1. 1 HYPERSENSITIVITY A damage to host mediated by preexisting immunity to self or foreign antigen

2. 2 Impact of allergic diseases allergic condition estimated number affected (million) Allergic rhinitis19.6 Chronic sinusitis32.5 Contact dermatitis & eczema5.8 12Skin rashes Asthma9-12 Anaphylaxis1-2

3. 3 Types of hypersensitivity reactions Type I: anaphylactic or immediate Type II:cytotoxic Type III:Immune complex Type IV:cell mediated or delayed Type I: anaphylactic or immediate Type II:cytotoxic Type III:Immune complex Type IV:cell mediated or delayed

4. 4 Type-I hypersensitivity The common allergy

5. 5 Anaphylaxis can be fatal

6. 6 Many organ are be affected by “allergy” The nasohprynx Rhinorrhea

7. 7 Many organ are be affected by “allergy” The nasohprynx Nasal polyps

8. 8 Many organ are be affected by “allergy” The nasohprynx Tonsillitis

9. 9 Many organ are be affected by “allergy” The skin Urticaria (hives)

10. 10 Many organ are be affected by “allergy” The skin eczema

11. 11 Many organ are be affected by “allergy” The eye conjunctivitis

12. 12 Many organ are be affected by “allergy” The lungs asthma

13. 13 Many organ are be affected by “allergy” The GI tract Vomiting and diarrhea

14. 14 Sensitization against allergens pollen

15. 15 Mast cell activation products  Histamine: bronchoconstriction, mucus secretion, vascular permeability, vasodilatation  Tryptase: proteolysis  Kininogenase: kinins - vascular permeability, vasodilatation, edema  ECFA: attract neutrophils and basophils  Histamine: bronchoconstriction, mucus secretion, vascular permeability, vasodilatation  Tryptase: proteolysis  Kininogenase: kinins - vascular permeability, vasodilatation, edema  ECFA: attract neutrophils and basophils Preformed mediators

16. 16 Mast cell activation products Newly formed mediators ã Leukotriene B4: attract neutrophils and basophils ã Leukotriene C4 & D4: same as heparin but 1000 x potent ã Prostaglandin D2: kinins - vascular permeability, vasodilatation, edema ã PAF: platelet aggregation, microthrombi formation, heparin release ã Leukotriene B4: attract neutrophils and basophils ã Leukotriene C4 & D4: same as heparin but 1000 x potent ã Prostaglandin D2: kinins - vascular permeability, vasodilatation, edema ã PAF: platelet aggregation, microthrombi formation, heparin release

17. 17 The activators of mast cells

18. 18 Allergy symptoms and cAMP  -agonist (epinephrine, isoproterenol)  -blocker (phenoxybenzamine) Phosphodiasterase inhibitor (theophylline)  -agonists phenyl epinephrine, nor- epinephrine  -blocker (propanolol) cAMP Relief from symptomsWorsening of symptoms

19. 19 Skin test for allergy

20. 20 Skin test for allergy

21. 21 Laboratory tests for allergy Total IgE: Competitive solid phase EIA Or allergen specific IgE Using wells coated with the allergen

22. 22 IgE levels in immediate hypersensitivity IgE Helminthic (worm) infections Atopic diseases  allergic asthma  allergic eczema  hay fever Miscellaneous diseases  Bronchopulmonary  aspergillosis  IgE myeloma Immunodeficiency  hyper-IgE syndrome  Wiscott-Aldrich syndrome

23. 23 Treatments for allergy ã Symptomatic Receptor blockers histamines Leukotriene Bronchodialators  -agonists ã Prevent mast cell degranulation Ca influx inhibitor (chromolyn sodium) Phosphodiesterase (theophylline) ã Immunotherapy (hyposensitization) ã Symptomatic Receptor blockers histamines Leukotriene Bronchodialators  -agonists ã Prevent mast cell degranulation Ca influx inhibitor (chromolyn sodium) Phosphodiesterase (theophylline) ã Immunotherapy (hyposensitization)

24. 24 Hyposensitization

25. 25 Principles of immunotherapy

26. 26 Type II hypersensitivity mechanism

27. 27 Type II hypersensitivity role of neutrophils

28. 28 Examples of type II hypersensitivity Most autoimmune diseases with autoantibody involvement Immunofluorescent staining of desmosomes in pemphigus

29. 29 Type II hypersensitivity induced by exogenous agents

30. 30 ã Red cells: Penicillin, chloropromazine, phenacetin ã Granulocytes: Quinidine, amidopyridine ã Platelets: sulphonamides, thiazides ã Red cells: Penicillin, chloropromazine, phenacetin ã Granulocytes: Quinidine, amidopyridine ã Platelets: sulphonamides, thiazides Examples of drug-induced type II hypersensitivity

31. 31 Pattern of staining in type II hypersensitivity

32. 32 Type III hypersensitivity Serum sickness mediated by immune complexes

33. 33 Types of immune complex disease autoimmunityself antigen kidney, joint, arteries, skin persistent infection bacterial, viral, parasitic, etc. infected organ, kidney inhaled antigens mold, plant or animal antigen lung injected material serum kidney, skin, arteries, joint cause antigen site of deposition

34. 34 Serum sickness

35. 35 Systemic lupus erythematosus

36. 36 Arthus reaction Type-II Weal & flare reaction Type-I

37. 37 Type III hypersensitivity mechanism

38. 38 Type III hypersensitivity the role of immune complex size Type III hypersensitivity the role of immune complex size

39. 39 Detection of immune complexes in tissue

40. 40 Detection of immune complexes in serum

41. 41 Detection of immune complexes in serum

42. 42 Type IV hypersensitivity ã Delayed reaction ã 36 to 48 hours ã Characterized by induration and erythema ã Also known as cell mediated hypersensitivity ã Tuberculin test is the most common example ã Delayed reaction ã 36 to 48 hours ã Characterized by induration and erythema ã Also known as cell mediated hypersensitivity ã Tuberculin test is the most common example

43. 43 Tuberculin test

44. 44 Contact dermatitis vs tuberculin reaction

45. 45 Poison ivy / poison oak reaction active hapten molecule

46. 46 Contact dermatitis reaction to leather

47. 47 Contact dermatitis reaction to mango sap

48. 48 Old Milwaukee helps?

49. 49 No! but it makes them feel better

50. 50 Granuloma in a leprosy patient

51. 51 Delayed hypersensitivity reactions persistent antigen stimulus, chronic infection M , 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

52. 52 Mechanism of damage in contact hypersensitivity

53. 53 Type IV hypersensitivity the three forms

54. 54 Comparison of hypersensitivity reactions TB test, poison ivy, granuloma farmers’ lung, SLE pemphigus, Goodpasture hay fever, asthma examples Type-IV Type-III Type-IIType-Icharacteristic antibodyIgEIgG, IgM none antigen Exogenouscell surface cellular 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