Anaphylaxis  (page 311) <ul><li>An acute, potentially fatal Type I hypersensitivity disorder & medical emergency. </li></u...
Anaphylaxis  (pages 311-312) <ul><li>The most common offending agents include: </li></ul><ul><li>Foods (peanuts, tree nuts...
Fig. 1 (10.19 Parham) .  Systemic anaphylaxis is caused by allergens that reach the bloodstream and activate mast cells (a...
Fig. 4 (10.9 Parham) . Activated eosinophils secrete toxic proteins contained in their granules and also produce cytokines...
Fig. 5 (10.24 Parham) .  Allergen-induced release of histamine by mast cells in skin causes localized swelling.   Basis of...
Fig. 6 (10.15 Parham) . Sensitization to an inhaled allergen.   Antigens that are leached from inhaled pollen are taken up...
Fig. 9 (10.22 Parham) .  The acute response in allergic asthma leads to T H 2-mediated chronic airway inflammation.   Conc...
Mary Hewitt Loveless, MD Stanford University:  AB, 1921; MD, 1925 M. H. Loveless & W. R. Fackler.  Wasp venom allergy and ...
Mary Hewitt Loveless, MD Stanford University:  AB, 1921; MD, 1925 M. H. Loveless & W. R. Fackler.  Wasp venom allergy and ...
* D.Zhu, C. L. Kepley, K. Zhang, T. Terada, T. Yamada & A. Saxon.  Nat. Med .  11 :446-9, 2005 .  ( Their experimental sub...
Fig. 1 (10.2 Parham) . There are four types of immune-mediated hypersensitivity reactions that can cause tissue damage.   ...
Fig. 1 (10.2 Parham) . There are four types of immune-mediated hypersensitivity reactions that can cause tissue damage.   ...
  Fig. 15 (7.26 Parham) .  IgE crosslinking on mast cell surfaces leads to the rapid release of mast-cell granules contain...
  Fig. 15 (7.26 Parham) .  IgE crosslinking on mast cell surfaces leads to the rapid release of mast-cell granules contain...
Fig. 16 (10.5 Parham) . Molecules synthesized and released by mast cells on stimulation by antigen binding to IgE.   Revie...
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Granmc course

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Granmc course

  1. 1. Anaphylaxis (page 311) <ul><li>An acute, potentially fatal Type I hypersensitivity disorder & medical emergency. </li></ul><ul><li>“ Anaphylactoid reactions” are clinically nearly identical to anaphylaxis, but do NOT involve IgE. </li></ul><ul><li>Anaphylaxis: Rapid onset after exposure to offending agent in previously sensitized person (but how does one know the sensitization status?). </li></ul><ul><li>Life-threatening (with: pruritus, urticaria, angioedema, bronchospasm, laryngeal edema, hyper-peristalsis, hypotension) and REQUIRES IMMEDIATE TREATMENT . </li></ul><ul><li>Mediated by IgE, with cross-linking of Fc  RI on mast cells & basophils, that release preformed and newly sensitized mediators. </li></ul>
  2. 2. Anaphylaxis (pages 311-312) <ul><li>The most common offending agents include: </li></ul><ul><li>Foods (peanuts, tree nuts, shellfish, etc.) </li></ul><ul><li>Horse serum, rabbit serum, monoclonal antibodies </li></ul><ul><li>Insect venom </li></ul><ul><li>Enzymes – aspariginase, chymopapain </li></ul><ul><li>Latex (a big problem for health care workers) </li></ul><ul><li>“ Allergy injections” for treatment ( ~ 1 / 10 million) </li></ul>
  3. 3. Fig. 1 (10.19 Parham) . Systemic anaphylaxis is caused by allergens that reach the bloodstream and activate mast cells (and basophils) throughout the body. Page 312
  4. 4. Fig. 4 (10.9 Parham) . Activated eosinophils secrete toxic proteins contained in their granules and also produce cytokines and inflammatory mediators. Page 317
  5. 5. Fig. 5 (10.24 Parham) . Allergen-induced release of histamine by mast cells in skin causes localized swelling. Basis of “allergy testing” in sensitized individuals. But what about individuals who may not have been suspected of being sensitized: e.g ., Case 2 (page 319)? Page 318
  6. 6. Fig. 6 (10.15 Parham) . Sensitization to an inhaled allergen. Antigens that are leached from inhaled pollen are taken up by antigen-presenting cells (APC) in the mucosa of the airway. These activate naïve T cells to become T H 2 effector cells, which secrete IL-4 and IL-13. Isotype switching by B cells in the presence of T H 2 help and IL-4/IL-13 leads to the development of plasma cells that secrete IgE. The IgE binds to Fc  RI on mast cells and basophils. Page 319
  7. 7. Fig. 9 (10.22 Parham) . The acute response in allergic asthma leads to T H 2-mediated chronic airway inflammation. Concept behind current therapy: allergic (“atopic”) asthma is a disorder of “chronic allergic inflammation” . Corticosteroids become a mainstay of therapy (see page 329 of notes). But…. Page 323
  8. 8. Mary Hewitt Loveless, MD Stanford University: AB, 1921; MD, 1925 M. H. Loveless & W. R. Fackler. Wasp venom allergy and immunity . Annals of Allergy 14 :347- 366 (Sept.-Oct.) 1956. [Dept. of Medicine of New York Hospital & Cornell University Medical College]
  9. 9. Mary Hewitt Loveless, MD Stanford University: AB, 1921; MD, 1925 M. H. Loveless & W. R. Fackler. Wasp venom allergy and immunity . Annals of Allergy 14 :347- 366 (Sept.-Oct.) 1956. [Dept. of Medicine of New York Hospital & Cornell University Medical College] Her experimental subjects were her patients.
  10. 10. * D.Zhu, C. L. Kepley, K. Zhang, T. Terada, T. Yamada & A. Saxon. Nat. Med . 11 :446-9, 2005 . ( Their experimental subjects were mice . ) A chimeric human-cat fusion protein blocks cat-induced allergy * * Figure from: Janet Kalesnikoff & S. J. Galli. Nipping cat allergy with fusion proteins. Nat. Med . 11 :381-2, 2005. Disclosure of conflict-of-interest: I am a member of the Scientific Advisory Board of Tunitas Therapeutics, Inc. , a start up company seeking to develop fusion proteins and other products for treating allergic disorders.
  11. 11. Fig. 1 (10.2 Parham) . There are four types of immune-mediated hypersensitivity reactions that can cause tissue damage. Review: Slide from lecture I
  12. 12. Fig. 1 (10.2 Parham) . There are four types of immune-mediated hypersensitivity reactions that can cause tissue damage. These basic immunological mechanisms can be directed against exogenous or endogenous antigens (or “autoantigens”)-in the latter case, this can result in autoimmune disorders (Bill Robinson lectures and see Parham chapter on Autoimmune diseases ). AutoImm.D.: AHA MG, GD SLE IDDM, RA, MS
  13. 13.   Fig. 15 (7.26 Parham) . IgE crosslinking on mast cell surfaces leads to the rapid release of mast-cell granules containing inflammatory mediators. Review: Slide from lecture I
  14. 14.   Fig. 15 (7.26 Parham) . IgE crosslinking on mast cell surfaces leads to the rapid release of mast-cell granules containing inflammatory mediators. As IgE levels increase, so does Surface expression of Fc  RI, making mast cells & basophils “ better” effector cells
  15. 15. Fig. 16 (10.5 Parham) . Molecules synthesized and released by mast cells on stimulation by antigen binding to IgE. Review: Slide from lecture I

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