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Immunology Test #3 Review Questions Spring 2012 1. What are kinases? How do they (in general) regulate cell-signaling events? 2. What are phosphatases? How do they (in general) regulate cell-signaling events? 3. Differentiate between scaffolds and adaptors. Be able to give one example of each of these types of proteins, and to tell how each is involved in a specific cell-signaling pathway. 4. What are small G proteins? How are they activated…in general…? Be able to give one example of a small G protein, and to tell how it is involved in a specific cell-signaling pathway. 5. What is an SH2 domain? An SH3 domain? A pleckstrin homology domain? What do each of these domains bind to? Be able to give at least one specific example of a cell-signaling pathway (including names of molecules) that involves each of these types of domains. 6. What are ubiquitin ligases? Be able to discuss two different ways..including the pathways involved… in which these proteins can regulate an immune response. 7. Describe, with specific examples, two different ways in which immune response signaling pathways can be turned off, or at least down-regulated. 8. Be able to name and discuss the roles of each component of the T Cell and B Cell receptor complexes. 9. What is an ITAM? Where are the B and T cell receptor complex ITAMs located, and how do they get phosphorylated? 10. Discuss the role of ZAP-70 in T cell activation, including how ZAP-70 is recruited to the T Cell Receptor complex, how it is activated, and how it in turn activates other molecules (be able to name them). 11. What are the roles of CD4/CD8 co-receptors in T Cell signaling? How are they recruited to the T Cell Receptor complex? 12. How to Csk and CD45 regulate Lck activation? What does Lck do? 13. How are LAT and SLP-76 recruited to the TCR complex and then activated? What are their roles in cell signaling? 14. How is PLC- activated? Be sure to discuss the role of the TCR co-stimulatory molecule CD28 and PI3K in this process. 15. What reaction does active PLC-catalyze? 16. Discuss the series of cellular events by which increased levels of IP3 leads to the activation of NFAT 17. Discuss the series of cellular events by which DAG activates a small G protein that leads to the activation of part of the AP-1 transcription factor. 18. Discuss the series of cellular events by which DAG activates PKC-θ, and how that activation leads to the activation of both NFkB and the other half of the AP-1 transcription factor. 19. Name the components of the B Cell Co-receptor complex, and describe their roles in B Cell Signaling. 20. How are the Src family kinases (Blk, Fyn, Lyn) activated during B cell activation? What do they phosphorylate once they are activated? 21. How is the Syk kinase activated and what, in turn, does it activate (and how)? 22. Describe the roles of BLNK and Btk in B cell signaling. 23. How is PLC-activated in B cells? 24. Be able to compare and contrast B cell and T cell signaling. In what ways are they similar, and in what ways do they differ? 25. Be able to list a few other types of cells that use ITAMs for activation. 26. How does CTLA-4 regulate T cell function? 27. What are ITIMs? Give a few examples and tell their functions. 28. Be able to describe how cytokines of the hematopoietin family cause the activation of new gene transcription (give the cell signaling events). 29. Be able to describe how binding of Fas to its ligand causes apoptosis (give the cell signaling events). 30. Describe the intrinsic pathway of apoptosis. 31. Describe the roles of sentinels, protectors and executioners in apoptosis. 32. In which central lymphoid compartments do B and T cell development occur? 33. Be able to describe the order of rearrangements of the immunoglobulin genes, and to tell the status of the rearrangements in each B cell developmental stage. 34. What is allelic exclusion, and when does it happen? 35. How is somatic recombination temporarily turned off in the large pre-B cells? 36. What types of cells in the bone marrow are critical to the maturation of B cells, and why? 37. Be able to describe the roles of IL-7, FLT3, CXCL12 and SCF in B cell development. 38. When somatic recombination turns back on, why don’t heavy chains continue to rearrange? 39. What is isotypic exclusion and when does it happen? 40. What is the pre-B cell receptor? Be able to discuss its structure, and to tell how it signals the B cell. What is the result of its signaling? 41. How are E2A and EBF involved in B cell development? 42. How is Pax5 involved in B cell development? 43. Why do immunoglobulin light chains get several chances to rearrange, while heavy chains only get one? 44. What is receptor editing, and when does it happen? 45. Define clonal deletion, clonal anergy and clonal ignorance. How does each happen? Which of these cell types (deleted, anergic or ignorant) is of the most concern in terms of autoimmune responses? Defend your answer. 46. In what cellular compartment does T cell selection occur? 47. What are double-negative thymocytes? What three types of cells make up the double-negative lineage? 48. Be able to describe the normal development of T cells. 49. What are DN1 cells, and what cell surface markers do they display? 50. Describe the order in which the TCR undergoes somatic rearrangement, and to tell in which developmental stage each rearrangement occurs. Be sure to also be able to state the status of CD45, Kit, CD25 and CD4/CD8 on these cells. 51. Why can TCR light chains undergo multiple rounds of somatic rearrangement, while the heavy chains do not? 52. In which T cell stage is the pre-T-cell receptor expressed? Describe its structure and its role in T cell development. 53. The thymus can be divided into several compartments. Describe the migration of developing T cells through these compartments as they mature, and then undergo positive and negative selection. 54. Describe how positive and negative selection are thought to occur, and how the affinity hypothesis is involved. Make sure to discuss all cell types involved in positive and negative selection, and how selection determines the CD4/CD8 fate of developing thymocytes. 55. Describe how signaling through the T cell receptor and the pre-T-cell receptor determine thymocyte fate. 56. Describe the waves of production that occur during fetal and newborn development, and how each gives rise to a unique population of T Cells.