感染与免疫.ppt

InfectionandImmunity,（Anti-viralimmunology）,1,2,由病原体引起，在人与人、动物与动物或人之间相互传播的一类疾病病原体：微生物或寄生虫（寄生虫病）。,1、甲类传染病甲类传染病也称为强制管理传染病，包括：鼠疫、霍乱。对此类传染病发生后报告疫情的时限，对病人、病原携带者的隔离、治疗方式以及对疫点、疫区的处理等，均强制执行。2、乙类传染病乙类传染病也称为严格管理传染病，包括：传染性非典型肺炎、艾滋病、病毒性肝炎、脊髓灰质炎、人感染高致病性禽流感、麻疹、流行性出血热、狂犬病、流行性乙型脑炎、登革热、炭疽、细菌性痢疾、阿米巴性痢疾、肺结核、伤寒和副伤寒、流行性脑脊髓膜炎、百日咳、白喉、新生儿破伤风、猩红热、布鲁氏菌病、淋病、梅毒、钩端螺旋体病、血吸虫病、疟疾、甲型H1N1流感（原称人感染猪流感）。对此类传染病要严格按照有关规定和防治方案进行预防和控制。其中，传染性非典型肺炎、炭疽中的肺炭疽、人感染高致病性禽流感和甲型H1N1流感这四种传染病虽被纳入乙类，但可直接采取甲类传染病的预防、控制措施。3、丙类传染病丙类传染病也称为监测管理传染病，包括：流行性感冒、流行性腮腺炎、风疹、急性出血性结膜炎、麻风病、流行性斑疹伤寒、地方性斑疹伤寒、黑热病、包虫病、丝虫病，除霍乱、细菌性和阿米巴性痢疾、伤寒和副伤寒以外的感染性腹泻病。对此类传染病要按国务院卫生行政部门规定的监测管理方法进行管理。2019年5月2日，卫生部已将手足口病列入传染病防治法规定的丙类传染病进行管理。,传染病InfectiousDiseases简介,手足口病皮疹分布:1.颊粘膜和手指2.手掌3.足底4.唇粘膜5.咽峡炎。个别患者可引起心肌炎、肺水肿、无菌性脑膜脑炎等并发症!,HFMD,3,AhumansyndromecausedbyintestinalvirusesofthePicornaviridaefamily.ThemostcommonstrainscausingHFMDareCoxsackieAvirusandEnterovirus71(EV71).,Hand,footandmouthdisease(HFMD)手-足-口病,4,Non-enveloped,positive-strandedRNAviruseswithanicosahedral(20)capsidGenomeRNAhasaproteinprimerfortranscriptionbyRNApolymerase,Picornavirus(smallRNAvirus),5,手足口病的流行病学,HFMD的流行：1957年新西兰首发，全球性传染病2019年在中国CoxA16和EV71共循环引发HFMD传染源和传播途径：粪-口途径传播呼吸道传播接触传播（疱疹液中含大量病毒）易感人群：婴幼儿和免疫力低下的人易感,6,9,I)Commonpathogens,10,Adenovirus,Herpesvirus,Papillomavirus,HepatitisBVirus,Parvovirus,Pockenvirus,DNA-Viren,11,RNA-Viren,Paramyxovirus,Rotavirus,Enterovirus,Influenza-Virus,Retrovirus,Mumps,Masern“,Coronavirus,SARS“,12,13,-anovelcoronavirus,SARS-SevereAcuteRespiratorySyndrome,OutbreakinMarch2019,14,HumanImmunodeficiencyVirus(HIV),RetrovirusMacrophagesCD4+Tcells,gp120,15,II)Hostdefensesystem,16,Fusionofaviruswiththeplasmamembraneafterattachmenttoacellsurfacereceptor,Fusionofaviruswiththemembraneofanendosome,17,Receptors,18,TBK1,IKKj,IKK/,IRF3/7,NF-B,MAPKs,IFN-/,Inflammatorycytokines,ATFs,AP-1,TLR3,Endosome,virus,dsRNA,TLR7/8,ssRNA,TLR9,CpGDNA,RIG-I,病毒感染过程中的病原识别受体,19,Viralinfectionandearlyhostresponses,20,CourseofImmuneResponseduringInfluenzaInfection,Upperrespiratoryinfection,Subbaraoetal.2019,Immunity,21,22,Goff(2019,Mol.Cell),宿主限制性因子的抗病毒作用,?,23,24,25,26,27,28,IFNg,29,30,Adaptiveimmuneresponse,31,32,33,ImmunologicalMemory,34,III)Viralescapemechanisms,mAb,35,EscapebyHiding,Bloodbarrier:brain,Kidney,36,EscapebyLatency,Theimmunesystemremainsignoranttolatentlyinfectedcellsthatdonotexpressviralantigens.,37,水痘,带状疱疹,Escapebyantigenicitychanges,38,Antigenshift,1900H3N8,1918H1N1(Spanish),1957H2N2(Asian),1968H3N2(HongKong),39,EscapebySubvertingAntigenProcessingandAntigenPresentation,40,EscapebyDestructionofImmuneCells,HIV-1virus,whichinfectsanddestroysCD4+Tcells,HBV,41,InhibitionofTargetCellLysis,42,InhibitionofNaturalKillerCellActivity,Inhibitionofnaturalkiller(NK)cellfunctions.Viralproducts(grayoutline)inhibitNKcellactivitybyprovidingclassImajorhistocompatibilitycomplex(MHC)decoys,CMVUL18,43,InhibitionofInterferons,InterferenceofCytokineFunctions,HIV,EB,Adenovirus(E3)TNF,44,CytokineMimetics,ReceptorMimetics,EBVproducesanIL-10likemolecule(212)thatinhibitssynthesisofIL-12andthusthegenerationofTh1immuneresponses.,Herpesvirusesandpoxvirusesencodeanumberofsecretedproteinsthatbindchemokinesorcytokines,Molluscumcontagiosumvirus,aswellasOrthopoxvirusspecies,secreteIL-18bindingproteins,InhibitionofInterleukin-18,45,InhibitionofComplementActivation,VCPbindsC3bandC4b,thusinhibitingtheirfunctionandcausingtheiraccelerateddegradation,46,MCMVencodesacrystallizedfragment(Fc)?receptorlikemoleculethatsubvertsantibody-mediatedlysisofinfectedcells,CrystallizedFragment(Fc)ReceptorMimetics,47,Immunetolerance,LCMV,HBV,48,immunopathology!,VI)病毒感染的致病机理,49,CellularimmunityAntibodyandcomplementCytokines,ViralinfectionandImmunopathology,Tissuedamagebyvirus-inducedimmuneresponses:,50,细胞因子在感染免疫病理中的作用,51,Molecularmimicry:aviralantigenshowssequencehomologywithaself-proteinImmunecomplexesAbnormalregulationofT-cellresponses,Autoimmunityafterviralinfection,52,V)ImmunologicalPreventionandTherapy,53,Vaccination,54,BACTERIALINFECTION,55,55,SepticshockBacterialinfectioninducedacuteinflammatorystates,Themortalityrateforsepticshockstillapproaches50%despiteantimicrobialtherapyandsupportivecare.,LPS:anendotoxinintheoutermembraneofGram-negativebacteria.,56,TheLPS-inducedTLR4pathways,57,Inflammatorycytokinesandsepticshock,Pro-inflammatorymediatorsTNF-interleukin1interferonInflammation,InnateImmunity:Anti-Infectiousresponse,Deleteriouseffects,Organdysfunction,Severe,58,59,1）结核分支杆菌,结核病(tuberculosis)是由结核杆菌(tuberclebacillus)引起的一种慢性肉芽肿性炎。以肺结核最常见，但可见于全身各器官。典型病变为结核结节形成伴有不同程度干酪样坏死。,Helicobacterpylori:inhabitsvariousareasofthestomachandduodenum.causesachroniclow-levelinflammationofthestomachliningisstronglylinkedtothedevelopmentofduodenalandgastriculcersandstomachcancer.,60,2)HelicobacterpyloriandCancer,ImmunohistochemicalstainingofH.pylorifromagastricbiopsy,Over80%ofindividualsinfectedwiththebacteriumareasymptomatic.,60,61,Inflammationinthestomach(gastritis)aswellasulcerationofthestomachorduodenum(pepticulcerdisease)istheresultofaninfectionofthestomachcausedbythebacteriumHelicobacterpylori.,61,Insusceptiblehosts,HelicobacterpyloricolonizesthestomachandinducesupregulationofexpressionofMHCclassIImoleculesandco-stimulatorymoleculesbyepithelialcells,facilitatingthepresentationofH.pyloriantigensbyepithelialcellstogastricmucosalTcells,whicharemainl