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Principles of Immunology
Hypersensitivity and Allergy4/11/06
”Education is a progressive discovery of our own ignorance”.
Will Durant
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Word/Terms List
Allergens Atopy Erythroblastosis fetalis Reagin Rhogam Serum sickness Tuberculin skin test
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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.
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Four types of Hypersensitivity
Type I IgE-mediated e.g.most common allergies
Type II IgG-mediated e.g.ABO transfusion reaction
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Four types of Hypersensitivity
Type III Immune-complex mediated e.g.serum sickness
Type IV T cell-mediated; delayed type e.g.tuberculin reaction
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Type I Hypersensitivity
Allergens Proteins Low molecular weight, soluble
Atopy-Predisposition to type I hypersensitivity Higher levels of circulating IgE Greater numbers of eosinophils
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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
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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
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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
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Type I Hypersensitivity
Clinical manifestations Allergic rhinitis Asthma Food allergies Systemic anaphylaxis
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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
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Type II Hypersensitivity
Cell associated antigens Transfusion reactions Hemagglutinins Complement mediated Clinical symptoms include fever, chills,
nausea
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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
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Type II Hypersensitivity
Drug induced hemolytic anemia Some antibiotics can be antigenic Bind nonspecifically to RBC surface
proteins Ab fixes C and lyses RBCs
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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
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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
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Type III Hypersensitivity
Arthus reaction Individual is sensitized to antigen Challenge is administered locally Reaction occurs locally Mast cell mediated
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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
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