Hypersensitivity MECHANISM OF HYPERSENSITIVITY REACTIONS Altered reaction 2nd exposure Exogenous and endogenous antigens may be triggered hypersensitivity

ty rxns Often associated w/inheritance of susceptibility genes Imbalance between effector mechnisms of immune responses and control mechanisms

TYPES 1. Immediate hypersensitivity (type I) 2. Antibody-mediated (type II) 3. Immune complex mediated (type III) 4. Cell mediated (type IV)

Immediate Hypersensitivity (Type I) rapid immunologic reaction (w/in mins.) after combination of Ag with Ab bound to mast cells of previous sensitized individuals most mediated by IgE antibodies release of vasogenic, spasmogenic subst., cytokines (recruitment of inflam. cells) Usually, Allergy

Most mediated by TH2m IgE ab, & mast cells Release of mediators & pro inflammatory cytokines Synthesis of IgE requires induction of CD4+ helper T cells of TH2 type (w/c produce multiple cytokines) IL-4 produced by TH2 cells is essential for IgE synthesis IL-3, 5, GM-CSF promotes production & survival of eosinophils

A. Systemic Usually follows injection of Ag (parenteral or oral administration) skin testing done to lower occurance Maybe in state of shock w/in mins (anaphylactic shock)

B. Local Exemplified by atopic allergies 1. Immediate or initial phase 5-30 mins after exposure Primary mast cell mediators resp. for initial phase Includes Biogenic amines (histamine) Chemotactic mediators (eosinophil & neutrophil) Enzymes (chymase & tryptase)

2. Late phase 2-24 hours after initial allergen exposure Driven by lipid mediators & cytokines Produced by mast cells Lipid mediators include LT-B4,C4,D4,E4 Prostaglandin D2 PAF Cytokines include TNF-a Interleukines GM-CSF chemokines

Masts cells BM derived near b.v., nerves, subepithelium have cytoplasmic membrane bound basophilic granules containing mediatiors IgE Fc receptors where the allergen normally bound

Basophils similar to mast cells found in the circulation can be recruited to inflammatory sites TH2 cells Initiation & propagation IL-4 B cells switch to IgE & TH2 production (autocrine) Promotes inflammation

Eosinophils Important in late phase Recruited by chemokines IL-5 most potent eosinophil activating cytokine Liberate: Proteolytic enzymes Major basic proteins Eosinophilic cationic protein