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