1. (3 Points) Asymptomatic HIV Infection Is a Phase During Chronic Infection with HIV During

1. (3 points) Asymptomatic HIV infection is a phase during chronic infection with HIV during which there are no symptoms of the infection and virus levels are relatively low. This is because a. seroconversion has occurred to generate antibodies that bind to and eliminate virus from the plasma and reduce viral load b. effector cytotoxic T cells have been generated that kill virally infected CD4+ cells and reduce viral load c. HIV causes the downregulation of surface MHC class I molecules on infected cells making them susceptible to killing by NK cells, which lowers virus levels d. the virus has entered a latent phase in infected T cells where its proviral DNA is integrated into the cell genome, but is not being transcribed so that few new viral particles are being made e. all of the above contribute equally to the reduction in viral loads during the asymptomatic phase

2. (3 points) A combination HIV vaccine approach is being prepared for a large scale immunization trial in Kenya. One component of the vaccine is a synthetic DNA plasmid containing an inserted cDNA coding for p24, a protein that makes up the internal viral capsid. With this approach, the investigators hope to generate a CD8-mediated immune response that will protect test subjects against possible HIV infection. The generation of a cytotoxic T cell response would most likely require that a. the plasmid be taken up by APC’s and p24 expressed intracellularly. The protein would be proteolyzed to peptides and some of these would be presented on the surface of the APC via MHC I molecules. b. the plasmid be taken up by cells (e.g., muscle) and p24 expressed and secreted. The protein would then be bound by B cells and also taken up by APC’s to be proteolyzed and presented on MHC II molecules to generate helper T cells. c. the plasmid replicate to high copy numbers in the injected cells to generate sufficient p24 gene product to cause cell death, generation of an inflammatory response and release of p24-derived antigenic peptides from the killed cell. d. For the generation of a cellular immune response, all of the above would need to occur.

3. (3 points) Inhibitors of HIV protease are currently in use in the clinic for the treatment of patients infected with HIV. These inhibitors can a. prevent the production of new HIV particles in cells that are already infected with the virus b. prevent the initial infection of a cell by an HIV virion c. prevent the reverse transcription of the viral genome in a cell infected with HIV d. block both the initial infection of a cell by an HIV virion and the replication of HIV within an already infected cell e. prevent the virus from entering a latent state within an infected cell 4. (3 points) Despite the efficacy of HIV protease inhibitors, they are never given alone, but are administered in combination with nucleoside reverse transcriptase inhibitors because a. protease inhibitors can block the fusion of viral envelopes with CD4 T cells, but do not prevent the assembly of new virions. b. protease inhibitors are effective only against circulating virus particles and have no effect on the replication of viruses already integrated into the host DNA. c. protease inhibitors actually stimulate rates of viral RNA reverse transcription unless a transcriptase inhibitor is also provided. d. resistance to single therapeutic agents arises rapidly due to the high mutation rates associated with viral replication.

5. (3 points) Frank was referred by his pediatrician to an allergy clinic due to persistent wheezing over a 2 week period. He was given an intradermal skin test to detect to which antigens he was allergic. Exposure to ragweed antigen generated a wheal and flare reaction within 20 minutes of its application. What initiated this wheal-and-flare reaction? a. The antigen bound to the surface of skin cells and then bound IgG molecules that activated complement resulting in the killing of the skin cells by ADCC and by phagocytic cells with Fc or complement receptors. b. The antigen was recognized by IgG molecules resulting in the formation of antigen- antibody complexes that fixed complement and stimulated a localized inflammatory response c. The antigen was taken up by macrophages and Langerhans cells in the skin and presented to effector TH1 T cells that secreted inflammatory cytokines that activated macrophages and recruited neutrophils d. The antigen was recognized by IgE molecules bound to the surfaces of local tissue masts cells that degranulated and released inflammatory mediators e. systemic anaphylaxis

6. (3 points) Paul is sensitive to poison ivy and suffers from contact dermatitis if the plant touches his skin. His good friend, Phil, suffers from X-linked agammaglobulinemia. What is the likelihood that Phil also will develop poison ivy sensitivity? a. Phil is less likely than Paul to develop a sensitivity to poison ivy since the elevated levels of IgM in his blood stream would react with the antigen making it unavailable to bind IgE b. Phil’s odds are much less than Paul’s since he cannot become sensitized to pentadecacatechol due to his inability to generate IgE c. Phil is much more likely that Paul to develop a sensitivity to poison ivy because his immune responses would be heavily skewed toward a TH2 response d. Phil is unlikely to develop a sensitivity to pentadecacatechol-modified protein antigens due to his inability to generate IgG and form antigen-antibody complexes e. Phil’s odds are the same as Paul’s since immunoglobulins do not play an important role in delayed hypersensitivity reactions.

7. (3 points) The incidence of an acute rheumatic episode (rheumatic fever) following streptococcal pharyngitis is 0.5-3%. Most major outbreaks occur under conditions of impoverished overcrowding where access to antibiotics is limited. Rheumatic heart disease accounts for 25-50% of all cardiac admissions internationally. The development of rheumatic fever is most closely related to which type of hypersensitivity reaction? a. Type I b. Type II c. Type III d. Type IV e. Type V

8. (3 points) Which type of an allergic reaction is most likely to cause rapid death by anaphylactic shock? a. allergic reactions mediated by T cells b. allergic reactions mediated by soluble immune complexes c. allergic reactions mediated by IgE d. a and b e. none of the above

9. (3 points) The reason why type I hypersensitivity reactions can occur seconds after an allergen enters the body in “sensitized” (previously been exposed to the allergen) individuals is: a. memory B cells that were generated during the first exposure to the allergen bind the allergen directly and this results in the rapid proliferation of plasma cells and production of antibodies and other mediators of inflammation b. IgE generated during the first exposure is bound tightly to the surface of mast cells and basophils and binds the allergen during the second exposure. This results in the crosslinking of FcR1 and the rapid release of histamine and other mediators of inflammation c. macrophages activated during sensitization engulf the allergen and rapidly release TNF- and other mediators of inflammation d. IgG molecules generated during the first exposure to the antigen remain in the circulation and bind the antigen rapidly during a second exposure forming immune complexes that activate complement e. the first exposure generates effector T cells that respond much more rapidly than naïve T cells resulting in the rapid release of IFN- and activation of macrophages upon subsequent exposures

10. (3 points) To determine if a patient was previously exposed to Mycobacterium tuberculosis, tuberculin (consisting of proteins from the bacterium) is injected intradermally. Forty-eight hours later, the site of injection is examined. A positive skin test for tuberculosis is a result of a. IgE-mediated hypersensitivity. b. Arthus reaction. c. delayed-type hypersensitivity. d. immune complex deposition. 11. (3 points) Would you expect newborns from mothers with multiple sclerosis to show symptoms of their mother’s disease? a. Yes, but only if the child is male since multiple sclerosis is X-linked b. Yes, because maternal IgG against myelin basic protein would appear in the blood of newborns c. Yes, because cytokines such as interferon- secreted by activated CD4 T cells can stimulate macrophages in the CNS of both the mother and infant d. No, because T cells do not cross the placenta e. Yes, but only if the mother and child share the MHC haplotyes that are found on the TH1 cells responsible for the mother’s disease.

12. (3 points) Inheritance of a HLA-DR -chain allotype with a lysine residue at position 71 and a glycine at position 86 increases the likelihood of a patient developing insulin-dependent diabetes mellitus (IDDM). This is most likely because a. the HLA-DR gene encodes glutamic acid decarboxylase, an autoantigen involved in the onset of IDDM. b. positions 71 and 86 occur in the antigen-binding groove of the MHC molecule, which could affect presentation of self antigens. c. the HLA-DR gene product shares epitopes with antigens present on the surface of the pancreatic  cells, which makes them susceptible to attack by cytotoxic T cells. d. patients with the HLA-DR polymorphism are more highly susceptible to bacterial infections, which can cause breaks in self tolerance.

13. (3 points) There is considerable support for the idea that infections contribute to the onset of autoimmune disease in genetically susceptible individuals. Which of the following is not likely to be a mechanism by which infections could contribute to autoimmune disease. a. antigens of the infectious agent resemble self-antigens such that B and/or T cells activated in response to the infection cross-react with self b. microorganisms, in the course of an infection, damage cells or tissues and release self- antigens that would normally be sequestered from the immune system c. activation of the innate immune system during an infection generates inflammatory cytokines that upregulate MHC class II expression on certain cells that don’t normally express MHC II. d. certain infectious agents skew the immune response selectively toward one dominated by TH2 T cells, which produce IL-4 at high levels and promote class switching in B cells to promote production of IgE anti-self antibodies. e. all of the above are reasonable mechanisms. Matching. (3 points each) For questions 14-16, match the case description with the most likely diagnosis from the list that follows the questions.

14. ____b____ A 32 year old pregnant female was seen in the obstetric clinic complaining of heat intolerance, weight loss, and fatigue. On examination, thyroid function tests showed undetectable thyroid-stimulating hormone (TSH), high levels of free T3 and T4 and positive TSH receptor antibodies. She gave birth to a normal female infant, with normal sized thyroid, but with high T3 and T4 levels. However, at 3 months of age, the baby had normal thyroid function.

15. ___c_____ A 21 year old woman presented with a 1 month history of double vision, difficulty swallowing and weakness in her upper arms. An IV injection of edrophonium, a short- acting cholinesterase inhibitor, completely abolished the neurological signs. Subsequent blood testing showed the presence of a high level of antibodies against the acetylcholine receptor.

16. ____d____ A 45 year old woman developed proteinuria and a skin rash. Serological examination identified elevated anti-nuclear and anti-dsDNA antibodies. A renal bioposy revealed glomerulonephritis, type I. Peripheral capillary walls contained dense protein-rich deposits which by immunofluorescence stained with IgM, IgG, lambda and kappa chains.

Choices for questions 14-16

a. Multiple sclerosis b. Graves’ disease c. Mysasthenia gravis d. Systemic lupus erythmatosus e. Rheumatoid arthritis

17. (3 points) Neisseria meningitides, a leading cause of bacterial meningitis in Africa, is an extracellular, encapsulated, pyogenic bacterium. If you were designing a childhood vaccine strategy to combat this infectious microorganism, what approach would you propose based on what you know about currently available vaccine strategies? a. The vaccine would contain a live, but attenuated strain of bacteria. b. The vaccine would consist of whole, heat or chemically killed bacterial particles. c. The vaccine would be a subunit vaccine that consists of purified capsular polysaccharides of the most prevalent strains. d. The vaccine would be a conjugate vaccine that consists of capsular polysaccharides coupled to a protein (e.g., toxoid). e. The vaccine would be a DNA vaccine consisting of cDNA’s coding for major bacteria metabolic proteins inserted into a bacterial plasmid. 18. (3 points) Treatment for Rh incompatibility involves the injection of IgG (e.g., Rhogam) that recognizes Rh proteins. Rhogam is injected shortly after the birth of the first child that is Rh incompatible with its biological mother. Which of the following molecular mechanisms best describes how Rhogam works? a. The IgG in Rhogam binds to maternal macrophages and inhibits the macrophage’s ability to present fetal Rh proteins. b. The IgG in Rhogam, when bound to fetal RBCs, binds to Fc receptors on maternal naïve B cells to inhibit their activation by fetal RBCs expressing Rh proteins. c. The IgG in Rhogam binds to the Rh proteins on maternal RBCs and masks the proteins so they will not be recognized by the fetal immune system d. The IgG in Rhogam binds to FcRs on dendritic cells and prevents the dendritic cells from presenting fetal Rh antigens e. None of the above explains how Rhogam works

19. (3 points) Due to concerns about bioterrorism, the government is again interested in stockpiling doses of vaccine against smallpox. This vaccine consists of live-attenuated vaccinia virus. “Live-attenuated” means that a. the virus was rendered inactive by treatment with heat or chemicals. b. the virus has been separated into components and only the antigenic components are used in the vaccine. c. the virus is unable to infect and grow in human cells, but can be grown in nonhuman cells. d. the virus can infect and proliferate in human cells to some extent, but is not very pathogenic. e. the virus has been generated by genetic engineering to contain genes coding for the surface proteins of a totally separate viral strain.

20. (3 points) The use of killed or inactivated viruses as vaccines has several advantages and disadvantages. Which of the following is an advantage of this approach? a. The vaccine generally does not have to be injected. b. Only small amounts of antigen are typically required. c. The immune response is primarily a cellular response rather than a humoral response. d. The vaccine can be administered often as a single dose or as few as two doses. e. The virus cannot undergo a mutational event that restores its pathogenicity.

21. (3 points) Individuals traveling to certain countries must be vaccinated against yellow fever, which is caused by a mosquito borne virus. A single administration of the vaccine affords long term protection. What is the most likely type of vaccine that is administered? a. a conjugate vaccine b. an inactivated (killed) virus c. a live, attenuated virus d. a subunit vaccine 22. (3 points) In the early 20th century, an estimated 1 in 20 children in the U.S. died from whooping cough caused by an infection with Bordetella pertussis. Vaccination against B. pertussis reduced the incidence of whooping cough more than 100-fold. The basis for the current vaccine is a. whole, killed bacteria b. a mixture of bacterial proteins including pertussis toxoid and one or more additional antigens c. a live-attenuated bacteria genetically engineered to lack a lipopolysaccharide required for pathogenicity d. a Bordetella capsular polysaccharide covalently linked to diptheria toxoid. e. the major cell surface antigen produced by recombinant DNA technology and purified from yeast cultures

23. (3 points) Children are routinely immunized for protection against infection with Streptococcus pneumoniae. A problem with infections with S. pneumoniae is the existence of multiple, antigenically distinct strains of the bacteria. What approach has been used to create a useful vaccine? a. A combination of polysaccharides from the most common strains have been linked to a toxoid and included in a single vaccine b. Several of the most common strains of the bacteria have been genetically engineered to lack the common virulence gene and are introduced together as a mixture of attenuated organisms c. a cell surface protein common to all strains of Streptococcus has been identified and used as a subunit vaccine d. rather than induce an antibody-mediated response, a cell-mediated immune response has been generated by immunization with a mixture of peptides derived from several Streptococcus surface antigens from proteins known to generate CTL responses.

24. (3 points) This year, the Centers for Disease Control declared the total eradication of rubella in the United States. Elimination of rubella was achieved by vaccination of children using which approach? a. immunization with a purified viral surface antigen (produced by genetic engineering) b. immunization with a split-virus preparation containing viral surface antigens, but no intact virions c. immunization with an inactivated or killed virus d. immunization with a live-attenuated rubella virus e. immunization with a conjugate vaccine composed of viral polysaccharides coupled to a toxoid 25. (3 points) The composition of the influenza vaccine for the northern hemisphere for winter of 2005-2006 has been decided. A trivalent vaccine containing the following has been recommended: 1) an A/New Caledonia/20/99(H1N1)-like virus, 2) an A/California/7/2004(H3N2)-like virus, and 3) a B/Shanghai/361/2002-like virus. Why are yearly vaccines recommended? a. influenza viruses readily undergo mutations causing multiple strains to arise that differ in their prevalence from year to year b. the influenza vaccine is composed of viral proteins so yearly booster shots are necessary to maintain immunity c. different viruses move from various animal hosts such as pigs or chickens to humans on a nearly yearly basis requiring new vaccinations each year d. the live-attenuated viral vaccine provides only short-term protection (5-6 months) and so must be administered yearly.

26. (3 points) A person with which of the following blood types would be most unlikely to mount an adverse transfusion reaction when receiving blood from an untyped or mismatched blood donor? a. O Rh- b. O Rh+ c. A Rh- d. AB Rh+ e. AB Rh-

27. (3 points) Chronic rejection is a serious problem that limits the length of time a transplanted organ survives in a recipient. Chronic rejection most likely arises due to a. recognition of mismatched ABO antigens on the surface of endothelial cells of the graft by pre-existing recipient antibodies b. generation of recipient antibodies against donor MHC class I molecules c. activation of recipient CD8+ T cells by donor APC’s presenting non-self peptides d. activation of recipient CD8+ T cells by recipient APC’s presenting peptides derived from donor MHC class I molecules.

28. (3 points) Even transplants between HLA-identical siblings require treatment with anti- rejection drugs. Tissue rejection in this case is primarily mediated by a. recognition of minor histocompatibility antigens on the surfaces of cells within the graft by recipient antibodies b. activation of recipient CD8+ T cells by peptides derived from minor histocompatibility antigens presented by MHC class I molecules d. activation of recipient CD4+ T cells by peptides derived from donor minor histocompatibility antigens taken up by recipient APC’s and presented on MHC class II molecules e. donor effector T cells attacking the host cells expressing peptides from minor histocompatibility antigens on the matching self-HLA molecules 29. (3 points) Graft-versus-host reactions differ from acute allograft rejections in that a. differences in minor histocompatibility antigens can affect acute allograft rejections, but are not important for graft-versus-host-reactions. b. acute allograft rejections, but not graft-versus-host reactions, primarily result from differences in major histocompatibility antigens c. acute allograft rejections primarily involve recipient T cells attacking the graft while graft-versus-host reactions involve donor T cells attacking recipient tissues d. matches between HLA antigens between donor and recipient are important for successful allograft transplant, but not necessary for a bone marrow transplant.

30. (3 points) Major advances in the survivability of grafted organs came with the discovery of cyclosporin A, a cyclic decapeptide derived from a soil fungus. Which of the following actions does not describe how cyclosporin A functions? a. to inhibit the target of cyclosporin A, calcineurin, cyclosporin A must first bind to cyclophilin b. treatment of a T cell with cyclosporin A inhibits activation of the transcription factor, NFAT c. treatment of a T cell with cyclosporin A inhibits the expression of IL-2 and the IL-2 receptor d. cyclosporin A inhibits the dephosphorylation of NFAT preventing it from translocating into the nucleus e. cyclosporin A binds the immunophilin FKBP to form a complex to bind to a protein kinase required for IL-2 function

31. (3 points) Autoimmune polyglandular disease results from defects in the autoimmune regulator (AIRE) gene. The characteristics of this rare disorder illustrate the importance of which of the following for the avoidance of autoimmune disease? a. negative selection of self-reactive T cells in the thymus b. requirement for co-stimulatory signals for the activation of naive T cells in response to nonself-peptides presented on self-MHC molecules c. negative selection of self-reactive B cells in germinal centers of secondary lymph nodes d. the induction of apoptosis in autoreactive B cells encountering soluble antigen e. the lack of expression of MHC class II molecules on non-immune cells

32. (3 points) The injection of a mouse with myelin basic protein (MBP) plus a potent adjuvant will cause paralysis. The symptoms of the disease can be transferred to a syngeneic mouse through the transfer of a. anti-MBP antibodies b. MBP-specific TH1 cells c. MBP-specific cytotoxic T cells d. activated macrophages 33. (3 points) Heterologous antibodies are used in passive immunization for the treatment of individuals exposed to venom from poisonous organisms. While they are successful for the neutralization of the poisons in the venom, their use runs the risk of causing a. development of anti-horse serum antibodies that cross-react with the patients own serum proteins b. development of anti-horse serum antibodies resulting in the deposition of antibody-antigen complexes that aggregate to the point that they fix complement and cause inflammation c. development of antibodies against horse red blood cells that cross-react with the patient’s red cells to cause autoimmune hemolytic anemia d. presentation of horse serum proteins to naive T cells causing a delayed-type hypersensitivity reaction

34. (1 point) Immune responses against alloantigens are termed a. alloreactions b. autoreactions c. isoreactions d. xenoreactions