Hypersensitivity and Allergy Principles of Immunology 4/11/06

Principles of Immunology
Hypersensitivity and Allergy
4/11/06
”Education is a progressive discovery of our own
ignorance”.
Will Durant
Word/Terms List
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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
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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
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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
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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
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IL3
Hematopoiesis
Interferon, TNF, IL 1 Extravasation
MCAF
Attracts macrophages
MIF
Retains macrophages