Which of the following tests is used to determine whether a particular allergen is responsible for asthma?

      1. measure wheal-and-flare diameter after intradermal injection of allergen
      2. measure Arthus reaction diameter after intradermal injection of allergen
      3. inject a controlled amount of allergen intradermally and observe urticaria
      4. measure peak expiratory flow rate (PEFR) following inhalation of allergen
      5. measure eosinophils in nasal secretions following inhalation of allergen.

       

      14–40  Which of the following are consequences of anaphylactic shock? (Select all that apply.)

      1. smooth muscle contraction
      2. immune complex deposition on blood vessels
      3. loss of blood pressure
      4. constriction of airways
      5. complement activation.

       

      14–41  During the course of a successful desensitization process, the patient’s antibodies will change from an _____isotype to an _____ isotype.

      1. IgG4:IgE
      2. IgE:IgM
      3. IgA:IgM
      4. IgG1:IgG4
      5. IgE:IgG4.

       

      14–42  Which of the following are potential means by which type I allergic reactions can be managed or treated? (Select all that apply.)

      1. Use antihistamines to block histamine binding to H1 histamine receptors.
      2. Use corticosteroids to suppress inflammation.
      3. Desensitize the patient by feeding them allergen and skewing the immune response from an IgE to an IgA response.
      4. Anergize allergen-specific T cells through vaccination with allergen-derived peptides.
      5. Administer Il-4, IL-5, or IL-1β to promote TH1 responses.
      6. Block high-affinity IgE receptors to prevent mast-cell degranulation.

       

      14–43  Anita Garcia, 17 years old, and her roommate Rosa Rosario were celebrating a friend’s birthday at a dessert buffet at a local restaurant when Anita developed acute dyspnea, and angioedema. She complained of an itchy rash, and then had difficulty swallowing. Rosa drove Anita to the emergency room two blocks away rather than wait for an ambulance. As they approached the hospital, Anita lost consciousness. This medical emergency would most probably result in immediate _____ before any subsequent treatment.

      1. subcutaneous injection of epinephrine
      2. intravenous injection of corticosteroids
      3. intravenous injection of antihistamine
      4. intravenous injection of antibiotics
      5. intravenous injection of a nonsteroidal anti-inflammatory drug.

       

      14–44  Look again at Question 14–43. What do you think Anita was suffering from? Given the circumstances in which the episode occurred, suggest a likely cause.

       

      THE IMMUNE SYSTEM, FOURTH EDITION

      CHAPTER 16: DISRUPTION OF HEALTHY TISSUE BY THE ADAPTIVE IMMUNE RESPONSE

      © Garland Science 2015

      161    Autoimmune diseases, which are classified on the basis of the effector mechanism that causes the symptoms, include all of the following types of hypersensitivity reaction except _____.

      1. type I
      2. type II
      3. type III
      4. type IV.

       

      16–2    Which type of autoimmune disease is correctly matched with its cause?

      1. type I: IgE-mediated
      2. type II: effector T cells
      3. type III: immune complex deposition in tissues
      4. type IV: extracellular matrix-associated autoantigens
      5. type V: cell-surface components.

       

      16–3    Match the type of hypersensitivity in column A with its description in column B.

      Column A Column B
      ___ a. type I 1. antibodies directed against extracellular matrix on the cell surface
      ___ b. type II 2. T cell-mediated
      ___ c. type III

       

      3. deposition of soluble immune complexes in tissues
      ___ d. type IV 4. IgE-mediated

       

       

      16–4    Which of the following is an example of a type II autoimmune response? (Select all that apply.)

      1. subacute bacterial endocarditis
      2. Goodpasture’s syndrome
      3. multiple sclerosis
      4. systemic lupus erythematosus
      5. myasthenia gravis.

       

      16–5    Which of the following is an example of a type III autoimmune response? (Select all that apply.)

      1. mixed essential cryoglobulinemia
      2. acute thrombocytopenia purpura
      3. systemic lupus erythematosus
      4. rheumatoid arthritis
      5. insulin-resistant diabetes.

       

      16–6    Which of the following is an example of a type IV autoimmune response? (Select all that apply.)

      1. pemphigus vulgaris
      2. autoimmune thrombocytopenia purpura
      3. subacute bacterial endocarditis
      4. type 1 diabetes
      5. multiple sclerosis.

       

      16–7    Explain why splenectomy is sometimes carried out in patients with persistent type II autoimmune diseases that affect leukocytes.

       

      16–8    If autoantibodies of the IgG or IgM isotype were produced with specificity for components found on the surface of erythrocytes, which of the following would occur? (Select all that apply.)

      1. formation of membrane-attack complex
      2. immune-complex deposition in renal glomeruli
      3. anemia
      4. hypothyroidism
      5. receptor-mediated phagoytosis via Fc receptors on phagocytes.

       

      16–9    Which of the following is the cause of red blood cell deficiency in autoimmune hemolytic anemia? (Select all that apply.)

      1. inability of red blood cells to develop normally in the bone marrow
      2. loss of red blood cells due to widespread pinpoint hemorrhages
      3. hemolysis by assembly of membrane-attack complexes
      4. phagocyte-mediated clearance in the spleen
      5. rapid turnover of red blood cells due to CD8 T-cell killing.

       

      16–10  All of the following are associated with Goodpasture’s syndrome except _____. (Select all that apply.)

      1. α chain of type IV collagen
      2. inflammation
      3. extracellular matrix antigen
      4. neutropenia
      5. renal tubules and glomeruli
      6. type III hypersensitivity reaction.

       

      16–11  _____ is a highly variable type III autoimmune disease in which immune complexes form and may cause glomerulonephritis of the kidney, arthritis of the joints, and vasculitis of the face.

      1. pemphigus vulgaris
      2. systemic lupus erythematosus
      3. rheumatoid arthritis
      4. multiple sclerosis
      5. Goodpasture’s syndrome.

       

      16–12  Individuals who have two defective alleles of the AIRE gene _____.

      1. exhibit symptoms of autoimmunity at a young age
      2. are unable to activate regulatory T cells
      3. exhibit decreased predisposition to autoimmune disease
      4. are very effective at inducing anergy of circulating autoreactive B and T cells
      5. are more likely to be women of African or Asian origin.

       

      16–13  All of the following autoimmune diseases are correctly matched with their HLA disease associations except _____.

      1. HLA-B27: ankylosing spondylitis
      2. HLA-DQ2: type 1 diabetes in Africans and Asians
      3. HLA-B35: birdshot retinopathy
      4. HLA-DR4: rheumatoid arthritis
      5. HLA-DQ6: narcolepsy.

       

      16–14  The haplotype A1–B8–DR3–DQ2 is associated with several common autoimmune diseases including all of the following except _____.

      1. ankylosing spondylitis
      2. systemic lupus erythematosus
      3. autoimmune hepatitis
      4. myasthenia gravis
      5. type 1 diabetes
      6. primary biliary cirrhosis.

       

      16–15  With the exception of ______, these autoimmune diseases are more prevalent in women than in men.

      1. rheumatoid arthritis
      2. multiple sclerosis
      3. ankylosing spondylitis
      4. Sjögren’s syndrome
      5. Graves’ disease.

       

      16–16  Which of the following is not a characteristic of Graves’ disease?

      1. weight loss
      2. enlarged thyroid gland
      3. elevated thyroid-stimulating hormone
      4. heat intolerance
      5. overproduction of T3 and T4.

       

      16–17  All of the following are true regarding thyroglobulin except _____.

      1. its tyrosine residues are iodinated and cross-linked
      2. it is broken down to produce thyroid hormones
      3. it is stored in follicles of the thyroid
      4. it signals the pituitary gland to stop releasing thyroid-stimulating hormone
      5. it is synthesized initially as a glycoprotein by thyroid epithelial cells.

       

      16–18  Which of the following describes myasthenia gravis?

      1. Ectopic lymphoid tissue forms and impairs endocrine function.
      2. Disruption of adhesion molecules of cellular junctions.
      3. Autoimmune response to proteins of anterior chamber of the eye.
      4. Chronic inflammation of the gut mucosa.
      5. The neuromuscular junction is compromised.

       

      16–19  Which of the following is associated with antagonistic autoantibodies against cell-surface receptors or adhesion molecules? (Select all that apply.)

      1. myasthenia gravis
      2. rheumatoid arthritis
      3. insulin-resistant diabetes
      4. Graves’ disease
      5. pemphigus vulgaris.

       

      16–20  The reason why babies born to mothers with Graves’ disease suffer passively from the disease for only a short while after birth is that _____.

      1. very little IgM is transported across the placenta
      2. only antibodies, and not the B cells making the autoantibodies, cross the placenta
      3. the newborn’s regulatory T cells suppress autoantibody production
      4. the newborn’s thyroid gland develops resistance to the effects of maternal autoantibodies
      5. thyroglobulin synthesis does not commence until months after birth.

       

      16–21  The formation of ectopic lymphoid tissues occurs in all of the following conditions except _____.

      1. pemphigus foliaceus
      2. chronic hepatitis C infection
      3. Hashimoto’s disease
      4. rheumatoid arthritis
      5. multiple sclerosis
      6. Graves’ disease.

       

      16–22  A(n) _____ binds to the antigen-binding site of another antibody.

      1. cryptic epitope
      2. anti-idiotypic antibody
      3. molecular mimic
      4. receptor antagonist
      5. autoantibody.

       

      16–23  All of the following are linked to the development of rheumatoid arthritis or are associated with its treatment except _____. (Select all that apply.)

      1. anti-immunoglobulin autoantibodies
      2. adalumumab
      3. leukocyte infiltration in synovial tissue
      4. joint inflammation
      5. pulmonary hemorrhage
      6. rituximab
      7. increased susceptibility if the person possesses the HLA-DRB1*04:01 or 04:04 allotypes.
      8. peptidyl arginine deiminases
      9. smoking
      10. rheumatic fever.

       

      16–24  It is believed that the allotype DRB1*_____ may confer protection against rheumatoid arthritis because it contains _____ amino acid residues at positions 70 and 71 that bind to different subsets of peptides compared with the allotypes that confer susceptibility to this disease.

      1. 04:01; acidic
      2. 04:02; acidic
      3. 04:04; basic
      4. 04:05; basic

      e          04:08; acidic.

       

      16–25  Celiac disease exhibits all of the following symptoms except _____.

      1. villous atrophy
      2. anemia
      3. diarrhea
      4. tissue ulceration
      5. malabsorption
      6. increased susceptibility to intestinal cancer.

       

      16–26  All of the following are characteristics of tissue transglutaminase except ____.

      1. generation of negatively charged peptides that bind well to the positively charged pockets of the DQ2 and DQ8 allotypes
      2. conversion of glutamine to glutamate by deamination
      3. upregulation during tissue inflammation
      4. stimulation of IgG or IgA autoantibodies in celiac disease
      5. predisposition to celiac disease if individual possesses particular polymorphic variants.

       

      16–27  Describe three types of unwanted and potentially harmful immune response.

       

      16–28  Which of the following describes processes by which self-reactive lymphocytes are rendered incapable of mounting an autoimmune response? (Select all that apply.)

      1. sequestration of autoantigens in immunologically privileged sites
      2. induction of anergy in peripheral compartments
      3. positive selection of autoimmune T lymphocytes in secondary lymphoid tissues
      4. negative selection of T lymphocytes in the thymus
      5. suppression by regulatory T cells
      6. negative selection of B lymphocytes in the bone marrow
      7. expression of AIRE in the bone marrow
      8. induction of alloreactive responses it the thymus
      9. somatic hypermutation to an alternative antigen specificity
      10. apoptosis in primary lymphoid tissue
      11. deprivation of T-cell help.

       

      16–29  From Table 16–29 below, match the autoimmune disease in column A with the corresponding antigen in column B and the consequence in column C. Use each answer only once. Then indicate whether the autoimmune disease is categorized as type II, III, or IV.

      Table Q16–29
      Column A Column B Column C
      a. Rheumatoid arthritis 1. Myelin basic protein, proteolipid protein A. Destruction of red blood cells by complement and phagocytosis, anemia
      b. Subacute bacterial endocarditis 2. DNA, histones, ribosomes, snRNP, scRNP B. Joint inflammation and destruction
      c. Autoimmune hemolytic anemia 3. Thyroid-stimulating hormone receptor C. Pancreatic β cell destruction
      d. Mixed essential cryoglobulinemia 4. Bacterial antigen D. Glomerulonephritis
      e. Multiple sclerosis 5. Rheumatoid factor IgG complexes E. Hyperthyroidism
      f. Systemic lupus erythematosus 6. Epidermal cadherin F. Blistering of skin
      g. Type 1 diabetes 7. Synovial joint antigen G. Glomerulonephritis, vasculitis, arthritis
      h. Graves’ disease 8. Rh blood group antigens H. Systemic vasculitis
      i. Pemphigus vulgaris 9. Pancreatic β cell antigen I. Brain degeneration, paralysis

       

      16–30  Describe the three immunological mechanisms responsible for the destruction of red blood cells in autoimmune hemolytic anemia.

       

      16–31  Characterize two properties of endocrine glands that render them susceptible to autoimmune attack.

       

      16–32  Hashimoto’s and Graves’ diseases both impair normal functioning of the thyroid gland but do so using different immunopathological mechanisms. Compare and contrast these mechanisms.

       

      16–33  Indicate whether each of the following statements is true (T) or false (F).

      ___a. During pregnancy, IgG antibodies and activated lymphocytes can cross the placenta and enter the circulatory system of the fetus.

      ___b. Blood plasma exchange (plasmapheresis) can be used to remove maternal IgG from the newborn.

      ___c. All autoimmune diseases involve a breach of T-cell tolerance.

      ___d. Newborns of mothers with T cell-mediated autoimmune diseases exhibit the same symptoms as their mothers.

      ___e. Autoimmune diseases can be induced after an infection.

       

      16–34

      1. What mechanism of self-tolerance is broken in the autoimmune syndrome APECED?
      2. What is the underlying genetic defect in APECED? Explain why it leads to a reduction in self-tolerance.

       

      16–35  You have isolated a subset of CD25+ CD4+ T cells from the blood that have T-cell receptors specific for a self antigen but do not proliferate when challenged with the antigen in vitro. What is the name given to these T cells, and what role are they thought to have in preventing autoimmunity?

       

      16–36  People who are heterozygous for HLA-DQ2 and HLA-DQ8 allotypes are at greater risk of developing type 1 diabetes than those who are homozygous for HLA-DQ2 or HLA-DQ8.

      1. Explain the reason for this increased susceptibility.
      2. Why is the above statement true mainly for people of northern European origin but not for some other ethnic groups?

       

      16–37

      1. Which patients affected by Goodpasture’s syndrome also succumb to pulmonary hemorrhage?
      2. Explain the reason for this complication.

       

      16–38  Explain the relationship between HLA-DRB1*04, smoking, the expression of peptidyl arginine deaminase, and rheumatoid arthritis.

       

      16–39  In the context of autoimmunity: (A) define molecular mimicry; and (B) provide an example.

       

      16–40  A recent therapy developed for the treatment of rheumatoid arthritis includes the use of _____ monoclonal antibodies that suppress the autoimmune response. (Select all that apply.)

      1. anti-TNF-α
      2. anti-C-reactive protein
      3. anti-CD20
      4. anti-rheumatoid factor
      5. anti-CD3.

       

      16–41  Chronic diseases in which the immune response is targeted toward autologous entities of one’s body are known as _____.

      1. hypersensitivity reactions
      2. innate immune reactions
      3. allergic reactions
      4. autoimmune diseases
      5. anergic reactions.

       

      16–42  Discuss why splenectomy is a viable treatment for chronic autoimmune diseases targeted at circulating neutrophils.

       

      16–43  Indicate whether each of the following statements is true (T) or false (F).

      ___ a. Autoimmune diseases are rarely resolved.

      ___ b. Autoimmune responses are the result of innate immune responses directed toward self antigens.

      ___ c. Some forms of autoimmune disease involve IgE autoantibodies.

      ___ d. During pregnancy the fetus is exposed to maternal leukocytes.

      ___ e. Ectopic lymphoid tissue resembling secondary lymphoid tissue may develop under the influence of lymphotoxin (LT).

       

      16–44  Match the autoimmune disease in column A with the consequence in column B.

      Column A Column B
      ___ a. type 2 diabetes 1. skin blistering
      ___ b. rheumatoid arthritis 2. joint deterioration
      ___ c. mixed essential cryoglobulinemia 3. keotacidosis
      ___ d. acute rheumatic fever 4. heart valve scarring
      ___ e. pemphigus vulgaris 5. systemic vasculitis

       

      16–45

      Match the autoimmune disease in column A with the autoantigen in column B.

      Column A Column B
      ___ a. mixed essential cryoglobulinemia 1. thyroid-stimulating hormone receptor
      ___ b. myasthenia gravis 2. cell wall components of Streptococcus
      ___ c. Graves’ disease 3. myelin basic protein
      ___ d. acute rheumatic fever 4. acetylcholine receptor
      ___ e. multiple sclerosis 5. rheumatoid factor IgG

       

      16–46  Which of the following would be consistent with a diagnosis of Goodpasture’s syndrome? (Select all that apply.)

      1. pulmonary hemorrhage
      2. joint inflammation
      3. glomerulonephritis
      4. anti-collagen IgG deposition in renal glomeruli
      5. hyperglycemia.

       

      16–47  Thyroid-stimulating hormone is made in the _____ and induces the release of thyroid hormones after proteolytic processing of _____.

      1. pituitary gland; thyroglobulin
      2. hypothalamus; thyroxine
      3. pancreas; thyroglobulin
      4. pituitary gland; thyroid-stimulating hormone receptor
      5. thyroid gland; thyroid peroxidase.

       

      16–48  Graves’ disease causes _____, whereas Hashimoto’s disease causes _____.

      1. hypothyroidism; hyperthyroidism
      2. hyperthyroidism; hypothyroidism
      3. hypoglycemia; hyperglycemia
      4. hyperglycemia; hypoglycemia
      5. glomerulonephtitis; systemic vasculitis.

       

      16–49

      1. What is ectopic lymphoid tissue?
      2. Give four examples where this type of tissue forms in autoimmune disease.

       

      16–50  How do the treatments for Hashimoto’s and Graves’ diseases differ, and why?

       

      16–51  Which of the following are correctly matched? (Select all that apply.)

      1. exocrine tissue: islets of Langerhans
      2. type 2 diabetes: insulin-dependent diabetes mellitus
      3. β cells of pancreas: insulin production
      4. α cells of pancreas: somatostatin production
      5. insulitis: lymphocyte infiltration in islets of Langerhans.

       

      16–52  Examples of rheumatic diseases caused by autoimmune responses include _____. (Select all that apply.)

      1. rheumatoid arthritis
      2. acute rheumatic fever
      3. multiple sclerosis
      4. autoimmune hemolytic anemia
      5. Sjögren’s syndrome
      6. systemic lupus erythematosus.

       

      16–53  Another name for anti-immunoglobulin autoantibodies is _____.

      1. C-reactive protein
      2. rheumatoid factor
      3. rituximab
      4. thyroglobulin
      5. ectopic antibodies
      6. infliximab.

       

      16–54  Rituximab, used in the treatment of rheumatoid arthritis, depletes _____ through a process involving the cross-linking of _____ on the surface of NK cells and the induction of antibody-dependent cell-mediated cytotoxicity.

      1. NK cells; NKG2D
      2. T cells: NKG2D
      3. inflammatory cytokines; TNF-alpha
      4. C-reactive protein; FcγRIII
      5. B cells; FcγRIII.

       

      16–55  Which of the following autoimmune diseases affect the nervous system? (Select all that apply.)

      1. myasthenia gravis
      2. mixed essential cryoglobulinemia
      3. Graves’ disease
      4. pemphigus vulgaris
      5. multiple sclerosis.

       

      16–56  _____ autoantibodies enhance receptor function.

      1. neutralizing
      2. opsonizing
      3. agonist
      4. complement-fixing
      5. antagonist.

       

      16–57  Antagonistic autoantibodies made against the insulin receptor cause _____. (Select all that apply.)

      1. type 1 diabetes
      2. hypoglycemia
      3. hyperglycemia
      4. insulin-resistant diabetes
      5. light-headedness.

       

      16–58  Deficiency in the production of AIRE results in _____. (Select all that apply.)

      1. normal expression of tissue-specific proteins in the bone marrow and thymus
      2. incomplete negative selection of developing T cells
      3. the development of autoimmune B-cell and T-cell responses against endocrine glands and other tissues
      4. death in infancy
      5. the development of autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED).

       

      16–59  Describe two different ways in which infection with bacteria or viruses compromises T-cell tolerance, leading to the production of effector T cells specific for self antigens.

       

      16–60  Ankylosing spondylitis has a strong association with polymorphisms found in _____.

      1. HLA-B27
      2. AIRE
      3. CTLA-4
      4. HLA-DQ6
      5. HLA-Cw6
      6. FoxP3
      7. TNF-α.

       

      16–61  Autoantibody specificities are affected by HLA class II polymorphisms. In the case of systemic lupus erythematosus, indicate which of the following associations between HLA-class II and autoantigens have been observed in these patients.

      1. HLA-DR3; nuclear ribonucleoprotein complex
      2. HLA-DR5; small cytoplasmic ribonucleoprotein complex
      3. HLA-DR2; double-stranded DNA
      4. HLA-DR4; single-stranded RNA
      5. HLA-DQ8; double-stranded RNA.

       

      16–62  Explain the mechanism that gives rise to a broadening B-cell response during the course of systemic lupus erythematosus.

       

      16–63  _____ is an example in which physical trauma provides access of lymphocytes to an otherwise immunologically privileged site. (Select all that apply.)

      1. rheumatoid arthritis
      2. multiple sclerosis
      3. type 1 diabetes
      4. myasthenia gravis
      5. sympathetic ophthalmia.

       

      16–64  Bacterial infections are associated with which of the following autoimmune diseases? (Select all that apply.)

      1. Reiter’s syndrome
      2. pemphigus vulgaris
      3. reactive arthritis
      4. rheumatic fever
      5. myasthenia gravis.

       

      16–65  _____ is the term used to describe how pathogen antigens resemble host antigens and can sometimes trigger autoimmune disease.

      1. intramolecular epitope spreading
      2. molecular mimicry
      3. intermolecular epitope spreading
      4. sympathetic senescence
      5. linkage equilibrium.

       

      16–66

      1. What is meant by the term ‘epitope spreading’?
      2. Name one autoimmune disease affecting the skin in which epitope spreading is involved, and explain how.

       

      16–67  The upregulation of _____ by IFN-γ can contribute to antigen-specific T-cell activation on thyroid epithelium.

      1. CD4
      2. CD8
      3. HLA class I
      4. HLA class II
      5. CD28.

       

      16–68  A(n) _____ is an epitope that is typically not accessible to the immune system but is revealed under inflammatory or infectious states.

      1. cryptic epitope
      2. molecular mimic
      3. regulatory peptide
      4. carrier
      5. adjuvant.

       

      16–69  The process by which the human thymus gradually decays is known as _____.

      1. apoptosis
      2. senescence
      3. involution
      4. the hygiene hypothesis
      5. self-tolerance.

       

      16–70  The autoreactive CD4 T cells of elderly people with rheumatoid arthritis _____. (Select all that apply.)

      1. express high levels of CD28
      2. are predominantly anergic
      3. express KIR2DS2
      4. are highly susceptible to apoptosis in inflamed joints
      5. produce IFN-γ.

       

      16–71  Amanda Chenoweth, 21 years of age, returned from a summer job as a pianist on a cruise ship where she was exposed daily to excessive sun; she developed a rash on her cheeks. She complained that her finger joints were stiff and painful, which made it difficult to play the piano, and that her hips became painful after sitting at the piano for long periods. Her blood sample tested positive for anti-nuclear antibodies and had decreased serum C3 levels. A urine albumin test showed elevated protein levels. A course of prednisone (an anti-inflammatory steroid) in combination with naprosyn (a nonsteroidal anti-inflammatory agent) was begun and her condition improved rapidly. What is the most likely cause and clinical name of her condition?

      1. deterioration of the central nervous system; multiple sclerosis
      2. cartilage destruction by bone-cell enzymes; rheumatoid arthritis
      3. immune complexes fixing complement in kidney, joints, and blood vessels; systemic lupus erythematosus
      4. autoantibodies against acetylcholine receptor at the neuromuscular junction; myasthenia gravis
      5. consumption of seafood to which she was allergic; acute systemic anaphylaxis.

       

      16–72  At 42 years old, Stephanie Goldstein developed occasional blurred and double vision, numbness and ‘pins and needles’ in her arms and legs (paresthesia), and bladder incontinence. After a month of these symptoms she went to her doctor, who sent her to the neurology specialist. An MRI scan revealed areas of demyelination in the central nervous system (CNS), and Stephanie was diagnosed with the autoimmune disease multiple sclerosis (MS). Which of the following best explains why some people are susceptible to the development of MS?

      1. Negative selection of autoreactive T cells occurs during T-cell development.
      2. Apoptosis of autoreactive B cells occurs in the bone marrow during B-cell development.
      3. An inability to produce immunological tolerance toward CNS-derived constituents results in the generation of self-reactive lymphocytes.
      4. An immunodeficiency inhibiting somatic recombination of immunoglobulins and T-cell receptors results in impaired lymphocyte development.
      5. Regulatory T cells fail to activate autoreactive T cells in secondary lymphoid organs.

       

      16–73  Anders Anderson, was seen by his pediatrician at 24 months old after a recent bout of diarrhea and vomiting. He had lost his appetite and complained that his stomach hurt. Anders was in the 5% centile for weight, had slender limbs, wasted buttocks, and a protuberant abdomen. Jejunal biopsy revealed abnormal surface epithelium, and villous atrophy with hyperplasia of the crypts. Which of the following would be a likely clinical finding in this patient?

      1. glomerulonephritis
      2. urticarial rash
      3. anti-gliadin IgA antibodies
      4. chronic wheezing
      5. low blood pressure.

       

      16–74  Seventeen-year-old Lisa Montague practiced piano for 3–4 hours each day while preparing for music college auditions. Some of her pieces required sustained arm-muscle activity and she began to find them hard to play, even though she had previously played them easily. When she also started to have difficulty swallowing and chewing, she told her mother, who took her to the emergency room, where the physician noticed drooping eyelids and limitation of ocular motility. An electromyogram detected impaired nerve-to-muscle transmission. Administration of pyridostigmine rapidly improved Lisa’s symptoms. Which of the following blood-test results would be most consistent with her condition?

      1. elevated rheumatoid factor
      2. elevated anti-myelin basic protein antibodies
      3. elevated anti-acetylcholine receptor antibodies
      4. elevated anti-nuclear antibodies
      5. elevated anti-Rh antibodies.

       

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