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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
 Often caused by medications, foods, and
insect stings
 It is a Type I hypersensitivity
History
 1st recorded 2640BC in hieroglyphics
– bee sting of a pharoah
 Richet & Portier
– South Seas
– Man-o-war
– coined term anaphylaxis
IgE
 Binds irreversible to FcεRI receptors on
mast cells, basophils, and eosinophils
 Is usually for parasitic infections
 E heavy chain
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
IgE FcRI Receptor
Symptoms
 Peripheral vasodilation
– vascular permeablility (edema)
 Bronchospasm
 Cardiac arrhythmias
 Smooth muscle contractions
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
 Secondary presentation of antigen produces
an immediate response controlled by mast
cells
 Granule contents are released
 Cell mediated response proceeds
Sensitization & Response
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
 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
 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
 Cardiovascular
– Decreased blood pressure
– Increased heart rate
– Edema (separation of endothelial cells &
increased permeability)
 Respiratory
– broncho constriction
 Gastrointestinal
– Smooth muscle contraction and diarrhea
 Skin
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
 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