Anaphylaxis IgE Mediated Hypersensitivity. What is anaphylaxis? An acute systemic allergic reaction...
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Transcript of Anaphylaxis IgE Mediated Hypersensitivity. What is anaphylaxis? An acute systemic allergic reaction...
What is anaphylaxis?What is anaphylaxis?
An acute systemic allergic reactionAn acute systemic allergic reaction The result of a re-exposure to an antigen The result of a re-exposure to an antigen
that elicits an IgE mediated responsethat elicits an IgE mediated response Usually caused by a common environmental Usually caused by a common environmental
protein that is not intrinsically harmfulprotein that is not intrinsically harmful Often caused by medications, foods, and Often caused by medications, foods, and
insect stingsinsect stings It is a Type I hypersensitivityIt is a Type I hypersensitivity
HistoryHistory
1st recorded 2640BC in hieroglyphics1st recorded 2640BC in hieroglyphics– bee sting of a pharoahbee sting of a pharoah
Richet & PortierRichet & Portier– South SeasSouth Seas– Man-o-warMan-o-war– coined term anaphylaxiscoined term anaphylaxis
IgEIgE
Binds irreversible to FcBinds irreversible to FcεεRI receptors on RI receptors on mast cells, basophils, and eosinophilsmast cells, basophils, and eosinophils
Is usually for parasitic infectionsIs usually for parasitic infections E heavy chainE heavy chain
Mast CellMast Cell
Has high affinity for IgE molecules (105 IgE/cell)Has high affinity for IgE molecules (105 IgE/cell) Originates in the bone marrow, reside in connective Originates in the bone marrow, reside in connective
tissuestissues Increases host response to parasitic infectionsIncreases host response to parasitic infections Contain immunological mediators in granules ie. Contain immunological mediators in granules ie.
Histamine, ECF-A, HMW-NCFHistamine, ECF-A, HMW-NCF 2 populations that vary in granule content and 2 populations that vary in granule content and
activityactivity– Connective tissue Connective tissue – Mucosal Mucosal
SymptomsSymptoms
Peripheral vasodilationPeripheral vasodilation– vascular permeablility (edema)vascular permeablility (edema)
BronchospasmBronchospasm Cardiac arrhythmiasCardiac arrhythmias Smooth muscle contractionsSmooth muscle contractions
SensitizationSensitization
Antigen is presented by antigen presenting Antigen is presented by antigen presenting cellscells
TTHH2 cells induce B cell activation2 cells induce B cell activation
– CD40 ligand and cytokinesCD40 ligand and cytokines
B cells undergo isotype switching and B cells undergo isotype switching and produce antibodyproduce antibody
Serum antibody is bound by the mast cellsSerum antibody is bound by the mast cells
The allergic responseThe allergic response
Secondary presentation of antigen produces Secondary presentation of antigen produces an an immediateimmediate response controlled by mast response controlled by mast cellscells
Granule contents are releasedGranule contents are released Cell mediated response proceedsCell mediated response proceeds
What is happening?What is happening?
Initial exposure sensitizes mast cells.Initial exposure sensitizes mast cells. Antigen specific IgE molecules attach to Antigen specific IgE molecules attach to
high affinity Fc receptors on the mast cell high affinity Fc receptors on the mast cell surface.surface.
Cross linking of IgE molecules on surface Cross linking of IgE molecules on surface causes intracellular signaling pathwaycauses intracellular signaling pathway– Inflammatory mediators are released upon Inflammatory mediators are released upon
degranulationdegranulation
Mediators InvolvedMediators Involved
Include histamine, proteases, chemotactic Include histamine, proteases, chemotactic factors, leukotrienes, prostaglandin D, and factors, leukotrienes, prostaglandin D, and cytokinescytokines
Primary: released before degranulationPrimary: released before degranulation– Interleukin 4 used by T cells induces B cell Interleukin 4 used by T cells induces B cell
maturationmaturation– IL-3 and IL-5 released by T and mast cells are IL-3 and IL-5 released by T and mast cells are
chemo attractants for eosinophilschemo attractants for eosinophils Secondary: come from granulesSecondary: come from granules
HistamineHistamine
Synthesized and stored in granulesSynthesized and stored in granules The primary mediator in the granulesThe primary mediator in the granules 3 receptors3 receptors
– H1: Smooth muscle & endotheliumH1: Smooth muscle & endothelium Increased IP3 & DAGIncreased IP3 & DAG
– H2: Gastric mucosa, cardiac muscle, mast cellsH2: Gastric mucosa, cardiac muscle, mast cells Increased cAMPIncreased cAMP
– H3: Pre-synaptic brainH3: Pre-synaptic brain Decreases histamine releaseDecreases histamine release
Tissue Effects of HistamineTissue Effects of Histamine
CardiovascularCardiovascular– Decreased blood pressureDecreased blood pressure– Increased heart rateIncreased heart rate– Edema (separation of endothelial cells & increased Edema (separation of endothelial cells & increased
permeability)permeability) RespiratoryRespiratory
– broncho constrictionbroncho constriction GastrointestinalGastrointestinal
– Smooth muscle contraction and diarrheaSmooth muscle contraction and diarrhea
SkinSkin– UrticariaUrticaria
TreatmentsTreatments
AntihistaminesAntihistamines– Block H1 and H2 receptorsBlock H1 and H2 receptors
Epinephrine for bronchospasmsEpinephrine for bronchospasms– stimulates the reformation of tight junctions stimulates the reformation of tight junctions
between endothelial cells between endothelial cells
IV fluids to support blood pressureIV fluids to support blood pressure DesensitizationDesensitization
Ant bitesAnt bites
Red Imported Fire AntRed Imported Fire Ant Venom (antigen)Venom (antigen)
– Composed largely of low MW alkaloids, also Composed largely of low MW alkaloids, also different proteinsdifferent proteins
– Each component is able to induce anaphylaxisEach component is able to induce anaphylaxis
Able to inject 100ng venom/biteAble to inject 100ng venom/bite Venom induces venom specific IgE antibody Venom induces venom specific IgE antibody
productionproduction