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1、病毒感染与自身免疫病VirusInfectionsandautoimmunityExogenousviruses:EBVMolecularmechanismforautoimmunityEnogenousviruses:HERVAutoimmunedisease:Arolefornewanti-viraltherapies?OutlineVirusInfectionsandautoimmunity(Background)自身免疫是机体失去对自身抗原的免疫耐受自身免疫病因与发病机制十分复杂:遗传背景，但环境因素和生活方式等的也有重要作用。研究表明：病毒和细菌等感染与自身免疫病的
2、发生、发展密切关系。一些病毒感染可导致机体失去对自身抗原免疫耐受，因而诱发、促进或加重自身免疫病。已证明某些病毒感染与一些自身免疫病密切相关，并发现病毒与宿主细胞的某些基因或其蛋白分子之间存在着结构类似性，因而可发生交叉免疫反应性。这种分子模拟假说获动物实验的支持。少数T细胞克隆逃避阴性选择进入外周识别自身抗原通过激活诱导细胞死亡（AICD)(FasL-Fas-凋亡）部分T细胞克隆逃避AICD识别自身抗原自身免疫病(AID)T细胞发育过程自身耐受形成及逃避机制B细胞发育过程自身耐受形成及逃避机制克隆清除结合－克隆无能克隆忽视不结合－克隆发育成熟激活自身免疫病自身免疫病激活B细
3、胞骨髓细胞表面抗原HostMHCLossofToleranceImmunesystemdefectsSusceptibilityGenesEndogenousVirusesAutoimmunediseaseEnvironmentandautoimmunityChemicalsubstancesMicrobialAgentsdrugsUVBlightVaccinestyphoid,influenza,meningococcal,tetanustoxoid,measles,mumps,andrubellaDiet/Nutrition新西兰小鼠(NzB)自发产生抗DNA抗红细胞抗体
4、溶血性贫血狼疮性肾炎自然发生新西兰小鼠(NZW)不发生系统性红斑狼疮(SLE)NZBXNZW(F1)杂交小鼠抗DNA和其他核抗体与人类SLE类似感染病毒感染病毒自身抗体效价更高自身免疫病的发生更早发生自身免疫病Theseobservationslendfurthersupportthatbothgeneticandenvironmentalfactorsplayaroleinautoimmunedisease.ExogenousvirusesExogenousmicrobialagents,suchasbacteriaorviruses,interactwithandsome
5、timesmightoverridethehumanimmunesystemtocauseinfectiousdiseases,cancersandautoimmunity.Exogenousviralagentshavealsobeenimplicatedaspotentialtriggersorpathogenicagentsofautoimmuneconditions.ViruseswhichhavebeenlinkedtothepathogenesisofSLEinclude：Epstein-BarrVirus(EBV)Cytomegalovirus(CMV),par
6、vovirus(细小)B19HumanPapillomaVirus(HPV),HumanHerpesVirus(HHV-6),HHV-7,HHV-8,DenguevirusHIVhumanTcelllymphotropicvirus(HTLV,人类嗜T细胞病毒)EBVasapotentialviralagentinSLEInSLE,EBVhasbeenhighlightedasapotentialpathogenicagentthroughserologicalstudiesofpatientsthathaveshownantibodiestoearlyantigens,ca
7、psidandlatentmembraneproteinsinmuchhigherfrequencyascomparedtocontrolsinpediatricSLE,99%ofpatientsareanti-EBVAb+comparedto70%ofcontrolsInpeoplewithSLE,thenumberofEBVinfectedBcellsiselevated10to100timesoverthelevelsincontrols,andtheamountoffreevirusinseru
