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

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

3. 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.

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

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

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

8. 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

10. 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

12. 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

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

16. 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

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

20. 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

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

23. 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

24. 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

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

27. 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