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Anaphylaxis. IgE Mediated Hypersensitivity. 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

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anaphylaxis

Anaphylaxis

IgE Mediated Hypersensitivity

what is anaphylaxis
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
history
History
  • 1st recorded 2640BC in hieroglyphics
    • bee sting of a pharoah
  • Richet & Portier
    • South Seas
    • Man-o-war
    • coined term anaphylaxis
slide4
IgE
  • Binds irreversible to FcεRI receptors on mast cells, basophils, and eosinophils
  • Is usually for parasitic infections
  • E heavy chain
mast cell
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
symptoms
Symptoms
  • Peripheral vasodilation
    • vascular permeablility (edema)
  • Bronchospasm
  • Cardiac arrhythmias
  • Smooth muscle contractions
sensitization
Sensitization
  • Antigen is presented by antigen presenting cells
  • TH2 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
the allergic response
The allergic response
  • Secondary presentation of antigen produces an immediate response controlled by mast cells
  • Granule contents are released
  • Cell mediated response proceeds
what is happening
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
mediators involved
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
histamine
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
tissue effects of histamine
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
treatments
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
ant bites
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