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

Anaphylactic/Atopic Hypersensitivity (Type I )

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 Study Guide Who develops Type I hypersensitivity?

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)

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 Study Guide Why is the Type I reaction usually a local event?

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 Study Guide What does tissue-fixing mean? Why is antigen binding not lost when the tissue-fixing ability is lost? What is the significance of thelong half-life of IgE when bound to the mast cell?

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 Study Guide What does your genetic backgroung put you at risk for?

Mast Cell Activation/Degranulation Antigen IgE Fc Receptor Study Guide What causes mast cell degranulation?

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 Study Guide What are the activities of the contents of the mast cell granules?

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 Study Guide What is the difference between IgG and IgE?

Risk of allergy: Family 50 40 percent of children with atopy 30 20 10 Study Guide Is there a genetic predisposition to be atopic? none one both number of parents with history of allergy

Risk of allergy: IgE Levels 100 Percent of subjects 80 60 40 20 <60 60-200 200-450 >450 Study Guide What does the level of circulating IgE tell you? % of population with given IgE concentration % of subjects with that IgE concentration who are atopic

T Cell Control of the IgE Response Thymectomy antigen Ts cells 8 6 specific IgE (arbitrary units) 4 2 Study Guide What is the role of the T-suppressor cell in atopy? control -1 1 2 3 4 5 Weeks

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

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)