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AnAphylAxisAnAphylAxis
IgE Mediated
Hypersensitivi
ty
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
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 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
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
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 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
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
SEnSItIzatIon & RESponSESEnSItIzatIon & RESponSE
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
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
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 &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
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
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
Done by :Done by :
Ghadah SidqiGhadah Sidqi
G(G(33)) ,, L(L(55)) ..

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Anaphylaxis ( IgE Mediated Hypersensitivity )

  • 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
  • 5.
  • 6.
  • 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
  • 8.
  • 9.
  • 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
  • 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
  • 16.
  • 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
  • 18.
  • 19.
  • 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
  • 24.
  • 25. Done by :Done by : Ghadah SidqiGhadah Sidqi G(G(33)) ,, L(L(55)) ..