The Immune Wars Part I

1. The Immune WarsPart I

2. General types of immunity Innate (aka non-specific) inborn pattern recognition Adaptive (aka specific, acquired) “learned” through exposure • exquisite specificity

3. Chapter 15 Innate Immunity Preview • First line of defense • Cells • Sensor system • Phagocytosis • Inflammation

4. First-line Defenses Physical barrier Antimicrobial chemicals Normal flora

5. Physical Barriers Skin • Sheets of tightly packed cells • Outermost layers are embedded with keratin (dry) • Cells continually slough off • Perspiration (salty) • Normal flora

6. Physical Barriers Mucous Membranes • Single layer of cells • Layer of mucus (traps particles, including microbes) • Often a mechanism to propel the mucus toward exit • (ex. mucociliary escalator, peristalsis)

7. Antimicrobial Chemicals • Lysozyme • Transferrin, lactoferrin • Gastric acid

8. The Cells of the Immune System

9. Cell Communication Surface receptors - “eyes, ears” Cytokines - chemical messengers; proteins released by cells that affect the behavior of other cells; “voice”

11. Cell Communication Surface receptors - “eyes, ears” Cytokines - chemical messengers; proteins released by cells that effect the behavior of other cells; “voice” Adhesion molecules - “hands”

12. Sensor Systems Toll-like receptors - surface receptors that allow cells to “see” molecules that signify the presence of microorganisms or viruses pattern recognition

13. Sensor Systems Toll-like receptors - surface receptors that allow cells to “see” molecules that signify the presence of microorganisms or viruses pattern recognition

14. Sensor Systems Thecomplement system- series of proteins that, when activated, result in destruction/removal of foreign material; cascade reaction C3 C5 • C3a + C3b  C5a + C5b “prepare for eating”

15. Sensor Systems Thecomplement system- series of proteins that, when activated, result in destruction/removal of foreign material; cascade reaction C3 C5 • C3a + C3b  C5a + C5b

16. Alternative Complement Systems

17. Sensor Systems Thecomplement system- series of proteins that, when activated, result in destruction/removal of foreign material; cascade reaction C3 C5 • C3a + C3b •  C5a + C5b

18. Sensor Systems Recognition of long double-stranded RNA • Signifies to a cell that it is infected with a virus • infected cell produces interferon Apoptosis = programmed cell death

19. Phagocytosis Macrophages Neutrophils (polymorphonuclear leukocytes, PMNs, polys)

20. Process of phagocytosis Chemotaxis Recognition and attachment • opsonins Engulfment (ingestion) • phagosome Fusion of the phagosome with lysosomes (forms a phagolysosome) Destruction and digestion Exocytosis

21. Specialized attributes of macrophages Fixed in tissue or routinely wander Clean up infection Long-lived (months) Can become activated • Specialized attributes of neutrophils First to migrate to site of infection Short-lived (days) Always have tremendous killing power

22. Specialized attributes of macrophages Fixed in tissue or routinely wander Clean up infection Long-lived (months) Can become activated • Specialized attributes of neutrophils First to migrate to site of infection Short-lived (days) Always have tremendous killing power

23. Inflammation Redness, pain, swelling, heat • Purpose: • Contain a site of damage • Localize the response • Restore tissue function • Factors that initiate the inflammatory response • Microbial cell products detected by toll-like receptors • Microbial surfaces (trigger the complement cascade) • Tissue damage

24. The Inflammatory Process • Pro-inflammatory cytokines released • Dilation of small blood vessels •  increased blood flow to the area • Leakage of fluids from vessels • Adherence of phagocytic cells to endothelial cells • Diapedesis Apoptosis - programmed cell death; does not trigger inflammation

25. Other responses Interferon Fever  metabolic rate;  response to invaders elevates temperature above optimum growth temperature of invader

26. Immune Wars Adaptive Immunity

27. Chapter16 Adaptive Immunity Preview • Characteristics of adaptive immunity • Lymphatic system • Humoral immunity • Antibody structure, function, classification, production (B cell activation) • Cellular immunity • T cell activation, function

28. Strategy of the Adaptive Immune Response Characteristics of adaptive immunity • Memory • Specificity • “Self” vs. non-self …..or harmless vs. danger “self” vs. dangerous non-self Antigen - Material to which an immune system mounts a response Development of the Response Effect step 1  step 2  step 3 finale

29. Strategy of the Adaptive Immune Response lymphocytes

30. Strategy of the Adaptive Immune Response • Extracellular antigens • Most bacteria • Toxins • Viral particles aka cell-mediated immunity (CMI) • Intracellular antigens • Viruses (inside a cell) • Intracellular bacteria • (Cancer cells)

31. Strategy of the Adaptive Immune Response

32. Strategy of the Adaptive Immune Response

33. Strategy of the Adaptive Immune Response

34. Strategy of the Adaptive Immune Response

35. Strategy of the Adaptive Immune Response

36. Anatomy of the Lymphoid System Lymphatic vessels Secondary lymphoid organs • Collect fluids, WBCs from the tissues • Where lymphocytes “hang out” to encounter antigens • Lymph nodes

37. P M lumen Anatomy of the Lymphoid System Lymphatic vessels Secondary lymphoid organs • Where lymphocytes “hang out” to encounter antigens • Lymph nodes • Spleen • Mucosal-associated lymphoid tissue • Peyer’s patches; M cells sample material in the intestine

38. Anatomy of the Lymphoid System Lymphatic vessels Secondary lymphoid organs • Where lymphocytes “hang out” to encounter antigens • Lymph nodes • Spleen • Mucosal-associated lymphoid tissue • Peyer’s patches; M cells sample material in the intestine • Skin-associated lymphoid tissue Primary lymphoid organs • Where lymphocytes develop • Bone marrow • Thymus

39. The Nature of Antigens • Proteins • Molecules w/ repeating identicalsubunits (ex. polysaccharides) • Epitopes/antigenic determinants 10-20 amino acids “antigenic” T helper cell dependent T helper cell independent

40. The Nature of Antibodies Magic bullet: bind antigen with high specificity Basic structure: Y-shaped molecule • Fab regions - antigen-binding regions • Fc region - “red flag” region

41. The Nature of Antibodies Structure and properties of antibodies Basic structure: Y-shaped molecule 200 a.a. 450 a.a. • Fab regions - antigen-binding regions • Fc region - “red flag” region • four protein chains - two heavy chains (H); two light chains (L) • variable region • constant region

42. Immunoglobulins = antibodies Immunoglobulin Classes (isotypes)

43. Protective outcomes of antigen-antibody binding

44. Protective outcomes of antigen-antibody binding

45. Protective outcomes of antigen-antibody binding

47. Clonal Selection and Expansion of Lymphocytes Basic principles are true for both B and T cells

48. Clonal Selection and Expansion of Lymphocytes Basic principles are true for both B and T cells Naïve lymphocytes -have a receptor, but have not “seen” antigen BCRs are membrane-bound antibodies ~1/2 billion naïve B cells, recognizing ~ 100 million different epitopes! Those that recognize “self” are eliminated during lymphocyte development

49. Clonal Selection and Expansion of Lymphocytes Basic principles are true for both B and T cells Activated lymphocytes - able to proliferate; have received confirmatory signals

50. Clonal Selection and Expansion of Lymphocytes Basic principles are true for both B and T cells Activated lymphocytes - able to proliferate; have received confirmatory signals