1. Lecture 16 Allergy Hay fever 20% Asthma ~5%

2. Figure 10-1

3. (hives) Allergies 4 types of hypersensitivity reactions

4. Delayed-type hypersensitivity Immune complex disease

5. Type I hypersensitivity- mediated by mast-cell degranulation. Preformed granules contain histamine, heparin, TNF, chondroitin sulfate, neutral proteases, and other. Mucosal mast cell/Connective tissue mast cell

6. Figure 10-4

7. Figure 10-5 In granules Produced after activation

8. Histamine Binds to histamine receptors: H1, H2, H3-cell-type specific Binding to H1 on: endothelial cells (increased permeability); smooth muscle (contraction); mucosal epithelium (mucus secretion)

9. Mediators Neutral proteases activate Metalloproteases - remodeling of the extracellular matrix TNF- inflammation Lipid Mediators (PGD 2, LTC 4 ) - inflammation Chemokines (MIP-1  ) - chemotaxis of leukocytes Cytokines - Production of eosinophils, Th2 cells Proteoglycans, heparin and chondroitin - sequester mediators, and effect a timed release

10. Prostaglandins and leukotrienes PGD 2 - vessel dilation and permeability and chemoattractant for neutrophils LTC 4 - same as histamine, but 100x more potent - late response. Leukotrienes used to be called Slow Reacting Substance of Anaphylaxis - SRS- A

11. Biologic effects of mediators

12. Biological effects of Eosinophil mediators Late stage of an allergic response includes the recruitment of eosinophils and Th2 cells contrast with a DTH (type IV) response which includes infiltration of macrophages and Th1 cells

13. Eosinophils

14. Figure 10-9 part 1 of 2 Products released by eosinophils

15. Figure 10-10

16. Figure 10-12

17. Figure 10-14

18. Figure 10-16 FEV1 - the forced expiratory volume of air in one second

19. Figure 10-18

20. Systemic anaphylaxis

21. Use of adrenaline to counteract the effects of system anaphylaxis In anaphylactic shock, blood vessels leak, bronchial tissues swell and blood pressure drops, causing choking and collapse. Adrenaline (epinephrine) acts quickly to constrict blood vessels, relax smooth muscles in the lungs to improve breathing, stimulate the heartbeat and help to stop swelling around the face and lips (angioedema).

22. Asthma

23. Figure 10-22 part 1 of 2

24. Figure 10-22 part 2 of 2

25. Histopathology of bronchial asthma

26. Treatment of asthma

27. New therapy for asthma and allergy: blocking the Fc portion of IgE from binding to the Fc  R on mast cells

28. Ragweed Control Histamine Skin test for allergy

29. Food allergies

30. Type II hypersensitivity is caused by antibodies to altered cell-surface components

31. Figure 10-27

32. Type III hypersensitivity reactions (Arthus Reaction) Antibody-Antigen Complexes Critical mediators appear to be C5a-receptor and Fc  RIII--probably present on mast cells

33. Figure 10-31

34. Figure 10-29

35. Figure 10-32

36. Type IV hypersensitivity - Delayed-type hypersensitivity

37. Figure 10-34 Also, note time scaleWhat is missing from this scheme?

38. Figure 10-35

39. Figure 10-36

41. Figure 10-23