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Principles of Immunology Hypersensitivity and Allergy 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. Allergens Atopy Erythroblastosis fetalis Reagin Rhogam Serum sickness Tuberculin skin test. Hypersensitivity and Allergy.

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Principles of Immunology Hypersensitivity and Allergy 4/11/06

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  1. Principles of ImmunologyHypersensitivity and Allergy4/11/06 ”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

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

  7. 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

  8. 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

  9. 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

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

  11. 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

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

  13. 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

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

  15. 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

  16. 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

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

  18. 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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