1. In the experiment done to identify TcR genes, what kind of genes isolated using their approach for the selection of clones would have produced electrophoretic patterns that did not vary between T cell clones? a. immunoglobulin genes b. CD3 genes c. hemoglobin genes d. complement genes e. all of the above (a-d)

2. Type I hypersensititivy can be initiated by exposure to peanut allergen. Predict the result of treating an allergic patient with injections with high concentrations of IgE Fc fragments. a. this treatment would have no effect b. this treatment would initiate mast cell degranulation c. this would stimulate anaphylactic shock d. this would diminish all mast cell degranulation regardless of antigen specificity e. none of the above (a-d) would occur

3. What role does a MAMP (microbial associated molecular pattern) receptor play? a. It activates negative selection in the thymus. b. It activates cells with pattern recognition receptors during the innate immune response. c. It activates the alternative pathway of the complement cascade. d. It blocks protein kinase activation. e. It regulates quorum sensing in bacteria.

4. Positive and negative selection occurs in the thymus in order to remove dysfunctional cells. What kinds of cells do these processes remove? a. cancer cells b. pre-T cells c. CD4+ cells d. CD8+ cells e. autoreactive and anergic T cells

5. Some infections down-regulate the expression of MHC on the surfaces of cells. These cells with reduced levels of MHC are detected and killed by: a. Th2 T cells expressing cytokines that support humoral immunity

b. Th17 cells that secrete IL17 c. Natural Killer (NK) cells

d. CD8 cytotoxic T cells

e. Macrophages stimulated by Th1 helper cells

1 6. What experimental result indicated to Peter Gorer that different strains of mice expressed different allelic forms of MHC on cells? a. The rejection of transplanted tissue in tail grafts b. The ability to generate antibodies against poly GAGA or GTGT repeats c. The ability of adsorbed rabbit anti-mouse erythrocyte antiserum to agglutinate RBCs from some strains and not others d. Immuno-precipitation of purified MHC proteins from hepatocytes e. Radioactive probe hybridization to different locations on a southern blot

7. The dual recognition phenomenon relates to two different molecular interactions that must occur for successful activation of T cells. These interactions are: a. Simultaneous recognition of peptide and MHC by the TcR

b. Sequential recognition of the peptide by two helper T cells c. Recognition of foreign peptide and co-stimulatory molecule

d. All of the above e. None of the above

8. What type of hypersensitivity is associated with the production of immune complexes that accumulate in the kidney? a. Type I

b. Type II c. Type III

d. Type IV e. Type V

9. Which of the following is not true of both MHC class I and MHC class II molecules? a. They present antigenic peptides to T cells b. They are expressed on antigen presenting cells c. They are synthesized and exported from the ER d. They are comprised of immunoglobulin-like domains e. The antigenic peptides they present are derived from endogenous cytosolic proteins

2 10. Processing exogenous antigen relies on the ______to prevent endogenous antigens from binding to class II antigen binding cleft (choose the letter with the appropriate word or phrase below)

a. the invariant CLIP protein

b. 2M protein c. MHC class I alpha chain

d. TAP e. Calmodulin

11. Which of the cell types listed below can routinely present both endogenous and exogenous antigen? a. macrophages

b. pre-T cells c. CD4+ cells

d. erythrocytes e. neuronal cells

12. The major histocompatibility complex (MHC) is one of the most polymorphic clusters of genes known. Predict an outcome in human populations that have reduced MHC polymorphism

a. They will be more resistant to new infections. b. These populations will have a more pronounced chemotactic response.

c. Larger humoral responses will result in these populations d. There will be potential “holes” in the immune response where specific antigens are not presented. e. There will be decreases in reproductive success.

13. Which of the following does not play a role in proper presentation of cytosolic intracellular antigens? a. MHC class I

3 b. Invariant chain

c. Beta-2 microglobulin d. Proteasome

e. TAP1 and TAP2

14. During negative selection in the thymus, what cellular function is activated to eliminate the 95-98% of the cells that fail?

a. These cells acidify their environment b. These cells accumulate in the lymph nodes

c. These cells apoptose d. These cells aggregate around the high endothelial veinules (HEV)

e. These cells abrogate TcR/MHC interactions

15. A UConn student (not in our immunology class) ignored the repeated emails regarding campus flu vaccine clinics, and ultimately came down with the flu during finals week. Which is true about the immune response to the flu virus infection?

a. MHC II would present the influenza virus antigen to Cytotoxic T cells, and this interaction would be stabilized by CD4.

b. MHC II would present the antigen to T Helper cells, and this interaction would be stabilized by CD8

c. Antibodies to the influenza virus would activate complement and render the student allergic to chicken soup

d. B cells would bind to MHC Class I molecules rendering them inaccessible to virus. e. None of the Above.

16. Which of the following characteristics makes Bacillus anthracis more virulent than closely related bacillus species in the soil? a. It is gram positive b. It is spore forming c. It contains a plasmid that encodes an exotoxin d. It quickly undergoes antigenic drift to evade an immune response e. It contains a protective antigen that cannot be recognized by antibodies

4 17. Which of the following strategies are used by infectious organisms to evade the host immune system? a. Release of soluble antigen to deflect immune responses to the pathogen b. Elicit granuloma formation to physically block access to the infection site by immune cells c. Down-regulation of MHC molecules d. Masking of the pathogen by adsorbed host cell proteins e. All of the above are used

18. How does the Plasmodium falciparum life cycle represent a challenge for successful production of a malaria vaccine? a. Sporozoites are resistant to CTL mediated killing b. b. Merozoites are resistant to antibody-mediated complement dependent killing c. The changing antigens associated with the different stages of the life cycle represent a “moving target” for effective immune protection d. All of the above (a-c) are true e. The mosquito vector injects an immunosuppressive protein that prevents effective f. anti-malarial immunity

19. A Rag 1 -/-/Rag 2 -/- “double knockout” mouse (that lacks functional Rag-1 and Rag-2 genes) would be unable to generate mature types of which of the following cells? a. B cells b. T cells c. Natural Killer Cells d. Macrophages e. a and b

20. Why was the smallpox vaccine successful in eradicating smallpox virus from nature? a. It prevented the spread of the virus to rats.

b. Since smallpox infection resulted in either death or life-long immunity, there was no human reservoir of infected patients

c. Smallpox only infects humans, so vaccination of an animal reservoir that might retain the virus was not necessary

d. Activation of smallpox immunity increased the fertility of those immunized, so the human population was selected to become more disease-resistant.

e. The B and C answers above are both correct

5 21. Why are mice that are defective in the production of one cytokine often apparently normal in the immune function? a. Cytokines can have redundant functions, so another cytokine can sometimes be substituted for the defective one. b. Cytokines are antagonistic, so the absence of a cytokine ensures a better immune response c. Cytokines are synergistic, so the absence of a cytokine protects the mice from a cytokine storm d. The answers above (a-c) are all correct

e. Cytokines have suppressive effects on brain function, so the absence of a cytokine will improve perception and avoidance of infectious pathogens

22. The hygiene hypothesis suggests that

a. Preventing exposure to microbial life will ensure fewer infections b. Routine administration of antibiotics will stimulate beneficial antibody responses

c. Selection within the human population of those with the most hygienic habits has decreased MHC polymorphisms

d. Exposure to environmental microbes during the early development of a functional immune response can result in a lower probability for autoimmune disease and hypersensitivities by shifting the balance in favor of a Th1-predominated response e. Exposure to sterilizing agents can alter endogenous protein antigenic structure and result in autoimmune disease

23. Activation of a classical complement cascade results in lysis of a nearby membrane because a. there is a membrane insertion of the membrane attack complex that forms

b. there is activation of apoptotic cascades c. there are changes in ionic distribution and hypotonic lysis

d. there is activation of serine proteases e. all of the above (a-d) are true

24. During T cell activation, a cascade of signaling events results in a phosphoinositol being cleaved into the active intermediates diacylglycerol (DAG) and inositol-1,4,5 triphosphate

6 (IP3) at the inner leaflet of the membrane by phospholipase C (PLC). Where does IP3 then exert its primary effect as it continues the progression of signals in the signal transduction cascade?

a. IP3 diffuses rapidly to the ER where it induces the release of calcium

b. IP3 directly activates protein kinase C (PKC) which activates NFB c. IP3 acts to dephosphoylate and activate NFAT

d. IP3 acts as a suppressor signal by blocking phosphorylation of p56lck to regulate activation

e. IP3 diffuses rapidly to the nucleus and acts as a transcription factor to turn on immediate genes

25. Which would be an appropriate method to measure the ability of a group of cells to mount a chemotactic response towards a particular chemoattractant? a. Boyden chamber assay b. ELISA c. Ouchterlony assay d. ELISPOT assay e. Western blot assay

26. Which of these proteins are NOT members of the immunoglobulin supergene family, and why? a. CD3 because it lacks the J chain that links members of the TcR together

b. IgM because it lacks kappa light chains c. CD4 because it is expressed on T cells

d.  (zeta), and  (eta) polypeptides of the TcR because they lack Ig-like domain structure e. CD8 because it is expressed on T cells

27. How might you verify that an individual had been successfully vaccinated with the flu vaccine? a. Use RT-PCR to measure antibody concentrations

b. Test for the total number of T cells in circulation c. Measure the ability of T cells from the vaccinated patient to kill influenza-infected target cells from a pig

d. Measure the presence of cells expressing an influenza-specific TcR using MHC class I multimers complexed with an influenza peptide e. All of the above would work

7 28. Peptide antigens generated in the cytosolic compartment (intracellular infection, e.g. virus) bind to____ MHC molecules for presentation to____ T cells. a. Class I; CD4+ b. Class II; CD4+ c. Class I; CD8+ d. Class II; CD8+ e. None of the above

29. What component of ZAS was probably responsible for the movement of neutrophils in the figure shown below (taken from “Chicken Soup Inhibits Neutrophil Chemotaxis” CHEST 2000; 118:1150–1157) a. The yeast extract-associated enzymes b. Serine proteases secreted by the neutrophils c. The chicken soup caused the chemotaxis as a foreign molecule d. The chicken soup provided nutrients essential for chemotaxis e. The zymosan activated serum included chemotactic fragments of complement proteins

30. Which of the following are molecular components that are required for efficient antibody- dependent cell-mediated cytotoxicity (ADCC)? a. complement proteins b. MHC I or MHC II recognition receptors c. CD28 d. Fc receptors e. Toll like receptors (TLRs)

Short answer questions:

31. What is the most common target of drugs? Give an example.

32. In the experiment to identify T cell receptor genes (Mac experiment) , what was the purpose of using the hydroxyappetite column?

8