Immunology Practice Questions - Block 1

The correct answer is D. This child has chronic granulomatous disease (CGD). The history indicates he has had recurrent infections with catalase- positive organisms and has a defect in generating oxygen radicals intracel- lularly in his phagocytic cells (the negative nitroblue tetrazolium test and neutrophil oxidative index). This genetic defect arises from a failure to pro- duce one of the subunits of NADPH oxidase, which makes the individual incapable of producing intracellular oxygen radicals. Redundant intracel- lular killing mechanisms (myeloperoxidase and lysosomal contents) are still functional in these patients, but when they are infected with catalase- positive organisms, the substrate for myeloperoxidase (hydrogen peroxide) is destroyed, and the only remaining intracellular killing mechanism (lyso- somes) is insufficient to protect from infection. C3 deficiency (choice A) would cause increased susceptibility to pyogenic infections because C3b is an important opsonin that enhances phagocytosis of extracellular organisms. All extracellular bacteria would be included in this list, not simply catalase-positive ones, as mentioned here. The NBT and NOI would not be negative in this case. Deficiency of CD18 (choice B) is the cause of leukocyte adhesion defi- ciency (LAD). Because CD18 is the common β chain of the β2 integrins, its absence compromises leukocyte function antigen (LFA)-1, as well as complement receptors 3 and 4. Patients with LAD suffer recurrent infec- tions with extracellular pathogens (not just catalase-positive ones) because of defective opsonization, mobilization, adhesion, and chemotaxis. The NBT and NOI would be positive. Deficiency of myeloperoxidase (choice C) results from a deficiency of an important granule enzyme in phagocytic cells. However, because there are so many redundant mechanisms of intracellular killing, these patients gen- erally have mild symptoms or none at all. A phagocyte granule structural defect (choice E) is responsible for the Chediak-Higashi syndrome. These patients have chemotactic and degranu- lation defects, lack NK activity, and have partial albinism.

A 2-year-old boy is admitted to the hospital for workup of a possible immu- nologic disorder. His history is remarkable for the occurrence of multiple skin infections involving Staphylococcus, Pseudomonas, and Candida. On examination the child has cervical lymphadenopathy and mild hepato- splenomegaly. Blood tests reveal an elevated erythrocyte sedimentation rate and neutrophilia. The nitroblue tetrazolium dye reduction test and neutro- phil oxidative index are negative. What is the most likely defect in this child? Immunology Practice Questions (A) C3 deficiency (B) Deficiency of CD18 (C) Deficiency of myeloperoxidase (D) NADPH oxidase deficiency (E) Phagocyte granule structural defect

The correct answer is B. This child has bare lymphocyte syndrome, a rare autosomal-recessive disease in which there is absence of MHC class II molecules on cells. Thus, her cells can recognize other cells as foreign and proliferate to T-cell mitogens, but they cannot be recognized by allogeneic lymphocytes because they do not express class II MHC antigens on their surface. The phrase which best describes the MHC class II molecule on this list is that it is designed to bind exogenously processed peptides. Other descriptions that could apply would be that it has two chains of similar length, is produced with an invariant chain, and is designed to present for- eign peptides to Th cells. It is designed to bind endogenously produced peptides (choice A) is a description that fits the class I MHC molecule. If this were a case of class I MHC deficiency, she would not have made a normal proliferative response to mismatched allogeneic cells. It possesses β2 microglobulin (choice C) is a description that fits the class I MHC molecule. It possesses two chains of unequal length (choice D) is a description of the class I MHC molecule. It has an α chain with 3 domains, and a smaller chain, β2 microglobulin, becomes associated with the α chain. It should be present on all nucleated cells in the body (choice E) describes the class I MHC molecule. Class II MHC will be found on all antigen- presenting cells in the body.

A 10-month-old infant girl is admitted to the hospital with signs of Pneumocystis jirovecii pneumonia. Studies of her peripheral blood dem- onstrate age-normal counts of CD19+ cells, but CD3+ and CD4+ cell numbers are depressed. Immunoelectrophoresis of her serum reveals a moderate hypogammaglobulinemia. Her peripheral blood lymphocytes proliferate normally in response to phytohemagglutinin and MHC class I mismatched allogeneic cells. In a one-way mixed lymphocyte reaction using her cells as the stimulator cells, allogeneic T lymphocytes did not proliferate. Which of the following best describes the molecule most likely lacking from her lymphocytes? (A) It is designed to bind endogenously produced peptides (B) It is designed to bind exogenously processed peptides (C) It possesses β2 microglobulin (D) It possesses two chains of unequal length (E) It should be present on all nucleated cells in the body

The correct answer is A. Because rabies antitoxin is a pooled, human immunoglobulin product, repeated inoculation will cause a patient to pro- duce anti-allotype antibodies. Allotypes are minor amino-acid sequence variations in the constant domains of heavy and light immunoglobulin chains. Their expression is genetically determined, and repeated exposure to molecules of foreign allotype can cause antibodies to be produced which recognize these sequence variations. Anti-epitope antibodies (choice B) would be produced by repeated inocu- lation of an immunogen. The epitope of the antigen has a three-dimen- sional complementarity with the idiotype of the antibody molecule. In this case, anti-epitope antibodies would be generated by rabies vaccination, but the question asks what the result of repeated exposure to immunoglobulins would be. Anti-idiotype antibodies (choice C) would be generated in a human if a monoclonal antibody preparation were repeatedly inoculated. The idiotype of an antibody is the three-dimensional shape of its antigen-combining site. It is unique to the antibodies produced by a clone of cells. Because the material mentioned in this case is a pooled human immunoglobulin, it would contain many different idiotypes and would be unlikely to elicit any one specific anti-idiotype antibody. Anti-isotype antibodies (choice D) are usually raised across species bar- riers. For example, to produce anti-human IgG, IgG pooled from many humans is repeatedly injected into rabbits, goats, or sheep. These animals will recognize the human determinants in the constant domains of the heavy and light chains (the isotypes) and will produce antibodies that spe- cifically recognize those determinants. Anti-rabies antibodies (choice E) are generated during vaccination. When the killed virus is administered, the patient makes an active, artificial response to the immunogen and produces immunoglobulins, which will protect against virus attachment. In this case, anti-rabies antibodies were inoculated, so there is no possibility that more of the same will be generated.

A 10-year-old child was bitten by a stray dog. The child is started on a course of anti-rabies post-exposure prophylaxis, beginning with inoculation of pooled human antirabies immunoglobulin. What would repeated inocula- tion of this antirabies immunoglobulin preparation be likely to induce? (A) Anti-allotype antibodies (B) Anti-epitope antibodies (C) Anti-idiotype antibodies (D) Anti-isotype antibodies (E) Anti-rabies antibodies

The correct answer is A. T-lymphocyte precursors that leave the bone mar- row and move to the thymus have neither CD4 nor CD8 coreceptors, and they have not rearranged the DNA of the variable domains of their antigen receptor, the TCR. CD4-, CD8-, and TCR+ (choice B) is not a possible T-cell phenotype. Once the TCR gene segments are rearranged and the TCR is expressed, the cells will bear both CD4 and CD8 coreceptors. CD4-, CD8+, and TCR+ (choice C) is the phenotype of cytotoxic T cells that would be in the circulation, not in the thymus, unless it were immedi- ately prior to their release into the circulation following the thymic selec- tion process. CD4+, CD8-, and TCR+ (choice D) is the phenotype of helper T cells that would be in the circulation, not in the thymus, unless it were immediately prior to their release into the circulation following thymic selection pro- cesses. CD4+, CD8+, and TCR+ (choice E) is the phenotype of cells in the thymic cortex. These are the cells that have rearranged their receptor genes and bear both CD4 and CD8 coreceptors. As the specificity of their TCR is tested, they will be directed to express either CD4 (and become a helper T cell) or CD8 (and become a cytotoxic T cell).

A 12-year-old child is diagnosed with a T-cell lymphoma. The phenotype of the malignant cell matches that of normal progenitor cells that leave the bone marrow to enter the thymus. What cell surface markers would you expect to find on the malignant cells? (A) CD4-,CD8-,TCR- (B) CD4-,CD8-,TCR+ (C) CD4-,CD8+,TCR+ (D) CD4+, CD8-, TCR+ (E) CD4+, CD8+, TCR+

The correct answer is A. This is a case of X-linked agammaglobulinemia, or Bruton agammaglobulinemia. It is caused by a mutation in a tyrosine kinase gene, which is important in B-cell maturation. The bone marrow becomes hypercellular with cells that cannot progress beyond the pre-B stage, while the peripheral blood lacks mature B lymphocytes. There will be no prolifera- tive response to B-cell mitogens (pokeweed mitogen), and CD19+ cells will be absent from the blood. Persons with this condition are unable to mount a normal antibody response; therefore, symptoms appear after the disap- pearance of maternal antibodies. Susceptibility to extracellular, encapsulated pathogens is profound. Common variable hypogammaglobulinemia (choice B) is a condition that usually appears in the late teens or early twenties. It is believed to be an autoimmune disease and is associated with the disappearance of immuno- globulin isotypes over time. DiGeorge syndrome (choice C), or congenital thymic aplasia, is a condition in which there is failure of formation of the third and fourth pharyngeal pouches. These infants have facial abnormalities, failure of formation of the parathyroids, and cardiac defects, as well as absence of T-lymphocyte development. Selective immunoglobulin deficiency (choice D) would not be manifested by a failure of B-cell development in the bone marrow. Selective IgA defi- ciency is most common of these and would manifest as increased suscepti- bility to mucosal-surface pathogens. Wiskott-Aldrich syndrome (choice E) is a complex immune deficiency with a triad of symptoms: eczema, thrombocytopenia, and immunodeficiency. It is inherited in an X-linked recessive fashion. These patients are prone to development of malignant lymphomas and have inability to respond to polysaccharide antigens.

A 14-month-old boy is referred to a specialist for diagnosis of a potential immunologic deficiency. For the past 4 months, the child has suffered repeated episodes of bacterial infections and attempts to induce immunity using the pneumococcal vaccine have failed. Studies of peripheral blood indicate an absence of cells responsive to pokeweed mitogen. Bone marrow aspirates are remarkable for hypercellularity of pre-B cells. What is the most likely diagnosis? (A) Bruton agammaglobulinemia (B) Common variable hypogammaglobulinemia (C) DiGeorge syndrome (D) Selective immunoglobulin deficiency (E) Wiskott-Aldrich syndrome

The correct answer is D. The standard screening test for HIV infection is the enzyme-linked immunosorbent assay, or ELISA. In this test, the virus p24 antigen is coated onto microtiter plates. Serum from the test subjects is added, followed by antihuman-immunoglobulin, which is labeled with an enzyme. When the substrate for the enzyme is added, if the antibodies listed have bound in sequence, there will be a color change in that microtiter well. Electrophoresis of HIV antigens in polyacrylamide gel (choice A) describes the Western blot, which is used as a confirmatory test of HIV infection. HIV antigen covalently coupled to RBC, patient serum, and anti-immuno- globulin (choice B) describes an erythrocyte agglutination test. There is no such test in use for diagnosis of HIV. The indirect Coombs test, which is used to detect Rh- mothers who have become sensitized to the Rh antigens of their fetuses, operates on this principle, however. HIV antigen covalently coupled to RBC, patient serum, and complement (choice C) describes either a complement-fixation or complement-medi- ated hemolysis assay. There is no such test in use for the diagnosis of HIV. HIV antigen, patient serum, anti-immunoglobulin serum, and radioactive ligand (choice E) describes a radioimmunoassay. This is not used in the standard screening for HIV.

A 16-year-old runaway heroin user visits a family planning/STD clinic irreg- ularly to receive birth control pills. In April 2004, the standard HIV screen performed by this clinic reports back that her test was positive. What does the primary test for HIV infection use? (A) Electrophoresis of HIV antigens in polyacrylamide gel (B) HIV antigen covalently coupled to RBC, patient serum, and anti-immu- noglobulin (C) HIV antigen covalently coupled to RBC, patient serum, and complement (D) HIV antigen, patient serum, anti-immunoglobulin serum, and enzyme- substrate ligand (E) HIV antigen, patient serum, anti-immunoglobulin serum, and radioactive ligand

The correct answer is D. CD3 is the signal transduction complex in T lymphocytes. When specific antigen binding has occurred on the surface of the cell, this complex is responsible for transferring the message to the cytoplasm of the cell. This culminates in intracytoplasmic phosphorylation events, which activate the cell and induce its proliferation (cloning). A cell lacking CD3 would be capable of binding specific antigen, but incapable of activation and proliferation in response to that first signal. Ability to bind cell-bound peptides (choice A) would not be affected by the absence of CD3. Binding to peptides presented by antigen-presenting cells is through interaction of the T-cell receptor with major histocompatibility antigens on the surface of other cells. Ability to express coreceptors (choice B) would not be affected by the absence of CD3, although cells would not be able to complete their differ- entiation in the thymus and become fully committed T cells. Ability to produce terminal deoxyribonucleotidyl transferase (choice C) would not be affected by the absence of the T-cell signal transduction complex. T-cell precursors rearrange their receptor gene segments (and use terminal deoxyribonucleotidyl transferase) in the absence of antigenic stimulation and before signal transduction through CD3 becomes critical. Ability to rearrange T-cell receptor gene segments (choice E) would not be affected by the absence of the T-cell signal transduction complex. T-cell pre- cursors rearrange their receptor gene segments in the absence of antigenic stimulation and before signal transduction through CD3 becomes critical.

A 2-year-old boy is evaluated for a severe combined immunodeficiency disease. His bone marrow has normal cellularity. Radioactive tracer studies demonstrate a normal number of T-cell precursors entering the thymus, but no mature T lymphocytes are found in the blood or peripheral organs. Cells populating the thymus are found to lack CD3. Which of the following capa- bilities would his cells lack? (A) Ability to bind cell-bound peptides (B) Ability to express CD4/CD8 coreceptors (C) Ability to produce terminal deoxyribonucleotidyl transferase (D) Ability to proliferate in response to specific antigen (E) Ability to rearrange T-cell receptor gene segments

The correct answer is B. This is a case of hereditary angioedema, caused by a deficiency in an important complement regulatory protein, C1-INH. When it is absent, the early components of the classical complement cas- cade are overused. It is normally diagnosed by the finding of depressed levels of complement component C4 in the blood. Depressed C3 (choice A) would not be a correlate of C1-INH deficiency. There are separate regulatory controls on abnormal complement activation that operate at the C3 level, so this condition is rarely found. Depressed C5 (choice C) would not be a correlate of C1-INH deficiency. There are separate regulatory controls on abnormal complement activation that operate at the C5 level, so this condition is rarely found. Elevated C1 (choice D) would not be found in this case because the condi- tion results in the overuse of early components of the classical complement cascade. Therefore, serum levels of C1, C4, and C2 would be decreased from normal values. Elevated C1, C4, and C2 (choice E) would not be found in this case because the condition results in the overuse of early components of the classical complement cascade. Therefore, serum levels of C1, C4, and C2 would be decreased from normal values.

A 2-year-old boy suffering from repeated painful bouts of inflammation of mucosal surfaces, especially affecting the lips, is brought to the pediatri- cian's office. The mother remembers similar symptoms in previous genera- tions of her family and fears a heritable tendency toward food allergy. What laboratory finding would best support the physician's suspicion? (A) Depressed C3 (B) Depressed C4 (C) Depressed C5 (D) Elevated C1 (E) Elevated C1, C4, and C2

The correct answer is B. This child has leukocyte adhesion deficiency (LAD), which is a genetic deficiency of CD18. CD18 is an essential compo- nent of a number of integrins, and absence of these molecules causes the inability of WBCs to migrate into sites of inflammation. Thus in this patient, the blood contained abnormally high numbers of neutrophils, but they were unable to extravasate. CD18 is a component of LFA-1, CR3, and CR4. Absence of CCR4 (choice A) would cause difficulties in extravasation and migration of activated T cells and monocytes. This chemokine receptor is not found on neutrophils and therefore would have no effect on neutrophil migration. Absence of interleukin-1 (choice C) might cause difficulties in producing the acute and chronic inflammatory responses. This cytokine, frequently referred to as the endogenous pyrogen, produces fever, acute phase protein produc- tion, and many other results critical to inflammation. However, the actions of IL-1 are extremely redundant with those of IL-6 and tumor necrosis factor-α, so such a condition might have no clinically observable effects. Absence of interleukin-4 (choice D) would result in defects in the ability to mount a normal IgE antibody response. This cytokine also serves as the major stimulus for the development of Th2 cells from naive helper T cells, so its absence would be likely to have profound effects on all aspects of the secondary antibody response. Absence of tumor necrosis factor-α (choice E) might cause difficulties in producing the acute and chronic inflammatory responses. This cytokine has many functions that are redundant with those of IL-1 and IL-6, so such a condition might have no clinically observable effects.

A 2-year-old child who has suffered recurrent bacterial infections is evalu- ated for immunologic deficiency. The child has age-normal numbers of CD19+ and CD3+ cells in the peripheral blood and an extreme neutro- philia. The nitroblue tetrazolium dye reduction test is normal. What is the most likely defect in this child? (A) Absence of CCR4 (B) Absence of CD18 (C) Absence of interleukin-1 (D) Absence of interleukin-4 (E) Absence of tumor necrosis factor-α

The correct answer is E. The only way to identify a neonatal infection serologically is by detection of pathogen-specific IgM antibodies. This is because the fetus receives IgG antibodies from the mother by active trans- port across the placenta. Because you cannot identify the source of the antibodies, IgG detection in the child can simply reflect this natural pas- sive type of protection. Because IgM does not cross the placenta, any IgM detected in the neonate is being produced in the child and is reflective of a response to infection. In this way, all children born to HIV-infected moth- ers will be seropositive by both ELISA and Western blot, but only 20% will actually be infected in utero, even in the absence of antiviral therapy. IgA (choice A) does not usually begin to be produced by a child until one to two years after birth. At the end of the first year, most children have no more than 20% of adult values, so it would not be a useful diagnostic in the neonate. Additionally, because Toxoplasma gondii is an intracellular parasite, IgA would not be the most effective immune response in any individual. IgD (choice B) will be produced by an infected neonate along with IgM because of alternative RNA splicing, but this is not a useful diagnostic. IgD rarely reaches levels easily detected by serology, and the immunoglobulin has the shortest half-life of all the immunoglobulins. The function of secreted IgD, if any, is not clear, so it is not a useful serologic test. IgE (choice C) does not usually begin to be produced by a child until well into the second year after birth. Additionally, because Toxoplasma gondii is an intracellular parasite, IgE would not be the most effective immune response in any individual. IgG (choice D) is not a useful serologic test in a neonate because it is impossible to determine the origin of such molecules. Children infected in utero will begin to produce IgG due to isotype switching late in gestation, but because the placenta is actively transporting all maternal IgG into the fetus, it is not possible to distinguish whether the child is actually infected or simply passively protected using this technique.

A 26-year-old obstetric patient becomes ill during the first trimester of preg- nancy with fever and lymphadenopathy. She is found to have a rising titer of anti-Toxoplasma gondii antibodies. She delivers a full-term baby with no apparent signs of in utero infection. The best test to diagnose acute infec- tion in the neonate would be a parasite-specific ELISA for which isotype of immunoglobulin? (A) IgA (B) IgD (C) IgE (D) IgG (E) IgM

The correct answer is A. Allotypes are minor amino-acid sequence varia- tions in the constant domains of heavy and light immunoglobulin chains. Their expression is genetically determined, and variations can be used as evidence in favor of paternity in some cases. Allotypic markers are most frequently used in studies of population genetics, as certain ethnic groups are likely to have similar allotypic markers on their immunoglobulins. Allotypic markers do not affect the biologic function of the immunoglobu- lin molecule. The term "idiotype" (choice B) describes the 3-dimensional shape of the antigen-combining site of an antibody or T-cell receptor molecule. Because each human is capable of producing many millions of different idiotypic sequences, these would not be useful in paternity cases. IgA2 (choice C) is an isotype of immunoglobulin. Because all normal human beings produce some amount of this immunoglobulin, it would not be useful in paternity cases. IgM (choice D) is an isotype of immunoglobulin. Because all normal human beings produce some amount of this immunoglobulin, it would not be useful in paternity cases. An isotype (choice E) is found in the heavy- or light-chain constant domains of an immunoglobulin. Thus, there are 5 heavy-chain isotypes (A, E, G, M, and D) and two light-chain isotypes (κ and λ). Because all human beings produce heavy- and light-chain isotypes, this would not be useful in paternity testing.

A 28-year-old man was brought into court for nonpayment of child sup- port. A 20-year-old woman insists that he is the father of her child. The court suggests before hearing the paternity case that various genetic tests be performed on the man, woman, and child. One of the sets of tests was for genetic immunoglobulin identification. Which immunoglobulin marker would be useful in this case? (A) Allotype (B) Idiotype (C) IgA2 (D) IgM (E) Isotype

The correct answer is C. The component of complement that is most important in clearance of extracellular pathogens such as Streptococcus pneumoniae is C3b. This fragment acts as an opsonin and enhances the ingestion and intracellular killing of the bacteria by phagocytic cells. C1 (choice A) is the first component of the complement cascade activated in the classic pathway. Although it is critical to initiating those events that can culminate in the production of the membrane attack complex, it is not the most important component for the clearance of infections such as this one. C2 (choice B) is the third component of the complement cascade activated in the classic pathway. Although it is critical to initiating those events that can culminate in the production of the membrane attack complex, it is not the most important component for the clearance of infections such as this one. C4 (choice D) is the second component of the complement cascade acti- vated during the classic pathway. Although it is critical to initiating those events that can culminate in the production of the membrane attack com- plex, it is not the most important component for the clearance of infections such as this one. C5 (choice E) is the fifth component of the complement cascade activated during the classic pathway and the first step in the formation of the mem- brane attack complex (C5b-9). It is not the most important component for the clearance of infections such as this one.

A 3-year-old boy has had several bouts with pneumonia. Streptococcus pneu- moniae was isolated and identified in each of the cases. The child was treated with penicillin each time, and the condition resolved. He is now being evalu- ated for a potential immunologic deficiency. Serum electrophoresis shows age-normal values for all isotypes of immunoglobulin, but serum levels of some components of complement are depressed. Which of the following deficiencies could explain his problem? (A) C1 (B) C2 (C) C3 (D) C4 (E) C5

The correct answer is B. Unusual frequency or severity of Neisseria infec- tions should always lead to a suspicion of a terminal complement compo- nent deficiency (C5, C6, C7, or C8). Neisseria seems to be highly susceptible to complement-mediated lysis, so any failure of production of the mem- brane attack complex predisposes the patient to recurrent bacteremias with these organisms. Common variable immunodeficiency (choice A) is a condition that usually appears in the late teens or early twenties. It is believed to be an autoimmune disease and is associated with the disappearance of immu- noglobulin isotypes over time. DiGeorge syndrome (choice C) is a condition in which there is failure of formation of the third and fourth pharyngeal pouches. Diagnosed in infancy, these individuals have facial abnormalities, failure of formation of the para- thyroids, and cardiac defects, as well as an absence of T-lymphocyte develop- ment. This condition predisposes to early viral and fungal infections. Selective IgA deficiency (choice D) would be expected to result in respiratory and gastrointestinal tract infections, autoimmune disease, and allergies. Severe combined immunodeficiency (choice E) typically presents with early susceptibility to viral and fungal agents. It is most frequently diagnosed in infancy, after the disappearance of maternally derived IgG antibodies.

A 31-year-old man is treated for a fourth episode of disseminated Neisseria gonorrhoeae infection in the last 5 years. He had no previous history of unusual or recurrent infections. If he has an immunologic defect, which of the following is most likely? (A) Common variable immunodeficiency (B) C8 deficiency (C) DiGeorge syndrome (D) Selective IgA deficiency (E) Severe combined immunodeficiency

The correct answer is E. IL-10 is produced by Th2 cells and inhibits Th1 cells. Because the response to poison ivy is a delayed-type hypersensitivity response and therefore is mediated by Th1 cells and macrophages, inhibit- ing their activity would minimize the severity of the reaction. γ-Interferon (choice A) is a product of Th1 cells, CTLs, and NK cells. It inhibits the proliferation of Th2 cells and therefore would skew the immune response toward a more potent cell-mediated arm. This is not a cytokine that would help this patient: It would make his condition worse. IL-2 (choice B) is a product of Th cells that induces the proliferation and enhances the activity of antigen-primed Th cells and CTLs. It would tend to increase the symptoms of this patient, not ameliorate them. IL-3 (choice C) is a product of Th cells and NK cells. It acts on hematopoietic cells to encourage myeloid cell development. It would neither hinder nor help this man's condition. IL-8 (choice D) is a product of macrophages and endothelial cells and acts on neutrophils to attract them to areas of inflammation. It would increase inflammation in the area.

A 36-year-old farmer has been exposed to poison ivy on several different occasions, and he usually gets very severe skin lesions. A pharmaceutical company is developing cytokines by recombinant DNA technology and formulating them in a fashion that they are readily absorbed through the skin. Which of the following cytokines administered topically could inhibit the severity of this reaction? (A) γ-Interferon (B) IL-2 (C) IL-3 (D) IL-8 (E) IL-10

The correct answer is E. This child has acute lymphoblastic leukemia (ALL), and the malignant cells have the characteristics of early B-cell precursors. This leukemia has peak incidence at approximately 4 years of age, is twice as common in whites than in non-whites, and is slightly more frequent in boys than in girls. A leukemic cell that is positive for terminal deoxyribonucleotidyl transferase (Tdt) is in the process of rearranging the gene segments for synthesis of the heavy chain of immunoglobulin but will not yet have completed a functional product. Tdt is active for all heavy- domain gene segment rearrangements but is not used during light-chain gene segment rearrangements. IgM monomers inserted in the membrane (choice A) would be found in leukemic cells that are at the mature B-cell stage. Such cells would have completed the rearrangements for both heavy and light chains and would lack Tdt as a marker. They would express surface MHC class II, CD19, and CD20 in addition to surface immunoglobulin. IgM monomers present in the cytoplasm (choice B) would be found in cells that have completed the rearrangement of their variable domain gene seg- ments. They would no longer express Tdt. Mu (m) chains inserted in the membrane (choice C) would be found in cells that have completed the rearrangement of their heavy chain variable domain gene segments, and these may transiently be expressed on the surface of a cell in association with a surrogate light chain before light chain rearrange- ment is complete. These cells would not be using their Tdt anymore. Mu (m) chains in the cytoplasm (choice D) would be found in leukemic cells that are more highly differentiated than those described. Once the variable domain gene segments for the heavy chain have been successfully rearranged in a cell, m chains can be found in the cytoplasm. In ALL, this is usually associated with a decreased expression of Tdt and appearance of CD10 (the common acute lymphoblastic leukemia antigen; CALLA) and CD20.

A 4-year-old Caucasian boy is brought to his pediatrician with complaints of abnormal bruising and repeated bacterial infections. A blood workup reveals thrombocytopenia and neutropenia and the presence of numerous small, dense lymphoblasts with scant cytoplasm. Immunophenotyping of the abnormal cells determines them to be extremely primitive B cells, which are CD19+, HLA-DR+, and Tdt+. Which of the following best describes the status of immunoglobulin chain synthesis most likely in these cells? (A) IgM monomers inserted in the membrane (B) IgM monomers present in the cytoplasm (C) Mu (m) chains inserted in the membrane (D) Mu (m) chains present in the cytoplasm (E) No immunoglobulin chain synthesis present

The correct answer is B. IgM and secretory IgA are similar in that they are held together by a J chain synthesized by the B cell or plasma cell. Without the presence of the J chain, IgM would exist only in monomeric form, and the macroglobulin peak would be absent on electrophoresis. Because pen- tameric IgM is important for capturing newly introduced foreign antigen and thus beginning the immune response, the child is delayed in his devel- opment of protective responses to vaccination. Because secretory IgA is a dimer that protects the mucosal surfaces, such a child would be especially susceptible to infectious agents crossing the mucosal surfaces. Absence of CD40 (choice A) would affect the production of IgG, IgA, and IgE, but would not prevent macroglobulin synthesis. Indeed, most patients with this defect have hyper-macroglobulinemia because the CD40/CD40L interac- tion is necessary for isotype switching. Absence of IL-4 (choice C) would cause problems with the ability to produce IgG, IgA, and IgE. This cytokine, produced by Th2 cells, is neces- sary for the differentiation and development of most antibody responses other than IgM. Thus, IgM levels either would not be affected or would be increased in a compensatory fashion. Absence of Tdt (choice D) would cause problems with the patient's abil- ity to perform the genetic rearrangements necessary to form the idiotype of the antibody molecule. They would not affect the isotype of antibody produced. Absence of Th2 cells (choice E) would affect the production of IgG, IgA, and IgE, but would not affect IgM production.

A 4-year-old boy is evaluated for a possible immunologic deficiency. He has suffered repeated infections of mucosal-surface pathogens and has shown delayed development of protective responses to the standard child- hood vaccinations. Immunoelectrophoresis of his serum demonstrates absence of a macroglobulin peak, and his sputum is devoid of secretory IgA. Normal numbers of B lymphocytes bearing monomeric IgM are found by flow cytometry, and serum levels of monomeric IgA, IgE, and each of the 4 subisotypes of IgG are normal. Which of the following deficiencies could account for these findings? (A) Absence of CD40 (B) Absence of J chains (C) Absence of IL-4 (D) Absence of Tdt (E) Absence of Th2 cells

The correct answer is D. The infections of this child with catalase-positive bacteria are characteristic of chronic granulomatous disease (CGD). While two thirds of CGD patients are male, one third has the autosomal recessive form of NADPH oxidase deficiency and can be female. Adenosine deaminase deficiency (choice A) produces a severe combined immunodeficiency. The infections seen are likely to be the result of T-cell deficiency (viral and fungal agents). In the absence of adenosine deaminase, deoxyadenosine phosphate builds up in T cells and is toxic to them. C1 inhibitor (choice B) is not an enzyme, and its absence does not predis- pose to infections. It is absent in the condition known as hereditary angio- edema, represented by recurrent, painful bouts of mucosal edema. Myeloperoxidase (choice C) deficiency is normally without clinical symp- toms. This is an enzyme that is important in intracellular killing in phago- cytes because it causes formation of toxic halide radicals. However, because oxygen radicals are more important in intracellular killing, MPO deficiency will present without symptoms. Superoxide dismutase (choice E) deficiency has not been described in leukocytes, and its absence would not be likely to predispose to infection.

A 4-year-old girl presents with a severe Staphylococcus aureus abscess. Her history is significant for a previous infection with Serratia marcescens. If she has an enzyme deficiency, which of the following is most likely? (A) Adenosine deaminase (B) C1 inhibitor (C) Myeloperoxidase (D) NADPH oxidase (E) Superoxide dismutase

The correct answer is A. The Mantoux test, or tuberculin test (or simply the TB skin test), is the classic clinical demonstration of the function of the delayed-type hypersensitivity response. This is a cell-mediated reaction caused by sensitization of Th1 cells and demonstrated by the influx and activation of macrophages in response to the cytokines that they elaborate. That a humoral immune response has occurred (choice B) is not true. Antibodies are not involved in the production of a DTH response, and they are not important products during infections with most intracellular pathogens. That the B-cell system is functional (choice C) is not true. B cells do not play a role in the DTH response, and they do not play a major role in defense during infections with most intracellular pathogens. That the B- and T-cell systems are functional (choice D) is not true. The DTH response certainly demonstrates that the Th1 response is functional, but it says nothing about the function of B cells. That the neutrophilic phagocyte system is functional (choice E) is not true. Neutrophils do not play a role in the elicitation of the DTH response. Neutrophils are the important cells in abscess formation, not granuloma formation.

A 42-year-old Nigerian man who is in the United States visiting with his brother comes into the hospital clinic. He complains of several months of weight loss, night sweats, mild sputum production, and the spitting up of blood. You run a PPD skin test and the results are positive. What can you conclude from this result? (A) A cell-mediated immune response has occurred (B) A humoral immune response has occurred (C) The B-cell system is functional (D) The B- and T-cell systems are functional (E) The neutrophilic phagocyte system is functional

The correct answer is D. An isograft is performed between genetically identical individuals. In human medicine, these are performed between monozygotic twins. In reality, even these "identical" individuals are not identical because minor mutations can occur during development. These sorts of grafts still require immunosuppression for success. They are, how- ever, the best chance for success other than autografts. An allograft (choice A) is a transplant between two members of the same species who are not genetically identical. These are the most common types of transplants used in medicine, but in this vignette, the twins are described as having identical MHC haplotypes. An autograft (choice B) is a transplant from one location in the body to another. This is the only form of transplantation that will succeed without immunosuppression. "Heterograft" (choice C) is not a word that is used in transplantation immunology. A xenograft (choice E) is a transplant that is performed across species barriers.

A 42-year-old auto mechanic has been diagnosed with end-stage renal dis- ease. His twin brother is HLA identical at all MHC loci and volunteers to donate a kidney to his brother. What type of graft transplant terminology is correct in this situation? (A) Allograft (B) Autograft (C) Heterograft (D) Isograft (E) Xenograft

The correct answer is D. CD25-positive TReg cells have been shown to have a role in maintenance of self-tolerance, and therefore, defects in these cells are being blamed in many cases of autoimmune disease. TReg cells secrete interleukin-10 which is an anti-inflammatory cytokine. Interferon-gamma (choice A) is a product of Th1 which activates mac- rophages and amplifies pro-inflammatory pathways in the body. It is not a product of TReg cells and would cause additional damage in a case of rheumatoid arthritis, so it would not be a logical goal of therapy. Interleukin-1 (choice B) is endogenous pyrogen which is responsible for the setting of the hypothalamic temperature point. It is a product of mac- rophages which activates Th1 cells, and therefore would be considered a pro-inflammatory cytokine rather than an anti-inflammatory one. Interleukin-2 (choice C) is a product of Th0 and Th1 cells which causes the proliferation of T cells and the effector cells of cell-mediated immunity. Although IL-2 is required for natural TReg development, it would not be expected to be increased with the therapy mentioned here. Transforming growth factor-beta (choice E) is a product of T cells and macrophages which is required for natural TReg development, but with this artificial therapy to increase TReg numbers, it would not be expected to be elevated.

A 50-year-old woman with severe rheumatoid arthritis is started on inflix- imab (anti-tumor necrosis factor-alpha). This therapy has been shown to increase the production of CD25-positive T cells. Which of the following is likely, therefore, to become elevated in this patient? Immunology Practice Questions (A) Interferon-gamma (B) Interleukin-1 (C) Interleukin-2 (D) Interleukin-10 (E) Transforming growth factor-beta

The correct answer is B. One of the most effective protective responses to infections with extracellular, encapsulated bacteria, such as Streptococcus pneumoniae, is complement-mediated opsonization. Because IgM is the most effective antibody at activating complement, generation of C3b frag- ments during this process coats the bacteria and makes them more suscep- tible to ingestion and intracellular killing by cells of the phagocytic system. ADCC (choice A), or antibody-dependent cell-mediated cytotoxicity, is a mechanism by which NK cells, neutrophils, macrophages, and eosinophils can use their Fc receptor to bind specific antibody and target an agent for lysis. No cells have Fc receptors for IgM, so this is not a mechanism that could act in concert with early IgM production. Cytotoxic T lymphocytes (choice C) identify altered-self/MHC class I mol- ecule conjugates on the surfaces of cells that are malignantly transformed or infected with intracellular pathogens. They are not a protective mechanism that acts in concert with any antibody molecule. LAK cells (choice D), or lymphokine-activated killer cells, are NK cells that have been stimulated in vitro with cytokines that enhance their killing activity. These cells have a function in early surveillance against altered-self cells, but are not believed to play a role in protection against extracellular pathogens, such as this one. NK cells (choice E) are members of the innate immune system and are believed to play a role in surveillance against tumor cells and other altered- self cells that fail to express MHC class I antigens on their surfaces. They would not act in concert with IgM production, and they would not be effec- tive against an extracellular pathogen, such as this one.

A 56-year-old homeless, alcoholic, and febrile man is brought to the emer- gency department after a difficult night during which his coughing kept everyone at the shelter awake. On arrival his pulse is rapid, and his breath- ing is labored with diffuse rales. Endotracheal aspirates produce a muco- purulent discharge containing numerous gram-positive cocci in chains. His serum contains high titers of IgM antibodies specific for the polysaccharide capsule of Streptococcus pneumoniae. The effector mechanism most likely to act in concert with this early IgM production to clear infection is (A) ADCC (B) complement-mediated opsonization (C) cytotoxic T lymphocytes (D) LAK cells (E) NK cells

The correct answer is A. IFNs of all types increase cellular expression of MHC class I and II products. Because CD8+ cells recognize their targets by MHC class I-dependent mechanisms, increases in the amount of these antigens on tumor-cell targets would increase susceptibility to cytotoxic killing. IL-1 (choice B) does not increase MHC class I molecule expression. The endogenous pyrogen is responsible for alteration of the hypothalamic tem- perature set point during acute inflammatory events. IL-2 (choice C) does not increase MHC class I molecule expression. It is produced by Th cells and causes proliferation of many classes of lympho- cytes. IL-10 (choice D) does not increase MHC class I molecule expression. It is a product of Th2 cells and inhibits Th1 cells; thus, it inhibits the cell- mediated arm of the immune response. TNF-α (choice E) does not increase MHC class I molecule expression. It may act directly on tumor cells to cause their necrosis and decrease angio- genesis. It is a product of Th1 cells that stimulates the effector cells of cell- mediated immunity.

A 6-year-old child from Zimbabwe is admitted to a U.S. oncology center for treatment of an advanced case of Burkitt lymphoma. Analysis of the malignant cells reveals that they are lacking MHC class I antigens on their surface. Which of the following cytokines produced by recombinant DNA technology could be injected into his solid tumor to increase this tumor cell's susceptibility to CD8+-mediated killing? (A) IFN-γ (B) IL-1 (C) IL-2 (D) IL-10 (E) TNF-α

The correct answer is E. The cortex of lymph nodes is a B-lymphocyte area. Thus, cells in this area would stain with fluorescent antibodies against CD19, the molecule that serves as a portion of the B-cell signal transduc- tion complex. This molecule would be found on all B cells, but would be absent from T cells, macrophages, and NK cells. CD2 (choice A) is a T-cell marker. T cells will be found in the paracortical areas of lymph nodes. CD3 (choice B) is a T-cell marker. It is the signal transduction complex of the T cell and will be found on all T cells. T cells will be found in the para- cortical areas of lymph nodes. CD4 (choice C) is a marker for helper T cells. These cells would be found in the paracortical areas of lymph nodes. CD16 (choice D) is the Fc receptor for IgG antibodies. It would be found on natural killer and phagocytic cells, which would not be numerous in the cortex of the lymph nodes. Phagocytic cells typically are found in the medullary cords.

A 6-year-old child is taken to his pediatrician because the parents are alarmed about an indurated fluctuant mass on the posterior aspect of his neck. The mass is nontender and shows no signs of inflammation. The child is examined carefully, and no other masses are found. The pediatri- cian decides to submit a biopsy of this area to a pathologist. The patholo- gist reports back that the mass is a lymph node with markedly increased numbers of cells in the cortical area. Fluorescent antisera to which of the cell surface markers is most likely to bind to cells in this area? (A) CD2 (B) CD3 (C) CD4 (D) CD16 (E) CD19

The correct answer is A. The killer cells cytotoxic to targets lacking MHC class I antigens are NK cells. These cells are members of the innate immune response, and as such their response is not enhanced over time. The most specific, inducible cytotoxic cells in the body are cytotoxic T lymphocytes (CTLs), which depend on MHC class I recognition of their target. Because this question asks how the tumor cells can be altered to make them better stimulators of an immune response, one approach would be to increase their expression of MHC class I molecules. This can be accomplished by treatment of the tumor cells with interferon (IFN)-γ. IFN-γ increases expression of both class I and II MHC products on cells. IL-2 (choice B) is a product of Th1 lymphocytes and induces proliferation of antigen-primed Th and cytotoxic T cells. It also supports their long-term growth. It would not have an effect on this patient's tumor cells. IL-8 (choice C) is a product of macrophages and endothelial cells and acts on neutrophils to cause their chemotaxis and extravasation into tissues. It would not have an effect on this patient's tumor cells. IL-10 (choice D) is a product of Th2 cells and acts on macrophages to sup- press their cytokine production. It therefore indirectly reduces cytokine production by Th1 cells and dampens the activation of the cell-mediated arm of the immune response. It would not have an effect on this patient's tumor cells. TNF-β (choice E) is a product of macrophages and NK cells and acts on tumor cells to cause direct cytotoxicity. It acts on inflammatory cells to induce cytokine secretion and causes the cachexia associated with chronic inflammation. It would not cause the patient's tumor cells to stimulate better immunity.

A 62-year-old accountant develops a solid tumor that is unresponsive to chemotherapy. He elects to participate in an experimental treatment pro- tocol to stimulate his own immune effector cells to recognize and kill the malignant cells. The tumor cells are found to have no expression of MHC class I antigens. Which of the following in vitro treatments of his tumor cells is likely to stimulate the most effective immune response when rein- fused into the patient? (A) IFN-γ (B) IL-2 (C) IL-8 (D) IL-10 (E) TNF-β

The correct answer is D. The transport of IgA dimers from the abluminal side of the mucosa to the lumen is mediated via attachment to polyimmunoglobu- lin receptors on mucosal cells. This allows endocytosis of IgA into the mucosal cell and secretion onto the other side. Secretory IgA found in the lumen of the bowel retains a residue of this receptor, secretory component, which further protects it from proteolytic cleavage inside the intestine. If this receptor were lacking, transport of IgA across the mucosa would not be possible, and the IgA dimers would be trapped on the abluminal side of the mucosa. Failure of isotype switching (choice A) is not a potential cause of such a con- dition because isotype switching occurs in secondary lymphoid organs and not in epithelial cells. Because the IgA dimers were present, isotype switch- ing had been successful, but transepithelial transport was not occurring. Failure of variable domain gene segment rearrangement (choice B) is not a potential cause of such a condition because variable domain gene-segment rearrangement occurs in the primary lymphoid organs and not in epithe- lial cells. Because immunoglobulin was being produced, these gene segment rearrangements had occurred successfully, but transepithelial transport was not occurring. Loss of J chain synthesis (choice C) would result in the inability of an indi- vidual to join dimers of IgA and pentamers of IgM. Because the question states that the individual was making IgA dimers, J chain is clearly being made successfully by the B cell. Loss of Th2 cells (choice E) would cause the patient to be unable to switch isotypes. These persons could make only IgM, and this patient clearly has successfully produced IgA.

A 64-year-old man undergoes surgery to excise 18 inches of bowel with adenocarcinoma. When the tissue and draining mesenteric lymph nodes are sent for pathologist's examination, the Peyer patches are noted to be hyperplastic with IgA-secreting plasma cells, but there is no secretory IgA found in the lumen of the colon. Which of the following changes in the bowel epithelium could explain this finding? (A) Failure of isotype switching (B) Failure of variable domain gene-segment rearrangement (C) Loss of J chain synthesis (D) Loss of the polyimmunoglobulin receptor (E) Loss of Th2 cells

The correct answer is A. The spleen is the secondary lymphoid organ that is responsible for primary surveillance against blood-borne antigens. Babesia microti is an intraerythrocytic parasite of humans, transmitted by the same vector tick as Lyme disease. Red blood cells (and their parasites) are filtered by the spleen, so splenectomy is a predisposing factor in devel- opment of serious disease with this parasite. Bordetella pertussis (choice B) is a mucosal surface pathogen that attaches to the upper airways. Although its toxin becomes blood-borne, the organ- ism itself is confined to the respiratory tree. Corynebacterium diphtheriae (choice C) is a mucosal surface pathogen that attaches to the upper airways. Although its toxin becomes blood-borne, the organism itself is confined to the respiratory tree. Enteroaggregative Escherichia coli (choice D) is an organism that causes diarrhea by producing a biofilm-like aggregation of organisms on the sur- face of the colonic mucosa, which impedes absorption. It is not likely to be a blood-borne pathogen. Human papilloma virus (choice E) produces localized infections in epithe- lial cells where it is transferred by human-to-human or human-to-fomite contact. It is not likely to be a blood-borne pathogen.

A 65-year-old woman was involved in an automobile accident that necessi- tated the removal of her spleen. To which of the following pathogens would she have the most increased susceptibility? (A) Babesia microti (B) Bordetella pertussis (C) Corynebacterium diphtheriae (D) Enteroaggregative Escherichia coli (E) Human papilloma virus

The correct answer is C. The lowest stimulation index (and the lowest amount of proliferation) is shown between sibling 1 and the prospec- tive recipient, both when the donor cells are used as stimulators and as responders. This means (most importantly) that the recipient will make little response to the graft and (less importantly, except in graft-versus-host disease) that the donor will make little response against the recipient. The father (choice A) is not the best choice of donors because the recipient makes 4 times the proliferative response to his cells as to those of sibling 1. The mother (choice B) is not the best choice of donors because the recipi- ent makes twice the proliferative response to her cells as to those of sibling 1. She would be the second-best choice, unless sibling 1 had an incompat- ible ABO blood group. Sibling 2 (choice D) is not the best choice of donors because the recipient makes 8 times the proliferative response to his cells as to those of sibling 1. Sibling 3 (choice E) is not the best choice of donors because the recipient makes 8 times the proliferative response to his cells as to those of sibling 1.

A child who requires a kidney transplant has been offered a kidney by both parents and 3 siblings. A one-way mixed lymphocyte reaction between prospective donors and recipient is performed, and the stimulation indices are shown. The stimulation index is the ratio of proliferation (measured by [3H]-thymidine incorporation) of the experimental group versus the nega- tive control group. Which of the prospective donors would be the best choice? (A) Father (B) Mother (C) Sibling 1 (D) Sibling 2 (E) Sibling 3

The correct answer is C. In this case, an attempt at postexposure prophy- laxis against tetanus is made by inoculating antitetanus immunoglobulin into the patient. When preformed immunologic products (immune cells or antibodies) are given to a patient, the procedure provides passive protection that is rapid but lacks immunologic memory. Because it is being adminis- tered in a medical setting, it is by definition artificial. Adaptive (choice A) immunity describes all immune responses that have specificity and memory. These immune responses are produced by specific B and T lymphocytes. Because this patient is being given a product of the adaptive immune response (antibodies), there will be no elicitation of an adaptive immune response in this individual. Artificial active (choice B) immunity is produced during the process of vac- cination. The patient is exposed to a modified pathogen or product. As a result, an active immune response to that inoculation is made. This sort of immunization causes the development of memory in the patient. Natural active (choice D) immunity would result after a recovery from an infection. Natural passive (choice E) immunity is acquired across the placenta and in the colostrum and breast milk, from mother to child. The child receives preformed antibodies (IgG across the placenta and IgA in milk), which serve to protect the child until a natural active immune response can be mounted.

A city sanitation worker is struck by a car and his leg is crushed against his sanitation truck. The extreme trauma to the leg necessitates amputa- tion above the knee. Although the patient's health records reflect a tetanus booster 6 years ago, the man is revaccinated and human, pooled antitetanus immunoglobulin is injected around the macerated tissue. Administration of immunoglobulin is an example of which of the following forms of immunization? (A) Adaptive (B) Artificial active (C) Artificial passive (D) Natural active (E) Natural passive

The correct answer is D. If the child is developing hemolytic disease of the newborn, then his erythrocytes will already be coated with maternal anti- Rh antibodies. Adding Coombs serum (antihuman gammaglobulin) to the baby's RBCs then will cause agglutination. This is the direct Coombs test. Mother's serum plus RhoGAM plus Coombs reagent (choice A) is not a set of reagents that will accomplish any diagnosis. RhoGAM is anti-RhD immunoglobulin, which is given to Rh- mothers at the termination of any Rh+ pregnancy. If the mother is sensitized, she is making IgG antibodies of the same specificity. Adding these 3 reagents together would tell you noth- ing of the baby's condition. Mother's serum plus Rh- RBCs plus Coombs reagent (choice B) is not a set of reagents that will accomplish any diagnosis. If the mother is Rh-, she will not make a response to Rh- RBCs, and addition of Coombs reagent will accomplish nothing. RhoGAM plus Rh+ RBCs from the baby (choice C) is not a set of reagents that will accomplish any diagnosis. RhoGAM will bind to Rh+ RBCs from the baby by definition, but adding these reagents together would tell you nothing of the baby's condition. Rh+ RBCs plus mother's serum plus Coombs (choice E) is the set of reagents necessary for the performance of the indirect Coombs test. This is a test used to determine if the mother is making IgG anti-Rh antibodies, which could cross the placenta and harm a fetus. The question asks about the direct Coombs test, not the indirect.

A direct Coombs test was performed on a baby in its seventh month of gesta- tion. The mother has had trouble with two earlier pregnancies, and she has never received RhoGAMTM. The physician is concerned about the possibility of erythroblastosis fetalis. What ingredients would be necessary to perform this procedure? (A) Mother's serum plus RhoGAM plus Coombs reagent (B) Mother's serum plus Rh- RBCs plus Coombs reagent (C) RhoGAM plus Rh+ RBCs from the baby (D) Rh+ RBCs from the baby plus Coombs reagent (E) Rh+ RBCs plus mother's serum plus Coombs reagent

The correct answer is E. The paracortex of a lymph node is a T-cell- dependent area. If this area is lacking cellularity, then the patient has a deficiency of T lymphocytes. B-lymphocyte numbers could be normal or even elevated. The only B-cell marker on this list is CD19, the marker which is used clinically to enumerate B cells in the body. CD2 (choice A), also known as LFA-2, is an adhesion molecule found on T cells, thymocytes, and NK cells. In a person with a T-cell deficiency, there would be decreased numbers of cells bearing this marker. CD3 (choice B) is found on all T cells. It is also called the "pan-T" cell marker. In a person with a T-cell deficiency, there would be decreased numbers of cells bearing this marker. CD4 (choice C) is found on all helper T lymphocytes. In a person with a T-cell deficiency, there would be decreased numbers of cells bearing this marker. CD8 (choice D) is found on all cytotoxic T lymphocytes. In a person with a T-cell deficiency, there would be decreased numbers of cells bearing this marker.

A lymph node biopsy of a 6-year-old boy shows markedly decreased numbers of lymphocytes in the paracortical areas. Analysis of his periph- eral blood leukocytes is likely to show normal to elevated numbers of cells expressing surface (A) CD2 (B) CD3 (C) CD4 (D) CD8 (E) CD19

The correct answer is D. This is a case of DiGeorge syndrome, which is a congenital failure in the formation of the third and fourth pharyn- geal pouches. As a result, individuals with this defect have aplastic thy- mus and parathyroids and facial, esophageal, and cardiac malformations. Immunologically, the absence of the thymus will ultimately have global effects on the development of all T-cell-mediated immune responses. At birth, the child will have IgG antibodies that have been transplacentally transferred from the mother, but by 9 months or so after birth, these will be gone and IgM will be the only isotype of immunoglobulin present. Phagocytic killing will be normal until that point, although after all the maternal IgG is gone, opsonization of bacteria will no longer be possible. Antibody-dependent cell-mediated cytotoxicity of parasite targets (choice A) will be depressed in this child because eosinophil-mediated ADCC requires IgE antibodies, and these cannot be produced without T-cell help. Cellularity of splenic periarteriolar lymphoid sheaths (choice B) will be decreased in this child because these are T-cell-dependent areas of the spleen. Cytotoxic killing of virus-infected targets (choice C) will be depressed in this child because cytotoxic T cells will be absent, and only NK cells will be available for antiviral protection. The proliferative response to concanavalin A (choice E) will be depressed in this child because concanavalin A is a T-cell mitogen. If there are no T cells, there will be no proliferation in response to this mitogen.

A newborn is evaluated for immunologic function. He has a distortion of the shape of his mouth, low-set and malformed ears, and widely spaced eyes. Radiographically, there is evidence of cardiac malformation and absence of a thymic shadow. Which of the following parameters would be normal in this child? (A) Antibody-dependent cell-mediated cytotoxicity of parasite targets (B) Cellularity of splenic periarteriolar lymphoid sheaths (C) Cytotoxic killing of virus-infected targets (D) Generation of oxygen metabolites in phagocytic cells (E) Proliferative response to concanavalin A

The correct answer is E. The description of painful abdominal edema and edema in the oral mucosa are typical of hereditary angioedema. This is a genetic deficiency of complement C1 inhibitor. When this important control protein is missing, there is excessive use of the classic complement pathway components, especially C4. This causes abnormal inflammation along the mucosal surfaces. Abnormal superoxide anion production by neutrophils (choice A) would result in predisposition to infections with extracellular pathogens. Abnormal T-cell function (choice B) would result in predisposition to infec- tions with viral and fungal pathogens, not edema of the mucosal surfaces. Abnormal T-cell numbers (choice C) would result in predisposition to infections with viral and fungal pathogens, not edema of the mucosal sur- faces. Defective neutrophil chemotaxis (choice D) would result in neutrophilia and failure to produce pus and abscesses in response to extracellular bacterial invasion.

A patient has been hospitalized 3 times for painful abdominal edema and is complaining now of swollen lips. What will laboratory findings in this patient most likely include? (A) Abnormal superoxide anion production by neutrophils (B) Abnormal T-cell function (C) Abnormal T-cell numbers (D) Defective neutrophil chemotaxis (E) Reduced C4 levels

The correct answer is D. The cell surface marker that would be useful to identify NK cells is CD56. The cells that have the highest fluorescence with antibodies to CD56 are found in quadrant D of panel 1. Panel 1, quadrant A (choice A) contains the cells with maximum fluores- cence with antibodies to CD3. These would be T lymphocytes. Panel 1, quadrant B (choice B) contains the cells double-labeled with CD3 and CD56. Because CD3 is the pan-T-cell marker and CD56 is an NK-cell marker, there are no double-labeled cells in this case. Panel 1, quadrant C (choice C) contains the cells that have background fluorescence with both CD3 and CD56. These are non-T, non-NK cells, so they could be B lymphocytes or any other leukocyte. Panel 2, quadrant A (choice E) contains the cells with maximum fluores- cence with antibodies to CD3. These are T lymphocytes. Panel 2, quadrant B (choice F) contains double-labeled cells, which fluo- resce with both antibody to CD3 and antibody to CD20. Because CD3 is a T-cell marker and CD20 is a B-cell marker, there are no cells in this quadrant. Panel 2, quadrant C (choice G) contains the cells with background fluo- rescence with both antibodies to CD3 and CD20. These would be non-B, non-T cells and would contain some NK cells, but other leukocytes would be included here, so this is not the best choice. Panel 2, quadrant D (choice H) contains the cells with maximum fluores- cence with antibody to CD20, which is a B-cell marker.

A patient with Chediak-Higashi syndrome is analyzed for ability to mobi- lize NK cells into the peripheral blood. His peripheral blood leukocytes are treated with fluorescent-labeled antibodies to CD3, CD56, and CD20 before they are passed through a fluorescence-activated cell sorter. The computer-generated results of this process are shown. In which quadrant of which panel would the natural killer cells be found? (A) Panel 1, quadrant A (B) Panel 1, quadrant B (C) Panel 1, quadrant C (D) Panel 1, quadrant D (E) Panel 2, quadrant A (F) Panel 2, quadrant B (G) Panel 2, quadrant C (H) Panel 2, quadrant D

The correct answer is D. Because malignant cells are clonal in origin, all the cells in this patient's lymphoma should be producing IgM monomers of a single idiotype. Treatment with anti-idiotype antibodies plus complement, therefore, would specifically kill only malignant cells, and leave all other B lymphocytes unharmed. Anti-CD3 antibodies plus complement (choice A) would kill all T lympho- cytes in the body. This lymphoma is clearly of B-cell origin because it is bearing IgM monomers. Anti-CD19 antibodies plus complement (choice B) would kill all B lym- phocytes in the body. It would not specifically target malignant cells. Anti-CD20 antibodies plus complement (choice C) would kill all B lym- phocytes in the body. It would not specifically target malignant cells. Anti-m chain antibodies plus complement (choice E) would kill all mature and naive B cells and immature B cells that had completed VDJ rearrange- ment of their heavy chain genes. It would not be specific for malignant cells.

A patient with a B-cell lymphoma is referred to an oncology clinic for the analysis of his condition. The malignant cells are found to be producing IgM monomers. Which of the following therapeutic regimens is most likely to destroy the malignant cells and no others? (A) Anti-CD3 antibodies plus complement (B) Anti-CD19 antibodies plus complement (C) Anti-CD20 antibodies plus complement (D) Anti-idiotype antibodies plus complement (E) Anti-m chain antibodies plus complement

The correct answer is C. Graft-versus-host disease (GVHD) is primarily a manifestation of sensitization of transplanted T cells against recipient tissues. The killing of mucosal and other epithelial cells is largely mediated through recognition of MHC class I incompatibility by transferred cyto- toxic cells or their precursors. However, eventually, continuous priming by the host's own tissues will elicit immune responses at the level of all the cells of the immune system. Activated macrophages (choice A) are involved in the delayed-type hyper- sensitivity response, but are not stimulated by MHC incompatibility, so if they become involved in pathology, it has to be secondary to Th stimulation. Antibodies and complement (choice B) are not involved in GVHD. Because bone marrow is a cellular transplant, it is the cells inside it that start the problem, not accidentally transferred antibodies or complement. LAK (lymphokine-activated killer) cells (choice D) are believed to be involved in the rejection of bone marrow transplants by the recipient (host- versus-graft), but not in GVHD. NK cells (choice E) are believed to be involved in the rejection of bone marrow transplants by the recipient (host-versus-graft), but not in GVHD.

A patient with acute myelogenous leukemia (AML) undergoes irradiation and chemotherapy for his malignancy while awaiting bone marrow trans- plantation from a closely matched sibling. Six months after the transplant, the immune response appears to be reconstituting itself welluntil 9 months postinfusion, when symptoms of generalized rash with desquama- tion, jaundice, and bloody diarrhea begin to appear. A second, more closely matched bone marrow donor is sought unsuccessfully, and 10 months after the transfer, the patient dies. What is the immunologic effector mechanism most closely associated with this rejection reaction? (A) Activated macrophages (B) Antibodies and complement (C) CD8+ lymphocytes (D) LAK cells (E) NK cells

The correct answer is A. Tumor cells transfected with the gene encoding IL-3 would produce IL-3. This is a cytokine that acts on the bone marrow to cause production and mobilization of myeloid cells. The goal of such ther- apy would be to induce the production of antigen-presenting cells, which might increase the presentation of tumor-cell antigens to cells important in cell-mediated cytotoxicity. B lymphocytes (choice B) would not be mobilized by such a treatment. The cytokine that favors development of lymphoid precursors in the bone marrow is IL-7. NK cells (choice C) would not be mobilized by such a treatment. Although NK cells are granular, they are derived from lymphoid, not granulocyte/ monocyte, precursors. The cytokine that favors development of lymphoid precursors in the bone marrow is IL-7. Plasma cells (choice D) are produced in the secondary lymphoid organs and submucosa. IL-7, which stimulates lymphoid precursors in the bone marrow, would have an indirect effect on plasma cell production, but they are not mobilized from the bone marrow. T lymphocytes (choice E) would not be mobilized by such a treatment. The cytokine that favors development of lymphoid precursors in the bone marrow is IL-7.

A patient with advanced metastatic melanoma decides to join an experi- mental treatment protocol in the hope that it will cause regression of his tumor masses. Malignant cells are aspirated from several of his lesions and transfected in vitro with the gene encoding IL-3 production. The transfected tumor cells are then reinfused into the patient. Mobilization of which of the following cells from the bone marrow would be likely to result from this treatment? (A) Antigen-presenting cells (B) B lymphocytes (C) NK cells (D) Plasma cells (E) T lymphocytes

The correct answer is B. Many drug allergies, such as the one described here, are hapten-carrier immune responses. The drug is not large enough by itself to elicit an immune response (it is a hapten), but when it becomes covalently coupled to the body's own proteins (which act as carriers), the combined molecule becomes immunogenic, and a response against one's own tissues is elicited. Acting as a B-cell mitogen (choice A) is not correct. B-cell mitogens, such as pokeweed mitogen and lipopolysaccharide, cause polyclonal proliferation of B cells and elaboration of IgM antibodies. The drug allergy described here is not a polyclonal response, but a specific anti-altered-self response generated by T and B lymphocytes and production of antibodies. Acting as a provider of costimulatory signals (choice C) is not correct. The costimulatory signals required to activate B and T lymphocytes include CD28/B7 and CD40/CD40L interactions. These are additional interactions (beyond the specific recognition of antigen) required for the activation of B and T lymphocytes. Although these costimulatory signals would be involved in the evolution of this allergic response, the streptomycin does not serve as a costimulatory signal. Acting as a superantigen (choice D) is not correct. Superantigens are materials that crosslink the variable β domain of the T-cell receptor and the α-chain of class II MHC molecules. They induce activation of all T cells that express receptors with a particular Vβ domain. The result- ing T-cell mitogenesis causes overproduction of T-cell and macrophage cytokines and system-wide pathology. Toxic shock syndrome toxin-1 and Streptococcus pyogenes erythrogenic exotoxins act as superantigens. Acting as an immunogen (choice E) is not correct because streptomycin is not large enough to be immunogenic. Immunogens must be large enough to have at least two epitopes. It is only through binding to a larger carrier protein (the patient's own tissue proteins) that a hapten such as a drug can become immunogenic.

A rabbit hunter in Arkansas is diagnosed with ulceroglandular tularemia and treated with streptomycin. Within a week, he returns to the hospital. The tula- remic papule, lymphadenopathy, and bacteremia have resolved, but he has now developed a raised, itching skin rash and a fever. The drug was discontinued, and the symptoms subsided. What was the role of streptomycin in this case? (A) It acted as a B-cell mitogen (B) It acted as a hapten (C) It acted as a provider of costimulatory signals (D) It acted as a superantigen (E) It acted as an immunogen

The correct answer is E. Lymph nodes are designed to filter tissue fluids. Fluids entering the lymph nodes do so through the afferent lymphatics and are released into the subcapsular sinus. From there, fluids percolate through the cortex, into the medulla, through the medullary cords, and finally exit through the efferent lymphatics in the hilum. The cortex (choice A) of the lymph node is directly beneath the subcapsular sinus. It would be the second region of the lymph node to be exposed to the radioactive tracer. The cortex is a B-lymphocyte-rich area. The medulla (choice B) of the lymph node is rich in macrophages. It would not receive the radioactive fluid until it had passed through the cortex and paracortex. The paracortex (choice C) of the lymph node is a T-cell area. It lies between the cortex and the medulla and thus would receive the radioactive fluid after the cortical areas. Primary follicles (choice D) are found in the cortex of the lymph node. These are areas of active B-lymphocyte proliferation and cloning. They would receive the radioactivity after it left the subcapsular sinus.

A radioactive tracer dye is injected subcutaneously into the forearm of an experimental subject. What is the first area of the first draining lymph node that would develop significant radioactivity? (A) Cortex (B) Medulla (C) Paracortex (D) Primary follicle (E) Subcapsular sinus

The correct answer is D. The goal of this therapy is to provide an increased pop- ulation of activated antigen-presenting cells primed with tumor cell antigens so that these can be presented to the Th cells involved in stimulation of cell-mediated immunity. The Th1 cell is the first cell listed which would be activated by such a treatment. B lymphocytes (choice A) would not be stimulated by such treatment. B lymphocytes bind to and are activated by unprocessed (not cell-bound) antigens. Cytotoxic T lymphocytes (choice B) would be indirectly stimulated by this treatment. Cytokines secreted by the activated Th1 cells would have the effect of increasing the number and cytotoxic activity of killer cells. NK cells (choice C) would be indirectly stimulated by this treatment. Cytokines secreted by the activated Th1 cells would have the effect of increasing the number and cytotoxic activity of killer cells. Th2 cells (choice E) would be stimulated by this treatment, but this is not the major goal of such therapy. Th2 cells stimulate humoral immunity, which is not the most important protective mechanism against tumor cells.

A woman with advanced metastatic breast cancer undergoes a radical mastectomy, followed by irradiation and chemotherapy. After a 2-year remission, a metastatic focus appears, and she enrolls in an experimental treatment protocol. In it, a sample of her aspirated bone marrow is treated with GM-CSF, TNF-α, and IL-2, then pulsed with membrane fragments of her tumor cells and reinfused. Which of the following cell subpopulations is the most directly targeted by this treatment? (A) B lymphocytes (B) Cytotoxic T lymphocytes (C) NK cells (D) Th1 cells (E) Th2 cells

The correct answer is A. The direct fluorescent antibody test is used to detect antigens in the tissues of a patient. The enzyme-linked immunosorbent assay (choice B) is a test usually used to detect antibody production. It can be modified to detect antigen, but not from a tissue specimen such as this one. The indirect fluorescent antibody test (choice C) is used to detect antibod- ies being produced in a patient. It is not used for detection of microbial antigens. Radioimmunoassay (choice D) is generally used to detect antibodies in a patient. Western blot (choice E) is used to detect antibodies in a patient, not antigen.

A young woman is in the care of an infertility specialist for evaluation of her inability to conceive since her marriage 5 years ago. As a first step in her examination, cervical scrapings are tested for the possibility of undiagnosed infection with Chlamydia trachomatis, which could cause fallopian tube scarring. Which of the following diagnostic tests could be used to identify chlamydial antigens in this specimen? (A) Direct fluorescent antibody test (B) Enzyme-linked immunosorbent assay (ELISA) (C) Indirect fluorescent antibody test (D) Radioimmunoassay (E) Western blot

The correct answer is E. The cytokine most strongly associated with stimu- lation of production of lymphoid cells from the bone marrow is interleukin (IL)-7. IL-1 (choice A) is the endogenous pyrogen. It is produced by macrophages and acts on the hypothalamus to raise the temperature set point. It is asso- ciated with systemic inflammatory processes, but is not known to have an effect on lymphopoiesis. IL-2 (choice B) is a product of T cells that stimulates proliferation of T cells in the periphery. It is not known to have an effect on lymphopoiesis. IL-3 (choice C) is the cytokine that is most strongly associated with stimu- lation of myeloid cell precursors in the bone marrow. IL-6 (choice D) is a second endogenous pyrogen. It causes production of acute-phase proteins from hepatocytes and acts on myeloid stem cells in the bone marrow to induce differentiation.

A young woman with acute myeloblastic leukemia is treated with intensive chemotherapy and achieves remission of her symptoms. Because the prog- nosis for relapse is relatively high, a bone marrow transplant is undertaken in her first remission. Which of the following cytokines administered with the bone marrow cells would have the beneficial result of stimulating lymphoid-cell development from the grafted stem cells? (A) Interleukin (IL)-1 (B) IL-2(C) IL-3(D) IL-6 (E) IL-7

The correct answer is B. In this case, high-risk individuals are vaccinated with the serotype of influenza virus that is predicted to be most common in this flu season. This elicits an active immunologic response in the patient and is artificial by definition because it is being administered in a medical setting. This sort of immunization causes the development of memory in the patient that will protect for the whole season, but it requires approxi- mately two weeks for development of protection. Adaptive (choice A) immunity describes all immune responses that have specificity and memory. These immune responses are produced by specific B and T lymphocytes. Although adaptive immunity will be elicited in these patients, this is not the best answer because it is imprecise. Artificial passive (choice C) immunity is achieved when preformed immu- nologic products (immune cells or antibodies) are given to a patient. These procedures provide passive protection that is rapid but lacks immunologic memory. Because it is administered in a medical setting, it is, by definition, artificial. Natural active (choice D) immunity would result following recovery from an infection. Natural passive (choice E) immunity is acquired across the placenta and in the colostrum and breast milk, from mother to child. The child receives preformed antibodies (IgG across the placenta and IgA in milk) that protect the child until a natural active immune response can be mounted.

All residents of a Chicago nursing home are inoculated intramuscularly with an H3N2 influenza A preparation. The goal of this protocol is to stimulate which of the following types of immunity? (A) Adaptive (B) Artificial active (C) Artificial passive (D) Natural active (E) Natural passive

The correct answer is C. This patient has a T-cell lymphoblastic lymphoma. In his case, the malignant cell is "double-positive": it possesses both CD4 and CD8. In a normal individual, these would only be found as an early developmental stage in the cortex of the thymus. Once cells have rearranged their receptor genes and been subjected to positive and negative selection, the cells leaving the thymus will express one coreceptor or the other but never both. Bone marrow (choice A) would contain T lymphocyte precursors that are double negative: They will lack both CD4 and CD8. Peripheral blood (choice B) would have mature T cells that have differenti- ated into either helper (CD4+) or cytotoxic (CD8+) cells. There should be no double-positive T cells in the peripheral blood. Thymic medulla (choice D) is the location of maturing T cells ready to circulate into the bloodstream and peripheral lymphoid organs. It would have only single-positive cells. Splenic periarteriolar lymphoid sheaths (choice E) are the T-cell-depen- dent areas of the spleen. They would have fully committed helper (CD4+) or cytotoxic (CD8+) cells.

An 18-year-old member of a college soccer team is seen by a physician because of chest tightness and dyspnea on exertion. A 15-cm mediastinal mass is detected radiographically. Eighty percent of the white blood cells in the peripheral blood are small, abnormal lymphocytes with lobulated nuclei and scant cytoplasm. Immunophenotyping of the abnormal cells shows them to be CD4+ and CD8+. Where would such cells normally be found in the body? (A) Bone marrow (B) Peripheral blood (C) Thymic cortex (D) Thymic medulla (E) Splenic periarteriolar lymphoid sheaths

The correct answer is D. The leukemic cells are pre-B cells. They have rear- ranged their immunoglobulin genes to encode a m heavy chain. MHC class II antigens are expressed beginning at the pro-B cell stage, as are CD19 and CD20. CD34 is a marker for early lymphohematopoietic stem and progeni- tor cells, and it functions as a cell-cell adhesion molecule. These cells would also have expressed CD10, the common acute lymphoblastic leukemia anti- gen (CALLA), which functions as a metalloendopeptidase. Immature B cells (choice A) have accomplished both and heavy and light immunoglobulin chain rearrangements and therefore express IgM molecules on their cell surface. They would be Tdt-negative, CD19- and CD20-positive, MHC class II-positive, and CD34-negative. Lymphoid progenitor cells (choice B) would not have completed any of the gene rearrangements necessary to create an immunoglobulin molecule. They would be Tdt-negative, MHC class II-negative, CD19- and CD20-negative, and CD34-positive. Mature B cells (choice C) possess surface IgM and IgD molecules and are capable of responding to foreign antigen. They are Tdt-negative, MHC class II-positive, CD19- and CD20-positive, CD34-negative, and may express CD40. Pro-B cells (choice E) are rearranging their immunoglobulin heavy chain gene segments but have not yet completed the process. Therefore, they have no completed chains either cytoplasmically or on their cell surfaces. They would be positive for Tdt, MHC class II, CD19, and CD20.

An 8-year-old boy is diagnosed with acute lymphoblastic leukemia. Flow cytometry is used to determine the immunophenotype of the malignant cells. The patient's cells are evaluated with monoclonal antibodies for MHC class II, CD19, and CD34, and are found to have high levels of fluorescence with all of these markers. They also possess cytoplasmic m heavy chains. What is the developmental stage of these cells? (A) Immature B cell (B) Lymphoid progenitor cell (C) Mature B cell (D) Pre-B cell (E) Pro-B cell

The correct answer is B. This is a case of X-linked agammaglobulinemia or Bruton agammaglobulinemia. During the early 1990s, the gene responsible for this condition was cloned. The normal counterpart of the mutant gene encodes a protein tyrosine kinase (Bruton tyrosine kinase, Btk), which is important in B-cell signaling. When it is absent or altered, B lymphocytes are unable to progress beyond the pre-B cell stage in the bone marrow. Thus, the bone marrow becomes hypercellular, while the peripheral blood is lacking mature B lymphocytes. Persons with this condition are unable to mount a normal antibody response; therefore, symptoms appear after the disappearance of maternal antibodies, and susceptibility to extracellular, encapsulated pathogens such as Streptococcus pneumoniae and Haemophilus influenzae is profound. Adenosine deaminase deficiency (choice A) is an example of a severe com- bined immunodeficiency disease (SCID). When this enzyme is absent, toxic metabolites build up in B and T lymphocytes and cause a general failure of the immune response. It would have clinical manifestations of both B- and T-lymphocyte defects, and not exclusively B lymphocytes, as described in this case history. A defect of the SAP gene (choice C) is believed to cause X-linked prolifera- tive disease, in which uncontrolled T-cell proliferation follows infection with Epstein-Barr virus. SAP stands for SLAM-associated protein, and SLAM (signaling lymphocytic activation molecule) is a potent T-cell coactivator. Defect of the WAS gene (choice D) causes Wiskott-Aldrich syndrome, in which a defect in CD43 (a cytoskeletal protein) causes defects in T cells and platelets. Patients with Wiskott-Aldrich syndrome display a triad of signs: thrombocytopenia, eczema, and immunodeficiency. ICAM-1 deficiency (choice E) would cause defects of antigen recognition and activation of lymphocytes. ICAM-1 is an adhesion molecule in the immunoglobulin superfamily of genes and is bound by LFA-1 integrin.

An acutely ill, 2-year-old boy is hospitalized with Staphylococcus aureus pneumonia, which is treated appropriately. The patient's history indicates similar bouts of bacterial infections in the past. He had recovered unevent- fully from measles 6 months ago. Physical examination discloses scant tonsillar tissue and no palpable lymphadenopathy. Immunoelectrophoresis reveals subnormal levels of gammaglobulins. The nitroblue tetrazolium and chemiluminescence assays indicate normal phagocytic killing. Which of the following disorders is most likely responsible for this child's condition? (A) Adenosine deaminase deficiency (B) Defect of the Btk gene (C) Defect of the SAP gene (D) Defect of the WAS gene (E) ICAM-1 deficiency

The correct answer is C. The cell surface marker which is typically used to identify B lymphocytes is CD19. This is a component of the B-cell/signal transduction complex and thus will be found on all B cells. Treatment of IgG with papain yields two monovalent antigen binding (Fab) fragments and destroys the function of the Fc portion of the molecule. Immunoglobulin molecules that are disrupted this way lose their ability to cross-link the receptors on cells, to promote precipitation or agglutination, and to activate cells by providing a first stimulatory signal. Monoclonal anti-CD19 IgG (choice A) is a divalent antibody molecule that recognizes the signal transduction complex on B cells. Monoclonal antibodies can cross-link cell-surface receptors and cause capping, cell activation, and precipitation. Agglutination is usually accomplished using IgM because a very large molecule is needed to overcome the zeta potential (repulsive charge) of erythrocytes. If IgG is used, a second developing anti- body must be added. Monoclonal anti-CD56 IgG (choice B) is a divalent antibody molecule that recognizes a molecule found on NK cells. Because both arms of the mol- ecule are intact, it is capable of causing capping, cell activation, precipita- tion, and agglutination if a developing antiserum is added. Papain-treated anti-CD56 IgG (choice D) would not be used for the study of B lymphocytes because CD56 is a marker for NK cells. Pepsin-treated anti-CD19 IgG (choice E) is a divalent molecule possessing two Fab fragments joined together (F[ab′]2), and a fragmented Fc region. The F(ab′)2 portion of the antibody is capable of causing capping, cell activation, precipitation, and, with a developing antiserum, agglutination. Pepsin-treated anti-CD56 IgG (choice F) is a divalent molecule possessing two Fab fragments joined together (F[ab′]2) and a fragmented Fc region. Its specificity is for NK cells. Additionally, the F(ab′)2 portion of the anti- body is capable of causing capping, cell activation, precipitation, and, with a developing antiserum, agglutination.

An antibody preparation is being used in a laboratory protocol to study B lymphocytes. The preparation does not activate the cells or cause capping. It does not cause precipitation of its purified ligand, and it does not cause agglutination of latex beads covalently coupled to its ligand. Which of the following is the most likely antibody preparation? (A) Monoclonal anti-CD19 IgG (B) Monoclonal anti-CD56 IgG (C) Papain-treated anti-CD19 IgG (D) Papain-treated anti-CD56 IgG (E) Pepsin-treated anti-CD19 IgG (F) Pepsin-treated anti-CD56 IgG

The correct answer is D. This patient is showing signs of toxic shock syn- drome, caused by infection of the blister with Staphylococcus aureus and the resultant elaboration of the exotoxin TSST-1. This toxin acts as a superantigen, cross-linking the variable β region of the TCR to the α chain of the class II MHC molecule. This binds Th cells and APC together without the specificity of antigen recognition, and so clonal proliferation of T cells and production of IFN-γ leads to activation of macrophages. As a result, the macrophages over- produce the cytokines IL-1, IL-6, and TNF-α, which are toxic at high levels. It acts as an IL-1 homologue (choice A) is not true. IL-1 is produced by macrophages as a result of T-cell activation, but TSST-1 does not itself act as an IL-1 homologue. It activates B lymphocytes polyclonally (choice B) is not true. TSST-1 acts on Th cells to stimulate macrophage cytokines. It does not have a direct effect on B-cell proliferation. It activates complement (choice C) is not correct. TSST-1 does not have an effect on complement. It stimulates neutrophils (choice E) is not correct. Although neutrophils are stimulated during Staphylococcus aureus infection and produce IL-1, which causes fever, the mechanism of action of TSST-1 and other superantigens is not through neutrophil activation.

An elderly man with diabetes develops a blister on the heel of his foot, which becomes infected. Although nursing staff in the home where he is a resident clean and treat the wound with topical antibiotic ointment, he develops a fever and hypotension, and a desquamating rash spreads from the site of the original blister. How does the toxin responsible for his symp- toms cause these signs? (A) It acts as an IL-1 homologue (B) It activates B lymphocytes polyclonally (C) It activates complement (D) It cross-links MHC class II molecules to TCRs polyclonally (E) It stimulates neutrophils

The correct answer is D. To generate tumor-specific killer cells in vitro that would kill tumor cells transfected with an altered-self MHC class I gene, one would need to start with potential killer cells that use MHC I as a stimulatory signal. The only cytotoxic cell in the body that meets these criteria is the cytotoxic T lymphocyte (CTL). In panel I, increasing levels of fluorescence with antibody to CD8 are plotted as one moves to the right, and increasing levels of fluorescence with antibody to CD4 are plotted as one moves upward. Thus, the cells most strongly positive with CD8 are found the farthest to the right in quadrant D of panel I. Panel I, quadrant A (choice A) would contain cells that are CD4+ and CD8-. These would be helper cells, and they would not be cytotoxic to transfected tumor cells. Panel I, quadrant B (choice B) would contain cells that are double-positive for CD4 and CD8. These cells would be found as immature thymocytes in the thymus and not in the blood; thus, there are no double-labeled cells shown in this quadrant. Panel I, quadrant C (choice C) contains the cells that have only background levels of fluorescence with antibodies to CD4 and CD8. These would be nonhelper, noncytotoxic cells, so they could be B lymphocytes, NK cells, or any other peripheral blood leukocyte. Panel II, quadrant A (choice E) would contain cells which are strongly CD4+ and CD20-. These are helper T lymphocytes. Panel II, quadrant B (choice F) would contain cells positive for CD4 and CD20. Because CD4 is a Th cell marker, and CD20 is a B-cell marker, such cells do not exist and thus this quadrant is empty. Panel II, quadrant C (choice G) contains the cells that have only back- ground levels of fluorescence with antibodies to CD4 and CD20. These would be nonhelper, non-B cells, so they could be cytotoxic T lymphocytes, NK cells, or any other peripheral blood leukocyte. Although this quadrant clearly contains some of the cytotoxic cells that this question asks about, there are other cells present, so this is not the best answer. Panel II, quadrant D (choice H) contains the cells strongly positive for CD20 and negative for CD4. These are B lymphocytes.

An experimental treatment for melanoma involves in vitro stimulation of tumor-specific killer cells with tumor cells transfected with a gene for production of altered-self MHC class I molecules. As a first step, peripheral blood leukocytes from the patient are incubated with fluorescent-labeled antibodies against CD4, CD8, and CD20. The cells are then subjected to flow cytometry and separated into different populations based on their expression of these cell surface markers. In which quadrant would you find the cell subpopulation most likely to produce a beneficial anti-tumor response in this protocol? (A) Panel 1, quadrant A (B) Panel 1, quadrant B (C) Panel 1, quadrant C (D) Panel 1, quadrant D (E) Panel 2, quadrant A (F) Panel 2, quadrant B (G) Panel 2, quadrant C (H) Panel 2, quadrant D

The correct answer is A. Although the ablation of the thymus in early child- hood will ultimately have far-reaching consequences in the development of many immune responses, the immune surveillance of tumors is performed only by cytotoxic T cells and NK cells, and thus would be profoundly affected by this treatment. Although NK cell numbers would not be affected by loss of the thymus, in the absence of Th1 cell cytokines, they would not be able to increase in number in response to challenge. Other parameters that could be depressed include immune responses to intracellular pathogens and second- ary antibody responses. Depressed oxygen-dependent killing by neutrophils (choice B) would not be expected in this case because neutrophils are components of the innate immune response and function in the absence of T-cell help. Depressed primary response to soluble antigens (choice C) would not be expected in this case because the IgM response to many antigens is T-cell independent. It is class switching that would be impossible without T-cell help. Increased cellularity of lymph node paracortical areas (choice D) would not be expected in this case because the paracortex of lymph nodes is a T-cell area. Therefore, following thymic irradiation, decreased cellularity of these regions would occur. Increased tendency toward atopy (choice E) would not be expected in this case because atopic allergies are those that involve IgE antibodies and mast cells. IgE cannot be produced without T-cell help, so athymic individuals will have decreased tendency toward atopy. Immunology Practice Questions

Before 1960, children with enlarged thymus glands were frequently irra- diated to functionally ablate this organ, whose role was not yet known. Over the lifetime of such individuals, which of the following conditions was likely to develop? (A) Depressed immune surveillance of tumors (B) Depressed oxygen-dependent killing by neutrophils (C) Depressed primary response to soluble antigens (D) Increased cellularity of lymph node paracortical areas (E) Increased tendency toward atopy

The correct answer is C. The interaction between the TCR and MHC class I/ peptide conjugates is stabilized by the CD8 coreceptor. By downregulating the expression of MHC class I antigens on the surface of infected cells, the virus protects the infected host cell from killing by cytotoxic T lymphocytes. CD2 (choice A), also known as LFA-2, is an adhesion molecule within the immunoglobulin superfamily of genes. Its ligand is the integrin LFA-3. It is found on T cells and mediates attachment to other lymphocytes and anti- gen-presenting cells. It does not have a coreceptor role that would impact MHC class I-restricted killing. CD4 (choice B) is the coreceptor that stabilizes the interaction between MHC class II antigens and the TCR. It is thus important for helper T cells, not cytotoxic T cells. CD16 (choice D) is the Fc receptor involved in binding to immune com- plexes and promoting antibody-dependent cell-mediated cytotoxicity. It is not involved in the MHC class I-restricted killing by cytotoxic T cells. CD56 (choice E) is a cell surface marker found on NK cells. Its function is unknown. However, since NK activity is enhanced in the absence of MHC class I antigen expression, the downregulation of these molecules by herpes simplex 1 and 2 actually makes infected cells more susceptible to the NK cell form of lysis.

Herpes simplex viruses are extremely successful pathogens because they have a variety of immunologic evasion mechanisms. For example, both HSV 1 and 2 depress the expression of MHC class I molecules on the surface of infected cells. Which coreceptor's binding would be inhibited by this tech- nique? (A) CD2 (B) CD4 (C) CD8 (D) CD16 (E) CD56

The correct answer is D. IL-2, IFN-γ, and TNF-β are all elaborated by the Th1 cell. TNF-β can also be made by NK cells. In tuberculoid leprosy, the Th1 arm of the immune response is most active, resulting in a protective (but also damaging) cell-mediated response and a dampening of the anti- body response. In lepromatous leprosy, the patient has an overabundance of Th2 responses, causing the production of a nonprotective antibody response. Cytotoxic T lymphocytes (choice A) are an effector cell in the cell-mediated immune response. They do not elaborate many cytokines but produce cytotoxic molecules, which cause the destruction of specific target cells. Epithelioid cells (choice B) are modified macrophages. They are extremely secretory and may produce IL-1, IL-6, TNF-α, IFN-γ, and GM-CSF. They are prominent in granulomas, and their cytokines would be elevated in a patient with tuberculoid leprosy, but that was not the question. Macrophages (choice C), once activated, may produce IL-1, IL-6, TNF-α, IFN-γ, and GM-CSF. They are prominent in granulomas, and their cytokines would be elevated in a patient with tuberculoid leprosy, but again, that was not the question. Th2 cells (choice E) would be elevated during lepromatous leprosy. The cytokines they secrete include IL-4, IL-5, IL-6, IL-10, IL-13 and TGFβ. These cells are stimulators of the humoral immune response.

Human infections with Mycobacterium leprae express a spectrum of clinical presentations depending on the extent and expression of their immune response to the intracellular organism. On one end of the spec- trum, patients with tuberculoid leprosy produce an effective cell-mediated immune response, which is successful at killing the intracellular organisms and, unfortunately, produces tissue damage. Patients with tuberculoid leprosy have granulomas that have elevated amounts of IL-2, IFN-γ, and TNF-β. The immune cell responsible for this pattern of cytokine produc- tion is the (A) Cytotoxic T lymphocyte (B) Epithelioid cell (C) Macrophage (D) Th1 cell (E) Th2 cell

The correct answer is A. Isohemagglutinins are IgM antibodies that will agglutinate the RBCs of individuals with another blood type. They are believed to be made due to exposure to cross-reactive antigens found on the surface of normal gut flora organisms. Thus, a person of blood group A will produce isohemagglutinins that will agglutinate type B cells. If these antibodies are pretreated with pepsin, a divalent F(ab′)2 fragment and destruction of the Fc will result. A divalent fragment is capable of causing agglutination. Lysed (choice B) is not correct because it would require the integrity of the complement-binding regions of the IgM, which are found in the Fc, and the question stem does not provide complement in the mix. Phagocytized (choice C) is not correct because it would require an intact cell-binding region in the Fc, and the question stem does not provide phagocytic cells in the mix. Precipitated (choice D) would be the correct answer if the antigen in ques- tion were a soluble protein. Proteins precipitate when treated with specific antibodies, particles agglutinate. The two particles used in laboratory medi- cine are latex beads and erythrocytes. If neither of these is mentioned, then the student can assume that treatment would result in precipitation, not agglutination. Precipitation has exactly the same requirements as agglutina- tion: a divalent antigen-binding molecule. Unaffected (choice E) would be the correct answer if papain had been used to treat the isohemagglutinins. Because papain produces two monovalent Fab fragments, these are incapable of cross-linking antigen (whether solu- ble protein or particle), so neither agglutination nor precipitation would be possible.

IgM isohemagglutinins from an individual of blood group A are treated with pepsin. When the product of this reaction is added to group B eryth- rocytes, they will be (A) agglutinated (B) lysed (C) phagocytized (D) precipitated (E) unaffected

The correct answer is D. Although this vaccine is no longer in use because of the possible side effects of Bordetella pertussis inoculation, in this case the whole, killed bacteria served as an adjuvant. They increased local inflam- mation, thus calling inflammatory cells to the site and prolonging exposure to the immunogen, the capsular polysaccharide of Haemophilus. A carrier (choice A) is not correct because a carrier is a protein covalently coupled to a hapten to elicit a response. There is no mention in the ques- tion stem here that the polysaccharide is chemically coupled to the bacte- ria; it is stated that they are only mixed together. A hapten (choice B) is not correct because a hapten is a single antigenic epitope, and a whole, killed bacterium such as Bordetella has many epitopes. A mitogen (choice C) is not correct because mitogens are substances that cause the polyclonal activation of immune cells. The mitogens most common- ly used in clinical laboratory medicine are lipopolysaccharide, concanavalin A, and pokeweed mitogen. An immunogen (choice E) is not correct because the immunogen in a vac- cine is the substance to which the immune response is being made. Because the object of the Hib vaccine is to immunize against Haemophilus influen- zae, Bordetella pertussis bacteria cannot be the immunogen.

In 1988 a new childhood vaccine was developed to protect against epidemic meningitis by mixing Haemophilus influenzae type B capsular polysaccharide with whole, killed Bordetella pertussis bacteria. The function of the whole, killed bacteria in this vaccine was as a(n) (A) carrier (B) hapten (C) mitogen (D) adjuvant (E) immunogen

The correct answer is D. The protective response to the tetanus toxoid depends on production of antibodies that prevent the binding of the toxin. After repeated immunizations, the population of memory B cells is stimu- lated, which is the goal of such prophylaxis. Memory B cells may have IgG, IgA, or occasionally IgE on their surfaces serving as antigen receptors. That their receptors would have high avidity (choice A) is not true because avidity decreases with repeated booster inoculations. This is because IgM, which is the immunoglobulin of the primary immune response and is the receptor on mature naive B lymphocytes, is replaced in secondary and sub- sequent responses by isotype switching to other isotypes such as IgG or IgA or IgE. All of these molecules have less avidity than IgM because they have fewer combining sites than IgM. The secondary and subsequent responses should have increased affinity (goodness-of-fit of idiotype for epitope), but decreased avidity. That they would be large and highly metabolic (choice B) is not true because memory lymphocytes are usually small and in a resting phase of the cell cycle. Activated lymphocytes are large and highly metabolic. That they would have low levels of adhesion molecules (choice C) is not true because memory lymphocytes express high levels of adhesion mol- ecules. This allows them to migrate to areas of active inflammation where they can have maximum benefit in protection of the host. That they would have surface IgM (choice E) is not true because this would describe mature, naive B lymphocytes that have not met their antigen before. As soon as the primary response begins, isotype switching to other classes of immunoglobulin is directed by Th cells.

In a lifetime, a person may receive a dozen or more tetanus toxoid inocula- tions. When boosters are administered at 10-year intervals, which of the following would be true of the B lymphocytes that respond? (A) Their receptors would have high avidity (B) They would be large and highly metabolic (C) They would have low levels of adhesion molecules (D) They would have surface IgG, IgA, or IgE (E) They would have surface IgM

The correct answer is D. Coombs reagent is antihuman IgG. It is necessary in the direct and indirect Coombs tests because in those cases, one is looking for IgG antibodies that could be transported across the placenta to harm an unborn child. IgG is a much smaller molecule than IgM, and is not capable of agglutinating erythrocytes without the addition of a "developing" anti- body. In the ABO blood typing test, the important isohemagglutinins are of the IgM variety, capable of agglutinating erythrocytes by themselves because of their sheer size. The statement that all antibodies made in response to blood glycoproteins are IgG (choice A) is not true because isohemagglutinins against ABO blood group antigens are IgM. The statement that complement-mediated lysis is not important in ABO incompatibilities (choice B) is not true because isohemagglutinins of the IgM variety are extremely powerful activators of complement-mediated lysis. The agglutination tests here, however, do not use complement- mediated lysis as the indicator system. That Coombs serum identifies only anti-Rh antibodies (choice C) is not true. Coombs serum is antihuman IgG. It will bind to the Fc portion of any human IgG molecule, regardless of its antigenic specificity. The statement that the high titer of natural isohemagglutinins makes Coombs reagent unnecessary (choice E) is not true. It is the isotype of these antibodies (IgM) and the size of that molecule that allows agglutination to proceed without a developing antibody.

In both ABO blood typing and the Coombs test for detection of hemolytic disease of the newborn, agglutination of coated erythrocytes is a positive test result. Why is addition of Coombs reagent not a necessary step in ABO blood typing? (A) All antibodies made in response to blood glycoproteins are IgG (B) Complement-mediated lysis is not important in ABO incompatibilities (C) Coombs serum identifies only anti-Rh antibodies (D) IgM pentamers are large enough to agglutinate erythrocytes directly (E) The high titer of natural isohemagglutinins makes Coombs reagent unnecessary

The correct answer is E. The description in the vignette is a type I hyper- sensitivity reactionthe only type of hypersensitivity that can be mani- fested in minutes. These are IgE-mediated responses and are an important protective response against helminth parasites that migrate through the tissues. The Arthus reaction (choice A) is an example of a type III (immune complex-mediated) pathology. These hypersensitivities develop when anti- gen is added to pre-existing antibody and immune complexes are filtered out of the circulation in the small vasculature. Complement is activated in these locations, and the underlying tissue is damaged. In this vignette, the killing is occurring in the skin and is associated within minutes with sting- ing, itching, and urticaria. Contact dermatitis (choice B) is an example of a type IV (delayed-type) hypersensitivity response. After the sensitizing exposure, symptoms of this type of hypersensitivity will occur in 48 to 72 hours (not minutes, as described here). Passive cutaneous anaphylaxis (choice C) is an example of a type I hyper- sensitivity reaction, but it is used to diagnose these conditions using passive transfer of serum. It is not a mechanism of protection, but a diagnostic technique. Serum sickness (choice D) is an example of a type III (immune complex- mediated) pathology. These hypersensitivities develop when antigen is added to pre-existing antibody and immune complexes are filtered out of the circulation in the small vasculature. Complement is activated in these locations, and the underlying tissue is damaged. In this vignette, the kill- ing is occurring in the skin and is associated within minutes with stinging, itching, and urticaria.

In native Egyptian populations, children are exposed to the cercariae of the fluke Schistosoma mansoni in early childhood when they wade in irri- gation ditches throughout the Nile Delta. On first exposure, the cercariae penetrate the skin and become schistosomula, which enter the circulation and eventually mature in the mesenteric veins. On subsequent expo- sures, schistosomula are frequently killed within minutes by an immune response in the skin manifested by intense itching, stinging, and urticaria. What is this protective immune response a manifestation of? (A) Arthus reaction (B) Contact dermatitis (C) Passive cutaneous anaphylaxis (D) Serum sickness (E) Type I hypersensitivity

The correct answer is A. The condition described here is an immune complex-mediated pathology. When large amounts of antigen are added into a situation where there is pre-existence of a large amount of antibody, the precipitation of those complexes in the small vasculature causes a type III hypersensitivity response. The only syndrome on this list that also has a type III etiology is the Arthus reaction. Atopic allergy (choice B) is a type I hypersensitivity, mediated by IgE antibodies and mast cells. Although many parasitic diseases elicit IgE and ADCC by eosinophils, the question stem clearly stipulates the presence of IgG antibodies, so a type I hypersensitivity reaction is ruled out. Goodpasture syndrome (choice C) and transfusion reaction (choice E) are examples of a type II, cytotoxic antibody hypersensitivity response. In these cases, antibody binds to cells or tissues of the body and elicits complement activation in those locations. The result is a tissue- or organ-specific pathol- ogy, and not a systemic problem as described here. The tuberculin reaction (choice D) is a type IV hypersensitivity response. Delayed-type hypersensitivities are mediated by Th1 and Th17 cells and their mediators and have no contribution whatsoever from antibodies.

In the 1960s, it was quickly ascertained that Peace Corps workers sent to schistosome-endemic areas were exposed to massive initial doses of cer- cariae before any protective immunity existed. In these individuals, IgG antibodies developed in response to the developing worms, and when the adults began their prodigious release of eggs into the circulation, the patients suffered acute and potentially life-threatening symptoms of fever, edema, arthralgia, and rash. Which of the following is another condition that arises by a similar immunologic mechanism? (A) Arthus reaction (B) Atopic allergy (C) Goodpasture syndrome (D) Tuberculin reaction (E) Transfusion reaction

The correct answer is D. Alternative RNA splicing allows a mature B cell to attach either δ or m constant domains on a single idiotype that has been generated by germ-line DNA rearrangements. Allelic exclusion (choice A) refers to the expression of products of either parental chromosome type, but not both. This allows lymphoid cells to express only one type of antigen receptor (one idiotype) per cell and is essential to cellular specificity of action. Allelic codominance (choice B) refers to the expression of products of both parental chromosomes simultaneously. It is found in the expression of MHC class I and II products, but not in the expression of antigen receptors. Affinity maturation (choice C) refers to the increase of affinity (binding strength) of a population of antibodies over time during the development of an immune response. Because the affinity of an antibody is dependent on the goodness-of-fit of its idiotype for its antigen, isotype switching does not affect the shape of the idiotype and does not change the affinity of the molecule. Somatic hypermutation (choice E) is the phenomenon that allows affinity maturation to occur. It is the accelerated mutation of DNA coding within the hypervariable region that occurs during B-cell proliferation in response to antigenic stimulation. Again, the isotype of the antibody does not affect the shape of the idiotype, and this term refers to a process that changes the shape of the idiotype.

Isotype switching during B-cell ontogeny dedicates mature B cells to pro- duction of a single heavy chain isotype, except in the case of IgM and IgD, which can be expressed concomitantly. How is this expression of both iso- types simultaneously possible? (A) Allelic exclusion (B) Allelic codominance (C) Affinity maturation (D) Alternative RNA splicing (E) Somatic hypermutation

The correct answer is C. The only substance on the list that is chemotactic for neutrophils is IL-8. Other neutrophil chemotactic factors that might have been mentioned would include C5a, leukotriene B4, and formyl methionyl peptides. Complement component 3b (choice A) is not chemotactic for neutrophils. It acts as an opsonin, enhancing the phagocytosis of coated particles. Immunoglobulin G (choice B) is not chemotactic for neutrophils. It acts as an opsonin, enhancing the phagocytosis of coated particles. Myeloperoxidase (choice D) is not chemotactic for neutrophils. It is an enzyme in the lysosomes of phagocytic cells that generates toxic halide radicals intracellularly when exposed to its substrate, hydrogen peroxide. Tumor necrosis factor-α (choice E) is not chemotactic for neutrophils. It is produced by macrophages and is involved with the production of chronic inflammation and cytotoxicity.

It has been learned in animal experiments that there are advantages to elic- iting nonspecific inflammation at the site of inoculation of antigen toward the ultimate development of a protective immune response to that immu- nogen. Which of the following substances, if introduced with a vaccine, would serve the purpose of attracting a neutrophilic infiltrate into the area? (A) Complement component 3b (B) Immunoglobulin G (C) Interleukin-8 (D) Myeloperoxidase (E) Tumor necrosis factor-α

The correct answer is A. The B7 molecule on antigen-presenting cells binds to the CD28 molecule on T lymphocytes and serves as a costimulatory signal for their activation. If the tumor cells could be induced to express this costimulatory molecule, they would provide the important activating signal to the T cells. CD2 (choice B) is the molecule on T lymphocytes that binds to LFA-3 on antigen-presenting cells. If the tumor cell were induced to express CD2, it would bind to the complementary structure on macrophages and not activate the T cells. CD4 (choice C) is the molecule on T lymphocytes that stabilizes the inter- action of MHC class II and the TCR. If the tumor cell were induced to express CD4, it would not increase the tumor-specific response. CD28 (choice D) is the molecule on T cells that binds to B7. If the tumor cell were induced to express CD28, it would bind to the complementary structure on macrophages and not activate the T cells. LFA-1 (choice E) is the molecule on T cells that binds ICAM-1 on the antigen-presenting cells. If the tumor cells were induced to express LFA-1, it would bind to the complementary structure on macrophages and not activate the T cells.

It has been learned in several experimental systems that proliferation and differentiation of T lymphocytes in response to tumor cells is low because tumor cells lack the necessary costimulatory molecules for lymphocyte activation. If melanoma cells from a patient were induced to express these costimulatory molecules by transfection, production of an effective antitu- mor response might occur. Which of the following molecules would be the best candidate for transfection of tumor cells to achieve this end? (A) B7 (B) CD2 (C) CD4 (D) CD28 (E) LFA-1

The correct answer is D. The best markers for identification of B lym- phocytes are CD19, CD20, and CD21. CD19 and CD21 form a coreceptor complex during B-cell activation. The role of CD20 in B-cell activation is unclear, although it forms a calcium-ion channel. CD21 is also a receptor for the C3d component of complement and the Epstein-Barr virus. CD3 (choice A) is the signal transduction complex of T cells. It is found on all T cells in association with the T-cell antigen receptor. CD4 (choice B) is found on all helper T lymphocytes. CD8 (choice C) is found on all cytotoxic T lymphocytes. CD56 (choice E) is a marker for human natural killer cells.

The blood from an 8-year-old boy was analyzed by flow cytometry. The cells were treated with fluorescent-labeled antibodies to various cell surface mark- ers before they were evaluated by flow cytometry. Which of the following markers would identify the B lymphocytes in the sample? (A) CD3 (B) CD4 (C) CD8 (D) CD19 (E) CD56

The correct answer is C. In lepromatous leprosy, the activation of the Th2 arm of the immune response results in elicitation of those cytokines that stimulate production of antibody (IL-4, IL-5, IL-6, IL-10, IL-13 and TGFβ) and those that inhibit the development of the protective cell-mediated immune response (IL-4 and IL-10). Therefore, hypergammaglobulinemia is a frequent finding in lepromatous leprosy. Autoimmunity (choice A) may develop after infectious processes, but there is no evidence that stimulation of Th2 cells, by itself, causes autoimmune disease. Granuloma formation (choice B) would be decreased after exposure to these cytokines. Granulomas are an expression of the delayed-type hyper- sensitivity response, which is a function of Th1 cells. IL-10 and IL-4 would depress the Th1 response. Immediate hypersensitivity (choice D) requires sensitized mast cells and IgE antibodies. Although this result could occur in persons predisposed to atop- ic allergy, it is not the most likely result of stimulation with Th2 cytokines. Inflammation (choice E) is primarily mediated by substances released during tissue injury (leukotrienes, histamine, etc.) and the cytokines of activated macrophages (IL-1, IL-6, and TNF-α). It is not enhanced by Th2 cytokines.

There is evidence that the immunologic pathway that distinguishes the selection between the two polar forms of leprosy depends on the initial means of antigen presentation, as well as individual human differences in response. If early events of antigen recognition elicit production of IL-4, IL-5, IL-6, and IL-10, lepromatous leprosy is more likely to result, with the outcome of failure to mount a protective delayed-type hypersensitivity response. What differential characteristic of the lepromatous form is pre- dicted based on the fact of overproduction of IL-4, IL-5, IL-6, IL-10, IL-13 and TGFβ in lepromatous lesions? (A) Autoimmunity (B) Granuloma formation (C) Hypergammaglobulinemia (D) Immediate hypersensitivity (E) Inflammation

The correct answer is D. CD8+ lymphocytes, or cytotoxic T lymphocytes recognize their target cells by binding to MHC class I molecules containing altered-self peptides. The class I molecule is a two-chain structure, with one long α chain that passes through the cellular membrane and a shorter chain called β2 microglobulin that becomes associated with the α chain. A β2 domain instead of a β2 microglobulin (choice A) describes the class II MHC molecule. It is loaded with peptides by the endosomal (exogenous) pathway and is recognized by CD4+ T cells. Invariant chains (choice B) are found blocking the peptide-binding groove of the class II MHC molecule immediately after synthesis. These chains are digested away when the class II MHC is exposed to the contents of the phagocytic vesicles of macrophages, and the groove is loaded with peptides from the ingested particle. A peptide-binding groove (choice C) would be found in both class I and II MHC molecules and is therefore not the best answer. Two similar chains (choice E) would be found in the class II MHC mol- ecule. It is composed of an α and a β chain of similar lengths, both of which have transmembrane domains. The class II MHC molecule is loaded with peptides by the endosomal (exogenous) pathway and is recognized by CD4+ T cells.

Toxoplasma gondii is an intracellular parasite that lives inside phagocytic and nonphagocytic cells by generating its own intracellular vesicle. This may allow it to avoid recognition and killing by CD8+ lymphocytes, which require the presentation of foreign peptides transported into the endoplas- mic reticulum and loaded onto MHC molecules that have (A) a β2 domain instead of a β2 microglobulin (B) invariant chains (C) a peptide-binding groove (D) a single transmembrane domain (E) two similar chains

The correct answer is A. The mucosal-associated lymphoid tissues (MALT) are the major sites of synthesis of IgA. IgA is a dimeric molecule held together by a J chain similar to that used in IgM. As IgA is transported across the epithelial surface, it acquires the secretory component, which functions both in transepithelial transport and protection from proteolytic cleavage. A monomeric immunoglobulin that crosses the placenta (choice B) describes IgG. IgG is the major immunoglobulin of the blood and is pro- duced in lymph nodes and spleen, but less commonly in the MALT. A monomeric immunoglobulin bound by mast cells (choice C) describes IgE. IgE is the immunoglobulin that causes immediate hypersensitivity by virtue of its attraction to the Fc receptors of mast cells. It is not the major immunoglobulin produced in the MALT, although it may be produced there. A monomeric immunoglobulin that opsonizes (choice D) describes IgG. IgG is the major immunoglobulin of the blood and is produced in lymph nodes and spleen, but less commonly in the MALT. A pentameric immunoglobulin that activates complement (choice E) describes IgM. IgM is the major immunoglobulin of the primary immune response and is produced in lymph nodes and spleen, but less commonly in the MALT. Immunology Practice Questions

Up until the 1970s, tonsillectomies were routinely performed on children with swollen tonsils. This procedure has lost its widespread appeal as we have learned the important role of mucosal-associated lymphoid tissue (MALT) in the protective immune response. What is the major immuno- globulin produced by the MALT? (A) A dimeric immunoglobulin with secretory component (B) A monomeric immunoglobulin that crosses the placenta (C) A monomeric immunoglobulin bound by mast cells (D) A monomeric immunoglobulin that opsonizes (E) A pentameric immunoglobulin that activates complement