自身免疫性疾病-英五班

AutoimmunityandAutoimmuneDiseasesGuangjieChenDept.ofImmunologyandMicrobiology2021AutoimmunityisdefinedasanacquiredimmunereactivityagainstselfantigensThenormalphysiologicalactivityessence ----autoimmuneresponseLowaffinityIgM----CD5+B1----“natural〞AbspectrumAutoimmunediseasesoccurwhenautoimmuneresponsesleadtotissuedamageThepathologicalactivityessence----autoimmuneresponseImmunologicaltolerancefailstoeliminateorcontrolpathogenicself-reactivelymphocytesBreakingofself-toleranceEhrlich’s“Horrorautotoxicus〞I.ThefeaturesandclassificationofAID1.Features2.ClassificationOrganspecificNonorganspecific

II.ThepathologicalmechanismofAID1.autoantibodybindingtocellmembrane2.autoantibodybindingtomembranereceptor3.autoantibodybindingtoextracellularcomponents4.Theeffectofimmunecomplexdeposition5.TheeffectofautoreactiveTcellTypeIIhypersensitivity〔autoantibody)Theeffectofautoantibodybindingtocellmembrane〔IgM、IgG〕AutoimmunehemolyticanemiathrombocytopenicpurpuraHemolyticdiseaseofthenewborninducedbyRhesusincompatibilityThe

effectofautoantibodytomembranereceptorMyastheniagravisGraves

diseaseThyroidepithelialcellTSH-RTSHT3、T4Anti-TSH-RAbFigure13-29part1of23.TheeffectofautoantibodytoextracellularcomponentsGoodpasturessyndrome

*antibasementmembrane〔kidney,lung〕typeIVcollagenAb4.Theeffectofimmunecomplexdeposition*TypeIIIhypersensitivity(1)SLE〔2〕RA(2)RA5.TheeffectofautoreactiveTcell*TypeIVhypersensitivityMultiplesclerosis(MS〕 Th1、Tc、MBPTypeIdiabetesmellitusTc→βcellIII.PathogenicfactorsrelatedtoAIDAntigen-relatedfactorsReleasingofsequesteredantigen

AlterationofselfantigenpropertiesMolecularmimicry

commonantigen→crossreaction

streptococcus—kidney,heart

Epitopespreading2.Abnormalitiesofimmuneregulation

Failureofself-tolerance

AbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersBrokencentralandperipheraltoleranceAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersAutoantigensAutoantigeninducedTcellexpansionAutoimmunelymphoproliferativesyndrome,ALPSAbnormalexpressionofFas/FasLPolyclonalactivationofTandBcellsAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersDysfunctionofTregAbnormalexpressionofMHC-II3.GeneticfactorsAssociationofHLA

withautoimmunediseaseOthergenes

C1q,C4

genedeficiency：SLE

DNasedeficiency

：SLE

mutantCTLA-4：Diabetes4.OtherfactorsGenderAgeEnvironmentfactorIV.ImmunologicalcontrolstrategiesDeletionfactorswhichinduceabnormalself-toleranceInhibitionofimmuneresponsetoautoAgRebuildingself-toleranceControlofinfectionAdministrationofimmunosuppressivedrug AntibodiesautoAg……

AutoreactiveT

cellSynovialfibroblastM

IFN-,IL-17IL-1,IL-15IL-1,TNF-ChondrocyteOsteoclastMMPs,IL-6,IL-8,GM-CSFCartilageandbonedestructionTNFinhibitorsIL-1inhibitorIL-6inhibitorOraltoleranceTcellvaccineMMPsTcellcostimulatoryblockersArchivumImmunologiaeetTherapiaeExperimentalis(AITE),2021,58：27-36TargetNameoftherapeuticProductofdescriptionStageofdevelopmentCurrentTNF-

EtanerceptSolublep75TNFR–humanIgG1FcfusionproteinLisencedInfliximabChimericmAbspecificforTNF-

LisencedAdalimumabHumanizedmAbspecificforTNF-αLisencedIL-1AnakinraIL-1raLisencedIL-6TocilizumabHumanizedmAbspecificforIL-6RPhaseIIIclinicaltrialsInperspectiveIL-1AMG108HumanizedmAbspecificforIL-1βPhaseIIclinicaltrialsIL-15HuMaxIL-15(AMG714)HuMaxIL-15(AMG714)PhaseIIclinicaltrialsIL-17LubbertsE(2008)IL-21AnderssonAKeta