CH. 4

4-4 Match the antibody term in Column A with its correct description in 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

a—2; b—5; c—4; d—3; e—1

4-25 Match the term in Column A with its description in 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

a—3; b—4; c—2; d—1; e—5

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.

(1) Gene rearrangements affect the variable region of immunoglobulins, whereas isotype switching affects the constant region. (2) Different recombination-signal sequences and enzymes are used for the two processes. (3) Isotype switching occurs only after antigen stimulation, whereas gene rearrangement occurs only during B-cell maturation in the bone marrow. (4) All isotype switch recombinations are productive, but not all gene rearrangements are. (5) Only heavy chains are involved in isotype switching, whereas both heavy-chain and light-chain genes are involved in somatic recombination.

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.

4-3 An antibody molecule is made of four polypeptide chains—two identical heavy chains and two identical and smaller light chains, with a total molecular weight of approximately 150 kDa. Each chain is made up of a series of structurally similar domains known as immunoglobulin domains. The amino-terminal portion of each H chain combines with one L chain, and the two carboxy-terminal portions of the H chains combine with each other, forming a Y-shaped quaternary structure. Disulfide bonds hold the H and L chains together, hold the two H chains together (interchain disulfide bonds), and stabilize the domain structure of the chains (intrachain disulfide bonds). The arms of the antibody molecule are called Fab (fragment antigen binding) and interact with antigen. The stalk is called Fc (fragment crystallizable) and is made up of H chains only. The amino-terminal domains of an H and an L chain together make up a site that binds directly to antigen and varies greatly between different antibodies. These domains are referred to as the variable region, and each antibody has two identical antigen-binding sites. The remaining domains of both H and L chains are the same in all antibodies of a given class (isotype). These domains are referred to as the constant region. The variable region of each chain includes hypervariable regions of amino acid sequences that differ the most between different antibodies. These are nested within less variable sequences known as the framework regions. The hypervariable regions make loops at one end of the domain structure and are also known as complementarity-determining regions because they confer specificity on the antigen-binding site.

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

A. Affinity maturation is the phenomenon observed during a B-cell response in which antibodies with increasing affinity for the antigen are produced as the response proceeds. This occurs as a result of the process known as somatic hypermutation. B. In somatic hypermutation, which occurs only in activated B cells, random point mutations are introduced into the rearranged V regions of H-chain and L-chain genes at a rate six orders of magnitude higher than spontaneous mutation. Some of these mutations give rise to immunoglobulin with higher affinity for the antigen than the original immunoglobulin. Those B cells producing higher-affinity surface immunoglobulin will be preferentially selected for activation by the antigen and will come to dominate the response, differentiating into plasma cells producing high-affinity antibodies.

A. What is an epitope? B. Define the term multivalent antigen. C. How does a linear epitope differ from a conformational epitope? D. Do antibodies bind their antigens via noncovalent bonding or via covalent bonding?

A. An epitope is the specific part of the antigen that is recognized by an antibody and binds to the complementarity-determining regions in the antibody variable domains. Epitopes are sometimes referred to as antigenic determinants. Epitopes can be part of a protein or can be carbohydrate or lipid structures present in the glycoproteins, polysaccharides, glycolipids, and proteoglycans of pathogens. B. Multivalent antigens are complex macromolecules that contain more than one epitope. C. Linear epitopes are epitopes in proteins that comprise a contiguous amino acid sequence. They are also called continuous epitopes. In contrast, a conformational epitope is formed by amino acids that are brought together as a result of protein folding and are not adjacent in the protein sequence. Conformational epitopes are also known as discontinuous epitopes. D. Antibodies bind antigens via noncovalent bonding such as hydrogen bonds, hydrophobic interactions, van der Waals forces, and electrostatic attraction.

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

A. Before antigen encounter, antibodies are produced in a membrane-bound form. After antigen encounter, antibodies are secreted in a soluble form. B. Immature, mature, and memory B cells produce membrane-bound antibodies. Plasma cells secrete soluble antibodies. C. The membrane-bound and soluble forms of antibody produced by a particular B cell possess the same antigen specificity.

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

A. Catalytic antibodies bind with a high degree of specificity to the target antigen and facilitate a chemical conversion of that antigen in a similar manner to the action of enzymes. If this reaction results in the alteration of that antigen so that it is no longer able to carry out its undesirable effect in the body, the catalytic antibody has therapeutic value. B.Examples would include: (1) converting toxic substances to less harmful molecules, and (2) converting addictive drugs to derivatives that no longer possess psychostimulating effects.

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

A. Igα and Igβ are essential for escorting immunoglobulins from the endoplasmic reticulum membrane to the cell membrane, where they remain associated with the immunoglobulin to form the functional B-cell antigen receptor. The long cytoplasmic tails of Igα and Igβ contain amino acid motifs that interact with intracellular signaling proteins after the receptor has been activated by the binding of antigen to the immunoglobulin. B. Igα and Igβ proteins have no need to be variable, because they do not interact directly with antigen. Igα and Igβ perform specific signaling functions, which require particular amino acid sequences and also have evolved a sequence and structure that enable them to interact with all the different immunoglobulin isotypes. Extensive variation in Igα and/or Igβ could therefore compromise their interaction with immunoglobulins and their signal transduction capabilities.

A. 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. B. 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? C. In what order do the various immunoglobulin loci rearrange?

A. In developing B cells, gene rearrangements within the genetic loci for immunoglobulin light and heavy chains can produce an almost unlimited variety of different variable regions, and thus produce the huge repertoire of antibodies with different specificities for many types of antigen. This gene rearrangement mechanism is called somatic recombination. In the germline configuration, before gene rearrangement, the immunoglobulin loci in progenitor B cells are composed of sequences encoding the constant regions and families of gene segments encoding different portions of the variable region. Heavy-chain loci contain a series of gene segments called variable (V), diversity (D), and joining (J). Light-chain loci contain only V and J gene segments. In somatic recombination in developing B cells, one of each family of gene segments is randomly selected and joined together to give a complete variable-region sequence, which is subsequently expressed as an immunoglobulin heavy or light chain. Immunoglobulin gene rearrangement is irreversible, leading to permanent alteration of the chromosome; it occurs exclusively in B cells. B. A D gene segment first joins to a J to form DJ, followed by a V becoming joined to DJ to form VDJ, which encodes a complete variable region. C. The heavy-chain locus rearranges before the light-chain loci. For light chains in humans, the κ locus rearranges first and is followed by the λ locus only if both κ loci fail to produce a successful rearrangement.

A. What is isotype switching? B. Explain the molecular mechanism of isotype switching. C. Why is isotype switching important?

A. Isotype switching is the process by which antibodies change their heavy-chain constant regions so as to acquire different effector functions, while preserving the variable region and antigen specificity. The light chain is unaffected. B. The molecular mechanism involves a recombination between sequences, called switch regions, which lie upstream (on the 5′ side) of heavy-chain C genes. All heavy-chain C genes except Cδ have a switch region. Recombination between two switch regions results in the excision of DNA (as a circular DNA molecule) between the two and the movement of the new heavy-chain C gene next to the preserved V region. Transcription will produce an mRNA encoding the same V-region sequence and the new C region. Switching can occur between the first switch region and any other switch region that lies downstream (on the 3′ side). Isotype switching is not random but is influenced by T-cell cytokines. C. Isotype switching is important because the different antibody isotypes have different effector functions, and efficient immune responses rely upon the production of the most appropriate effector function to combat the particular pathogen.

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?

A. Neutralization: IgM, IgG1, IgG2, IgG3, IgG4, IgA B. Opsonization: IgG1, IgG2, IgG3, IgG4, IgA C. Sensitization for killing by NK cells: IgG1, IgG3 D. Sensitization of mast cells: IgG1, IgG3, IgE E. Activation of complement: IgM, IgG1, IgG2, IgG3, IgA F. Transport across epithelium: IgM, IgA (dimer) G. Transport across placenta: IgG1, IgG2, IgG3, IgG4 H. Diffusion into extravascular sites: IgM, IgG1, IgG2, IgG3, IgG4, IgA (monomer), IgE

A. What is the difference between polyclonal antibodies and monoclonal antibodies? B. How is each produced?

A. Polyclonal antibodies are a mixture of antibodies of different specificities and affinities for a particular antigen. They are the product of numerous different B cells. Monoclonal antibodies have a single specificity and affinity for a given antigen. They derive from a single B cell. B. Polyclonal antibodies are produced in vivo by immunizing an animal with antigen, allowing sufficient time for an immune response to occur and then preparing antiserum containing the antibodies from the blood. Monoclonal antibodies are made in vitro from individual cell lines derived from single B cells. This is achieved by producing a hybrid immortalized cell line through the fusion of an antibody-producing B cell with a myeloma tumor cell to produce an antibody-producing 'hybridoma.' A hybridoma producing the desired antibody can then be cloned and grown on to produce unlimited amounts of monoclonal antibody.

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

A. The four types of therapeutic antibody include (i) mouse monoclonal antibodies, (ii) chimeric monoclonal antibodies, (iii) humanized monoclonal antibodies, and (iv) fully human monoclonal antibodies. B. (i) Mouse monoclonal antibodies are produced from hybridoma cell lines obtained by immortalizing mouse B cells by fusing them with a tumor cell. Hybridomas secreting antibody with the appropriate specificity for antigen are cloned and propagated. (ii) Chimeric monoclonal antibodies are produced by fusing the coding regions of the variable regions of mouse monoclonal antibodies, known to have specificity for a particular antigen, with the coding regions of human constant regions. (iii) Humanized monoclonal antibodies retain only the complementarity-determining regions of mouse monoclonal antibodies, and all remaining regions are replaced with human-derived regions. (iv) Fully human monoclonal antibodies are made either by using human hybridoma cell lines or by using transgenic mice whose immunoglobulin genes have been replaced by human immunoglobulin genes. C. (i) Fully human monoclonal antibodies are the most desirable, because (ii) they will not stimulate an anti-constant region antibody response in the recipient and can therefore be used for repeated treatment in chronic diseases without complications and without reducing therapeutic efficacy. (iii) Adalimumab is an example of a fully human monoclonal antibody used to treat rheumatoid arthritis. It neutralizes the inflammatory cytokine TNF-α to decrease inflammation of the joints.

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?

An individual with this genetic defect would be unable to rearrange either immunoglobulin or T-cell receptor genes somatically. There would be a severe combined immunodeficiency (SCID) owing to the absence of mature B cells and T cells.

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

CDR3 of the light chain is composed mainly of the coding joint between the V and J segments, which is formed during somatic recombination, with junctional diversity being generated by the addition of P and N nucleotides. CDR3 of the heavy chain is composed mainly of the D gene segment plus its coding joints with a V gene segment on one side and a J gene segment on the other. P and N nucleotides are also added to these joints during recombination. In addition, the D gene segment sequences differ between immunoglobulins.

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

Gene rearrangement by somatic recombination involves recombination signal sequences (RSSs) that flank V, D, and J segments and are recognized by the enzymes involved in cutting and rejoining the gene segments. An RSS is composed of a conserved nonamer sequence and heptamer sequence separated by a spacer region. There are two types of RSS, one with a spacer of 12 bp and one with a spacer of 23 bp. To ensure that segments are brought together in the right order, an RSS with a 12-bp spacer is always brought together with one with a 23-bp spacer. This is called the 12/23 rule. This ensures that in the heavy-chain locus, V rearranges to DJ and not directly to J or another V, and in the light-chain locus, V rearranges to J and not to another V

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?

Hemagglutinin and neuraminidase epitopes, because epitopes exposed on the surface of pathogens stimulate antibodies.

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.

Mice are used routinely to generate monoclonal antibodies. The constant regions of mouse antibodies are sufficiently different from the constant regions of human antibodies in amino acid composition that, if mouse antibodies are infused into a patient, an immune response will be stimulated and directed against the mouse constant-region epitopes. This immune response neutralizes the monoclonal antibody and in practice limits its intended use to one effective dose. When monoclonal antibodies are used for serological or diagnostic purposes in the laboratory, the monoclonal antibodies do not need to be humanized because laboratory assays are performed in vitro.

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

Naive B cells express IgM and IgD simultaneously through a mechanism involving alternative ways of processing the RNA transcript before translation. A primary transcript containing leader (L), V, D, J, Cμ, and Cδ is produced first. This transcript contains two distinct polyadenylation signal sequences, one following the Cμ exons (pA1) and the other following the Cδ exons (pA2). Processing results in the removal of either Cμ or Cδ exons (plus introns) through alternative splicing. The resulting mRNAs, which encode either Cμ or Cδ, are polyadenylated at the pA1 or pA2 site, respectively

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?

The B cells in a person carrying such a defect would be unable to switch antibody isotype and would be unable to produce any antibody other than IgM. Because IgM antibodies can implement fewer effector functions than IgG antibodies, which constitute the main class of antibody produced in an adaptive immune response, one would expect that immunity would be impaired. In addition, no IgA antibodies could be produced, leaving the person highly vulnerable to infection through mucosal surfaces. There are, in fact, rare inherited genetic deficiencies that result in an inability to switch isotype. They are called hyper IgM immunodeficiencies because the patient is unable to produce any antibody other than IgM. The most frequent one affects the expression of a cell-surface molecule called CD40 ligand in T cells, which is required for the interaction between T cells and B cells that stimulates isotype switching, as we shall learn later in this book.

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).

The rejoining and repair of DNA during the recombination process leads to additional variation in sequence at the junctions between the rearranged gene segments. This is called junctional diversity and contributes considerably to the final diversity of immunoglobulin specificities. Two sources of junctional diversity are introduced: P (palindromic) and N (nontemplated) nucleotides. P nucleotides are generated through endonuclease activity and repair around a hairpin loop at the ends of the gene segments to be joined. N nucleotides are nucleotides added at random at the junctions by terminal deoxynucleotidyl transferase (TdT) activity.

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

Whether immunoglobulin is expressed as a transmembrane-anchored protein or a secreted protein is determined by alternative processing of the heavy-chain RNA transcript. All the heavy-chain C genes contain MC (membrane-coding) exons, which encode the transmembrane region and cytoplasmic tail, and an SC (secretion-coding) exon, which encodes the carboxy terminus of the secreted antibody. The primary RNA transcript contains the MC and SC exons. In naive resting B cells or memory B cells, cleavage and polyadenylation of the transcript at a site (pAm) following the MC exons and deletion of the SC exon by RNA splicing produces the membrane-bound immunoglobulin. On B-cell activation and differentiation into plasma cells, the SC exon is retained in the transcript, and a polyadenylation signal sequence, pAs, immediately following it is used to produce an mRNA encoding the secreted form of the heavy chain

4-15 The enzyme responsible for recombining V, D, and J segments during somatic recombination is called a. V(D)J recombinase b. terminal deoxynucleotidyl transferase c. exonuclease d. DNA polymerase e. DNA ligase.

a

4-20 All of the following are utilized in the binding of antibodies to antigens except a. interchain disulfide bonds b. hydrogen bonding c. hydrophobic interactions d. electrostatic forces (salt bridges) e. van der Waals interactions.

a

4-28 With the exception of B cells, all other cells of the body have the immunoglobulin genes in the a. germline configuration b. monoclonal form c. recombined configuration d. expressed configuration e. chimeric form.

a

A circulating B cell that has never before encountered antigen expresses _____ on the cell surface: a. IgM and IgD b. IgM c. IgD d. IgM and IgG e. IgG f. IgE.

a

Identify the correct order of gene segments in a rearranged heavy-chain gene in a naive B cell. a. L-VDJ-Cμ-Cδ b. VDJ-Cμ-Cδ-L c. L-VDJ-Cδ-Cμ d. VDJ-L-Cμ-Cα1 e. L-VDJ-Cμ-Cα1

a

Identify which of the following is not associated with activation-induced cytidine deaminase (AID) activity. a. diversification of the VH domain but not the VL domain b. synthesized in proliferating B cells during active immune responses c. somatic hypermutation d. isotype switching e. conversion of cytosine to uracil.

a

The _______ contribute to antigen specificity of immunoglobulins, and _______ make up the more conservative flanking regions. a. hypervariable loops; framework regions b. constant domains; variable domains c. heavy chains; light chains d. variable gene segments; joining gene segments e. antigenic determinants; complementarity determining regions.

a

The antibody transported across mucosal epithelia is _____: a. IgA b. IgD c. IgE d. IgG e. IgM.

a

The five classes (isotypes) of immunoglobulins comprise a. IgA, IgD, IgE, IgG, IgM b. IgA, IgC, IgD, IgE, IgG c. IgA, IgD, IgE, IgH, IgM d. IgA, IgD, IgE, IgG, IgK e.IgA, IgD, IgE, IgG, IgS.

a

The highest degree of diversity resulting from somatic recombination is concentrated ____________ of the VH and VLdomains, whereas the point mutations caused by somatic hypermutation are found ____________. a. in CDR3; throughout the V region b. in CDR3; in CDR1 and CDR2 of VH and VL domains c. in CDR1 and CDR2; in CDR3 d. in CDR1 and CDR2; throughout the V region e. in all three CDRs; in C regions.

a

The process used to produce either surface or secreted forms of the immunoglobulin heavy chain is called a. alternative RNA processing b. isotype switching c. somatic recombination d. somatic hypermutation e. opsonization.

a

Which immunoglobulin is transported most efficiently across mucosal epithelium? a. IgA b. IgD c. IgE d. IgG e. IgM.

a

Which of the following can be found in serum in a monovalent form? a. IgG4 b. IgD c. IgA1 d. antibodies made up of four C domains e. IgG3.

a

Which of the following statements about the production and use of monoclonal antibodies is incorrect? a. Production of monoclonal antibodies requires a purified form of antigen. b. A monoclonal antibody has specificity for only one epitope of an antigen. c. B cells are fused with a tumor cell called a myeloma, to immortalize the resulting hybridoma. d. Monoclonal antibodies made in mice have limited therapeutic potential. e. Humanized monoclonal antibodies reduce complications associated with using mouse monoclonal antibodies.

a

Which of the following statements regarding immunoglobulins is correct? a. Immunoglobulins make up five classes (or isotypes) called IgA, IgD, IgE, IgG, and IgM. b. Regardless of their isotype, immunoglobulins all have the same effector function. c. Antibodies consist of four identical heavy chains and four identical light chains. d. Peptide bonds hold the heavy and light chains together. e. The constant regions make up the antigen-binding site.

a

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.) a. CDR loops b. antigen c. hypervariable region d. antigenic determinant e. conformational epitope.

a, c

Which of the following statements regarding Igα and Igβ proteins are correct? (Select all that apply.) a. They associate with all isotypes of antibodies on the cell membrane. b. They are not required to form the fully functional B-cell receptor. c. They facilitate signal transduction through their long cytoplasmic tails. d. They are linked to one another by disulfide linkages. e. They are made by somatic rearrangement.

a, c, d

4-29 Indicate which of the following statements is false. (Select all that apply.) a. Immunoglobulin heavy- and light-chain loci are encoded on the same chromosome. b. Light chains contain V and J segments, whereas heavy chains contain V, D, and J segments. c. The Vκ gene segments are duplicated in about 50% of the human population. d. All immunoglobulin loci include a leader sequence. e. On the heavy-chain locus, V rearranges to D first, and then J joins the combined VD sequence. f. Immunoglobulin heavy-chain loci undergo two rounds of somatic recombination, whereas light-chain loci undergo only one.

a, e

Indicate which of the following statements are true (T) or and which are false (F) with reference to immunoglobulin structure. a. __The antibody secreted by a plasma cell has a different specificity for antigen than the immunoglobulin expressed by its B-cell precursor. b. __The amino-terminal regions of heavy and light chains of different immunoglobulins all differ in amino acid sequence. c. __A flexible hinge region holds the heavy chain and light chain together. d. __The heavy-chain constant region is responsible for the effector function of immunoglobulins. e. __λ and κ light chains have different functions.

a—F; b—T; c—F; d—T; e—F

4-12 The immunoglobulin heavy-chain gene consists of _______ segments, whereas the immunoglobulin light-chain gene consists of _______ segments. a. κ; λ b. VDJ; VJ c. VJ; VDJ d. P; N e. RAG-1; RAG-2.

b

4-16 Which of the following is not a component of V(D)J recombinase? a. Artemis b. Terminal deoxynucleotidyl transferase c. RAG-1/RAG-2 d. DNA ligase IV e. DNA-dependent protein kinase and the associated Ku protein.

b

4-17 Which of the following corresponds to the antigen-binding site of immunoglobulins? a. VH:CH b. VH:VL c. VL:CL d. CH:CL e. VH:CL.

b

4-34 The enzyme responsible for adding N nucleotides is a. V(D)J recombinase b. terminal deoxynucleotidyl transferase c. uracil-DNA-glycosylase (UNG) d. DNA ligase e. activation-induced cytidine deaminase (AID).

b

4-38 Junctional diversity during gene rearrangement results from the addition of a. switch region nucleotides b. P and N nucleotides c. V, D, and J nucleotides d. recombination signal sequences e.mutations in complementarity-determining regions.

b

4-5 All of the following comprise heavy-chain isotypes of immunoglobulin except a. α b. β c. γ d. δ e. ε

b

4-6 Which of the following statements regarding immunoglobulin light chains is correct? a. κ associates with only particular heavy-chain isotypes. b. There is no functional difference between κ and λ. c. A given antibody may contain just κ, or just λ, or both. d. Most antibodies in humans contain λ light chains. e. Light chains possess only framework regions, not hypervariable regions.

b

All of the following are required for isotype switching except a. switch-region recombination b. J chain c. activation-induced cytidine deaminase (AID) d. B-cell proliferation e. uracil-DNA glycosylase (UNG).

b

The five isotypes of immunoglobulin differ from each other in their _____: a. light-chain constant regions b. heavy-chain constant regions c. light-chain variable regions d. heavy-chain variable regions e. heavy-chain variable and constant regions.

b

Which of the following is mismatched? a. surface immunoglobulin: B-cell antigen receptor b. affinity maturation: isotype switching c. constant region of antibodies: binding to complement proteins d. activation-induced cytidine deaminase: somatic hypermutation e. switch sequences: class switching.

b

_____ is secreted into the bloodstream, whereas _____ is secreted into mucus such as gastrointestinal fluid, colostrum, saliva, tears, and sweat. a. monomeric IgM: pentameric IgM b. monomeric IgA: dimeric IgA c. monomeric IgA: dimeric IgG d. monomeric IgA: monomeric IgM e. dimeric IgA: pentameric IgM.

b

4-14 Which of the following describes two recombination signal sequences required for a permitted somatic recombination event? a. VH 7-12-9::9-23-7 JH b. Vλ7-23-9::9-23-7 Jλ c. DH 7-12-9::9-23-7 JH d. Vκ7-12-9::7-23-9 Jκ e. VH 9-23-7::7-12-9 DH.

c

4-23 A _____ antibody is one that facilitates a chemical reaction involving the antigen to which it binds and interacts. a. conformational b. multivalent c. catalytic d. hypervariable e. monoclonal.

c

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. a. V regions b. D regions c. C regions d. J regions e. MC regions.

c

4-30 Which of the following statements is correct concerning membrane-coding (MC) exons of immunoglobulin genes? a. MC exons are located upstream (5′) of the constant-domain exons. b. MC exons code for amino acids that anchor and stabilize the light chain to the membrane of B cells. c. MC exons specify transmembrane hydrophobic amino acids that associate with the B-cell membrane. d. MC exons are removed from primary RNA transcripts as a consequence of alternative mRNA splicing when secreted antibodies are produced by plasma cells. e. Somatic hypermutation causes alteration in the coding sequence of MC exons.

c

4-32 In contrast with leader peptides and the C regions, the V regions in immunoglobulin heavy-chain genes a. encode hydrophobic amino acids that anchor the immunoglobulin chains to B-cell membranes b. comprise the smallest number of gene segments in the human immunoglobulin loci c. are composed of V, D, and J gene segments that must undergo gene rearrangement to generate a transcribable exon d. do not undergo somatic hypermutation e. are not subject to allelic exclusion.

c

4-36 The process of gene rearrangement in immunoglobulin and T-cell receptor genes is called a. somatic hypermutation b. isotype switching c. somatic recombination d. apoptosis e. clonal selection.

c

4-9 Which one of the following features renders all IgG antibodies less susceptible to proteolysis than the other antibody classes? a. length of the hinge region b. ability to exchange chains with other IgG antibodies c. presence of additional disulfide bonds d. capacity to activate complement e. degree of accessibility for binding to C1.

c

Naive B cells are recognized by their expression of a. no immunoglobulins on the cell surface because somatic recombination has not yet commenced b. both membrane-bound and secreted forms of immunoglobulin c. both IgM and IgD on the cell surface d. V(D)J recombinase e. uracil-DNA-glycosylase (UNG).

c

The mutational mechanism that results in the production of antibodies that bind antigen with higher affinity is called _____: a. somatic recombination b. isotype switching c. somatic hypermutation d. clonal selection e. antigen processing.

c

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: a. complement fixation b. neutralization c. isotype switching d. somatic hypermutation e. somatic recombination.

c

The process of _____ results in the amplification of particular B cells with specificity for antigen: a. germline recombination b. somatic recombination c. clonal selection d. antigen processing e. antigen presentation.

c

Which immunoglobulin's main function is to mediate sensitization of mast cells? a. IgA b. IgD c. IgE d. IgG e. IgM.

c

Which of the following does not describe B-cell receptors? a. B-cell receptors are membrane-bound and secreted. b. B-cell receptors consist of a variable region and a constant region. c. B-cell receptors lack specificity and can bind to a number of different antigens. d. B-cell receptors possess specificity and can therefore bind only to unique epitopes. e.B cell receptors undergo affinity maturation as a consequence of somatic hypermutation

c

_____, _____, and _____ are the three most abundant antibodies in blood: a. IgA, IgD, and IgE b. IgA, IgE, and IgG c. IgA, IgG, and IgM d. IgE, IgG, and IgM e.IgD, IgE, and IgM.

c

4-18 Another term commonly used to describe hypervariable loops is a. multivalency b. framework regions c. hinge region d. complementarity-determining regions e. signal joint.

d

4-27 Identify the incorrect statement regarding flow cytometry. a. Samples must be incubated with fluorescent molecules (such as fluorescent antibodies) before analysis. b. 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. c. A one-dimensional histogram measures the amount of fluorescence versus cell number. d. Samples must consist of a single cell type and not be composed of multiple cell types. e. A laser is used to detect labeled cells. f. A stream of cells in single file is generated by a nozzle.

d

4-31 In what way does the κ light chain differ from the λ light chain? a. κ performs a different function from λ when bound to the immunoglobulin heavy chain. b. κ, but not λ, is encoded on the same chromosome as the heavy-chain locus. c. κ contains a VJ region, whereas λ contains a VDJ region. d. The κ locus encodes a single C segment, whereas the λ locus has more than one. e. κ contains a transmembrane domain but lambda does not.

d

4-33 Which of the following is matched incorrectly? a. κ light-chain locus: chromosome 2 b. coding joint: nonhomologous end-joining of V and J gene segments c. λ light-chain locus: four or five C gene segments d. affinity maturation: addition of P and N nucleotides e. recombination signal sequence: heptamer-spacer-nonamer.

d

4-35 Which of the following enzymes facilitates the process of affinity maturation? a. DNA ligase b. V(D)J recombinase c. terminal deoxynucleotidyl transferase d. activation-induced cytidine deaminase (AID) e. exonuclease.

d

A newborn derives passive immunity from its mother as a result of placental transfer of _____ during pregnancy. a. IgA b. IgD c. IgE d. IgG e. IgM.

d

All of the following processes occur in mature B cells after antigen encounter except a. alternative splicing b. affinity maturation c. proliferation d. somatic recombination e. isotype switching

d

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 _______. a. isotype switching b. neutralization c. allelic exclusion d. affinity maturation e. somatic rearrangement.

d

IgM and IgD are co-expressed on naive B cells by a process called a. isotype switching b. somatic recombination c. somatic hypermutation d. alternative mRNA splicing e. affinity maturation.

d

Neutralizing antibodies a. interfere with antigen degradation b. facilitate uptake of antigen through Fc regions c. stimulate complement activation d. inhibit interaction of antigen with human cell surfaces e. sensitize mast cells and basophils.

d

Which of the following determines the isotype of an immunoglobulin? a. the composition of the hypervariable regions b. whether the immunoglobulin is membrane-bound or secreted c. its light chain d. its heavy chain e. the composition of the cytoplasmic tails of Igα and Igβ

d

_______ forms dimers, whereas _______ forms pentamers. a. IgG; IgD b. IgE; IgM c. IgD; IgM d. IgA; IgM e. IgM; IgG.

d

Which of the following does not activate complement? (Select all that apply.) a. IgG1 b. IgG2 c. IgG3 d. IgG4 e. IgA f. IgE g. IgM h. IgD.

d, f, h

4-10 Which of the following is mismatched? a. 100-110-amino-acid motif: immunoglobulin domain b. discontinuous epitope: amino acids that are separated in the protein chain but come together in the folded protein c. heavy-chain classes: IgG, IgA, IgM, IgE, IgD d. multivalent antigen: antigen that carries several epitopes of the same or different specificity e. four C domains: IgM and IgD.

e

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. a. the 5′ side; both sides; the 3′ side b. the 5′ side; the 5′ side, the 5′ side c. the 3′ side; both sides; the 3′ side d. both sides; both sides; both sides e.the 3′ side; both sides; the 5′ side.

e

The name given to a fully activated and differentiated B cell that secretes antibody is a. T cell b. antigen-presenting cell c. hematopoietic cell d. secretory cell e. plasma cell.

e