Anaphylaxis ( IgE Mediated Hypersensitivity )

1. AnAphylAxisAnAphylAxis
IgE Mediated
Hypersensitivi
ty

2. WhAtWhAt is AnAphylAxis?is AnAphylAxis?
 An acute systemic allergic reactionAn acute systemic allergic reaction
 The result of a re-exposure to an antigenThe result of a re-exposure to an antigen
that elicits an IgE mediated responsethat elicits an IgE mediated response
 Usually caused by a common environmentalUsually caused by a common environmental
protein that is not intrinsically harmfulprotein that is not intrinsically harmful
 Often caused by medications, foods, andOften caused by medications, foods, and
insect stingsinsect stings
 It is a Type I hypersensitivityIt is a Type I hypersensitivity

3. 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

4. igEigE
 Binds irreversible to FcBinds irreversible to FcεεRI receptors onRI 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

7. 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 inOriginates in the bone marrow, reside in
connective tissuesconnective tissues
 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 and2 populations that vary in granule content and
activityactivity
– Connective tissueConnective tissue
– MucosalMucosal

10. IgE FcRI REcEptoRIgE FcRI REcEptoR

11. SymptomSSymptomS
 Peripheral vasodilationPeripheral vasodilation
– vascular permeablility (edema)vascular permeablility (edema)
 BronchospasmBronchospasm
 Cardiac arrhythmiasCardiac arrhythmias
 Smooth muscle contractionsSmooth muscle contractions

12. SEnSItIzatIonSEnSItIzatIon
 Antigen is presented by antigen presentingAntigen 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 andB cells undergo isotype switching and
produce antibodyproduce antibody
 Serum antibody is bound by the mast cellsSerum antibody is bound by the mast cells

13. thE allERgIc RESponSEthE allERgIc RESponSE
 Secondary presentation of antigen producesSecondary presentation of antigen produces
anan immediateimmediate response controlled by mastresponse controlled by mast
cellscells
 Granule contents are releasedGranule contents are released
 Cell mediated response proceedsCell mediated response proceeds

14. SEnSItIzatIon & RESponSESEnSItIzatIon & RESponSE

15. What is happening?What is happening?
 Initial exposure sensitizes mast cells.Initial exposure sensitizes mast cells.
 Antigen specific IgE molecules attach toAntigen specific IgE molecules attach to
high affinity Fc receptors on the mast cellhigh affinity Fc receptors on the mast cell
surface.surface.
 Cross linking of IgE molecules on surfaceCross linking of IgE molecules on surface
causes intracellular signaling pathwaycauses intracellular signaling pathway
– Inflammatory mediators are released uponInflammatory mediators are released upon
degranulationdegranulation

17. Mediators involvedMediators involved
 Include histamine, proteases, chemotacticInclude histamine, proteases, chemotactic
factors, leukotrienes, prostaglandin D, andfactors, leukotrienes, prostaglandin D, and
cytokinescytokines
 Primary: released before degranulationPrimary: released before degranulation
– Interleukin 4 used by T cells induces B cellInterleukin 4 used by T cells induces B cell
maturationmaturation
– IL-3 and IL-5 released by T and mast cells areIL-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

20. 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

21. tissue effects of histaMinetissue effects of histaMine
 CardiovascularCardiovascular
– Decreased blood pressureDecreased blood pressure
– Increased heart rateIncreased heart rate
– Edema (separation of endothelial cells &Edema (separation of endothelial cells &
increased permeability)increased permeability)
 RespiratoryRespiratory
– broncho constrictionbroncho constriction
 GastrointestinalGastrointestinal
– Smooth muscle contraction and diarrheaSmooth muscle contraction and diarrhea
 SkinSkin
– UrticariaUrticaria

22. TreaTmenTsTreaTmenTs
 AntihistaminesAntihistamines
– Block H1 and H2 receptorsBlock H1 and H2 receptors
 Epinephrine for bronchospasmsEpinephrine for bronchospasms
– stimulates the reformation of tight junctionsstimulates the reformation of tight junctions
between endothelial cellsbetween endothelial cells
 IV fluids to support blood pressureIV fluids to support blood pressure
 DesensitizationDesensitization

23. anT biTesanT biTes
 Red Imported Fire AntRed Imported Fire Ant
 Venom (antigen)Venom (antigen)
– Composed largely of low MW alkaloids, alsoComposed 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 antibodyVenom induces venom specific IgE antibody
productionproduction

25. Done by :Done by :
Ghadah SidqiGhadah Sidqi
G(G(33)) ,, L(L(55)) ..