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-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
 MIF
Attracts macrophages
Retains macrophages