Hypersensitivity reactions dr somesh - MICROBIOLOGY

HYPERSENSITIVITY REACTION - SECOND MBBS STUDENTS - UNDERGRADUATE STUDENTS - MEDICAL COLLEGE - POWERPOINT

1. Hypersensitivity reactions Dr. SOMESHWARAN RAJAMANI, MBBS, MD Assistant professor, Department of Microbiology, Karpagam Faculty of medical sciences and Research.

2. Introduction Immunity – protective – overcome infectious agents (antigens) and toxins Immune response – may also be injurious to host Sensitised individual respond to specific antigenic stimuli in an inappropriate or exaggerated manner 1/7/2015 2

3. In protective part of immunity – antigen is the focus of attention and what happens to it Example: Bacteriolysis , Toxin neutralization 1/7/2015 3

4. In hypersensitivity antigens are of little concern and often innocuous or bland substances such as serum proteins or pollen Hypersensitivity is concerned with what happens to host as a result of immune reaction 1/7/2015 4

5. definition Injurious consequences in the sensitized host, following contact with specific antigens. Deals with injurious aspect of heightened and exaggerated immune response leading to tissue damage, disease or even death Concerned with what happens to the host rather than what happens to the antigen. 1/7/2015 5

6. 1/7/2015 Essentials for Hypersensitivity Contact with allergen Sensitizing/priming dose Induction of AMI/CMI Shocking dose 6

7. classification TRADITIONAL CLASSIFICATION COOMB AND GELL (1963) CLASSIFICATION Traditional classification is based on the time required for a sensitized host to develop clinical reactions on re-exposure to the specific antigen Coomb and Gell classification is based on mechanism of pathogenesis 1/7/2015 7

8. TRADITIONAL CLASSIFICATION IMMEDIATE HYPERSENSITIVITY: (B cell or antibody mediated) Anaphlaxis Atopy Antibody mediated damage Arthus phenomenon Serum sickness DELAYED HYPERSENSITIVITY Infection (Tuberculin) type Contact dermstitis type 1/7/2015 8

9. IMMEDIATE HYPERSENSITIVITY DELAYED HYPERSENSITIVITY Appears and recedes rapidly Appears slowly and lasts longer Induced by antigens or haptens by any route Antigen or hapten intradermally or with Freund’s adjuvant or by skin contact Circulating antibodies present and responsible for reaction; ‘antibody mediated’ reaction. Circulating antibodies may be absent and not responsible for reaction; ‘cell mediated’ reaction Passive transfer possible with serum Cannot be transferred with serum; but possible with T cells or transfer factor Desensitisation easy, but short-lived Difficult, but long-lasting 1/7/2015 9

10. COOMB AND GELL CLASSIFICATION (4 types) Type l : IgE mediated Type ll : Cytolytic & Cytotoxic Type lll : Immune complex Type lV : Delayed hypersensitivity 1/7/2015 10

11. I III II IV 1/7/2015 11

12. 1/7/2015 Coombs & Gell Classification (1963) Type of reaction Clinical syndrome Time required for manifestation Mediators Type l Anaphylaxis Atopy Minutes IgE : histamine & other pharmacological agents Type ll Ab mediated damage- thrombocytopenia, hemolytic anemia Variable : hours to days IgG : Igm , C Type lll Arthus reaction Serum sickness Variable : hours to days IgG : Igm , C, leucocytes Type lV Tuberculin Contact dermatitis Hours to days T cells ; lymphokines ; macrophages 12

13. 1/7/2015 Type I reactions IgE dependant / Reagin , mediated Occur in 2 forms: Anaphylaxis – acute, potentially fatal, systemic form. Atopy – chronic or recurrent, non fatal, localized form. 13

14. 1/7/2015 Anaphylaxis Ana- without, Phylaxis -protection Classical immediate hypersensitivity reaction Sensitization Most effective when Ag is introduced parenterally Minute quantities are enough Interval of 2-3 weeks needed between sensitizing & shocking dose 14

15. ANAPHYLAXIS Once sensitized it remains so for long time Shocking dose most effective by IV route then IP, then SC then ID The shocking Ag must be same or similar to Sensitizing Ag 1/7/2015 15

16. ANAPHYLAXIS Mechanism: Cytotropic IgE – IgE antibodies bound to surface of mast cells and basophils FcER receptors analogous to TCR is present in these cells 1/7/2015 16

17. Anaphylaxis in vitro Schultz Dale phenomenon: Intestinal or uterine muscle strips – from sensitized guinea pigs – kept in a bath of ringer’s solution – contarct vigorously on addition of specific antiserum 1/7/2015 17

18. ANAPHYLAXIS Primary mediators: Histamine, Serotonin, Chemotactic factors Secondary mediators: Prostaglanins and Leukotrienes, Platelet activating factor (PAF) Others: anaphylatoxins , bradykinin 1/7/2015 18

19. Theobald-Smith phenomenon: Guinea pigs - Sublethal load of sea anemones – toxin - immune 1/7/2015 19

20. ANAPHYLACTOID REACTION Intravenous Trypsin or peptone - HS 1/7/2015 20

21. B cell Histamine, tryptase, kininegenase, ECFA Leukotriene-B4, C4, D4, prostaglandin D, PAF Newly synthesized mediators TH2 IL13 Sensitization against allergens and type-I hypersensitivity 1/7/2015 21

22. 1/7/2015 Type I Reactions Humans – Itching of scalp & tongue, flushing of skin, difficulty in breathing, nausea, vomiting, diarrhea, acute hypotension, loss of consciousness, death (rare) Causes Serum therapy, antibiotics, insect stings Treatment Adrenalin 0.5 ml (1 in 1000 solution) SC/IM repeated up to 2 ml in 15 min 22

23. 1/7/2015 Cutaneous (Local) Anaphylaxis Follows I.D. injection (small shocking dose) – a local wheal & flare response is seen. Wheal – central pale area of puffiness due to edema Flare - surrounds wheal, caused by hyperemia and subsequent erythema. Uses : - Testing for hypersensitivity Precaution – Keep adrenalin injection ready to combat severe fatal reaction. 23

24. 1/7/2015 Atopy Refers to naturally occurring familial hypersensitivities of human beings : - Hay fever - Asthma Antigens involved in atopy can be Inhalants – pollen, house dust Ingestants – eggs, milk Contact allergens. 24

25. 1/7/2015 Type-I hypersensitivity The common allergy 25

26. 1/7/2015 Diagnosis Skin tests (ID injection ) - with allergens like pollen, cat or dust mite Children - 3x3 mm wheal Adults – 4x4 mm wheal + ve test takes 5 -15 mins to develop, persist for 30 mins or more – IMMEDIATE RESPONSE. 2. Radioallergosorbent test (RAST) - to measure the levels of Ig E in serum. 26

27. 1/7/2015 Type II (Cytotoxic) Reactions Involve activation of complement by IgG or IgM binding to an antigenic cell. Antigenic cell is lysed. 27

28. 1/7/2015 Type II Hypersensitivity Role of complement and phagocytes 28

29. 1/7/2015 Type II Hypersensitivity Reactions Reactions against blood cells & platelets Incompatible blood transfusion. Hemolytic disease of the newborn. Autoimmune hemolytic anemias , thrombocytopenia. Reactions against Tissue Antigens Myasthenia gravis & LATS in Grave’s disease Pemphigus vulgaris 29

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31. 1/7/2015 Type II hypersensitivity induced by exogenous agents 31

32. 1/7/2015 Involve reactions against soluble antigens circulating in serum. Usually involve IgA antibodies. Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage. Glomerulonephritis : Inflammatory kidney damage. Occurs when slightly high antigen-antibody ratio is present. Type III (Immune Complex) Reactions 32

33. 1/7/2015 APC TH2 B cell Sensitization for Type III hypersensitivity 33

34. 1/7/2015 Immune Complex Mediated Hypersensitivity 34

35. 1/7/2015 Serum Sickness Systemic form of type lll HS . Appears 7-12 days following the injection of large doses of foreign serum (Diphtheria antitoxin). ICs are deposited on the endothelial lining of blood vessels in various parts of the body. Features – fever, LN pathy , splenomegaly, arhthritis , glomerulonephritis, endocarditis, rashes, abdominal pain, nausea & vomiting. 35

36. 1/7/2015 Serum sickness 36

37. 1/7/2015 Arthus Reaction Local reaction consisting of edema, induration & hemorrhage. Followed by repeated SC injection with a foreign serum/ normal horse serum. Intense local reaction – edema, induration, hemorrhagic necrosis Reaches peak after 4 - 10 hrs , disappears by 48 hrs. 37

38. 1/7/2015 Type 4: Delayed Hypersensitivity Takes more than 12 hrs to develop. Involve CMI reactions. Provoked by intracellular microbial infections or haptens like simple chemicals Varieties of Delayed HS : Contact 48-72 hrs Tuberculin 48-72 hrs Granulomatous 21-28 days 38

39. 1/7/2015 Contact Dermatitis Eczematous reaction at the point of contact with an allergen, like Metals – nickel, chromium Simple chemicals – dyes Drugs – Penicillin Cells involved in Contact HS Langerhans cells Keratinocytes 39

40. 1/7/2015 Contact Dermatitis Lesions – vary from macules & papules to vesicles that break down leaving behind raw weeping areas Detected by ‘Skin Patch Test’ * Allergen is applied to the skin under an adherent dressing. * Itching appears in 4- 5 hrs. * Local reaction after 24- 48 hrs : Erythema to vesicle or blister formation 40

41. 1/7/2015 Clinical & Patch test appearance of contact hypersensitivity 41

42. 1/7/2015 Tuberculin Type Hypersensitivity Tuberculin type – ID inoculation of PPD in sensitized individual leads to induration & inflammation in 48-72 hrs. This is not the same as skin test done for Type I hypersensitivity. Used for diagnosis / exclusion of diagnosis of many bacterial / fungal / parasitic / viral and autoimmune diseases. 42

43. 1/7/2015 Diseases Manifesting Granulomatous HS Leprosy Tuberculosis Schistosomiasis Sarcoidosis Crohn’s disease 43

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46. 1/7/2015 SCWARTZMANN REACTION Not an immune reaction Pertubation in factors affecting intravascular coagulation Ex: Waterhouse Freiderichsen syndrome Meningococcal septicemia 46

47. 1/7/2015 Type-IV Type-III Type-II Type-I characteristic Comparison of hypersensitivity reactions TB test, poison ivy, granuloma farmers’ lung, SLE pemphigus, Goodpasture hay fever, asthma examples antibody IgE IgG, IgM IgG, IgM none antigen exogenous cell surface intracellular soluble response time 15-30 min. Min.-hrs 3-8 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 antibody antibody transfer with 47

48. summary Hypersensitivity – injurious 4 types – Type I, II, III, IV I, II, III – Immediate IV- Delayed Differences between immediate and delayed HS Examples for Type I, II, III and IV HS 1/7/2015 48

49. THANK YOU 1/7/2015 49