Anaphylaxis

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Anaphylaxis

• IgE Mediated Hypersensitivity

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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

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History

• 1st recorded 2640BC in hieroglyphics
• bee sting of a pharoah
• Richet Portier
• South Seas
• Man-o-war
• coined term anaphylaxis

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IgE

• Binds irreversible to FceRI receptors on mast
  cells, basophils, and eosinophils
• Is usually for parasitic infections
• E heavy chain

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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

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IgE FcRI Receptor
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Symptoms

• Peripheral vasodilation
• vascular permeablility (edema)
• Bronchospasm
• Cardiac arrhythmias
• Smooth muscle contractions

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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

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The allergic response

• Secondary presentation of antigen produces an
  immediate response controlled by mast cells
• Granule contents are released
• Cell mediated response proceeds

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Sensitization Response
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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

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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

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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

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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

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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

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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