Hypersensitivity

types of hypersensetivity

1. Hypersensitivity

2. Definitions Hypersensitivity - injurious consequences in the sensitized host, following contact with specific antigens. Allergy "altered state of reactivity" to common environmental antigens.(von Pirquet ) Atopy - "out of place," and often used to describe patients with IgE -mediated diseases.

3. Allergen refers to an antigen that triggers an IgE response in genetically predisposed individuals Proteins 10 – 70 kd size Priming/ sensitizing dose – initial contact with the antigen sensitizes the immune system, leading to the priming of the appropriate B or T lymphocytes Shocking dose – subsequent contact with the allergen causes manifestations of hypersensitivity.

4. Classification Based on time required for a sensitised host to develop clinical reactions on re – exposure Immediate Delayed Based on different mechanisms of pathogenesis Type 1 ( IgE mediated) Type 2 ( cytotoxic or cell stimulating) Type 3 (immune complex) Type 4 ( cell mediated)

5. Immediate hypersensitivity Delayed hypersensitivity Appears and recedes rapidly Induced by antigens by any route B cell or Antibody mediated Appears slowly, lasts longer Induced by antigens intradermally or skin contact T cell mediated

6. Type 1 reactions ( IgE dependent) Anaphylaxis – acute, potentially fatal, systemic Atopy - chronic, nonfatal, localized

7. Mechanism of anaphylaxis IgE molecules bind to the surface receptors of mast cells and basophils Shocking dose Antigen combines with cell bound IgE Cross linking between adjacent antibody molecules Increased permeability of cells to calcium ions Degranulation Release of inflammatory mediators

8. Mechanism of atopy Predisposition genetically determined Tendency to produce IgE antibodies in unusually large quantities

9. Type 2 Reaction: cytolytic and cytotoxic Ig G and rarely Ig M antibodies Bind to antigenic cell Lysis of cell Cell surface antigens (autoimmune anemias ) Adsorption of antigens on cell surface (drugs) Cell surface receptor and disrupts normal function ( LATS – Graves disease)

10. Type 3 reactions – immune complex diseases Antigen – antibody complexes Complement activation Release of inflammatory mediators Increased vascular permeability Infiltration with neutrophils

11. Type 4 – Delayed hypersensitivity Sensitized T cells Contact with specific antigen Release cytokines Effects on leucocytes, macrophages and tissue cells

12. Summary Type of reaction Clinical syndrome Time required for manifestation Mediators Type 1: IgE type Anaphylaxis, atopy minutes Histamine, prostaglandins, others Type 2: cytolytic & cytotoxic Antibody mediated damage Variable IgG , IgM Type 3: immune complex Arthus reaction, serum sickness Variable IgG , IgM , Leucocytes Type 4: delayed hypersensitivity Tuberculin test, contact dermatitis Hours – days T cells, macrophages