“Immunology deals with understanding how the body distinguishes between what is self and

1. “Immunology deals with understanding how the body distinguishes between what is self and what is nonself; all the rest is technical detail.” (Benjamini et al.) The word immunity is derived from a Latin word meaning exempt from taxation

2. Historical perspectives on immunology Ancient Greece: if people recovered from the plague they didn’t catch it again 1718- Lady Montagu- variolation 1798- Edward Jenner Louis Pasteur (1800s)- vaccine design cholera (in chickens) anthrax (in sheep)

3. Von Behring and Kitasato, 1890 serum from immunized animals could be transferred to other animals and protect them (Kabat: immunoglobulin, 1930s) Metchnikoff, 1883- phagocytes could ingest microbes more phagocytes in immunized animals Chase, Glick, 1950s importance of lymphocytes

4. Lymphocytes are antigen-specific Why? Clonal selection theory (Jerne, Talmadge, Burnet, 1950s) is the prevailing paradigm

5. Clonal selection theory p. 15

6. Clonal selection theory T and B cells with different antigen specificities exist before they encounter antigen Lymphocytes have antigen-specific receptors on their surfaces Once receptor combines with antigen, the cells proliferate and differentiate into clones Somehow, cells that recognize self-antigens are prevented from developing

7. The immune reaction consists of two related activities: Recognition (of a specific foreign substance pathogen or antigen) Response that eliminates or neutralizes that substance memory- subsequent exposure to that substance leads to a faster, more intense response

8. What are the components of the immune response? There are many! Innate (non-specific; immediate) Acquired (adaptive)- specific, has memory

9. Components of innate immunity Prevent entry of pathogen Prevent growth of pathogen Kill the pathogen Eliminate pathogen and repair damage

10. p. 5

11. Ingestion by phagocytes p. 40

12. Introduction to inflammation p. 8

13. Vasodilationerythema (redness) and heat capillaries are more permeable Influx of fluid (edema) Influx of phagocytes, which release enzymes that kill cells. Pus is produced Various chemicals are produced in the inflammatory response- by the microbes, the damaged cells, plasma proteins, and immune cells

14. Acute-phase proteins (activate complement) Histamine (promotes vasodilation) Kinins- become activated and promote vaso- dilation Bradykinin- stimulates pain receptors Increase in capillary permeability allows blood-clotting proteins to enter tissue What cells act in innate immunity?

15. Hematopoiesis In bone marrow p. 25

16. Neutrophils Basophils Eosinophils Macrophages Natural killer cells

17. If “innate immune cells” are not antigen-specific, • how do they become activated? • Janeway, et al. proposes three mechanisms • (summarized Science 296, 2002) • Microbial nonself- cells detect conserved • sequences that are present on microbes but • not self (LPS, peptidoglycan) • costimulatory signal by antigen-presenting • cells (APCs) • 2. Missing self- ligands that are normally present • inhibit immune response. Example: MHC • class I

18. p. 333

19. Other structures signal different functions On senescent or apoptotic cell- targeted for phagocytosis Cell damage; necrosis- repair? Or does it induce an immune response (danger model)

20. Acquired immunity Unlike innate mechanisms, these have: Specificity Diversity Memory Self-nonself recognition Principal types of cells are lymphocytes and “antigen-presenting cells”

21. p. 11

22. Immunological molecules • Antigen receptors • Antibodies • Class I MHC molecules • Class II MHC molecules • Cytokines • Membrane-bound receptors • Plasma proteins • Adhesion molecules • Enzymes

23. MHC and antigen recognition p. 13

24. Requirement for antigen-presenting cells p. 14

25. Examples of antigen-presenting cells Macrophages Dendritic cells B cells

26. Acquired immunity: Clonal selection Proliferation Enhanced secondary response

27. p. 17

28. Components of immune activation: Antigen recognition Requirement of T cell help for B cell activation (Bretscher and Cohn) Requirement of costimulatory signals for T cells From antigen-presenting cells (APCs) APCs themselves may not be constitutively active

29. Danger model (first proposed in early 1990s; Matzinger and Fuchs) Activation signal may be damaged tissue or cells How does immune system continue to recognize “self” throughout development? Why do different types of immune responses occur in different tissues? Why are fetuses tolerated by the pregnant woman?

30. p. 12

31. p. 16, humoral response

32. p. 16, cell-mediated

33. Immunological molecules • Antigen receptors • Antibodies • Class I MHC molecules • Class II MHC molecules • Cytokines • Membrane-bound receptors • Plasma proteins • Adhesion molecules • Enzymes

34. p. 19

35. What happens when the immune system malfunctions? Allergy and asthma Graft rejection and graft-vs-host disease Autoimmune disease Immune deficiency