Principles of Immunology Hypersensitivity and Allergy 4/11/06

Principles of Immunology

Hypersensitivity and Allergy4/11/06

”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

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