HYPERSENSITIVITY REACTIONS PATHOLOGY1.pptx

PATHOGENESIS,

1. HYPERSENSITIVITY REACTIONS Dr. p. Tejaswi reddy , MBBS, MD Asst. professor pathology

2. 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 In protective part of immunity – antigen is the focus of attention and what happens to it Example: Bacteriolysis, Toxin neutralization

3. 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

4. Essentials for Hypersensitivity Contact with allergen Sensitizing/priming dose Induction of AMI/CMI Shocking dose

5. 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.

6. 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

7. TRADITIONAL CLASSIFICATION 1. IMMEDIATE HYPERSENSITIVITY: (B cell or antibody mediated) Anaphlaxis Atopy Antibody mediated damage Arthus phenomenon Serum sickness 2. DELAYED HYPERSENSITIVITY Infection (Tuberculin) type Contact dermatitis type

8. COOMB AND GELL CLASSIFICATION(4 types) 1. Type l : IgE mediated 2 . Type ll : Cytolytic & Cytotoxic 3. Type lll : Immune complex 4. Type lV : Delayed hypersensitivity

9. IgE dependant / Reagin , mediated Occur in 2 forms: Anaphylaxis – acute, potentially fatal, systemic form. Atopy – chronic or recurrent, non fatal, localized form.

10. TYPE I HS Ana- without, Phylaxis-protection Classical immediate hypersensitivity reaction Sensitization 1. Most effective when Ag is introduced parenterally 2. Minute quantities are enough 3. Interval of 2-3 weeks needed between sensitizing & shocking dose

11. 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 Mechanism: Cytotropic IgE – IgE antibodies bound to surface of mast cells and basophils FcER receptors analogous to TCR is present in these cells

12. Schultz Dale phenomenon: Intestinal or uterine muscle strips – from sensitized guinea pigs – kept in a bath of ringer’s solution – contract vigorously on addition of specific antiserum Primary mediators: Histamine, Serotonin, Chemotactic factors Secondary mediators: Prostaglanins and Leukotrienes, Platelet activating factor (PAF) Others: anaphylatoxins, bradykinin Theobald-Smith phenomenon: Guinea pigs - Sublethal load of sea anemones – toxin - immune

13. IMMEDIATE REACTION 1. Activation of TH2 Cells and Production of IgE Antibody

14. In the late-phase reaction, eosinophils that are recruited amplify and sustain the inflammatory response without additional exposure to the triggering antigen TH2 cytokine IL-5 is the most potent eosinophil-activating cytokine known Eosinophils liberate two unique proteins called major basic protein and eosinophil cationic protein, which damage tissues Late-phase reaction is a major cause of symptoms allergic asthma Treatment of these diseases requires the use of steroids, rather than anti-histamine drugs, which are of benefit in the immediate reaction

15. Humans – Itching of scalp & tongue, flushing of skin, difficulty in breathing, nausea, vomiting, diarrhoea, 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

16. CUTANEOUS 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.

17. ATOPY Refers to naturally occurring familial hypersensitivities of human beings : Hay fever - Asthma Antigens involved in atopy can be 1. Inhalants – pollen, house dust 2. Ingestants – eggs, milk 3. Contact allergens.

18. DIAGNOSIS 1. 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

19. TYPE 2 HS MECHANISMS 1. Opsonization and phagocytosis

20. inflammation

21. Cellular dysfunction

22. TYPE 2 CYTOTOXIC REACTIONS Involve activation of complement by IgG or IgM binding to an antigenic cell. Antigenic cell is lysed.

23. TYPE 2 HYPERSENSITIVITY REACTIONS Reactions against blood cells & platelets 1. Incompatible blood transfusion. 2. Hemolytic disease of the newborn. 3. Autoimmune hemolytic anemias , 4. thrombocytopenia. Reactions against Tissue Antigens Myasthenia gravis & LATS in Grave’s Pemphigus vulgaris

24. TYPE 3 HYPERSENSITIVITY REACTIONS Involve reactions against soluble antigens circulating in serum. 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.

25. Results from repeated or prolonged exposure to an antigen Occurs in several diseases, such as systemic lupus erythematosus (SLE), which is associated with persistent antibody responses to autoantigens

26. 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, lymphadenopathy, splenomegaly, arthritis, glomerulonephritis, endocarditis, rashes, abdominal pain, nausea & vomiting.

27. 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. Takes more than 12 hrs to develop. Involve CMI reactions.

28. TYPE 4 HYPERSENSITIVITY REACTION Takes more than 12 hrs to develop. Involve CMI reactions. Provoked by intracellular microbial infections or haptens like simple chemicals Varieties of Delayed HS : 1. Contact 48-72 hrs 2. Tuberculin 48-72 hrs 3. Granulomatous 21-28 days

29. CONTACT DERMATITIS Eczematous reaction at the point of contact with an allergen, like 1. Metals – nickel, chromium 2. Simple chemicals – dyes 3. Drugs – Penicillin Cells involved in Contact HS 1. Langerhans cells 2. Keratinocyte

30. 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

31. TUBERCULIN TYPE HS 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. Leprosy, Tuberculosis, Schistosomiasis, sarcoidosis, crohns disease

32. SCWARZTMANN REACTION Not an immune reaction Pertubation in factors affecting intravascular coagulation Ex: Waterhouse Freiderichsen syndrome Meningococcal septicemia

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