AnaphylaxisAnaphylaxis

IgE Mediated

Hypersensitivity

WhatWhat is anaphylaxis? 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 activity2 populations that vary in granule content and activity

– 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

Done By :Done By : Ghadah Sidqi Ghadah Sidqi G(G(33)) , , L(L(55)) . .