HYPERSENSITIVITY-TYPE 1 Mechanism .pptx

hypersensitivity

1. HYPERSENSITIVITY REACTIONS

2. History Paul Portier and Charles Richet Portuguese man o war jellyfish- Toxins Lower doses of toxins into dogs- 2 nd dose – vomiting ,diarrhoea, asphyxia and death Richet coined the word “ anaphylaxis ”- Nobel prize (1913)

3. Hypersensitivity Undesirable injurious consequences in the sensitized host, following subsequent contact with specific antigen or allergens

4. CLASSIFICATION Gell and Coombs (1963) - FOUR CATEGORIES Types I, II, and III : Antibody-mediated Immediate hypersensitivity- few minutes to hours Type IV : Cell-mediated Delayed hypersensitivity – hours to days

5. TYPE I HYPERSENSITIVITY REACTIONS ANAPHYLAXIS ( ana= without, phylaxis= protection) Acute, Fatal ATOPY - r ecurrent ,localized non fatal form F amilial predisposition,high level of IgE

6. Structure of IgE

7. TYPE I HYPERSENSITIVITY REACTIONS

8. Mechanism Sensitization phase – Exposed for the first time to the sensitizing dose of an antigen • Most effective - parenterally , but may occur by any route • Very minute dose

9. Allergen is processed by APC presented to the CD4 helper T cells. Activated TH cells differentiated into TH2 cells - secrete IL4 IL4 induces B cells - IgE producing plasma cells + memory cells. Fc region of IgE binds to high affinity FcR present on the mast cell surface Such sensitised mast cells coated with IgE waiting for the interaction with antigen during subsequent challenge.

10. • Effector phase – Same allergen is introduced subsequently ( shocking dose ) Encounters with the Fab region of IgE coated on mast cells. IgE cross linkage initiates degranulation. Granules release chemical mediators

11. Degranulation occurs in two phases, • Primary mediators – Preformed chemical mediators which are already synthesized by mast cells, are immediately released Eg - Histamine and Serotonin • Secondary mediators - mast cells synthesize them following stimulation by allergen Eg – PG , Leukotrienes