|
|
|||
|
Immunology High Yield
IMMUNOLOGY HIGH YIELD
Chapter 2: Elements of Innate and Acquired Immunity Review Questions For each question, choose the ONE BEST answer or completion. 1. Which of the following generally does not apply to bone marrow (a primary lymphoid organ) and secondary lymphoid organs? A. cellular proliferation B. differentiation of lymphocytes C. cellular interaction D. antigen-dependent response E. none of the above 2. Which of the following apply uniquely to secondary lymphoid organs? A. presence of precursor B and T cells B. circulation of lymphocytes C. terminal differentiation D. cellular proliferation E. All of the above. 3. Which of the following does not apply to "innate" immune mechanisms? A. absence of specificity B. activation by a stimulus C. involvement of multiple cell types D. a memory component 4. Which of the following is the major function of the lymphoid system? A. innate immunity B. inflammation C. phagocytosis D. acquired immunity E. None of the above. 5. Removal of the bursa of Fabricius from a chicken results in A. a markedly decreased number of circulating T lymphocytes. B. anemia. C. delayed rejection of skin graft. D. low serum levels of antibodies in serum. E. All of the above. F. None of the above. 2 6. The germinal centers found in the cortical region of lymph nodes and the peripheral region of splenic periarteriolar lymphatic tissue A. support the development of immature B and T cells. B. function in the removal of damaged erythrocytes from the circulation. C. act as the major source of stem cells and thus help to maintain hematopoiesis. D. provide an infrastructure that on antigenic stimulation contains large populations of B lymphocytes and plasma cells. E. are the sites of NK-cell differentiation. 7. Which of the following is correct? A. NK cells proliferate in response to antigen. B. NK cells kill their target cells by phagocytosis and intracellular digestion. C. NK cells are a subset of polymorphonuclear cells. D. NK-cell killing is extracellular. E. NK cells are particularly effective against certain bacteria. Chapter 2: Elements of Innate and Acquired Immunity Answers to Review Questions 1. D Cellular proliferation, differentiation of lymphocyte, and cellular interactions can take place in bone marrow (or bursa of Fabricius). However, antigen-dependent responses occur in the secondary lymphoid organs, such as the spleen and lymph nodes. 2. C Terminal differentiation of B cells into plasma cells occurs only in secondary lymphoid organs, such as the spleen and lymph nodes. Circulation of lymphocytes and cellular proliferation (but not antigen-dependent responses of terminal differentiation) also take place in the primary lymphoid organs, such as the bursa of Fabricius, or its equivalent, and the thymus. The bone marrow is the site where pluripotential stem cells differentiate into precursor B and T cells. 3. D Innate immunity has none of the antigenic specificity exhibited by acquired immunity. It is activated by such stimuli as the invasion of the foreign particles into the body. Innate immunity involves multiple cell types, such as those of the monocytic series (macrophages) and those of the granulocytic series (neutrophils, eosinophils, etc.). 4. D The major function of the lymphoid system is the recognition of foreign antigen by lymphocytes, which leads to the acquired immune response. Functions such as phagocytosis and inflammation do not necessarily require the lymphoid system, and they constitute part of innate immunity. 5. D Removal of the bursa of Fabricius from a chicken results in low levels of antibodies in serum, since this organ serves as a primary lymphoid organ in which B lymphocytes (which eventually synthesize and secrete antibodies) undergo maturation. The removal of the organ will not result in a marked decrease in the number of circulating T lymphocytes, nor will it result in anemia, characterized by a marked decrease in erythrocyte count, since erythrocytes undergo maturation outside the bursa. Bursectomy has no effect on rejection of skin grafts. 6. D On antigenic stimulation, the germinal centers contain large populations of B lymphocytes undergoing mitosis and plasma cells secreting antibodies. Virgin immunocompetent lymphocytes are developed in the primary lymphoid organs, not in the secondary lymphoid organs, such as the spleen and lymph nodes. Germinal centers do not participate in the removal of damaged erythrocytes, nor are they a source of stem cells; the latter are found in the bone marrow. 7. D NK cells are large granular lymphocytes. Their number does not increase in response to antigen. Their killing is extracellular, and their target cells are virus-infected cells or tumor cells. They are not particularly effective against bacterial cells. 4 Chapter 3: Immunogens and Antigens Review Questions For each question, choose the ONE BEST answer or completion. 1. The following properties render a substance immunogenic: A. high molecular weight. B. chemical complexity. C. sufficient stability and persistence after injection. D. All of the above. E. All of the above are essential but not sufficient. 2. The protection against small pox afforded by prior infection with cowpox represents A. antigenic specificity. B. antigenic cross-reactivity. C. enhanced viral uptake by macrophages. D. innate immunity. E. passive protection. 3. Converting a toxin to a toxoid A. makes the toxin more immunogenic. B. reduces the pharmacologic activity of the toxin. C. enhances binding with antitoxin. D. induces only innate immunity. E. increases phagocytosis. 4. Haptens A. require, carrier molecules to be immunogenic. B. react with specific antibodies when homologous carriers are not employed. C. interact with specific antibody even if the hapten is monovalent. D. cannot stimulate secondary antibody responses without carriers. E. All of the above. 5. An immunologic adjuvant is a substance that A. reduces the toxicity of the immunogen. B. enhances the immunogenicity of haptens. C. enhances hematopoiesis. D. enhances the immune response against the immunogen. E. enhances immunologic cross-reactivity. 6. An antibody made against the antigen tetanus toxoid (TT) reacts with it even when the TT is denatured by disrupting all disulfide bonds. Another antibody against TT fails to react when the TT is similarly denatured. The most likely explanation can be stated as follows: A. The first antibody is specific for several epitopes expressed by TT. B. The first antibody is specific for the primary amino acid sequence of TT, whereas the second is specific for conformational determinants. C. The second antibody is specific for disulfide bonds. D. The first antibody has a higher affinity for TT. 6 Chapter 3: Immunogens and Antigens Answers to Review Questions 1. E All of the properties are essential but not sufficient, since, for immunogenicity, the substance must be foreign to the immunized individual. 2. B The protection against smallpox provided by prior infection with cowpox is an example of antigenic cross-reactivity. Immunization with cowpox leads to the production of antibodies capable of reacting with smallpox because the two viruses share several identical, or structurally similar, determinants. 3. B Conversion of a toxin to a toxoid is performed in order to reduce the pharmacologic activity of the toxin, so that sufficient toxoid can be injected to induce an immune response. 4. E Haptens are substances, usually of low molecular weight and univalent, that, by themselves, cannot induce immune responses (primary or secondary), but can do so if conjugated to high-molecular-weight carriers. The haptens can and do interact with the induced antibodies, without it being necessary that they be conjugated to the carrier. 5. D An immunologic adjuvant is a substance that, when mixed with an immunogen, enhances the immune response against that immunogen. It does not enhance cross-reactivity, nor does it enhance hematopoiesis. An adjuvant does not enhance the immune response against a hapten, which requires its conjugation to an immunogenic carrier to induce a response against the hapten. The adjuvant has no relevance to possible toxicity of an immunogen. 6. B Antibodies can recognize single epitopes formed by primary sequence structures or secondary, tertiary, and quaternary conformational structures. Denaturing a protein by disrupting disulfide bonds generally destroys conformational determinants. Therefore it is likely that the first antibody reacts with a primary amino acid sequence determinant that is present on both native and denatured TT, while the second antibody sees a conformational determinant only on native TT. 7 Chapter 4: Antibody Structure and Function Review Questions For each question, choose the ONE BEST answer or completion. 1. The class-specific antigenic determinants (epitopes) of immunoglobulins are associated with A. L chains. B. J chains. C. disulfide bonds. D. H chains. E. variable regions. 2. The idiotype of an antibody molecule is determined by the amino acid sequence of the A. constant region of the L chain. B. variable region of the L chain. C. constant region of the H chain. D. constant regions of the H and L chains. E. variable regions of the H and L chains. 3. Injection into rabbits of a preparation of pooled human IgG could stimulate production of A. anti-heavy-chain antibody. B. anti-chain antibody. C. anti-chain antibody. D. anti-Fc antibody. E. All are correct. 4. A polyclonal antiserum raised against pooled human IgA will react with A. human IgM. B. light chains. C. human IgG. D. J chain. E. All are correct. 5. An individual was found to be heterologous for IgG1 allotypes 3 and 12. The different possible IgG1 antibodies produced by this individual will never have A. two H chains of allotype 12. B. two L chains of either or . C. two H chains of allotype 3. D. two H chains, one of allotype 3 and one of allotype 12. 8 6. Papain digestion of an IgG preparation of antibody specific for the antigen hen egg albumin (HEA) will A. lose its antigen specificity. B. precipitate with HEA. C. lose all interchain disulfide bonds. D. produce two Fab molecules and one Fc fragment. E. None of the above. 7. The first immunoglobulin synthesized by the fetus is A. IgA. B. IgE. C. IgG. D. IgM. E. None; the fetus does not synthesize immunoglobulins. 8. The following properties of human IgG are true except: A. It can pass through the placenta. B. It can be cleaved by pepsin and yet remain divalent. C. Its half-life is approximately 23 days. D. It induces the formation of leukocytes. E. It participates in the activation of complement. F. It has the longest half-life of all Ig isotopes. 9. The relative level of specific IgM antibodies can be of diagnostic significance because A. IgM is easier to detect than the other isotypes. B. viral infection often results in very high IgM responses. C. IgM antibodies are more often protective against reinfections than are the other isotopes. D. relatively high levels of IgM often correlate with a first recent exposure to the inducing agent. 10. The primary and secondary antibody responses differ in A. the predominant isotype generated. B. the number of lymphocytes responding to antigen. C. the speed at which antibodies appear in the serum. D. the biologic functions manifested by the Ig isotypes produced. E. All of the above. 9 Chapter 4: Antibody Structure and Function Answers to Review Questions 1. D The five classes of Ig molecules are defined by the H chains (, , , , ). 2. E The idiotype is the antigenic determinant of an Ig molecule, which involves its antigen-combining site, which in turn consists of contributions from the variable regions of both L and H chains. 3. E All are correct statements. Since a pool of IgG is injected, it can be assumed that both and chains will be present and that antibodies will be made against them, as well as against the other determinants (H chain and Fc region) present in all IgG molecules. 4. E All are correct statements. Antibody to IgA will have antibody specific for and light chains, which, of course, will react with IgG and IgM, both of which have andchains. Antibody will also be present against J chain if the IgA used for immunization was dimeric. 5. D In any immunoglobulin produced by a single cell, the two H chains and the two L chains are identical. Therefore, any antibody molecule in this individual would have either allotype 3 H chains or allotype 12 H chains, not a mixture. Similarly, the antibody would have either two or two chains. 6. D Papain digestion cleaves the IgG molecules above the hinge region, generating two Fab molecules and an Fc fragment. the Fab fragments can still bind to HEA, but since they are not held together by disulfide binds, they cannot precipitate the antigen. This contrasts with the effects of pepsin treatment of IgG, which cleaves below the hinge region, leaving intact one divalent (F(ab)2 molecule capable of precipitating the antigen. Fragments of pepsin-treated HEA-specific antibody will have the same affinity for the antigen as the original Fab regions of the antibody, since the CDR regions of the molecules are preserved. 7. D The first (and only) immunoglobulin synthesized by the fetus is IgM. The IgG present in the fetus is maternal IgG that has passed through the placenta. No other immunoglobulins are found in the fetus. 8. D Human IgG is the only Ig that passes across the placenta. It has a half-life of 23 days, the longest of all Ig isotypes. It can be cleaved by pepsin to yield a divalent antibody portion F(ab)2, and it participates in the activation of complement. It does not induce the formation of leukocytes. Thus all the statements are true except D. 9. D Only the last statement is correct. Relatively high levels of IgM often correlate with first recent exposure to an inducing agent, since IgM is the first isotype synthesized in response to an immunogen. All other statements are not true. 10. E All are correct. The statements are self-explanatory. 10 Chapter 5: Antigen-Antibody Interactions, Immune Assays, and Experimental Systems Review Questions For each question, choose the ONE BEST answer or completion. 1. Primary interactions between antigens and antibodies involve all of the following except A. covalent bonds. B. van der Waals forces. C. hydrophobic forces. D. electrostatic forces. E. a very close fit between an epitope and the antibody. 2. If an IgG antibody preparation specific for hen egg lysosome (HEL) is treated with papain to generate Fab fragments, which of the following statements concerning the avidity of such fragments is true? A. They will have a longer avidity for HEL as compared with the intact IgG. B. They will have a higher avidity for HEL as compared with the intact IgG. C. There will have the same avidity for HEL as the intact IgG. D. They will have lost their avidity to bind to HEL. E. They will have the same avidity, but will have a lower affinity for HEL. 3. Western assays used to test serum samples for the presence of antibodies to infectious agents, such as HIV, are particularly useful as diagnostic assays because A. they are more sensitive than ELISA. B. antibodies specific for multiple antigenic epitopes can be detected. C. they provide quantitative data for sample analysis. D. they allow multiple samples to be tested simultaneously. E. they are less expensive and take less time to perform as compared with ELISA. 4. The major difference between transgenic mice and knockout mice is that A. transgenic mice always employ the use of cloned genes derived from other species. B. transgenic mice have foreign genes that integrate at targeted loci through homologous recombination. C. transgenic mice have a functional foreign gene added to their genome. D. knockout mice always have a unique phenotype. 5. SCID mice have a genetic defect that prevents development of functional A. hematopoietic cells. B. B cells and T cells. C. T cells and NK cells. D. pluripotential stem cells. E. myeloid cells. 11 6. Which of the following statements regarding B cell hybridomas is false? A. They are immortal cell lines that produce antibodies of a single specificity. B. They are derived from B cells that are first cloned and grown in cell culture for short periods. C. They contain a large nucleus formed by the fusion of two nuclei. D. They can be used to manufacture diagnostic or therapeutic monoclonal antibodies. E. They are derived by fusing B cells with malignant plasma cells that are unable to secrete immunoglobulin. 7. An ELISA designed to test for the presence of serum antibody for a new strain of pathogenic bacteria is under development. Initially, a monoclonal antibody specific for a single epitope of the organism was used both to sensitize the wells of the ELISA plate and as the enzyme-labeled detecting antibody in a conventional sandwich ELISA. The ELISA failed to detect the antigen despite the use of a wide range of antibody concentrations. What is the most probably cause of this problem? A. The antigen is too large. B. The antibody has a low affinity for the antigen. C. The monoclonal antibody used to sensitize the wells is blocking access of the epitope, thus when the same antibody is enzyme-labeled, it cannot bind to the antigen. D. The enzyme-labeled antibody used should have been a different isotype than the sensitizing antibody. E. The monoclonal antibody used is probably unstable. 12 Chapter 5: Antigen-Antibody Interactions, Immune Assays, and Experimental Systems Answers to Review Questions 1. A No covalent bonds are involved in the interaction between antibody and antigen. The binding forces are relatively weak and include van der Waal's forces, hydrophobic forces, and electrostatic forces. A very close fit between an epitope and the antibody is required. 2. A Avidity denotes the overall binding energy between antigens and multivalent antigens. Since the valency of the Fab fragments is one as compared with the HEL-specific IgG molecule, which has a valence of 2 (due to the presence of two Fab regions), the avidity of the fragments will be lower. Choice E is incorrect since the affinity of the Fab fragments will be the same as each of the Fab regions of the intact IgG molecule. 3. B In Western assays, electrophoretic separation techniques are used to resolve the molecular mass of a given antigen or mixtures of antigens. Since antibody responses to infectious agents generate polyclonal responses by virtue of the complex antigenic determinants expressed by such agents, Western assays can confirm the presence of these antibodies, which react with the electrophoretically separated antigens of known molecular weights. 4. C Cloned foreign genes from either the same or other species are introduced into mice to generate a transgenic strain. Integration is random and occurs in both somatic and germ line cells. Choice D is incorrect because sometimes knockout mice do not have a phenotype unique caused by the replacement of a functional gene with one that is nonfunctional, probably due to the activity of redundant or compensatory mechanisms. 5. B SCID mice possess an autosomal recessive mutation that causes a disorder in which B and T cells fail to develop. Like their human counterparts, SCID mice are compromised with respect to lymphoid defense mechanisms. Pluripotential stem cells present in SCID mice can give rise to other hematopoietic lineages, including cells in the myeloid lineage and NK cells. 6. B The method used to general B cell hybridomas employs the fusion of B cells (e.g., from the spleen and lymph nodes) harvested from immunized mice with a selected population of malignant plasma cells unable to secrete immunoglobulin. Antigen-specific B cells are not cloned first and then fused with such plasma cells. 7. C In a sandwich ELISA, an antibody (often monoclonal) is used to coat ELISA wells followed by blocking with a nonspecific protein to saturate any unbound sites. The antigen is then added, followed by the addition of a second antigen-specific antibody that is enzyme-labeled. A polyclonal, antigen-specific antibody is often used as the enzyme-labeled reagent. This is done because the epitope detected by the coating antibody (a monoclonal antibody in this case) may be blocked by that antibody, thus preventing its access if the same monoclonal were used as the enzyme-labeled detecting antibody. 13 Chapter 6: The Genetic Basis of Antibody Structure Review Questions For each question, choose the ONE BEST answer or completion. 1. The DNA for an H chain in a B cell making IgG2 antibody for diphtheria toxoid has the following structure: 5-V17D5J2 C2C4CC23. How many individual rearrangements were required to go from the embryonic DNA to this B-cell DNA? A. 1 B. 2 C. 3 D. 4 E. none 2. If you had 50 V, 20 D, and 6 J regions able to code for a heavy chain, and 40 V and 5 J region genes able to code for a light chain, you could have a maximum repertoire of A. 76 + 45 = 121 antibody specificities. B. 76 X 45 = 3,420 specificities. C. (470 X 5) + (50 X 20 X 6) = 6,200 specificities. D. (40 X 5) X (50 X 20 X 6) = 1,200,000 specificities. E. more than 1,200,000 specificities. 3. The antigen specificity of a particular B cell A. is induced by interaction with antigen. B. is determined only by the L-chain sequence. C. is determined by H + L-chain variable region sequences. D. changes after isotype switching. E. is determined by the heavy-chain constant region. 4. If you could analyze, at the molecular level, a plasma cell making IgA antibody, you would find all of the following except A. a DNA sequence for V, D, and J genes translocated near the CDNA exon. B. mRNA specific for either or light chains. C. mRNA specific for J chains. D. mRNA specific for chains. E. a DNA sequence coding for the T-cell receptor for antigen. 14 5. The ability of a single B cell to express both IgM and IgD molecules on its surface at the same time is made possible by A. allelic exclusion. B. isotype switching. C. simultaneous recognition of two distinct antigens. D. selective RNA splicing. E. use of genes from both parental chromosomes. 6. Which of the following statements concerning the organization of immunoglobulin genes is correct? A. V and J regions of embryonic DNA have already undergone a rearrangement. B. Light-chain genes undergo further rearrangement after surface IgM is expressed. C. VH gene segments can rearrange with Jor Jgene segments. D. The VDJ segments coding for an immunoglobulin VH region m ay associate with different heavy-chain constant region genes. E. After VDJ joining has occurred, a further rearrangement is required to bring the VDJ unit next to the Cgene. 7. Which of the following does not contribute to the generation of diversity of B-cell antigen receptors? A. multiple V genes in the germ line B. random assortment of L and H chains C. imprecise recombination of V and J or V, D, and J segments D. inheritance of multiple C-region genes E. somatic hypermutation 8. Which of the following concerning Ig expression on a B cell is incorrect: A. The light chains of the IgM and IgD have identical amino acid sequences. B. The constant parts of the heavy chains of the IgM and IgD have different amino acid sequences. C. The IgM and IgD have different antigenic specificities. D. If the B cell is triggered by antigen and T-cell signals to proliferate and differentiate into antibody secreting plasma cells, the cell can potentially secrete IgG, IgE, or IgA antibody. E. The IgM on the surface will have either light chains or light chains, but not both. 15 9. Which of the following plays a role in changing the antigen binding site of a B cell after antigenic stimulation? A. junctional diversity B. combinatorial diversity C. germ-line diversity D. somatic hypermutation E. differential splicing of primary RNA transcripts __________________________________________________ __________________________ Case Study As a member of a research team studying a tribe found in a remote region of New Guinea, you make the astonishing discovery that they have only two V genes for the L chain and three V genes for the H chain of immunoglobulins. Nevertheless, they seem healthy and able to resist the diversity of pathogenic organisms endemic to the area. Suggest how this might be accomplished. 16 Chapter 6: The Genetic Basis of Antibody Structure Answers to Review Questions 1. C Three DNA rearrangements are required. First, D5 J2 rearrangement occurs, followed by V17 D5J2. This permits synthesis of IgM and IgD molecules using V17D5J2. The third rearrangement is the class switch of V17D5J2CCto V17D5J2C2, leading to the synthesis of IgG2 molecules. 2. E While 1,200,000 would be the product of all possible combinations of genes, the generation of many more antibody specificities is likely as a result of imprecise recombinations of VJ or VDJ segments, insertional diversity, and somatic hypermutation. 3. C The antigenic specificity is determined by the sequences and hence the structure formed by the combination of heavy- and light-chain variable regions. 4. D As a consequence of the rearrangement of the VDJ to C in the IgA producing cell the C gene will have been deleted. The other DNA sequences and mRNA species will be found in the cell. 5. D The simultaneous synthesis of IgM and IgD is made possible by the alternate splicing of the primary RNA transcript 5VDJCC3; to give either VDJCor VDJCmessages. 6. D This is the basis of isotype or class switching. 7. D The presence of multiple CH region genes, although the basis for functional diversity, does not contribute to the diversity of antigen-specific receptors. 8. C The IgM and IgD expressed on a single B cell use the same heavy- and light-chain V(D)J gene units and, therefore, have the same antigenic specificity. 9. D Of the mechanisms described for generating diversity of Ig molecules, only somatic hypermutation affects the antigen binding site after antigen stimulation. __________________________________________________ __________________________ Answer to Case Study Despite the paucity of V-region genes, these individuals presumably retain other mechanisms for generating diversity. These include the presence of multiple J and D gene segments in the germ line, junctional diversity due to deletion or insertion of bases at joining sites, random assortment of H and L chains, and somatic hypermutation. It is, therefore, conceivable that, even with their limited V-gene repertoire, they can generate sufficient diversity of antibody specificity to survive. 17 Chapter 7: Biology of the B Lymphocyte Review Questions For each question, choose the ONE BEST answer or completion. 1. The earliest stages of B-cell differentiation A. occur in the embryonic thymus. B. require the presence of antigen. C. involve rearrangement of -chain gene segments. D. involve rearrangement of surrogate light-chain gene segments. E. involve rearrangement of heavy-chain gene segments. 2. Which of the following is expressed on the surface of the mature B lymphocyte? A. CD40 B. MHC class II molecules C. CD32 D. IgM and IgD E. All of the above. 3. Which of the following statements is incorrect? A. Antibodies in a secondary immune response generally have a higher affinity for antigen than antibodies formed in a primary response. B. Somatic hypermutation of V region genes may contribute to changes in antibody affinity observed during secondary responses. C. Synthesis of antibody in a secondary response occurs predominantly in the blood. D. Isotype switching occurs in the presence of antigen. E. Predominantly IgM antibody is produced in the primary response. 4. Immature B lymphocytes A. produce only chains. B. are progenitors of T as well as B lymphocytes. C. express both IgM and IgD on their surface. D. are at a stage of development where contact with antigen may lead to unresponsiveness. E. must go through the thymus to mature. 5. Antigen binding to the B-cell receptor A. transduces a signal through the antigen-binding chains. B. invariably leads to B-cell activation. C. transduces a signal through the Igand Igmolecules. D. results in macrophage activation. E. leads to cytokine synthesis, which activates T cells. 18 6. Which of the following would not be found on a memory B cell: A. Igand Ig B. heavy chains C. heavy chains D. surrogate light chains E. light chains 19 Chapter 7: Biology of the B Lymphocyte Answers to Review Questions 1. E The earliest events in B-cell differentiation take place in fetal liver and bone marrow in the adult and involve rearrangement of heavy-chain V, D, and J gene segments. 2. E All the molecules are expressed on the surface of the mature B cell. 3. C Antibody synthesis in secondary responses occurs predominantly in lymph nodes, not blood. 4. D In immature B cells, which express only IgM, contact with antigen leads to unresponsiveness rather than activation. 5. C The molecules Igand Ig, which are associated with the surface Ig molecule, transduce a signal following antigen binding to surface Ig. 6. D Surrogate light chains are expressed only at the pre-B cell stage of B-cell differentiation. Chapter 8: The Role of the Major Histocompatibility Complex in the Immune Response Review Questions For each question, choose the ONE BEST answer or completion. 1. All the following are characteristics of both MHC class I and class II molecules except: A. They are expressed codominantly. B. They are expressed constitutively on all nucleated cells. C. They are glycosylated polypeptides with domain structure. D. They are involved in presentation of antigen fragments to T cells. E. They are expressed on the surface membrane of B cells. 2. MHC class I molecules are important for which of the following? A. binding to CDS molecules on T cells B. presenting exogenous antigen (e.g., bacterial protein) to B cells C. presenting viral protein to antigen-presenting cells such as macrophages D. binding to CD4 molecules on T cells E. binding to Ig on B cells 3. Which of the following is incorrect concerning MHC class II molecules? A. B cells may express different MHC class II molecules on their surface. B. MHC class II molecules are synthesized in the endoplasmic reticulum of many cell types. C. Genetically different individuals express different MHC class II alleles. D. MHC class II molecules are associated with 2-microglobulin on the cell surface. E. A peptide that does not bind to an MHC class II molecule will not trigger a CD4 + T cell response. 4. Products of TAP-1 and -2 genes A. bind 2-microglobulin. B. prevent peptide binding to MHC molecules. C. are part of the proteasome. D. transport peptides into the endoplasmic reticulum for binding to MHC class I. E. transport peptides into the endoplasmic reticulum for binding to MHC class II. 21 5. Which of the following is incorrect concerning the processing of an antigen, such as a bacterial protein, in the acid compartments of the cell? A. It results in production of potentially immunogenic peptides that associate with MHC class II molecules. B. Predominantly exogenous antigens are processed by this pathway. C. It may lead to activation of CD4 + T cells. D. It may lead to the activation of CD8 + T cells. E. Bacterially derived peptides displace a fragment of the invariant chain from the MHC class II binding groove. 6. Which of the following statements about the MHC is incorrect? A. It codes for complement components. B. It codes for both chains of the MHC class I molecule. C. It codes for both chains of the MHC class II molecule. D. It is associated with susceptibility and resistance to different diseases. E. The total set of MHC alleles on the chromosome is known as the MHC haplotype. 22 Chapter 8: The Role of the Major Histocompatibility Complex in the Immune Response Answers to Review Questions 1. B MHC class I molecules are expressed on nearly all nucleated cells, but the constitutive expression of MHC class II molecules is more limited (B cells, dendritic cells, and thymic epithelial cells). MHC class II expression can be induced on other cell types (such as macrophages, endothelial cells, and human T cells) by cytokines. 2. A As described further in Chapters 9 and 10, the interaction of CD8 on the T cell and an invariant region of MHC class I molecule is crucial in the triggering of CD8 + T cells. 3. D The MHC class I molecule, not the MHC class II molecule, associates with 2- microglobulin. 4. D The products of the TAP-1 and -2 genes selectively transport peptides 8-9 amino acids in length from the cytoplasm into the ER where they bind to MHC class I molecules. 5. D CD8 + T cells are generally not activated by processing in acid compartments; exogenous antigen processing in acid compartments results in the generation of peptides, some of which can displace the CLIP fragment of the invariant chain from the MHC class II binding groove. The peptide-MHC class II complexes move to the cell surface and can interact with a CD4 + T cell with the appropriate receptor. 6. B The 2-microglobulin gene is located outside the MHC, on a different chromosome. 23 Chapter 9: Biology of the T Lymphocyte Review Questions For each question, choose the ONE BEST answer or completion. 1. Which of the following statements concerning T-cell development is correct? A. Progenitor T cells that enter the thymus from the bone marrow have already rearranged their T cell receptor genes. B. Interaction with thymic non-lymphoid cells is critical. C. Maturation in the thymus requires the presence of foreign antigen. D. MHC class II molecules are not involved in positive selection. E. Mature, fully differentiated T cells are found in the cortex of the thymus. 2. The development of self-tolerance in the T-cell compartment is important for the prevention of autoimmunity. Which of the following results in T-cell self-tolerance? A. allelic exclusion B. somatic hypermutation C. thymocyte proliferation D. positive selection E. negative selection 3. Which of the following statements is correct? A. The TCR chains transduce a signal into a T cell. B. A cell depleted of its CD4 molecule would be unable to recognize antigen. C. T cells with fully rearranged chains are not found in the thymus. D. T cells expressing the receptor are found only in the thymus. E. Immature CD4 + CD8 + T cells form the majority of T cells in the thymus. 4. Which of the following is incorrect regarding mature T cells that use as their antigen-specific receptor? A. They co-express CD3 on the cell surface. B. They may be either CD4 + or CD8 + . C. They interact with peptides derived from nonself antigens. D. They can further rearrange their TCR genes to express as their receptor. E. They circulate through blood and lymph and migrate to secondary lymphoid organs. 24 5. CD4 A. binds directly to peptide antigen. B. binds to an invariant portion of MHC class I molecules. C. binds to an invariant portion of MHC class II molecules. D. binds to CD8 on the T cell surface. E. binds to the peptide-binding site of MHC class II. 6. Which of the following statements is incorrect concerning TCR and Ig genes? A. In both B- and T-cell precursors, multiple V-, D-, J-, and C-region genes exist in an unrearranged configuration. B. Rearrangement of both TCR and Ig genes involves specific recombinase enzymes that bind to specific regions of the genome. C. Both Ig and TCR are able to switch C-region usage. D. Both Ig and TCR exhibit allelic exclusion. E. Both Ig and the TCR use combinatorial association of V, D, and J genes and junctional imprecision to generate diversity. 7. Which of the following statements is incorrect concerning antigen-specific receptors on both B and T cells? A. They are clonally distributed transmembrane molecules. B. They have extensive cytoplasmic domains that interact with intracellular molecules. C. They consist of polypeptides with variable and constant regions. D. They are associated with signal transduction molecules at the cell surface. E. They can interact with peptides derived from nonself antigens. 25 Chapter 9: Biology of the T Lymphocyte Answers to Review Questions 1. B Interaction of thymocytes with thymic stromal cellscortical epithelial cells and inter-digitating dendritic cells at the corticomedullary junctionis critical in T cell development. 2. E Negative selection removes developing T cells with potential reactivity to self-molecules. 3. E CD4 + CD8 + T cells form the majority of cells in the thymus. 4. D The genes of T cells that use as their receptor cannot further rearrange to use as their receptor; TCR gene segments are interspersed with the locus and are deleted when the locus rearranges. 5. C CD4 expressed on T cells binds to an invariant or nonpolymorphic region of all MHC class II molecules. 6. C The ability to change the heavy-chain constant region while retaining the same antigen specificity is a property unique to Ig. The other features are common to both the TCR and Ig. 7. B Both the TCR and Ig have short cytoplasmic tails. The signal transduction molecules associated with the antigen-binding chains interact with intracellular molecules 26 Chapter 10: Activation and Function of T and B Cells Review Questions For each question, choose the ONE BEST answer or completion. 1. The role of the antigen-presenting cell in the immune response is all of the following except A. the limited catabolism of polypeptide antigens. B. to allow selective association of MHC gene products and peptides. C. to supply second signals required to fully activate T cells. D. to present non-self peptides associated with MHC class II molecules to B cells. E. to present peptide-MHC complexes to T cells with the appropriate receptor. 2. Which of the following statements about interleukin 2 (IL-2) is incorrect? A. It is produced primarily by activated macrophages. B. It is produced by CD4 + T cells. C. It can induce the proliferation of CD4 + T cells. D. It binds to a specific receptor on CD4 + T cells. E. It can activate CD8 + T cells in the presence of antigen. 3. CD40 Ligand (CD154) is expressed by which of the following? A. B cells B. dendritic cells C. resting T cells D. activated T cells E. all leukocytes 4. Which of the following statements about the activation of CD4 + cells in incorrect? A. Binding of peptide + MHC to the TCR results in rapid phosphorylation of tyrosine residues in proteins associated with the TCR. B. Intracellular calcium levels rise rapidly following activation. C. Only peptide bound in the groove of MHC class II activates the CD4 + T cell. D. Interaction of B7 and CD28 stabilizes IL-2 mRNA so effective IL-2 translation occurs. E. The activated cell synthesizes IL-2 and a receptor for IL-2. 5. Which of the following statements about cytokines synthesized by CD4 + TH1 and TH2 subsets is incorrect? A. Cytokines produced by TH1 cells include IFN-and TNF-. B. Cytokines produced by TH2 cells are important in allergic responses. C. TH1 cells secrete cytokines that induce macrophage and NK cell activation. D. TH2 cells secrete cytokines that activate CD8 + T cells. E. TH2 cell cytokines may inhibit the action of TH1 cells. 27 6. Which of the following statements about CD8 + CTL is incorrect? A. They lyse targets by synthesizing perforin and granzymes. B. They cause target cell apoptosis. C. They cannot kill CD4 + T cells. D. They interact with their target through paired cell surface molecules. E. They must be activated before exerting their cytotoxic function. 7. Infection with vaccinia virus results in the priming of virus-specific CD8 + T cells. If these vaccinia virus-specific CD8 + T cells are subsequently removed from the individual, which of the following cells will they kill in vitro? A. vaccinia-infected cells expressing MHC class II molecules from any individual B. influenza-infected cells expressing the same MHC class I molecules as the individual C. uninfected cells expressing the same MHC class I molecules as the individual D. vaccinia-infected cells expressing the same MHC class I molecules as the individual E. vaccinia-infected cells expressing the same MHC class II molecules as the individual 8. Bacterial lipopolysaccharide (LPS), a T-independent antigen, stimulates antibody production in mice. Which of the following is incorrect? A. The antibody produced will be predominantly IgM. B. Memory B cells will not be induced. C. IL-4 and IL-5 are required for the production of antibody during the response. D. The polymeric nature of the antigen crosslinks B-cell surface receptors. E. B cell activation involves phosphorylation of intracellular molecules. __________________________________________________ __________________________ Case Study Great effort is now being directed at developing vaccines for a variety of diseases. In one study, it was found that antibody to a particular epitope on a protein of the pathogens surface membrane was protective. The structure of this epitope was determined to be a peptide 10 amino acids in length. This peptide was synthesized and used to immunize individuals exposed to the pathogen. Disappointingly, no protection was seen. Can you suggest any reasons for this failure? 28 Chapter 10: Activation and Function of T and B Cells Answers to Review Questions 1. D The antigen-presenting cell does not present peptide + MHC class II to B cells. The other statements are all features of the antigen-presenting cell. 2. A IL-2 is produced almost exclusively by activated T cells. 3. D CD40 ligand (CD154) is expressed on the surface of the CD4 + T cell as a consequence of the activation that follows the binding of peptide + MHC class II to the TCR. 4. C Agents other than peptides bound to MHC class II can activate CD4 + T cells; these include superantigens, antigens presented by CD1, and polyclonal inactivators. 5. D TH1 rather than TH2 cells secrete cytokines that activate CD8 + T cells. 6. C A CDS + CTL can kill any cell expressing an MHC class I molecule in association with a non-self peptide, including, for example, a CD4 + T cell infected with HIV. 7. D The principle of MHC restriction indicates that the TCR of CD8 + T cells interacts with target cells that express specific peptide bound to self-MHC class I molecules. Thus, vaccinia-primed CD8 + T cells recognize and hence kill only vaccinia-infected targets that express self MHC class I. 8. C T-independent antigens, because they do not generate T cell-derived cytokines, do not produce IL-4 or IL-5. Thus, no isotype switching or memory cell induction occurs in response to T-independent antigens. __________________________________________________ __________________________ Answer to Case Study Several possibilities may be considered, such as size and complexity of the peptide, which are required for immunogenicity. The more likely failure, however, was that the response to the pathogens membrane protein was almost certainly a thymus-dependent response. Therefore, immunization with the epitope seen by the B cells would not work unless epitopes seen by helper T cells were also present. Attempts at producing synthetic vaccines are now directed toward incorporating the B cell-specific epitopes in carriers containing adequate helper T epitopes that will induce both help and memory responses. This would provide a better possibility for protection following exposure to the pathogen. 29 Chapter 11: Control Mechanisms in the Immune Response Review Questions For each question, choose the ONE BEST answer or completion. 1. An individual does not make an immune response to a self-protein because A. self-proteins cannot be processed into peptides. B. peptides from self-proteins cannot bind to MHC class I. C. peptides from self-proteins cannot bind to MHC class II. D. lymphocytes that express a receptor reactive to a self-protein are inactivated by deletion or anergy. E. developing lymphocytes cannot rearrange V genes required to produce a receptor for self-proteins. 2. Which of the following statements is incorrect. A. Interaction of Fas and FasL can lead to apoptosis. B. Both Fas and Fas L can be expressed on activated T cells. C. Both Fas and Fas L can be expressed on B cells. D. Cells in immunologically privileged sites can express FasL. E. FasFasL-mediated apoptosis prevents uncontrolled T-cell clone growth. 3. Which of the following is incorrect concerning immune tolerance? A. Tolerance induction is antigen-specific. B. Tolerance results from inactivation and/or elimination of B and/or T cells. C. Tolerance can be induced in both young and old individuals. D. Immature neutrophils are more susceptible to tolerance than mature neutrophils. E. The breakdown of tolerance can result in autoimmunity. 4. Which of the following statements is incorrect concerning the immune response to antigens? A. Reactivity is influenced by extremes of age. B. Greater immune responses are produced when antigen is given with adjuvant. C. Impaired nutrition depresses immunity. D. The presence of pre-existing antibody does not affect the subsequent response to antigen. E. Different protein antigens stimulate different levels of antibody production. 5. All of the following procedures would be likely to induce tolerance to a protein antigen except A. intramuscular injection of the antigen in adjuvant. B. intravenous injection of deaggregated protein. C. injection of cyclosporine with the antigen. D. injection of antigen at a stage in development before mature lymphocytes appear. E. intravenous injection of small amounts of antigen. 30 6. When a tolerogenic injection of a protein antigen is given experimentally, it can be shown that A. B-cell tolerance is more rapidly induced than T-cell tolerance. B. B-cell tolerance is lost as new B cells come from the bone marrow. C. B-cell tolerance can be induced only when low doses are used. D. T-cell tolerance can be induced only when high doses are used. E. T-cell tolerance is shorter lasting than B-cell tolerance. 7. Blocking any of the following processes can result in peripheral tolerance in mature T cells except A. the interaction of costimulatory molecules on T cells with their ligands on APC. B. intracellular signal transduction mechanisms. C. negative selection of thymocytes. D. activation of the IL-2 gene. E. the binding of antigen with MHC molecules. 31 Chapter 11: Control Mechanisms in the Immune Response Answers to Review Questions 1. D Negative selection generally ensures that a lymphocyte expressing a receptor reactive to a self-protein is inactivated by deletion or anergy. 2. C B cells express Fas but not FasL. 3. D Tolerance can be induced only in lymphocytes that express an antigen-specific receptor. 4. D Preexisting antibody may exert a negative feedback on the subsequent response to antigen. 5. A Injection into muscle and in the presence of adjuvant are likely ways to induce activate rather than tolerize the immune response. The remaining procedures generally induce tolerance. The use of cyclosporine in blocking transplantation rejection is discussed further in Chapter 19. 6. B T-cell tolerance is more rapidly achieved, occurs with lower doses, and lasts longer than B-cell tolerance. As new B cells are produced by the bone marrow, tolerance in this compartment wanes. T-cell tolerance, by contrast, persists because the thymus of an adult no longer actively produces new T cells. 7. C Interfering with negative selection of thymocytes disrupts central rather than peripheral T cell tolerance. 32 Chapter 12: Cytokines Review Questions For each question, choose the ONE BEST answer or completion. 1. Which of the following statements regarding the functional properties of cytokines is false? A. They typically have pleiotropic properties. B. They often exhibit functional redundancy. C. They often display antigen specificity. D. They exhibit synergistic or antagonistic properties. E. They assist in the regulation and development of immune effector cells. 2. When IL-2 is secreted by antigen-specific T cells activated due to presentation of antigen by APCs, what happens to naïve antigen-nonspecific T cells in the vicinity? A. They proliferate due to their exposure to IL-2. B. They often undergo apoptosis. C. They begin to express IL-2 receptors. D. They secrete cytokines associated with their TH phenotype. E. Nothing happens. 3. Which of the following cytokines have receptors that exhibit structural similarity that helps to account for their functional redundancy? A. IL-3, IL-15, and GM-CSF B. IL-1, IL-2, and M-CSF C. IL-2, IL-3, and IL-8 D. IL-3, TNF-, and RANTES E. IL-3, IL-4, and IFN- 4. What type of immune response is not mediated by the TH1 subset? A. responses to viral infections B. delayed-type hypersensitivity C. activation of cytotoxic T cells D. activation of IgE synthesis E. responses to intracellular pathogens 33 5. IL-1, IL-6, and TNF-are pro-inflammatory cytokines that are known to A. cause increased vascular permeability. B. act in concert with chemokines to promote migration of inflammatory cells to sites of infection. C. initiate acute-phase responses. D. have endogenous pyrogen properties. E. All of the above. 6. Which of the following cytokines plays a role in terminating inflammatory responses? A. IL-2 B. IL-4 C. TGF- D. IFN- E. IL-3 7. All of the following are induced by the chemokine IL-8 except A. activation of neutrophils. B. attraction of neutrophils to sites of tissue damage. C. wound healing. D. extravasation of neutrophils. E. reduction of cytokine production by TH1 cells. 8. Superantigens cause a burst of cytokine production by T cells due to their ability to A. crosslink the Vsegments of T cell receptors with class II MHC molecules on APCs. B. crosslink the Vsegments of T cell receptors with class II MHC molecules on APCs. C. crosslink T cell receptors and CD3. D. crosslink multiple cytokine receptors on a large population of T cells. E. crosslink CD3. __________________________________________________ __________________________ Case Study A 7-year-old boy with an infected wound on his leg is admitted to the emergency department. His mother states that a high fever with diarrhea occurred during the last 12 hours. Within the last 2 hours he had become very lethargic, was unable to stand, and was very disoriented. The attending physician observes that his blood pressure is dangerously low, and suspects that the boy is suffering from bacterial septic shock caused by the wound infection. Discuss the etiology of bacterial septic shock, as well as the role of cytokines in the pathogenesis of this disease. Speculate on future therapeutic strategies that might be employed by using monoclonal antibodies or other biologic agents to treat this disease. 34 Chapter 12: Cytokines Answers to Review Questions 1. C Cytokines secreted by a single lymphocyte following antigen-specific activation do not exhibit antigen specificity. Instead, they regulate the activities of other cells involved in an immune response by binding to cytokine receptors expressed by these cells. 2. E Since these cells have not been activated by antigen, they do not express the high affinity IL-2 receptor. Hence they remain quiescent. 3. A The receptors for IL-3, IL-5, and GM-CSF contain the common chain, which is responsible for signal transduction. Therefore, cytokine binding to each of these receptors probably induces a similar activation signal. 4. D The TH1 subset is responsible for classical cell-mediated functions (answers A, B, C, and E). Synthesis of IgE is mediated by cytokines produced by TH2 cells. 5. E The answer is self-explanatory. 6. C Among the cytokines listed, TGF-plays a role in terminating inflammatory responses by promoting the accumulation and proliferation of fibroblasts and the deposition of extracellular matrix proteins required for tissue repair. 7. E IL-8 chemotactically attracts and activates neutrophils and induces their adherence to vascular endothelium. Thus, IL-8 also plays an important role in wound healing. It also promotes their extravasation into tissues. It plays no role in regulation of cytokine production by TH1 cellsa biologic property ascribed to IL-10 produced by TH2 cells. 8. A Superantigens bind simultaneously to class II MHC molecules and to the Vdomain of the T cell receptor activating all T cells bearing a particular Vdomain. Thus, they activate large numbers of T cells (between 5% and 25%), regardless of their antigen specificity, causing them to release harmful quantities of cytokines. __________________________________________________ __________________________ Answer to Case Study Bacterial septic shock is a condition that can develop within a few hours following infection by certain gram-negative bacteria, including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Enterobacter aerogenes, and Neisseria meningitidis. The symptoms are often fatal and include a drop in blood pressure, fever, diarrhea, and widespread blood clotting in various organs. It develops when bacterial cell wall endotoxins stimulate macrophages to overproduce IL-1 and TNF-. Therapeutic strategies using monoclonal antibodies capable of neutralizing the effects of IL-1 and TNF-or antagonists such as IL-1 receptor antagonist (IL-1Ra) may offer hope for the treatment of bacterial septic shock in humans. 35 Chapter 13: Complement Review Questions For each question, choose the ONE BEST answer or completion. 1. A patient is admitted with multiple bacterial infections and is found to have a complete absence of C3. Which complement-mediated function would remain intact in such a patient? A. lysis of bacteria B. opsonization of bacteria C. generation of anaphylatoxins D. generation of neutrophil chemotactic factors E. None of the above. 2. Which of the following screening tests would be most useful for confirming a presumptive diagnosis of a congenital absence of a complement component? A. quantitation of serum opsonic activity B. quantitation of serum hemolytic activity C. quantitation of C3 content of serum D. quantitation of C1 content of serum E. electrophoretic analysis of patient's serum 3. Complement is required for A. lysis of erythrocytes by lecithinase. B. NK-mediated lysis of tumor cells. C. phagocytosis. D. bacteriolysis by specific antibodies. E. All of the above. 4. Which of the following is associated with the development of systemic lupus erythematosus (SLE)? A. deficiencies in C1, C4, or C2 B. deficiencies in C5, C6, or C7 C. deficiencies in the late components of complement D. increases in the serum C3 level E. increases in the levels of C1, C4, or C2 5. Active fragments of C5 can lead to the following, except A. contraction of smooth muscle. B. vasodilation. C. attraction of leukocytes. D. attachment of lymphocytes to macrophages. E. All of the above. 36 6. The alternative pathway of complement activation is characterized by the functions listed below, except A. activation of complement components beyond C3 in the cascade. B. participation of properdin. C. generation of anaphylatoxin. D. use of C4. 7. Decay-accelerating factor (DAF) regulates the complement system to prevent complement-mediated lysis of cells. This involves A. dissociation of C4b2a or the C3bBb enzyme complex. B. blocking the binding of C3 convertase to the surface of bacterial cells. C. inhibiting the membrane attack complex from binding to bacterial membranes. D. acting as a cofactor for the cleavage of C3b. E. causing dissociation of C5 convertase. 8. The following activate(s) the alternative pathway of complement: A. lipopolysaccharides B. some viruses and virus-infected cells C. fungal and yeast cell walls (zymosin) D. many strains of gram-positive bacteria E. All of the above. 9. Which component(s) of complement could be missing and still leave the remainder of the complement system capable of activation by the alternative pathway? A. C1, C2, and C3 B. C3 only C. C2, C3, and C4 D. C1, C2, and C4 E. C1, C3, and C4 10. An antigenantibody immune complex in a C3-deficient individual will still result in A. anaphylatoxin production. B. depression of factor B. C. production of chemotactic factors. D. activation of C2. E. activation of C5. 37 Chapter 13: Complement Answers to Review Questions 1. E All these functions are mediated by complement components that come after C3 and in its absence cannot be activated. 2. B The hemolytic assay would reveal a defect in any one of the complement components, since all are required to effect hemolysis. The tests for specific components are likely to work only if you happen to pick the right one. They are not useful for screening. Electrophoretic analysis is good for the major serum components (albumin and globulin), but unlikely to give information on many of the complement components. 3. D Complement is required for lysis of bacteria by specific anti-bacteria IgM or IgG. Complement is not required for phagocytosis or lysis of erythrocytes by lecithinase. However, the C3b opsonins, that are generated during complement activation, enhance phagocytosis of the opsonized particle. Although some tumor cells can initiate the alternate pathway of complement activation, complement plays no role in NK-mediated lysis of these cells. 4. A Inherited homozygous deficiency of the early proteins of the classical complement pathway (C1, C4, or C2) are strongly associated with the development of systemic lupus erythematosus (SLE). Such deficiencies probably result in abnormal processing of immune complexes in the absence of a functional classical pathway of complement fixation. Serum levels of C3 or C4 decrease in SLE due to the large number of immune complexes that bind to them. Deficiencies in the late components are associated with recurrent infections with pyogenic organisms. 5. D C5a is an anaphylatoxin, which induces degranulation of mast cells, resulting in the release of histamine, causing vasodilation and contraction of smooth muscles. C5a is also a chemotaxin, attracting leukocytes to the area of its release where the antigen is reacting with antibodies and activates the complement system. It does not promote the attachment of lymphocytes to macrophases. 6. D The alternative pathway of complement activation connects with the classical pathway at the activation of C3. Thus, it does not require C1, C4, or C2. Properdin is essential for the activation through the alternative pathway, since it stabilizes the complex (C3bBb) formed between C3b and activated serum factor B, which acts as a C3 convertase and activates C3. During the activation of the alternative pathway, both C3a and C5a are generated; both are anaphylatoxins and cause degranulation of mast cells. 7. A As a cell surface regulator of complement activation, DAF destabilizes both the alternate and classical pathway C3 convertases (C4b2a or C3bBb). Like the other regulators of complement activation (RCA), including CR1, factor H, and C4bBP, these proteins accelerate decay (dissociation) of C3 convertase, releasing the component with enzymatic activity (C2a or Bb) from the component bound to the cell membrane (C4b or C3b). 8. E Each of the pathogens and particles of microbial origin listed can initiate the alternate pathway of complement activation. Parasites (e.g., trypanosomes) and teichoic acid from gram-positive cell walls can also activate complement using this pathway. 38 9. D C3 is required for the alternative pathway of complement activation, while C1, C2, or C4 are not required. 10. D The immune complex will activate C2 (and C4), but will not activate C3 or any other components. Since the alternative pathway of complement activation also requires C3, this pathway will not be activated. Anaphylatoxins and chemotactic factor generation require C3, while the synthesis of factor B is not related to C3. 39 Chapter 14: Hypersensitivity Reactions: Antibody-Mediated (Type I) Reactions Review Questions For each question, choose the ONE BEST answer or completion. 1. The usual sequence of events in an allergic reaction is as follows: A. The allergen combines with circulating IgE, and the IgE:allergen complex binds to the mast cells. B. The allergen binds to IgE fixed to mast cells. C. The allergen is processed by antigen-presenting cells and the binds to histamine receptors. D. The allergen is processed by antigen-presenting cells and the binds to mast cells. E. The allergen combines with IgG. 2. Epinephrine A. causes bronchodilation. B. is effective even after anaphylactic symptoms commence. C. relaxes smooth muscle. D. decreases vascular permeability. E. All of the above. 3. A human volunteer agrees to be passively sensitized with IgE specific for a ragweed antigen (allergen). When challenged with the allergen intradermally, he displayed a typical skin reaction due to an immediate hypersensitivity reaction. If the injection with sensitizing IgE was preceded by an injection (at the same site) of Fc fragments of human IgE followed by intradermal injection with allergen, which of the following outcomes would you predict? A. No reaction would occur because the Fc fragments would interact with the allergen and prevent it from gaining access to the sensitized mast cells. B. No reaction would occur because the Fc fragments would interact with the IgE antibodies making their antigen-binding sites unavailable for binding to antigen. C. No reaction would occur because the Fc fragments would interact with Fcreceptors on mast cells. D. The reaction would be exacerbated due to the increased local concentration of IgE Fc fragments. E. The reaction would be exacerbated due to the activation of complement. 40 4. The following mechanism(s) may be involved in the clinical efficacy of desensitization therapy to treat patients with allergies to known allergens: A. enhanced production of IgG, which binds allergen before it reaches mast cells B. skewing of T cell responses from TH2 to TH1 C. decreased sensitivity of mast cells and basophils to degranulation by allergen D. decreased production of IgE antibody E. All of the above. 5. Immediate hypersensitivity skin reactions A. usually occur within 24 hours. B. exhibit a raised wheal due to infiltration by mononuclear cells. C. exhibit a red flare due to vasodilation. D. cannot be elicited by monovalent haptens. E. All are correct. 6. Mast cells A. are found circulating in the blood. B. release their granules following lysis. C. are basophilic after complete degranulation. D. are very similar to basophils. E. All are correct. 7. Antihistamines A. bind to receptors for histamine, thereby preventing the histamine from exerting a pharmacologic effect. B. are more effective given before, rather than after, the onset of allergic symptoms. C. do not influence the activity of leukotrienes. D. do not affect binding of IgE to mast cells. E. All are correct. 8. In the RAST assay for ragweed pollen A. the patient's serum is first mix |
|
|||
|
Immunology High Yield (cont)
40 4. The following mechanism(s) may be involved in the clinical efficacy of desensitization therapy to treat patients with allergies to known allergens: A. enhanced production of IgG, which binds allergen before it reaches mast cells B. skewing of T cell responses from TH2 to TH1 C. decreased sensitivity of mast cells and basophils to degranulation by allergen D. decreased production of IgE antibody E. All of the above. 5. Immediate hypersensitivity skin reactions A. usually occur within 24 hours. B. exhibit a raised wheal due to infiltration by mononuclear cells. C. exhibit a red flare due to vasodilation. D. cannot be elicited by monovalent haptens. E. All are correct. 6. Mast cells A. are found circulating in the blood. B. release their granules following lysis. C. are basophilic after complete degranulation. D. are very similar to basophils. E. All are correct. 7. Antihistamines A. bind to receptors for histamine, thereby preventing the histamine from exerting a pharmacologic effect. B. are more effective given before, rather than after, the onset of allergic symptoms. C. do not influence the activity of leukotrienes. D. do not affect binding of IgE to mast cells. E. All are correct. 8. In the RAST assay for ragweed pollen A. the patient's serum is first mixed with a radiolabeled anti-IgE. B. only IgE anti-ragweed antibodies are detected. C. the patient's serum competitively inhibits binding of the anti-IgE. D. monovalent IgE is used. E. complement is utilized. 41 9. Which of the following statements is false? A. IL-4 and IL-13 produced by TH2 cells play a key role in regulating IgE responses. B. Interferon-produced by TH1 cells can downregulate IgE responses. C. In normal individuals, a balance between TH1-derived and TH2-derived cytokines helps to maintain normal levels of IgE. D. IL-4 levels are higher in atopic patients. E. In IL-4 knockout mice, IgE production is normal following their exposure to parasites due to the regulatory activity of IL-13. 10. Anaphylactic reactions A. evolve in minutes and abate within 30 minutes. B. may be followed by inflammatory sequelae hours later. C. are the consequences of released pharmacologic agents. D. may involve components of mast-cell granule matrix. E. All of the above. __________________________________________________ __________________________ Case Study While playing tennis on a warm day, a young man felt a wasp on his arm and brushed it off, but still received a mild sting, which he ignored. Ten minutes later he felt dizzy and began to itch under his arms and on his scalp. When he broke out in hives and felt a tightness in his chest, he headed for the hospital. On the way he felt cold and clammy, and collapsed on the seat of the taxi. In the emergency unit, his pulse was barely detectable. What happened and why? 42 Chapter 14: Hypersensitivity Reactions: Antibody-Mediated (Type I) Reactions Answers to Review Questions 1. B Allergic (also known as atopic) individuals have already made IgE responses to specific allergens. IgE binds passively to cells expressing high-affinity Fc receptors for IgE (e.g., mast cells) and interacts with the allergen when present. This results in cross-linking of the high-affinity FcR, resulting in mast-cell degranulation. The allergen does not need to be processed by APCs in order to bind to IgE. 2. E All are effects of epinephrine, and make it useful for treatment of acute anaphylactic symptoms. 3. C Since the IgE Fc fragments would bind to the high-affinity FcR expressed on the surface of mast cells, the allergen-specific IgE would not have access to these receptors and, therefore, would not bind to these cells. When the allergen is introduced intradermally, while it would bind to the allergen-specific IgE at the site, this would not result in cross-linking of FcR, which are saturated with soluble IgE Fc fragments. Hence no immediate hypersensitivity reaction would take place. 4. E All are considered to be involved to varying degrees in injection therapy. 5. E All are correct statements. 6. D Mast cells release granules physiologically and not by lysing, they are basophilic before but not after they degranulate, and they are not found circulating freely. Mast cells are similar to circulating basophils. 7. E All are correct statements. 8. B The RAST assay measures IgE antibody that is allowed to bind to allergen coupled to an insoluble matrix. It detects IgE anti-ragweed antibodies. It does not utilize monovalent IgE, and complement is not utilized in the test. 9. E IL-4 knockout mice do not make IgE responses when challenged with parasites, such as Nippostrongylus brasiliensis. This finding is consistent with the fact that IL-4 plays a key role in the regulation of IgE responses by B cells. 10. E All are true. A and C are true of the classic "wheal and flare" type response, while B and D describe features of the "late-phase" response, which is a complication of some anaphylactic reactions. __________________________________________________ __________________________ Answer to Case Study This is a classic case of systemic anaphylaxis. In the emergency room, epinephrine was promptly administered and the symptoms due to vascular permeability (hives, low blood pressure), and smooth muscle constriction (difficulty in breathing) were reversed. When he revived sufficiently, he revealed 43 that he had been stung by similar-looking insects in the past, the last time 3 months ago, but without any noticeable effects. These stings were apparently the priming injections building up sufficient levels of IgE antibody to sensitize his mast cells. Thus the last sting, despite the fact that little venom was injected, was sufficient to precipitate a systemic reaction. A careful skin test, involving intradermal injection of very dilute wasp venom, should show an immediate "wheal and flare" response, confirming the existence of sensitivity. The young man should be advised to (1) avoid wasps, (2) carry an emergency vial of injectable epinephrine, and (3) undergo desensitization therapy aimed at hyposensitization to the wasp venom antigen. 44 Chapter 15: Hypersensitivity Reactions: Antibody-Mediate (Type II) Cytotoxic Reactions and Immune Complex (Type III) Reactions Review Questions For each question, choose the ONE BEST answer or completion. 1. Which of the following clinical diseases is most likely to involve a reaction to a hapten in its etiology? A. Goodpasture's syndrome B. hemolytic anemia after treatment with penicillin C. rheumatoid arthritis D. farmer's lung E. Arthus reaction 2. An IgA antibody to a red blood cell antigen is unlikely to cause autoimmune hemolytic anemia because A. it would be made only in the gastrointestinal tract. B. its Fc region would not bind receptors for Fc on phagocytic cells. C. it can fix complement only as far as C1, C4, C2. D. it has a too-low affinity. E. it requires secretory component to work. 3. The glomerular lesions in immune complex disease can be visualized microscopically with a fluorescent antibody against A. IgG heavy chains. B. light chains. C. C1. D. C3. E. All of the above. 4. The lesions in immune complex-induced glomerulonephritis. A. are dependent on erythrocytes and complement. B. result in increased production of urine. C. require both complement and neutrophils. D. are dependent on the presence of macrophages. E. require all nine components of complement. 45 5. Serum sickness occurs only A. when anti-basement membrane. B. in cases of extreme excess of antibody. C. when IgE antibody is produced. D. when soluble immune complexes are formed. E. in the absence of neutrophils. 6. Immune complexes are involved in the pathogenesis of A. poststreptococcal glomerulonephritis. B. pigeon breeder's disease. C. serum sickness. D. an edematous hemorrhagic reaction in the skin of a beekeeper, 2 hours after he was stung for the 20 th time. E. All of the above. 7. The Arthus reaction and farmers' lung differ because A. only the former is due to antigen-antibody complexes. B. the mode of contact with the antigen is different. C. only the former requires complement. D. only the latter can occur in farmers. E. the reactions in farmer's lung are much more rapid. 8. The final damage to vessels in immune complex-mediated arthritis is due to A. cytokines produced by T cells. B. histamine and SRS-A. C. the C5, C6, C7, C8, C9 membrane attack complex. D. lysosomal enzymes of polymorphonuclear leukocytes. E. cytotoxic T cells. 9. Serum sickness is characterized by A. deposition of immune complexes in blood vessel walls when there is a moderate excess of antigen. B. phagocytosis of complexes by granulocytes. C. consumption of complement. D. appearance of symptoms before free antibody can be detected in the circulation. E. All of the above. 10. Type II hypersensitivity A. is antibody-independent. B. is complement-independent. C. is mediated by CD8 + T cells. D. requires immune complex formation. E. involves antibody-mediated destruction of cells. 46 11. A patient is suspected of having farmer's lung. A provocation test involving the inhalation of an extract of moldy hay is performed. A sharp drop in respiratory function is noted within 10 minutes and returns to normal in 2 hours, only to fall again in another 2 hours. The most likely explanation is that A. the patient has existing T cell-mediated hypersensitivity. B. this is a normal pattern for farmer's lung. C. the patient developed a secondary response after the inhalation of antigen. D. the symptoms of farmer's lung are complicated by an IgE-mediated reactivity to the same antigen. E. All of the above. __________________________________________________ __________________________ Case Study A technician in a snake venom-producing farm got careless one day and was bitten by a rare lethal Egyptian cobra. He was rushed to the emergency department, and a call went out immediately for antivenom serum. Fortunately some was located, and within 5 hours he was given 15 ml intravenously. The next day he received another 10 ml, the last available. Within days he was well on the way to recovery and left the hospital a week later. He returned 10 days after leaving the hospital complaining of joint pain, fever, and recurrent itchy hives on his trunk, arms, and legs. What do you suspect is happening, and how would you confirm it? 47 Chapter 15: Hypersensitivity Reactions: Antibody-Mediate (Type II) Cytotoxic Reactions and Immune Complex (Type III) Reactions Answers to Review Questions 1. B Penicillin can function as a hapten, binding to red blood cells and inducing a hemolytic anemia. A, C, and D are examples of immune aggregate (type III) reactions requiring complement and neutrophils for pathologic effects. 2. B Since phagocytic cells have Fc receptors for IgG, bound IgA would not cause engulfment and damage. Thus, A, C, D, and E are false. 3. E The lesions in immune complex disease are dependent on the presence of antigen, antibody, and complement. Hence all can be demonstrated by immunofluorescence at a lesion: A and B, because they are parts of IgG; C and D, because they are the early components of complement activated by the immune aggregated. 4. C Damage by immune complexes requires complement components to attract neutrophils, which are the agents responsible for subsequent tissue damage. Lysis by the final sequence of C6, C7, C8, and C9 is not required. 5. D Anti-basement membrane antibodies may produce damage, but can be distinguished from serum sickness lesions by their ribbonlike appearance compared to the lumpy-bumpy appearance of serum sickness lesions. Excess of antibody would clear antigen rapidly with few lesions. IgE antibody is responsible for anaphylactic reactions, and neutrophils are required for the lesions typical of serum sickness. 6. E All are examples of type III hypersensitivity reactions: A, by production of antibody, which reacts with normal kidney antigen; B, by inhalation of antigens from pigeon droppings; C, serum sickness is a classical example of an immune complex disease; and D is a description of an Arthus reaction in someone who has been immunized by repeated injection of bee venom. 7. B Both the Arthus reaction and farmer's lung are examples of immune aggregate reactions that require complement and neutrophils. The former involves antigen injected into the skin; the latter involves inhaled antigen. 8. D Neither T cells nor mast cells are responsible for the final tissue damage in immune complex disease. Therefore A, B and E are eliminated. The final lytic complex of complement is similarly not involved, since complement activation up to C5 is sufficient to bring in the polymorphonuclear leukocytes, whose lysosomal enzymes cause the tissue damage. 9. E All are characteristics of serum sickness. 10. E Type II hypersensitivity reactions occur following development of antibodies against target antigens expressed on normal cells or cells with altered membrane determinants. Antibodies bind to the surface of these cells and mediate damage or destruction by one or more mechanisms, including complement-mediated reactions. CD8 + cytotoxic T cells and immune complexes are not involved in these reactions. 48 11. D The type III response in farmer's lung and similar occupational diseases has an onset of symptoms usually several hours after exposure. The appearance of breathing difficulties within minutes could create a strong suspicion that a type I anaphylactic response is also present. Presumably, the patient made both IgE and IgG antibodies to the actinomycete antigens. A positive wheal and flare reaction on skin testing would provide further confirmation. __________________________________________________ __________________________ Answer to Case Study Most antivenoms of exotic species such as snake, spider, and scorpion would be made in horses. The horse antiserum neutralized the toxin and saved the patient's life. However, being a foreign protein, it induced an immune response with resultant formation of antigen-antibody complexes in joints and the activation of complement to give anaphylatoxins were responsible for the join pain, hives, and itching he experienced. It is possible that he could subsequent develop symptoms of glomerulonephritis as well. Treatment would consist of corticosteroid administration for its general antiinflammatory effects. Confirmatory studies of your diagnosis might include looking for depressed levels of serum C3 and C4 as a result of activation in tissue by the antigen-antibody aggregates. In the convalescent stage, one might also find antibody to horse Ig as a final definitive proof of your diagnosis. 49 Chapter 16: Hypersensitivity Reactions: T-Cell-Mediated, Type IV -- Delayed-Type Hypersensitivity Review Questions For each question, choose the ONE BEST answer or completion. 1. Which of the following does not involve cell-mediated immunity? A. contact sensitivity to lipstick B. rejection of a liver graft C. serum sickness D. tuberculin reaction E. immunity to chicken pox 2. A positive delayed-type hypersensitivity skin reaction involves the interaction of A. antigen, complement, and cytokines. B. antigen, antigen-sensitive lymphocytes, and macrophages. C. antigen-antibody complexes, complement, and neutrophils. D. IgE antibody, antigen, and mast cells. E. antigen, macrophages, and complement. 3. Cell-mediated immune responses are A. enhanced by depletion of complement. B. suppressed by cortisone. C. enhanced by depletion of T cells. D. suppressed by antihistamine. E. enhanced by depletion of macrophages. 4. Delayed skin reactions to an intradermal injection of antigen may be markedly decreased by A. exposure to a high dose of X-irradiation. B. treatment with antihistamines. C. treatment with an antineutrophil serum. D. removal of the spleen. E. decreasing levels of complement. 5. Patients with DiGeorge syndrome who survive beyond infancy would be capable of A. rejecting a bone marrow transplant. B. mounting a delayed-type hypersensitivity response to dinitrochlorobenzene. C. resisting intracellular parasites. D. forming antibody to T-dependent antigens. E. All of the above. F. None of the above. 50 6. Which of the following statements is characteristic of contact sensitivity? A. The best therapy is oral administration of the antigen. B. Patch testing with the allergen is useless for diagnosis. C. Sensitization can be passively transferred with serum from an allergic individual. D. Some chemicals acting as haptens induce sensitivity by covalently binding to host proteins acting as carriers. E. Antihistamines constitute the treatment of choice. 7. Positive skin tests for delayed-type hypersensitivity to intradermally injected antigens indicate that A. a humoral immune response has occurred. B. a cell-mediated immune response has occurred. C. both T cell and B cell systems are functional. D. the individual has previously made IgE responses to the antigens. E. immune complexes have been formed at the injection site. 8. T cell-mediated immune responses can result in A. formation of granulomas. B. induration of the reaction site. C. rejection of a heart transplant. D. eczema of the skin in the area of prolonged contact with a rubberized undergarment. E. All of the above. __________________________________________________ __________________________ Case Study As a member of an anthropologic research team, you have occasion to visit a primitive tribe in the remote reaches of the Amazon jungle. During your visit the natives conduct a ceremony celebrating the rites of passage for young males. This consists, among other things, of covering their bodies with elaborate patterns of stripes and circles using a variety of colors extracted from local plants. On your return 3 weeks later, you are asked to look at a young male who has developed alarmingly itchy and weepy red areas of skin that run in sharply demarcated stripes across his back and on one arm. Remembering your introductory course in immunology, you make an educated guess as to the cause. How, under such primitive conditions, could you confirm your diagnosis? 51 Chapter 16: Hypersensitivity Reactions: T-Cell-Mediated, Type IV -- Delayed-Type Hypersensitivity Answers to Review Questions 1. C Serum sickness is an example of those reactions mediated by an antibody-antigen complex that involves components of the complement system and neutrophils. All others involve cell-mediated immunity to a significant extent. 2. B Cell-mediated reactions result from the triggering of T cells by antigen with recruitment of macrophages. Neither antibody, complement, nor mast cells plays a role in this process, although they do play a role in immediate hypersensitivity responses. 3. B Cortisone has a general antiinflammatory effect and is also lytic for some T cells. Complement plays no role, and antihistamines have little effect on this type of response. Depletion of T cells or macrophages would suppress, not enhance, this type of response, since the response is dependent on these cells. 4. A High doses of X-irradiation will destroy T cells, which are responsible for initiating the response. Histamine, neutrophils, spleen, and complement do not play a role, and any treatment that affects them would not affect a DTH response. 5. F Patients with DiGeorge syndrome have a congenital thymic aplasia and lack all T cell functions. Since A, B, and C are all aspects of a cell-mediated immune response, they would be absent. Additionally, formation of antibody against these antigens is dependent on helper T cells and, therefore, would not occur in these patients. 6. D Patch testing consists of application of the offending allergen under an occlusive dressing, and a positive DTH response after 24-48 hours is considered evidence of sensitivity; thus B is wrong. The allergens involved are those capable of penetrating skin and binding to host carrier proteins; thus D is correct. Oral ingestion of antigen, which in certain experimental situation, was shown to be an effective therapeutic maneuver in humans; thus A is wrong. Corticosteroids, not antihistamines, constitute the treatment of choice for contact sensitivity; thus E is also incorrect. Passive transfer of cell-mediate immune responses is accomplished with T cells, not with serum, thus C is wrong. 7. B A delayed-type hypersensitivity reaction, evidenced by erythema and induration within 24-72 hours of antigen injection, indicates that a cell-mediated reaction has occurred. Such reactions do not involve antibody produced by B cells, thus A, C, D, and E are incorrect. 8. E All of these effects are manifestations of cell-mediated immunity. Induration usually takes place at the reaction site. Formation of granulomas is characteristic of a chronic DTH reaction. Rejection of the heart is an example of an allograft response. Some of the chemicals used to cure rubber can induce contact sensitivity after prolonged exposure of the skin to them. 52 Answer to Case Study The appearance of the skin lesion and its sharp demarcations and weepy, itchy nature all suggest contact sensitivity. One of the dyes used to paint the body is most likely the sensitizer and, since it persisted on the skin, was also able to provoke a T cell-mediated reaction after the initial expansion of the specific clones. In the absence of sophisticated testing equipment, a simple patch test using samples of the various dyes applied to healthy areas of skin should show a localized contact reaction 24-48 hours later at the site to which the causative dye was applied. (In the laboratory one might also look for an in vivo proliferative response of the patient's peripheral blood lymphocytes to added dye. A biopsy of the lesion should reveal an intense infiltrate of mononuclear cells.) 53 Chapter 17: Autoimmunity Review Questions For each question, choose the ONE BEST answer or completion. 1. Most autoimmune diseases are caused by A. single genetic defect. B. known infectious organism. C. constellation of genetic and environmental events. D. hormonal dysregulation. E. B-cell defect. 2. Identifying an autoimmune disease in humans is often accomplished by A. finding an antibody against self-components. B. passively transferring specific T cells from a patient to a healthy individual. C. showing that T cells or antibodies are the cause of the tissue damage. D. circumstantial evidence, such as MHC association and clinical improvement, with immunosuppressive drugs. E. finding the definitive agent or agents responsible for the disease. 3. The following is/are possible mechanism(s) for the recognition of self-components by the immune system in autoimmune diseases: A. alteration of a self-antigen so it is recognized as foreign B. leakage of sequestered self-antigen C. loss of suppressor cells D. infection with a microorganism that carries a cross-reactive antigen E. Any of the above. 4. Rheumatoid factor, found in synovial fluid of patients with rheumatoid arthritis, is most frequently found to be A. IgM reacting with L chains of IgG. B. IgM reacting with H-chain determinants of IgG. C. IgE reacting with bacterial antigens. D. antibody to collagen. E. antibody to DNA. 5. The pathology in autoimmune diseases due to antibody may be a result of A. the formation of antigen-antibody complexes. B. antibody blocking a cell receptor. C. antibody-induced phagocytosis. D. antibody-induced complement mediated lysis. E. Any of the above. 54 6. Autoimmune hemolytic anemia: A. is usually due to warm agglutinins belonging to the IgM class directed against Rh antigens on red blood cells. B. may be due to the production of either cold agglutinins after viral infection or autoantibodies following drug treatment. C. is the result of cytotoxic T cells lysing red blood cells. D. does not generally involve complement components in red blood cell lysis. E. can be characterized by a negative Coombs test. 7. Systemic lupus erythematosus A. is due to a mutation in double-stranded DNA. B. is a classic example of a T-cell-mediated autoimmune disease. C. has multiple symptoms and affects many organs. D. results from antibodies specific to thyroid. E. affects only skin epithelial cells. 8. Diseases in with TH1 cells and cytotoxic CD8 + T cells probably play major roles in their pathology include all of the following except A. myasthenia gravis. B. Hashimoto's thyroiditis. C. rheumatoid arthritis. D. multiple sclerosis. E. insulin-dependent diabetes mellitus. 9. A patient is found to have a form of diabetes in which his immune system is destroying his pancreatic islet cells. |