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Lecture 7 Hypersensitivity Reactions Immune responses that result in tissue injury Immune responses that result in tissue injury.

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Presentation on theme: "Lecture 7 Hypersensitivity Reactions Immune responses that result in tissue injury Immune responses that result in tissue injury."— Presentation transcript:

1 Lecture 7 Hypersensitivity Reactions Immune responses that result in tissue injury Immune responses that result in tissue injury

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

3 Immune-Mediated Hypersensitivities

4 Anaphylactic/Atopic Hypersensitivity (Type I )

5 Atopy Describes the clinical features of individuals who develop Type I hypersensitivity Describes the clinical features of individuals who develop Type I hypersensitivity increased vascular permeability increased vascular permeability local edema local edema itching itching Strong hereditary linkages Strong hereditary linkages Mediated by a serum factor termed "reagin" Mediated by a serum factor termed "reagin" "Wheal and flare" reaction "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 site of allergen entry local synthesis results in sensitization of local mast cells local synthesis results in sensitization of local mast cells spillover of IgE enters circulation and sensitizes mast cells and basophils systemically spillover of IgE enters circulation and sensitizes mast cells and basophils systemically

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

9 IgE Levels in Disease Normal levels do not preclude atopy Normal levels do not preclude atopy 30% of random population allergic to at least one common allergen 30% of random population allergic to at least one common allergen Genetic background puts individual at risk Genetic background puts individual at risk family history indicates predisposition for atopy family history indicates predisposition for atopy cannot predict specific reactions(s) cannot predict specific reactions(s) higher level of IgE associated with increased risk of atopy 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 agentActivity HistamineIncreases vascular permeability; elevates level of cyclic AMP HeparinAnticoagulation SerotoninIncreases vascular permeability SRS-AIncreases vascular permeability; causes contraction of human broncholes ChymaseProteolysis HyaluronidaseIncreases vasuclar permeability Eos. Chem. FactorChemoattraction of eosinophils Neut. Chem. FactorChemoattraction of neutrophils Platelet Agg. FactorAggregates platelets

12 Comparison of IgE and IgG1 Structure heavy chain domains 5 vs. 4 heavy chain domains 5 vs. 4 mol. wt.188,000 vs. 146,000 mol. wt.188,000 vs. 146,000 carbohydrate12% vs. 2-3% carbohydrate12% vs. 2-3% half-life (serum) 2 1/2 vs. 21d half-life (serum) 2 1/2 vs. 21d

13 Risk of allergy: Family noneoneboth number of parents with history of allergy 50 40 30 20 10 0 percent of children with atopy

14 Risk of allergy: IgE Levels 100 80 60 40 20 0 <60 <6060-200200-450>450 Percent of subjects % of population with given IgE concentration % of subjects with that IgE concentration who are atopic

15 T Cell Control of the IgE Response 54321 Weeks 8 6 4 2 0 specific IgE (arbitrary units) antigen Ts cells Thymectomy control 0

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

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


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