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Type i hypersensitivity ppt presentation mode

  1. 1. Type I Hypersensitivity reactionDr.Pavulraj.SM.V.Sc., scholar,Division of PathologyIndian Veterinary ResearchInstitute, India
  2. 2. Introduction• Hypersensitivity - excessive, undesirablereactions produced by the normal immunesystem• Hypersensitivity reactions require a pre-sensitized (immune) state of the host• 1906 – Von Pirquet coined term:hypersensitivity
  3. 3. • Gell-Coombs Classified the reactions into fourtypes based on the mechanisms involved andtime taken for the reaction Hypersensitivityreactions can be divided into four types: typeI, type II, type III and type IV
  4. 4. 3 involve antibody-• Type I (immediate): mediated by IgE (MastCells)• Type II: mediated by IgG or IgM• Type III (immune complex disease): IgG &complementOne involves antigen specific cells• Type IV: Delayed type hypersensitivity, cellmediated immune memory response. Type IHypersensitivity
  5. 5. TYPE I Hypersensitivity• Type I hypersensitivity – immediateor anaphylactic hypersensitivity• Immediate hypersensitivity is mediated by IgE• The primary cellular component in thishypersensitivity is the mast cell or basophil• The reaction is amplified by neutrophils andeosinophils
  6. 6. • 1902 - Charles Richet and Paul Portierdiscovered anaphylaxis• The symptoms resulting from allergicresponses are known as anaphylaxis• Includes: Hay fever, asthma, eczema, beestings, food allergies• Exposure may be by ingestion, inhalation,injection or direct contact
  7. 7. Allergens• Allergens are nonparasite antigens that canstimulate a type I hypersensitivity response.• Allergens bind to IgE and trigger degranulationof chemical mediators
  8. 8. Characteristics of allergens• Small 15-40,000 MW proteins• Protein components – Often enzymes• Low dose of allergen• Mucosal exposure• Most allergens promote a Th2 immune
  9. 9. Atopy• Atopy is the term for the genetic trait to havea predisposition for localized anaphylaxis• Atopic individuals have higher levels of IgE andeosinophils
  10. 10. Mechanisms of allergic responseSensitization• Repeated exposure to allergens initiatesimmune response that generates IgE isotype• Th2 cells required to provide the IL-4 requiredto get isotype switching to IgE
  11. 11. Mechanisms of allergic responseSensitization• The IgE can attach to Mast cells by Fc receptor,which increases the life span of the IgE• Half-life of IgE in serum is days whereasattached to FcεR it is increased to months
  12. 12. Mechanisms of allergic responseFc ε receptors (FcεR)• FcεR1 - high affinity IgE receptor found onmast cells/basophils/activated eosinophils• Allergen binding to IgE attached to FcεR1triggers release of granules from the mast cell
  13. 13. Mechanisms of allergic responseEffector Stage of Hypersensitivity• Secondary exposure to allergen• Mast cells are primed with IgE on surface• Allergen binds IgE and cross-links to activatesignal with tyrosine phosphorylation, Ca++influx, degranulation and release of mediators
  14. 14. Mediators of Type I HypersensitivityImmediate effectsHistamineConstriction of smooth muscles.Bronchiole constriction = wheezing.Constriction of intestine = cramps-diarrhea.Vasodilation with increased fluid into tissuesCausing increased swelling or fluid in mucosa.Activates enzymes for tissue breakdown.• Leukotrienes• Prostaglandins
  15. 15. Primary MediatorsPre-formed mediators in granules• Histamine• Cytokines TNF-α, IL-1, IL-6.• Chemoattractants for Neutrophils andEosinophils• Enzymes– Tryptase, Chymase, Cathepsin– Changes in connective tissue matrix, tissuebreakdown
  16. 16. Secondary mediatorsMediators formed after activation• Leukotrienes• Prostaglandins• Th2 cytokines- IL-4, IL-5, IL-13, GM-CSF
  17. 17. Continuation of sensitization cycle• Mast cells control the immediate response• Eosinophils and neutrophils drive late orchronic response.• More IgE production further driven byactivated Mast cells, basophils, eosinophils
  18. 18. Localized anaphylaxis• Target organ responds to direct contact withallergen• Digestive tract contact results in vomiting,cramping, diarrhea• Skin sensitivity usually reddened inflamedarea resulting in itching• Airway sensitivity results in sneezing andrhinitis or wheezing and asthma
  19. 19. Systemic anaphylaxis• Systemic vasodilation and smooth musclecontraction leading to severe bronchioleconstriction, edema, and shock• Similar to systemic inflammation
  20. 20. Other types of anaphylaxis
  21. 21. Diagnostic tests for immediatehypersensitivitySkin (prick and intradermal) tests• Measurement of total IgE and specific IgEantibodies against the suspected allergens• Total IgE and specific IgE antibodies aremeasured by a enzyme immunoassay (ELISA)• Increased IgE levels are indicative of an atopiccondition• A genetic predisposition for atopic diseases
  22. 22. Intra dermal test
  23. 23. REFERENCES• Brostoff, J., Scadding, G. K., Male, D., & Roitt, I. M. (1991). Introduction toImmune Responses. In J.Brostoff, G. K. Scadding, D. Male, & I. M. Roitt(Eds.), Clinical Immunology ( New York: Gower Medical Publishing)• Gell, P. G. H. & Coombs, R. R. A. (1963). The classification of allergicreactions underlying disease. In R.R.A.Coombs & P. G. H. Gell (Eds.),Clinical Aspects of Immunology ( Blackwell Science)• Shamberger, R. (2008). Types of Food Allergy Testing. Townsend Letter,January, 71-72• Kuby immunology, Sixth edition• Yamasaki, S. & Saito, T. (2005). Regulation of mast cell activation throughFcepsilonRI. Chem.Immunol.Allergy, 87, 22-31.