1. Immunology overview Kristine Krafts, M.D. September 16 , 2013

2. A hairy person (or someone who doesn’t mind being hairy) Dendritic cell

3. Dendritic cell • Hairy projections • Eats bugs • Presents antigens

4. An indiscriminate bully Natural killer cell

5. Natural killer cell • A brute • Indiscriminate killer • Part of innate immune • system Natural killer cell (top) killing infected cell (bottom)

6. A person who is always helpful Helper T cell

7. Helper T cell • Helps other cells do • their jobs • Recognizes MHC II • Part of adaptive • immunity

8. A highly trained, expert killer Cytotoxic T cell

9. Cytotoxic T cell • Deadly, accurate killer • Recognizes MHC I • Part of adaptive immune • system

10. An extremely productive person B cell

11. B cell • Turns into plasma cell • Makes antibodies • Part of adaptive immune • system

12. Someone who likes to eat Macrophage

13. Macrophage • Eats bugs • Presents antigen • Part of adaptive immune • system

14. Someone filled with toxic chemicals Neutrophil

15. Neutrophil • Eats stuff • Releases toxic stuff • Part of adaptive immune • system

16. A sick person Infected cell

17. Infected cell • Virus laden • Expresses MHC I • Gets killed by cytotoxic T • cell

18. Immunology Overview • Definitions • Cells • Lymphocytes • Antigen-presenting cells • Effector cells • Responses • The innate immune response • Capturing and displaying antigens • Cell-mediated immunity • Humoral immunity • Immunologic memory

19. Immunology Overview • Definitions

20. Definitions • Immunity = protection against infections • Immune system = collection of cells and molecules that defend us against microbes • Immune deficiencies → infections • Immune excesses → autoimmune diseases

21. Innate (Natural) Immunity • Always present (innate); doesn’t change over time • First line of defense when bugs come • Major components: • Epithelial barriers (skin, GI, respiratory) • NK cells • Complement

22. Adaptive (Acquired) Immunity • Second line of defense • More specific (adaptive) and powerful than innate • Major components: • Lymphocytes • Lymphocyte products • Two types of adaptive immunity: • Humoral immunity (mediated by antibodies) • Cellular immunity (mediated by T cells)

24. Immunology Overview • Definitions • Cells • Lymphocytes • Antigen-presenting cells • Effector cells

25. White Blood Cell Development

26. White blood cells

27. Immunology Overview • Definitions • Cells • Lymphocytes

28. Lymphocytes • Present in lymphoid organs and in blood • Groups • T-lymphocytes (grow up in thymus) • B-lymphocytes (grow up in bone marrow) • Each one has receptors for a specific antigen • Recognize millions of different antigens! • Diversity generated by: • rearrangement of antigen receptor genes • different joining of the gene segments • Gene rearrangement studies

29. Lymphocyte (could be B cell or T cell!)

30. Lymphoid tissues • Lymphocytes grow up in primary organs, then travel to secondary organs, searching for antigens. • Primary organs • thymus • bone marrow • Secondary organs • lymph nodes • spleen • mucosal and cutaneous lymphoid tissues

31. Lymph node Follicle Interfollicular area (brown)

32. T-Lymphocytes • Live in blood, bone marrow, lymphoid tissues • Two basic functions: • kill stuff • help other cells do their jobs • T-cell receptor (TCR) complex recognizes antigens • binds antigen • sends signals to the T cell • Antigens must be: • displayed by other cells… • …AND bound to an MHC receptor

33. The T-Cell Receptor

34. The T-Cell Receptor Bound to Antigen Antigen-presenting cell T cell

35. T-Lymphocytes • Helper T cells • CD4+ (and CD8-) • help B cells make antibodies • help macrophages eat bugs • Cytotoxic T cells • CD8+ (and CD4-) • kill virus-infected cells and tumor cells

36. Helper T cell Cytotoxic T cell

37. Cytotoxic T cells surrounding tumor cell

38. MHC • Collection of genes on chromosome 6 • Three regions: class I, class II, class III • Highly polymorphic! • Gene products: • class I molecules • class II molecules • class III molecules (and other stuff) Major histocompatibility (MHC) complex

39. class II MHC genes class III MHC genes class I MHC genes class II MHC molecule class I MHC molecule

40. MHC • Encoded by three loci: HLA-A, HLA-B, HLA-C • Display antigens from within the cell (e.g., viral antigens) to CD8+ T cells. • Present on all nucleated cells! (Good idea.) Class I MHC molecules

41. MHC • Encoded by three loci: HLA-DP, HLA-DQ, HLA-DR • Display extracellular antigens (e.g., bacterial antigens the cell has eaten) to CD4+ T cells • Present mainly on antigen presenting cells, like macrophages! (Makes sense.) Class II MHC molecules

44. B-Lymphocytes • Live in blood, bone marrow, lymphoid tissues • Basic function: make antibodies (immunoglobulins) • B-cell receptor complex recognizes antigens • binds antigen • sends signals to T cells • Antigens can be free and circulating (don’t have to be bound to MHCs or displayed by other cells to be recognized!)

45. The B-Cell Receptor

46. The B-Cell Receptor Bound to Antigen B cell

47. Natural Killer Cells • Belong to innate immunity arm • No highly variable receptors like T and B cells • Main job: recognize and kill damaged or infected cells • Antigens can be free and circulating (don’t have to be bound to MHCs or displayed by other cells to be recognized!)

48. Natural killer cell

49. Natural killer cell (top) killing infected cell (bottom)

50. Immunology Overview • Definitions • Cells • Lymphocytes • Antigen-presenting cells