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HypersensitivityGuangjieChenDept.ofImmunologyandMicrobiology2015TheBigBangTheory
Hypersensitivity(allergy)
Hypersensitivityisaninappropriateimmuneresponse,whichisheightenedreactivitytoanantigen,suchresponseleadtotissuedamage,immunopathology.ThevarioushypersensitivitystateswereclassifiedintoIthroughIVtypesbyGellandCoombs.TypeI,IIandIIIreactionsaremediatedbyantibodies,whereastypeIVreactionsaremediatedbyTcells.PlanetreeCastor-oilplantDustmiteLevelsofIgEandatopicdiseasesIgE
andIgEreceptorsIgE----FcRI(ITAM)
AntigenindirectlycrosslinksFcR
onmastcellsorbasophils?(3)CellsMastcell/basophils:FcεRIeosinophils:expressFcεRIafterstimulationofIL-5,MCP-3CrosslinkDegranulationReleaseofpreformedmediatorsandnewlyproducedmediatorsLightphotomicrographandElectronmicrographofMastcellactivationAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaunders2.MechanismofTypeIhypersensitivitySensitizationphase
ExcitationphaseEffectorphase
1.Sensitizationphaseallergenenterthebody
stimulateAg-specificBcellsdifferentiatedtoplasmacells
productionofIgEBindwith
high-affinityFcRIwhichexpressedbymastcellsandbasophilsActivatedmastcelloractivatedbasophilBiologicalactivemediators:
1.preformedmediators:histamine,eosinophilchemotacticfactor(ECF),kininogenase,tryptase
2.newlyproducedmediators:leukotrienes,prostaglandinD2,plateletactivatingfactor,cytokines3.Effectorphase
Immediatephase—severalsecondsaftercontactofallergen,canpersistseveralhours,causedbyhistamineLatephase—6-12haftercontactofallergen,canpersistseveraldaysDistributionandfunctionofhistaminetypeoftissue
effect
clinical
receptor
contraction
relaxationmanifestationH1airwaysmoothmuscles
+asthma
alimentarytractmuscles+diarrhea,vomit
vascularendothelialcell+edema
H2vascularsmoothmuscle+shockDifferentsubstancescrosslinkFcR3.IgEmediatedallerigicdiseases(typeIhypersensitivity)(1)anaphylacticshockcausedbydrugs(2)anaphylacticshockcausedbyanimalserum(TAT)(3)hypersensitivityreactioninrespiratorytract
allerigicrhinitis,bronchialasthma(5)hypersensitivityreactioninskin(4)hypersensitivityreactioningastrointestinaltract
seafood,milkBeestingurticariaAllergicreactioninresponsetotestantigenscanbedividedintoanimmediateresponseandalate-phaseresponseAsthmaticresponseinthelungswithnarrowingoftheairwaysPFER:peakexpiratoryflowrate4.PrincipalsofpreventionandtherapyfortypeIhypersensitivity(3)DrugtherapyHygienehypothesisTheremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.II.TypeIIhypersensitivity(cytotoxichypersensitivity)
MechanismoftypeIIhypersensitivity(1)Ag
cellsurfaceAg→Ab(IgG)(2)specificAb,complementandeffectorcell
ADCC、CDC、phagocytosis2.CommondiseasescausedbytypeIIhypersensitivity(1)transfusionreactionsBloodtype
Ag Ab/serumA A anti-BB B anti-AAB A、B noneO H anti-A、anti-B(2)HemolyticdiseaseofthenewborninducedbyRhesusincompatibility(3)Autoimmunehemolyticanemiainfection:changedepitopedrug:hapten
(4)Gravesdisease(specialtype)
ThyroidepithelialcellTSH-RTSHT3、T4Anti-TSH-RAbIII.TypeIIIhypersensitivity(solubleimmunecomplex)
MechanismoftypeIIIhypersensitivity
largeimmunecomplexes-----phagocytosis
smallimmunecomplexes-----kidneyfiltration
medieum
immunecomplexes-----existforalongtime,depositinsmallvessels2.CommondiseasescausedbytypeIIIhypersensitivity(1)localimmunecomplex-mediateddiseases
1903ArthusArthus
reaction,arthus-likereaction
InhaledantigeninducedtypeIIIhypersensitivityDiseasesantigen
haydustfarmer'slung
furproteinfurrier'slung
pigeondroppingspigeon-fancier'sdisease
Penicilliumcaseisporescheesewasher'sdisease
Hiddenmoldsporesmaplebarkstripper'sdisease(2)Systemicimmunecomplex-mediateddiseases
SerumsicknessPoststreptococcalglomerulonephritisRheumatoidarthritisSystemiclupuserythematosus
SerumsicknessIV.TypeIV
hypersensitivity(cellmediated,delayedtype)
MechanismoftypeIVhypersensitivityAg→effectorcellInflammationandcytotoxicityTh1Tc2.CommondiseasescausedbytypeIVhypersensitivity(1)Infectivehypersensitivity
Leprosy
TuberculosisAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersContactdermatitiscausedbyivyprison(2)
ContactdermatitisAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersExample:purifiedproteinderivative(PPD),aproteinAgofmycobacteriumtuberculosis,elicitsaDTHreaction,calledtuberculinreaction.Positiveskintestresponseisclinicalindicatorforevidenceofpreviousoractivetuberculosisinfection.Keypoints:DefinitionofhypersensitivityreactionsMechanismofhypersensitivityreactionoffourtypesRelateddiseasesEssay
DiscussONEofthefollowingstatementsHygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentdue
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