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Lecture 20 Hypersensitivity Reactions

Lecture 20 Hypersensitivity Reactions. Immune responses that result in tissue injury. Immune-mediated hypersensitivity reactions. Type I - Anaphylactic/Atopic Type II - Cytotoxic Type III - Toxic Complex Type IV - T-cell mediated. Immune-Mediated Hypersensitivities.

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Lecture 20 Hypersensitivity Reactions

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  1. Lecture 20Hypersensitivity Reactions • Immune responses that result in tissue injury

  2. Immune-mediated hypersensitivity reactions • Type I - Anaphylactic/Atopic • Type II - Cytotoxic • Type III - Toxic Complex • Type IV - T-cell mediated

  3. Immune-Mediated Hypersensitivities

  4. Anaphylactic/Atopic Hypersensitivity(Type I )

  5. Atopy • Describes the clinical features of individuals who develop Type I hypersensitivity • increased vascular permeability • local edema • itching • Strong hereditary linkages • Mediated by a serum factor termed "reagin" • "Wheal and flare" reaction

  6. Immediate and Late-Phase Reactions Wheal-and-flare reaction (lasts up to 30 min post injection) Late-phase reaction (develops approximately eight hours later and persists several hours)

  7. IgE response is a local event • site of allergen entry • local synthesis results in sensitization of local mast cells • spillover of IgE enters circulation and sensitizes mast cells and basophils systemically

  8. Characteristics of IgE • Heat labile • Fc binding destroyed by heating at 56°C for 30 min • antigen binding is not lost • Half-life • serum half-life is 2 1/2 days (IgG is 21 days) • mast cell bound half-life is 12 weeks

  9. IgE Levels in Disease • Normal levels do not preclude atopy • 30% of random population allergic to at least one common allergen • Genetic background puts individual at risk • family history indicates predisposition for atopy • cannot predict specific reactions(s) • higher level of IgE associated with increased risk of atopy

  10. Mast Cell Activation/Degranulation Antigen IgE Fc Receptor

  11. Contents of the Mast Cell Granules Active agent Activity Histamine Increases vascular permeability; elevates level of cyclic AMP Heparin Anticoagulation Serotonin Increases vascular permeability SRS-A Increases vascular permeability; causes contraction of human broncholes Chymase Proteolysis Hyaluronidase Increases vasuclar permeability Eos. Chem. Factor Chemoattraction of eosinophils Neut. Chem. Factor Chemoattraction of neutrophils Platelet Agg. Factor Aggregates platelets

  12. Comparison of IgE and IgG1 Structure • heavy chain domains 5 vs. 4 • mol. wt. 188,000 vs. 146,000 • carbohydrate 12% vs. 2-3% • half-life (serum) 2 1/2 vs. 21d

  13. Risk of allergy: Family 50 40 percent of children with atopy 30 20 10 0 none one both number of parents with history of allergy

  14. Risk of allergy: IgE Levels 100 Percent of subjects 80 60 40 20 0 <60 60-200 200-450 >450 % of population with given IgE concentration % of subjects with that IgE concentration who are atopic

  15. T Cell Control of the IgE Response Thymectomy antigen Ts cells 8 6 specific IgE (arbitrary units) 4 2 control 0 -1 0 1 2 3 4 5 Weeks

  16. Hyposensitization Allergen injections Symptoms IgG Activity Lymph. Trans. IgE Time

  17. Clinical Tests for Allergy • Skin Tests • Immediate Response (wheal & flare reaction; 20 min) • increased vascular permeability • local edema • itching • Late Reactions (5-24 hr) • RAST (Radio Allergo Sorbant Test)

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