1. What is the function of HLA-DM? What is the cellular and molecular phenotype of HLA-DM deficient cells? What cells express HLA-DM?
2. Cheetahs were nearly hunted to extinct recently and consequently are genetically very similar (a genetic bottleneck), especially in their HLA loci. Please explain why cheetahs are highly susceptible to viral infections.
3. Compare and contrast how antigens are loaded for presentation by MHC Class I and II molecules in professional cells.
T Cell Receptor
4. In what ways is the generation of the T-cell receptor similar to the B-cell receptor? In what ways are they different?
5. Explain positive and negative selection in the thymus in conjunction with a discussion of co-receptor expression.
6. List three differences between the ?? T cell receptor and the ???
T and NK Cells
7. In cancer, although tumor-specific CD8 T lymphocytes are frequently found to have infiltrated the tumor, they often fail to show any capacity to kill the tumor cells in vivo. Suggest at least one pathway that you propose to be important to explain the ineffectuality of these tumor-infiltrating CD8 cells. What kinds of approaches may be used to obtain efficient tumor killing by such cells? (Hint: In some ways, cancerous cells are very similar to virally-infected cells.)
8. Some viruses encode in their genome an IAP gene, which is able to prevent host cell apoptosis when transcribed/translated. In immunological terms, why would viruses carry this gene?
9. Describe the mechanism by which T cells bind to an APC and recognize antigen. Include in your answer the role of TCR:MHC interactions, the role of other cell surface markers (like CD2, LFA-1, LFA-3, ICAM-1), and the role of CD3 .
10. Adaptive immunity relies on the ability of the immune system to recognize and respond appropriately to a limitless array of antigenic structures. Theoretically, there may be a price to pay for such a malleable and dynamic immune response: auto-reactivity. Describe two layers of protection T cells have evolved to control reactions against self antigens and innocuous environmental antigens. For each mechanism, describe the molecular and cellular process for how reactivity is prevented.
11. Draw a picture of an activated macrophage activating with TH0 cell.
12. How do NK cells detect the presence of an infected cell? What are the molecular consequences of this detection? In other words, how do the molecules secreted by NK cells kill the infected cell?
Cytokines
13. Why would people with a deficiency in IFNg be particularly susceptible to mycobacterial bacteria, which are known to reside in the cytoplasm of macrophages?
14. Superantigens are secreted bacterial or viral peptides known to strengthen the interaction between class II MHC molecules and TCRs, and in some cases even cause cross-linkage between MHC and TCR molecules. If in the periphery (re: not in the thymus), many superantigens promote the proliferation of TH1 cells. Why would an extracellular bacterium like Staphylococcus want to promote the development of Th1 cells? Detail the molecular and cellular pathways used in the generation of this response.
15. Explain T cell effector functions and the cytokines that drive development in each lineage. Explain how cytokines show pleiotropy and inhibitory functions.