1. Anaphylaxis IgE Mediated Hypersensitivity

2. What is anaphylaxis?  An acute systemic allergic reaction  The result of a re-exposure to an antigen that elicits an IgE mediated response  Usually caused by a common environmental protein that is not intrinsically harmful  Often caused by medications, foods, and insect stings  It is a Type I hypersensitivity

3. History  1st recorded 2640BC in hieroglyphics –bee sting of a pharoah  Richet & Portier –South Seas –Man-o-war –coined term anaphylaxis

4. IgE  Binds irreversible to FcεRI receptors on mast cells, basophils, and eosinophils  Is usually for parasitic infections  E heavy chain

7. Mast Cell  Has high affinity for IgE molecules (105 IgE/cell)  Originates in the bone marrow, reside in connective tissues  Increases host response to parasitic infections  Contain immunological mediators in granules ie. Histamine, ECF-A, HMW-NCF  2 populations that vary in granule content and activity –Connective tissue –Mucosal

10. IgE FcRI Receptor

11. Symptoms  Peripheral vasodilation – vascular permeablility (edema)  Bronchospasm  Cardiac arrhythmias  Smooth muscle contractions

12. Sensitization  Antigen is presented by antigen presenting cells  T H 2 cells induce B cell activation –CD40 ligand and cytokines  B cells undergo isotype switching and produce antibody  Serum antibody is bound by the mast cells

13. The allergic response  Secondary presentation of antigen produces an immediate response controlled by mast cells  Granule contents are released  Cell mediated response proceeds

14. Sensitization & Response

15. What is happening?  Initial exposure sensitizes mast cells.  Antigen specific IgE molecules attach to high affinity Fc receptors on the mast cell surface.  Cross linking of IgE molecules on surface causes intracellular signaling pathway –Inflammatory mediators are released upon degranulation

17. Mediators Involved  Include histamine, proteases, chemotactic factors, leukotrienes, prostaglandin D, and cytokines  Primary: released before degranulation –Interleukin 4 used by T cells induces B cell maturation –IL-3 and IL-5 released by T and mast cells are chemo attractants for eosinophils  Secondary: come from granules

20. Histamine  Synthesized and stored in granules  The primary mediator in the granules  3 receptors –H1: Smooth muscle & endothelium  Increased IP3 & DAG –H2: Gastric mucosa, cardiac muscle, mast cells  Increased cAMP –H3: Pre-synaptic brain  Decreases histamine release

21. Tissue Effects of Histamine  Cardiovascular –Decreased blood pressure –Increased heart rate –Edema (separation of endothelial cells & increased permeability)  Respiratory –broncho constriction  Gastrointestinal –Smooth muscle contraction and diarrhea  Skin –Urticaria

22. Treatments  Antihistamines –Block H1 and H2 receptors  Epinephrine for bronchospasms –stimulates the reformation of tight junctions between endothelial cells  IV fluids to support blood pressure  Desensitization

23. Ant bites  Red Imported Fire Ant  Venom (antigen) –Composed largely of low MW alkaloids, also different proteins –Each component is able to induce anaphylaxis  Able to inject 100ng venom/bite  Venom induces venom specific IgE antibody production