Lecture 7 Hypersensitivity Reactions n Immune responses that

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

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

Immune-Mediated Hypersensitivities

Anaphylactic/Atopic Hypersensitivity (Type I )

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

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)

Ig. E response is a local event n site of allergen entry n local synthesis results in sensitization of local mast cells n spillover of Ig. E enters circulation and sensitizes mast cells and basophils systemically

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

Ig. E Levels in Disease n n n 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 n cannot predict specific reactions(s) n higher level of Ig. E associated with increased risk of atopy n

Mast Cell Activation/Degranulation Antigen Ig. E Fc Receptor

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

Comparison of Ig. E and Ig. G 1 Structure n n 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. 21 d

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

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

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

Hyposensitization Allergen injections Symptoms Ig. G Activity Lymph. Trans. Ig. E Time

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