AnaphylaxisAnaphylaxis

IgE Mediated HypersensitivityIgE Mediated Hypersensitivity

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

IgE FcRI ReceptorIgE FcRI Receptor

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

Sensitization & ResponseSensitization & Response

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