Principles of Immunology Hypersensitivity and Allergy 4/11/06 ”Education is a progressive discovery of our own ignorance”. Will Durant

Word/Terms List Allergens Atopy Erythroblastosis fetalis Reagin Rhogam Serum sickness Tuberculin skin test

Hypersensitivity and Allergy Hypersensitivity-An exaggerated immune response that may cause damage to the host. The trigger is often an innocuous antigen Allergy-A hypersensitive response to an environmental antigen. Often presents as “hay fever”, asthma, dermatitis or anaphylaxis.

Four types of Hypersensitivity Type I IgE-mediated e.g.most common allergies Type II IgG-mediated e.g.ABO transfusion reaction

Four types of Hypersensitivity Type III Immune-complex mediated e.g.serum sickness Type IV T cell-mediated; delayed type e.g.tuberculin reaction

Type I Hypersensitivity Allergens Proteins Low molecular weight, soluble Atopy-Predisposition to type I hypersensitivity Higher levels of circulating IgE Greater numbers of eosinophils

Type I Hypersensitivity Mechanism Allergen is recognized by naïve B cell B cell stimulated by T helper cell through IL4 IgE specific for allergen is recognized by mast cell Cross linkage of IgE on mast cells Mast cell degranulates

Mast Cell Degranulation Leukotrienes Smooth muscle contraction; vascular permeability Platelet activating factor Activates platelets Histamine Vascular permeability; smooth muscle contraction Cytokines IL4- Stimulates T helper response IL3- Activates eosinophils TNF- Promotes inflammation Chemokines MIP- Attracts macrophages

Mast Cell Receptors Fc epsilon RI Alpha chain Gamma chain Ig superfamily Alpha, beta and gamma chains Alpha chain Two Ig like domains; extracellular Gamma chain Homodimer; two intracytoplasmic tails ITAMs Cross linkages activates PTKs Cell signaling leads to degranulation

Type I Hypersensitivity Clinical manifestations Allergic rhinitis Asthma Food allergies Systemic anaphylaxis

Prausnitz-Kustner Reaction Described in 1921 Injected allergen caused specific local reaction (Wheal and flare) Called reagins Later identified in 1960’s to be new class of antibody Rabbit Ab against serum from ragweed sensitive individuals could neutralize allergic reaction

Type II Hypersensitivity Cell associated antigens Transfusion reactions Hemagglutinins Complement mediated Clinical symptoms include fever, chills, nausea

Type II Hypersensitivity Erythroblastosis fetalis Rh+ fetus born to Rh- mother First pregnancy sensitizes Subsequent pregnancies result in anti Rh Ab Mild to severe anemia in fetus Rhogam

Type II Hypersensitivity Drug induced hemolytic anemia Some antibiotics can be antigenic Bind nonspecifically to RBC surface proteins Ab fixes C and lyses RBCs

Type III Hypersensitivity Soluble antigens complexed with Ab Deposit in tissue or on walls of blood vessels C activation Mast cell binds Fc; degranulates Fc gamma RIII receptors Neutrophils drawn to area; release of lytic enzymes cause type III reaction

Type III Hypersensitivity Serum Sickness Response to foreign protein in serum,e.g horse serum (tetanus antitoxin) Deposition of immune complexes systemically Systemic reactions Fever, vasculitis, arthritis, nephritis

Type III Hypersensitivity Arthus reaction Individual is sensitized to antigen Challenge is administered locally Reaction occurs locally Mast cell mediated

Type IV Hypersensitivity T cell mediated T helper 1 cells Effector response is through macrophages not T cytotoxic cells Cytokine mediated IL3 Hematopoiesis Interferon, TNF, IL 1 Extravasation MCAF Attracts macrophages MIF Retains macrophages