W6感染与免疫医学PPT

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1、InfectionandImmunity12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)。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

2、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

3、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。2008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。 传染病传染病InfectiousDiseases简介简介手足口病皮疹分布手足口病皮疹分布:1.颊粘膜和手指颊粘膜和手指2.手掌手掌3.足底足底4.唇粘膜唇粘膜5.咽峡炎。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个别患者可引起心肌炎、肺水肿、无菌性脑膜脑炎等并发症!HFMD3A human syndrome caused by intestinal viruses of the Pic

4、ornaviridae family. The most common strains causing HFMD are Coxsackie A virus and Enterovirus 71 (EV71).Hand, foot and mouth disease (HFMD)手-足-口病4Non-enveloped,positive-strandedRNAviruseswithanicosahedral(20)capsidGenomeRNAhasaproteinprimerfortranscriptionbyRNApolymerasePicornavirus(small RNA virus

5、)5手足口病的流行病学手足口病的流行病学HFMD的流行:的流行:1957年新西兰首发,全球性传染病年新西兰首发,全球性传染病2008年在中国年在中国CoxA16和和EV71共循环引发共循环引发HFMD传染源和传播途径:传染源和传播途径:粪粪-口途径传播口途径传播呼吸道传播呼吸道传播接触传播(疱疹液中含大量病毒)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易感人群:婴幼儿和免疫力低下的人易感6Aimsforstudiesinthefieldof“InfectionandImmunity”MechanismPreventionTherapies垃圾猪养殖场垃圾猪养殖场78Av

6、ianinfluenza(禽流感)(禽流感)HA:(hemagglutinin): 血细胞凝集素;NA: (neuraminidase): 神经氨酸苷酶。Avian influenza HA viruses bind alpha 2-3 sialic acid receptors, while human influenza HA viruses bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors.Av

7、ian flu: Asia, low hygiene conditions and close quarter.Spreading: poultry trades or wild bird migrations?9I)Commonpathogens10AdenovirusHerpesvirusPapillomavirusHepatitis B VirusParvovirus100 nmPockenvirusDNA-Viren11100 nmRNA-Viren ParamyxovirusRotavirusEnterovirusInfluenza-VirusRetrovirusMumps, Mas

8、ern“CoronavirusSARS“1213- a novel coronavirus SARS- Severe Acute Respiratory Syndrome Outbreak in March 200314Human Immunodeficiency Virus (HIV)RetrovirusMacrophagesCD4+ T cellsgp12015II)Hostdefensesystem16FusionofaviruswiththeplasmamembraneafterattachmenttoacellsurfacereceptorFusionofaviruswiththem

9、embraneofanendosome17ReceptorsVirusVirusReceptorReceptorHIVHIVCCR5 ,CD4 ,CCR5 ,CD4 ,CXCR4 CXCR4 EB-VirusEB-VirusCR2CR218TBK1IKKj jIKK/ /IRF3/7NF-BMAPKsIFN-/Inflammatory cytokinesATFsAP-1TLR3EndosomevirusdsRNATLR7/8ssRNATLR9CpGDNARIG-I病毒感染过程中的病原识别受体病毒感染过程中的病原识别受体19Viralinfectionandearlyhostresponses2

10、0CourseofImmuneResponseduringInfluenzaInfectionUpperrespiratoryinfectionSubbaraoetal.2006,Immunity2122Goff (2004, Mol. Cell)宿主限制性因子的抗病毒作用宿主限制性因子的抗病毒作用?232425262728IFN 2930APCCD4+MHCIMHCIIBTCRCD8+IgEIgGGIIIIIIVIEffect/Injuryvia:antibodycytotoxicitycytokinesAntigensTissuedamageAdaptiveimmuneresponse31

11、3233ImmunologicalMemory34III)ViralescapemechanismsmAb35EscapebyHidingBloodbarrier:brainKidney36EscapebyLatencyThe immune system remains ignorant to latently infected cells that do not express viral antigens.37水痘水痘带状疱疹带状疱疹EscapebyantigenicitychangesAntigenic drift and shift in influenza virusAntigeni

12、c drift and shift in influenza virus38Antigenshift1900 H3N81918 H1N1 (Spanish)1957 H2N2 (Asian)1968 H3N2 (Hong Kong)cell infected withhuman and avian strains of influenza virusreassortment of vRNAshuman virus H1N1avian virusHA and HN genes from avian strain, kept five genes from circulating human st

13、rainMixture of viruses, includingH2N2 virus39EscapebySubvertingAntigenProcessingandAntigenPresentation40EscapebyDestructionofImmuneCellsHIV-1 virus, which infects and destroys CD4 + TcellsHBV41InhibitionofTargetCellLysis42InhibitionofNaturalKillerCellActivityInhibition of natural killer (NK) cell fu

14、nctions. Viral products ( gray outline) inhibitNK cell activity by providing class I major histocompatibility complex (MHC) decoysCMVUL1843InhibitionofInterferonsInterferenceofCytokineFunctionsHIV,EBAdenovirus(E3)TNF44CytokineMimeticsReceptorMimeticsEBVproducesanIL-10likemolecule(212)thatinhibitssyn

15、thesisofIL-12andthusthegenerationofTh1immuneresponses.HerpesvirusesandpoxvirusesencodeanumberofsecretedproteinsthatbindchemokinesorcytokinesMolluscumcontagiosumvirus,aswellasOrthopoxvirus species,secreteIL-18bindingproteinsInhibitionofInterleukin-1845InhibitionofComplementActivationVCPbindsC3bandC4b

16、,thusinhibitingtheirfunctionandcausingtheiraccelerateddegradation46MCMVencodesacrystallizedfragment(Fc)?receptorlikemoleculethatsubvertsantibody-mediatedlysisofinfectedcellsCrystallizedFragment(Fc)ReceptorMimetics47ImmunetoleranceLCMVHBV48immunopathology!VI)病毒感染的致病机理病毒感染的致病机理49CellularimmunityAntibo

17、dyandcomplementCytokinesViralinfectionandImmunopathologyTissue damage by virus-induced immune responses:50细胞因子在感染免疫病理中的作用细胞因子在感染免疫病理中的作用Nature Immunology (2006) J Pathol. (2006)IP-10expressionafterSARSvirusinfectionSARSpatientControlJ Immunol. (2005)WTIFN R-/-IFNababR-/-EEIFNsinfluenceEosinophilinfi

18、ltration51Molecularmimicry:aviralantigenshowssequencehomologywithaself-proteinImmunecomplexesAbnormalregulationofT-cellresponsesAutoimmunityafterviralinfection52V)ImmunologicalPreventionandTherapy53Vaccination54BACTERIAL INFECTION5555Septic shock Bacterial infection induced acute inflammatory states

19、 Bacterial infection induced acute inflammatory states The mortality rate for septic shock still approaches 50% despite antimicrobial therapy and supportive care.LPS:an endotoxin in the outer membrane of Gram-negative bacteria.56The LPS-induced TLR4 pathwaysThe LPS-induced TLR4 pathways 57Inflammato

20、ry cytokines and septic shockPro-inflammatory mediatorsTNF-interleukin 1interferon InflammationInnate Immunity:Anti-Infectious response Deleterious effectsOrgan dysfunctionSevere58591)结核分支杆菌)结核分支杆菌结核病结核病(tuberculosis)(tuberculosis)是由结核杆菌是由结核杆菌(tubercle bacillus)(tubercle bacillus)引起的一种慢性肉芽肿性炎。以肺结核最常

21、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。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。 Helicobacter pyloriHelicobacter pylori : :l l inhabits various areas of the stomach and duodenum. inhabits various areas of the stomach and duodenum. l l causes a chronic low-level inflammation of the stomach l

22、ining causes a chronic low-level inflammation of the stomach lining l l is strongly linked to the development of duodenal and gastric ulcers is strongly linked to the development of duodenal and gastric ulcers and stomach cancer. and stomach cancer. 602) Helicobacter pylori and CancerImmunohistochem

23、ical staining of H. pylori from a gastric biopsy Over 80% of individuals infected with the bacterium are asymptomatic.6061 Inflammation in the stomach (gastritis) as well as ulceration of the stomach or duodenum (peptic ulcer disease) is the result of an infection of the stomach caused by the bacter

24、ium Helicobacter pylori.61In susceptible hosts, Helicobacter pylori colonizes the stomach and induces upregulation of expression of MHC class II molecules and co-stimulatory molecules by epithelial cells, facilitating the presentation of H. pylori antigens by epithelial cells to gastric mucosal T ce

25、lls, which are mainly of the T helper 1 (TH1)-cell type. 623)MYCOPLASMA INFECTIONMycoplasmas are widespread in nature as conditional Mycoplasmas are widespread in nature as conditional pathogenpathogen, which may be the unique prokaryote that which may be the unique prokaryote that can cohabit with eukaryote and interact permanently with can cohabit with eukaryote and interact permanently with mammalian cellsmammalian cells6363考试:考试:1)60分:课本的基础知识分:课本的基础知识2)40分:应用和发挥(题目自己定)分:应用和发挥(题目自己定)3)附加)附加20分:平时表现分:平时表现,文献报告文献报告64

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