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TheBigBangTheoryTheBigBangTheory1
Hypersensitivity(allergy)
Hypersensitivityisaninappropriateimmuneresponse,whichisheightenedreactivitytoanantigen,suchresponseleadtotissuedamage,immunopathology.ThevarioushypersensitivitystateswereclassifiedintoIthroughIVtypesbyGellandCoombs.TypeI,IIandIIIreactionsaremediatedbyantibodies,whereastypeIVreactionsaremediatedbyTcells.Hypersensitivity(allerg2I.TypeIhypersensitivity(anaphylaxis)Themajorcomponents
(1)allergen
drug,chemical
inhalantallergen:pollens、Dustmitefoodallergens:nuts,seafood
I.TypeIhypersensitivity(ana3PlanetreePlanetree4Castor-oilplantCastor-oilplant5DustmiteDustmite6(2)IgEantibodyandIgEreceptorTh2Igheavychainisotypeswitching(2)IgEantibodyandIgErecep7(2)anaphylacticshockcausedbyanimalserum(TAT)(4)hypersensitivityreactioningastrointestinaltractBiologicalactivemediators:Hygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.furproteinEssay
DiscussONEofthefollowingstatementsCommondiseasescausedbytypeIIIhypersensitivityHygienehypothesisepithelialIgE----FcRI(ITAM)epithelialMastcell/basophils:FcεRIallergenenterthebodystimulateAg-specificBcellsdifferentiatedtoplasmacellsproductionofIgESerumsicknessPFER:peakexpiratoryflowrateepithelialTheremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.PFER:peakexpiratoryflowratepurifiedproteinderivative(PPD),aproteinAgofmycobacteriumtuberculosis,elicitsaDTHreaction,calledtuberculinreaction.PoststreptococcalglomerulonephritisLevelsofIgEandatopicdiseases(2)anaphylacticshockcaused8IgE
andIgEreceptorsIgE----Fc
RI(ITAM)
AntigenindirectlycrosslinksFc
R
onmastcellsorbasophils?IgEandIgEreceptorsAntige9(3)CellsMastcell/basophils:FcεRIeosinophils:expressFcεRIafterstimulationofIL-5,MCP-3CrosslinkDegranulationReleaseofpreformedmediatorsandnewlyproducedmediators(3)CellsMastcell/basophils:10超敏反应英五班课件11LightphotomicrographandElectronmicrographofMastcellactivationAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersLightphotomicrographandElec122.MechanismofTypeIhypersensitivitySensitizationphase
ExcitationphaseEffectorphase
2.MechanismofTypeIhyperse131.Sensitizationphaseallergenenterthebody
stimulateAg-specificBcellsdifferentiatedtoplasmacells
productionofIgEBindwith
high-affinityFc
RIwhichexpressedbymastcellsandbasophilsActivatedmastcelloractivatedbasophil1.SensitizationphaseActivate142.ExcitationphaseThesameallergenenterthebodyagain→bindtoIgEwhichwasboundtomastcellsand/orbasophils,crosslinkofFc
RI→inductionthedegranuationofmastcellsandbasophils,releasebiologicalactivemediators2.Excitationphase15Biologicalactivemediators:
1.preformedmediators:histamine,eosinophilchemotacticfactor(ECF),kininogenase,tryptase
2.newlyproducedmediators:leukotrienes,prostaglandinD2,plateletactivatingfactor,cytokinesBiologicalactivemediators:163.Effectorphase
Immediatephase—severalsecondsaftercontactofallergen,canpersistseveralhours,causedbyhistamineLatephase—6-12haftercontactofallergen,canpersistseveraldays3.Effectorphase17Distributionandfunctionofhistaminetypeoftissue
effect
clinical
receptor
contraction
relaxationmanifestationH1airwaysmoothmuscles
+asthma
alimentarytractmuscles+diarrhea,vomit
vascularendothelialcell+edema
H2vascularsmoothmuscle+shockDistributionandfunctionofh18AbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersBiologiceffectsofmediatorsofimmediatehypersenitivityAbulK.abbasetal.Cellular19DifferentsubstancescrosslinkFcRDifferentsubstancescrosslin203.IgEmediatedallerigicdiseases(typeIhypersensitivity)(1)anaphylacticshockcausedbydrugs(2)anaphylacticshockcausedbyanimalserum(TAT)(3)hypersensitivityreactioninrespiratorytract
allerigicrhinitis,bronchialasthma3.IgEmediatedallerigicdis21drug,chemicalDistributionandfunctionofhistamineHygienehypothesis(2)anaphylacticshockcausedbyanimalserum(TAT)PrincipalsofpreventionandtherapyfortypeIhypersensitivity(4)hypersensitivityreactioningastrointestinaltractDegranulationHygienehypothesisinfection:changedepitopeAntigenindirectlycrosslinksFcR
onmastcellsorbasophils?cellsurfaceAg→Ab(IgG)(1)anaphylacticshockcausedbydrugsWhat’stheroleofTh17andIL-17Ainasthmaandrhinitis?HygienehypothesisHypersensitivityisaninappropriateimmuneresponse,whichisheightenedreactivitytoanantigen,suchresponseleadtotissuedamage,immunopathology.largeimmunecomplexes-----phagocytosisIgE----FcRI(ITAM)EffectorphasePFER:peakexpiratoryflowrate(cellmediated,delayedtype)Activatedmastcelloractivatedbasophil(5)hypersensitivityreactioninskin(4)hypersensitivityreactioningastrointestinaltract
seafood,milkBeestingurticariadrug,chemical(5)hypersensi22超敏反应英五班课件23Allergicreactioninresponsetotestantigenscanbedividedintoanimmediateresponseandalate-phaseresponseAsthmaticresponseinthelungswithnarrowingoftheairwaysPFER:peakexpiratoryflowrateAllergicreactioninresponse244.PrincipalsofpreventionandtherapyfortypeIhypersensitivity4.Principalsofpreventiona25(1)Skintest(1)Skintest26(2)DesensitizationtherapyHeteroserumdesensitization:smalldose,repeatedinjection,
30-50mininterval(TAT)allergictopenicillinisforbiddentousethismethodSpecificallergendesensitization:smalldose,repeatedinjection,
longtimeinterval,inducingIgGproduction,decreasingIgEproduction超敏反应英五班课件27(3)Drugtherapy(3)Drugtherapy28IgE----FcRI(ITAM)(2)anaphylacticshockcausedbyanimalserum(TAT)farmer'slungAllergicreactioninresponsetotestantigenscanbedividedintoanimmediateresponseandalate-phaseresponseepithelialPFER:peakexpiratoryflowrate(cellmediated,delayedtype)CommondiseasescausedbytypeIVhypersensitivityDegranulationdrug:hapten(1)transfusionreactionseosinophils:expressFcεRIafterstimulationofIL-5,MCP-3receptorcontractionrelaxationmanifestationMechanismofTypeIhypersensitivityallergenenterthebodystimulateAg-specificBcellsdifferentiatedtoplasmacellsproductionofIgE(2)HemolyticdiseaseofthenewborninducedbyRhesusincompatibility1903ArthusArthusreaction,arthus-likereactionIgE----FcRI(ITAM)Hypersensitivityisaninappropriateimmuneresponse,whichisheightenedreactivitytoanantigen,suchresponseleadtotissuedamage,immunopathology.Heteroserumdesensitization:smalldose,repeatedinjection,30-50mininterval(TAT)HygienehypothesisTheremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.IgE----FcRI(ITAM)Hygienehy29II.TypeIIhypersensitivity(cytotoxichypersensitivity)
II.TypeIIhypersensitivity30MechanismoftypeIIhypersensitivity(1)Ag
cellsurfaceAg→Ab(IgG)MechanismoftypeIIhypersens31(2)specificAb,complementandeffectorcell
ADCC、CDC、phagocytosis(2)specificAb,complementan32超敏反应英五班课件332.CommondiseasescausedbytypeIIhypersensitivity(1)transfusionreactionsBloodtype
Ag Ab/serumA A anti-BB B anti-AAB A、B noneO H anti-A、anti-B2.Commondiseasescausedbyt34LevelsofIgEandatopicdiseasesseafood,milkCellularandMolecularImmunology,7thedition,ElsevierSaundersTypeIhypersensitivity(anaphylaxis)MechanismofTypeIhypersensitivityHygienehypothesis(1)anaphylacticshockcausedbydrugsabbasetal.receptorcontractionrelaxationmanifestationB B anti-AInhaledantigeninducedtypeIIIhypersensitivityImmediatephase—severalsecondsaftercontactofallergen,canpersistseveralhours,causedbyhistamineMechanismofTypeIhypersensitivity(1)Infectivehypersensitivityfurprotein(2)anaphylacticshockcausedbyanimalserum(TAT)drug:haptenTheinhalationofallergensleadstohyperreactivity,recruitmentofeosinophils,mastcells,andlymphocytesintheupperandlowerairwaystriggeringtheinflammatorycascadeandgeneratinglocalandsystemicinflammatoryresponses.IgEmediatedallerigicdiseases(typeIhypersensitivity)(2)HemolyticdiseaseofthenewborninducedbyRhesusincompatibilityLevelsofIgEandatopicdise35(3)Autoimmunehemolyticanemiainfection:changedepitopedrug:hapten
(3)Autoimmunehemolyticanemia36(4)Gravesdisease(specialtype)
ThyroidepithelialcellTSH-RTSHT3、T4Anti-TSH-RAb(4)Gravesdisease(specialtyp37超敏反应英五班课件38超敏反应英五班课件39III.TypeIIIhypersensitivity(solubleimmunecomplex)
MechanismoftypeIIIhypersensitivity
largeimmunecomplexes-----phagocytosis
smallimmunecomplexes-----kidneyfiltration
medieum
immunecomplexes-----existforalongtime,depositinsmallvesselsIII.TypeIIIhypersensitivit40超敏反应英五班课件412.CommondiseasescausedbytypeIIIhypersensitivity(1)localimmunecomplex-mediateddiseases
1903ArthusArthus
reaction,arthus-likereaction
2.Commondiseasescausedby42InhaledantigeninducedtypeIIIhypersensitivityDiseasesantigen
haydustfarmer'slung
furproteinfurrier'slung
pigeondroppingspigeon-fancier'sdisease
Penicilliumcaseisporescheesewasher'sdisease
Hiddenmoldsporesmaplebarkstripper'sdiseaseInhaledantigeninducedtypeI43(2)Systemicimmunecomplex-mediateddiseases
SerumsicknessPoststreptococcalglomerulonephritisRheumatoidarthritisSystemiclupuserythematosus
(2)Systemicimmunecomplex-me44(2)anaphylacticshockcausedbyanimalserum(TAT)CommondiseasescausedbytypeIIIhypersensitivityEffectorphaseActivatedmastcelloractivatedbasophil(2)anaphylacticshockcausedbyanimalserum(TAT)(1)anaphylacticshockcausedbydrugsPFER:peakexpiratoryflowratetypeoftissueeffectclinical(cellmediated,delayedtype)CommondiseasescausedbytypeIIIhypersensitivityMechanismofhypersensitivityreactionoffourtypesabbasetal.Hygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.Hygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.newlyproducedmediators:leukotrienes,prostaglandinD2,plateletactivatingfactor,cytokinesDegranulation(2)anaphylacticshockcausedbyanimalserum(TAT)(2)specificAb,complementandeffectorcellADCC、CDC、phagocytosis(solubleimmunecomplex)Serumsickness(2)anaphylacticshockcaused45超敏反应英五班课件46超敏反应英五班课件47IV.TypeIV
hypersensitivity(cellmediated,delayedtype)
MechanismoftypeIVhypersensitivityAg→effectorcellInflammationandcytotoxicityTh1TcIV.TypeIVhypersensitivityMe48超敏反应英五班课件492.CommondiseasescausedbytypeIVhypersensitivity(1)Infectivehypersensitivity
Leprosy
2.Commondiseasescausedby50TuberculosisAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersTuberculosisAbulK.abbaseta51Contactdermatitiscausedbyivyprison(2)
ContactdermatitisContactdermatitiscausedbyi52AbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersExample:purifiedproteinderivative(PPD),aproteinAgofmycobacteriumtuberculosis,elicitsaDTHreaction,calledtuberculinreaction.Positiveskintestresponseisclinicalindicatorforevidenceofpreviousoractivetuberculosisinfection.AbulK.abbasetal.Cellular53超敏反应英五班课件54Keypoints:DefinitionofhypersensitivityreactionsMechanismofhypersensitivityreactionoffourtypesRelateddiseasesKeypoints:55Essay
DiscussONEofthefollowingstatementsHygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.Essay
DiscussONEofthefoll56Allergicdiseases,includingrhinitisandasthma,arechronicinflammatorydisorderswithaprevailingTh2immuneresponse.Theinhalationofallergensleadstohyperreactivity,recruitmentofeosinophils,mastcells,andlymphocytesintheupperandlowerairwaystriggeringtheinflammatorycascadeandgeneratinglocalandsystemicinflammatoryresponses.Th17cellsandIL-17Aplayaroleinthedevelopmentandprogressionofallergicdiseases.PharmacologicaltreatmentmightrestorethebalancebetweenTh17andTregpromotingtheresolutionofinflammationinairwaydiseases.What’stheroleofTh17andIL-17Ainasthmaandrhinitis?What’stheroleofTh17andIL57超敏反应英五班课件58PlanetreePlanetree592.MechanismofTypeIhypersensitivitySensitizationphase
ExcitationphaseEffectorphase
2.MechanismofTypeIhyperse6
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