1. Type III hypersensitivity (immune complex)

2. Introduction Large amounts of immune complexes can lead to tissue damage, either in local sites or systemically, which mediated by activation of complements, neutrophils, basophils, and platelets.

3. APC TH2 B cell Sensitization for Type III hypersensitivity

5. Type III hypersensitivity mechanism

6. Antigen: Soluble antigens Antibodies: IgG, IgM, IgA Intermediate size immune complex

7. Effectors: 1.Complement 2.Neutrophils 3.Platelet 4.Mast cells

8. Conditions of immune complex formation 1.Size of immune complex 2.Tissue structures such as blood vessel walls, synovial membrane of joints, glomerular basement membrane.

9. not

10. Figure 10-32

12. Clinical diseases ： Localized ： Arthus reaction ， Arthus-like reaction Systemic ： Serum sickness ， streptococcal nephritis ， polyarteritis nodosa ， SLE

14. Development of a localized Arthus reaction

15. Arthus reaction Type-III Wheal & flare reaction Type-I

16. Serum sickness

18. Systemic lupus erythematosus Antigen involved : DNA, nucleoproteins, others Nephritis, arthritis, vasculitis

19. Post-streptococcal glomerulonephritis

20. Chronic infection by HBV

21. 21 Detection of immune complexes in tissue

22. Features of type III sensitivity ① Mediated by immune complexes ② Complement activation ③ Infiltrated by neutrophils, platelets, and basophils. ④ Tissue injury directly cause by lytic enzymes

23. Type IV hypersensitivity Delayed type hypersensitivity

24. 24 Type IV hypersensitivity ãDelayed reaction ã36 to 48 hours ãCharacterized by induration and erythema ãAlso known as cell mediated hypersensitivity ãTuberculin test is the most common example ãDelayed reaction ã36 to 48 hours ãCharacterized by induration and erythema ãAlso known as cell mediated hypersensitivity ãTuberculin test is the most common example

25. Introduction This occurs from 24 hour after contact with an antigen and is mediated by T cells together with dendritic cells, macrophages and cytokines characterized by induration and erythema. The persistent presence of the antigen e.g. chronic mycobacterial infections, results in granulomas. Skin contact with a number of small molecules (chemicals and plant molecules) can also result in delayed hypersensitivity.

26. APC Mechanism of damage in contact hypersensitivity TH1 NK MθMθ MθMθ LAK preTc Tc IL2, TNFα IFNγ IL2 TNFα IFNγ NO2

27. Figure 10-35 Numerous cytokines participate in the DTH reaction

28. The formation of a granuloma

29. Tuberculin test

30. Granuloma in a leprosy patient

31. contact dermatitis

32. Contact dermatitis reaction to mango sap

33. Contact dermatitis reaction to leather

34. Old Milwaukee helps?

35. No! but it makes them feel better

36. 36 Delayed hypersensitivity reactions persistent antigen stimulus, chronic infection Mθ, giant cells, epitheloid cells, fibroblasts hardening 21-28 days granuloma intradermal: tuberculin, lepromin, etc. lymphocytes, monocytes local induration 48-72 hours tuberculin epidermal: heavy metals, poison ivy, rubber, latex T cells, later macrophages eczema 48-72 hours contact dermatitis antigen and site histologyclinical appearance time of reaction type

37. 37 Type IV hypersensitivity the three forms

38. Type-IV Type-III Type-IIType-Icharacteristic Comparison of hypersensitivity reactions TB test, poison ivy, granuloma farmers’ lung, SLE Autoimmune hemolytic anemia, Graves’ hay fever, asthma examples antibodyIgEIgG, IgM none antigen exogenouscell surface intracellular soluble response time 15-30 min. Min.-hrs3-8 hours 48-72 hours or longer appearance Weal & flare Lysis & necrosis Erythema & edema Erythema & induration baso- and eosinophils Ab and complement histology PMN and complement Monocytes & lymphocytes T-cells antibody transfer with

41. Review questions: 1.Please compare the mechanisms of 4 types of hypersensitivity. 2.Which type of hypersensitivity can penicillin cause?