Hypersensitive Reactions Types II,III & IV

1. Hypersensitive ReactionsTypes II,III & IV Hugh B. Fackrell

2. Hypersensitive Reactions • Assigned Reading • Content Outline • Performance Objectives • Key terms • Key Concepts • Short Answer Questions

3. Assigned Reading • Chapter: 17 pp 413-439 • Janis Kuby’s Immunology 3rd Ed

4. Gell & Coombs Classification Type I Hypersensitivity: IgE mediatiated Type II Hypersensitivity: Antibody mediated cytotoxic Type III Hypersensitivity: Complex mediated cytotoxic Type IV Hypersensitivity: DTH mediated Content Outline

5. Type II Hypersensitivity • Antibody Dependent Cytotoxicity • Antibody Dependent Cell mediated Cytotoxicity • Target antigens are found on cell or tissues • Antibody binds to Target Antigen • complement activated cell destruction • Ig binds to Fc receptors on NK cells

6. Type II Hypersensitivity: Antibody mediated cytotoxic • Transfusion reactions • Hemolytic disease of the newborn • Drug induced hemolytic anemia • Nephrotoxic (Masugi type) nephtritis • Autoimmune hemolytic anemias • Anti receptors/ hormone autoimmune diseases • Hashimoto’s thyroiditis myasthenia gravis

7. Transfusion Reactions • Major Incompatibility • recipient has Abs to donor RBCs • chills, fever, pain & shock • large amounts of hemoglobin released • blood pressure drops, renal failure, coagulation • Minor Incompatibility • Donor has Abs to recipient RBCs • slowly falling hematocrit

8. Hemolytic disease of the newborn

9. Direct Antiglobulin Test

10. Nephrotoxic Nephritis • Antibodies against glomerular basement membrane • Goodpasture’s syndrome • (also lung basement membrane) • Linear binding of Ab • fixation of complement • Inflammatory cells

11. Goodpasture’s syndrome

12. Immune complexes in autoimmune disease

13. Autoantibodies in Diabetes

14. Thryoiditis • Graves Disease • Antibodies to receptor of Thyroid Stimulating Hormone (TSH-R) • Hyperthyroidism • Hashimotos Thyroiditis • Autoantibodies to thyroid proteins • TDTH cells: lymphocyte infiltration • hypothyroidism- Goiter

15. Antibodies to thyroid microsomes

16. Hyperacute Graft Rejection

17. Graft rejection: histology

18. Acute Graft Rejection

19. Acute Graft rejection: Obstructed lumen

20. Acute Graft Rejection 4

21. Type III Hypersensitivity • Immune Complex Reactions • Antigens are in solution in plasma or interstitial fluids. Abs combine with these Ags, fix complement and initiate the consequences of the complement cascade

22. Type III Hypersensitivity: Complex mediated cytotoxic • Localized reactions • Arthus type skin reactions • complex mediated glomerulonephritis • bumpy deposits • Generalized reactions • Serum sickness

23. Generalized or Systemic Type III • Acute Systemic Reactions • drug reactions penicillin • Post streptococcal acute glomerulonephritis • aggregate “anaphylaxis”- cyroprecipitates • Chronic Systemic Reactions • Infections • Auotimmune conditions SLE RA • Cutaneous vasculitis

24. Antigen Antibodies Conc Ag:AB Complexes Time (days) Serum Sickness

25. Arthus Reactions

26. Extrinsinic Allergic Alveolitis

27. SLE: Immune complexes

28. SLE ab react with nuclei

29. Type IV Hypersensitivity: DTH mediated • T DTH Cells • TC • TH1 • Cytokines • IL-2, MIF, TNF, Interferon • Macrophages • lytic enzymes

30. Type IV Granulomas • Effective against intracellular parasites • Granulomatous lesions • M. leprae, M. tuberculosis

31. Type IV: Contact Hypersensitivity • Small molecules complex with skin proteins • pentadecacatechol poison ivy, poison oak • cosmetics, hair dyes • solvents formaldehyde, turpentine • nickel rubber • Complex internalized by APC • MHC-II • Response 48-72 hours

32. Contact Hypersensitivity

33. Contact hypersensitivity histology

34. Sarcoidosis

35. Skin grafts

36. Histology of Normal skin

37. Transplanted skin histology early

38. Histology of Transplanted skin late

39. Tuberculin type hypersensitivity

40. Performance Objectives

41. Key Terms • allergen, allergy, anaphylactic shock,anaphylaxis, anergy, atopy, basophils, • contact sensitivity, degranulation, delayed type hypersensitivity, • desenstization, granulomas, homocytotropic antibodies, hypersensitivity,

42. hyposensitivity, immediate hypersensitivity, late phase reaction, mast cells, • sensitization, senstizing dose, shocking dose, systemic anaphlyaxis, triple response: edema, erythema, wheal and flare, • tubercles, tuberculin skine reaction, tuberculosis, Type I hypersensitivity, • Type II hypersensitivity, Type II hypersensitivity, Type IV hypersensitivity.

43. Key Concepts • List the Gell & Coombs classification for hypersensitivity reactions; give examples of each type. • Describe stimulatory hypersensitivity and give a specific example • Discuss the difference between primary and secondary exposure to antigen in imunity and in hypersensitivity

44. Describe the structural and functional characteristics of IgE. • Discuss the cytotropic nature of IgE • Differentiate betweeen the cyclooxygenase and lipoxygenase pathways of mediator production

45. Describe the role of mast cells in immediate hypersensitivity reactions. • Distinguish between release of preformed and newly formed mediators from mast cells and give examples of each type of mediator • Discuss the hallmarks of delayed type hypersensitivity

46. Explain the mechanisms of Delayed Type Hypersensitivity induction and development • Distinguish between different types of Delayed type hypersensitivity. • Describe tuberculosis in terms of hypersensitivity reactions.

47. Short Answer Questions

48. By derivation, what does allergy mean and what does hypersensitivity mean? Are they synonymous? • The main difference between immediate and delayed types of hypersensivitiy is the time of appearance of the reactions. True/False? If false, name the main differences. • What is the type II reaction described by Gell & Cooombs? Does this reaction require complement?

49. Is there a tendency to immediate hypersenstivity reactions? Explain? • Differentiate between antigen and allergen. • What immune and nonimmune cells are involved in immediate hypersensivity?

50. What class of antibody in responsible for immediate hypersenstivity? Describe some structural and biological characteristics of this antibody? • What do we mean by homocytotropic antibodies? • Briefly describe the result of the interaction of IgE, with mast cells • a) in the presence of allergen. • b) in the absence of allergen.