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Allergy

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Allergy

  1. 1. Principles of Immunology Hypersensitivity and Allergy 4/11/06 <ul><li>”Education is a progressive discovery of our own ignorance”. </li></ul><ul><ul><li> </li></ul></ul><ul><ul><li>Will Durant </li></ul></ul>
  2. 2. Word/Terms List <ul><li>Allergens </li></ul><ul><li>Atopy </li></ul><ul><li>Erythroblastosis fetalis </li></ul><ul><li>Reagin </li></ul><ul><li>Rhogam </li></ul><ul><li>Serum sickness </li></ul><ul><li>Tuberculin skin test </li></ul>
  3. 3. Hypersensitivity and Allergy <ul><li>Hypersensitivity -An exaggerated immune response that may cause damage to the host. The trigger is often an innocuous antigen </li></ul><ul><li>Allergy- A hypersensitive response to an environmental antigen. Often presents as “hay fever”, asthma, dermatitis or anaphylaxis. </li></ul>
  4. 4. Four types of Hypersensitivity <ul><li>Type I </li></ul><ul><ul><li>IgE-mediated </li></ul></ul><ul><ul><li>e.g.most common allergies </li></ul></ul><ul><li>Type II </li></ul><ul><ul><li>IgG-mediated </li></ul></ul><ul><ul><li>e.g.ABO transfusion reaction </li></ul></ul>
  5. 5. Four types of Hypersensitivity <ul><li>Type III </li></ul><ul><ul><li>Immune-complex mediated </li></ul></ul><ul><ul><li>e.g.serum sickness </li></ul></ul><ul><li>Type IV </li></ul><ul><ul><li>T cell-mediated; delayed type </li></ul></ul><ul><ul><li>e.g.tuberculin reaction </li></ul></ul>
  6. 7. Type I Hypersensitivity <ul><li>Allergens </li></ul><ul><ul><li>Proteins </li></ul></ul><ul><ul><li>Low molecular weight, soluble </li></ul></ul><ul><li>Atopy -Predisposition to type I hypersensitivity </li></ul><ul><ul><li>Higher levels of circulating IgE </li></ul></ul><ul><ul><li>Greater numbers of eosinophils </li></ul></ul>
  7. 8. Type I Hypersensitivity <ul><li>Mechanism </li></ul><ul><ul><li>Allergen is recognized by naïve B cell </li></ul></ul><ul><ul><li>B cell stimulated by T helper cell through IL4 </li></ul></ul><ul><ul><li>IgE specific for allergen is recognized by mast cell </li></ul></ul><ul><ul><li>Cross linkage of IgE on mast cells </li></ul></ul><ul><ul><li>Mast cell degranulates </li></ul></ul>
  8. 10. Mast Cell Degranulation <ul><li>Leukotrienes </li></ul><ul><ul><li>Smooth muscle contraction; vascular permeability </li></ul></ul><ul><li>Platelet activating factor </li></ul><ul><ul><li>Activates platelets </li></ul></ul><ul><li>Histamine </li></ul><ul><ul><li>Vascular permeability; smooth muscle contraction </li></ul></ul><ul><li>Cytokines </li></ul><ul><ul><li>IL4- Stimulates T helper response </li></ul></ul><ul><ul><li>IL3- Activates eosinophils </li></ul></ul><ul><ul><li>TNF- Promotes inflammation </li></ul></ul><ul><li>Chemokines </li></ul><ul><ul><li>MIP- Attracts macrophages </li></ul></ul>
  9. 12. Mast Cell Receptors <ul><li>Fc epsilon RI </li></ul><ul><ul><li>Ig superfamily </li></ul></ul><ul><ul><li>Alpha, beta and gamma chains </li></ul></ul><ul><li>Alpha chain </li></ul><ul><ul><li>Two Ig like domains; extracellular </li></ul></ul><ul><li>Gamma chain </li></ul><ul><ul><li>Homodimer; two intracytoplasmic tails </li></ul></ul><ul><ul><li>ITAMs </li></ul></ul><ul><li>Cross linkages activates PTKs </li></ul><ul><ul><li>Cell signaling leads to degranulation </li></ul></ul>
  10. 14. Type I Hypersensitivity <ul><li>Clinical manifestations </li></ul><ul><ul><li>Allergic rhinitis </li></ul></ul><ul><ul><li>Asthma </li></ul></ul><ul><ul><li>Food allergies </li></ul></ul><ul><ul><li>Systemic anaphylaxis </li></ul></ul>
  11. 16. Prausnitz-Kustner Reaction <ul><li>Described in 1921 </li></ul><ul><ul><li>Injected allergen caused specific local reaction (Wheal and flare) </li></ul></ul><ul><ul><li>Called reagins </li></ul></ul><ul><ul><li>Later identified in 1960’s to be new class of antibody </li></ul></ul><ul><ul><li>Rabbit Ab against serum from ragweed sensitive individuals could neutralize allergic reaction </li></ul></ul>
  12. 17. Type II Hypersensitivity <ul><li>Cell associated antigens </li></ul><ul><ul><li>Transfusion reactions </li></ul></ul><ul><ul><li>Hemagglutinins </li></ul></ul><ul><ul><li>Complement mediated </li></ul></ul><ul><ul><li>Clinical symptoms include fever, chills, nausea </li></ul></ul>
  13. 20. Type II Hypersensitivity <ul><li>Erythroblastosis fetalis </li></ul><ul><ul><li>Rh+ fetus born to Rh- mother </li></ul></ul><ul><ul><li>First pregnancy sensitizes </li></ul></ul><ul><ul><li>Subsequent pregnancies result in anti Rh Ab </li></ul></ul><ul><ul><li>Mild to severe anemia in fetus </li></ul></ul><ul><ul><li>Rhogam </li></ul></ul>
  14. 22. Type II Hypersensitivity <ul><li>Drug induced hemolytic anemia </li></ul><ul><ul><li>Some antibiotics can be antigenic </li></ul></ul><ul><ul><li>Bind nonspecifically to RBC surface proteins </li></ul></ul><ul><ul><li>Ab fixes C and lyses RBCs </li></ul></ul>
  15. 23. Type III Hypersensitivity <ul><li>Soluble antigens complexed with Ab </li></ul><ul><ul><li>Deposit in tissue or on walls of blood vessels </li></ul></ul><ul><ul><li>C activation </li></ul></ul><ul><ul><li>Mast cell binds Fc; degranulates </li></ul></ul><ul><ul><li>Fc gamma RIII receptors </li></ul></ul><ul><ul><li>Neutrophils drawn to area; release of lytic enzymes cause type III reaction </li></ul></ul>
  16. 24. Type III Hypersensitivity <ul><li>Serum Sickness </li></ul><ul><ul><li>Response to foreign protein in serum,e.g horse serum (tetanus antitoxin) </li></ul></ul><ul><ul><li>Deposition of immune complexes systemically </li></ul></ul><ul><ul><li>Systemic reactions </li></ul></ul><ul><ul><li>Fever, vasculitis, arthritis, nephritis </li></ul></ul>
  17. 25. Type III Hypersensitivity <ul><li>Arthus reaction </li></ul><ul><ul><li>Individual is sensitized to antigen </li></ul></ul><ul><ul><li>Challenge is administered locally </li></ul></ul><ul><ul><li>Reaction occurs locally </li></ul></ul><ul><ul><li>Mast cell mediated </li></ul></ul>
  18. 27. Type IV Hypersensitivity <ul><li>T cell mediated </li></ul><ul><ul><li>T helper 1 cells </li></ul></ul><ul><ul><li>Effector response is through macrophages not T cytotoxic cells </li></ul></ul><ul><ul><li>Cytokine mediated </li></ul></ul><ul><ul><ul><li>IL3 Hematopoiesis </li></ul></ul></ul><ul><ul><ul><li>Interferon, TNF, IL 1 Extravasation </li></ul></ul></ul><ul><ul><ul><li>MCAF Attracts macrophages </li></ul></ul></ul><ul><ul><ul><li>MIF Retains macrophages </li></ul></ul></ul>

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