1、Infection and Immunity（Anti-viral immunology）1传染病传染病Infectious Diseases简介简介由病原体引起，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
2、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 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
3、、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。2HFMD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!3Hand,foot and mouth disease(H
4、FMD)手-足-口病?A human syndrome caused by intestinal viruses of the Picornaviridae family.?The most common strains causing HFMD are Coxsackie A virus and Enterovirus 71(EV71).4Picornavirus(small RNA virus)?Non-enveloped,positive-stranded RNA viruses?with an icosahedral(20)capsid?Genome RNA has a protein
5、 primer for transcriptionby RNA polymerase5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2019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6?9I)Common pathogens10DNA-VirenAdenovirusParvovir
6、us100 nmHepatitis B VirusPockenvirusHerpesvirusPapillomavirus11RNA-VirenRetrovirusInfluenza-VirusRotavirus100 nmParamyxovirus?Mumps,Masern“Coronavirus?SARS“Enterovirus1213SARS-Severe Acute Respiratory Syndrome-a novel coronavirus Outbreak in March 201914Human Immunodeficiency Virus (HIV)gp120Retrovi
7、rusMacrophagesCD4+T cells15II)Host defense system16Fusion of a virus with the plasma membrane after attachment to a cell surface receptorFusion of a virus with the membrane of an endosome 17ReceptorsVirusReceptorHIVCCR5,CD4,CXCR4 EB-VirusCR218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EndosomevirusdsRNACpGDNATLR3s
8、sRNATLR9TLR7/8RIG-IIKK/?/TBK1IKKjMAPKsIRF3/7NF-BAP-1ATFsIFN-/Inflammatory cytokines19Viral infection and early host responses20Course of Immune Response during Influenza Infection Upper respiratory infectionSubbarao et al.2019,Immunity2122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EntryReceptor Block(Fv4)RTUncoating
9、Block(TRIM5?(Lv1,Ref1)DNA DeaminationTransport(APOBEC3G)Trafficking Block(Fv1)IN?TranscriptionTranslationRNA Degradation(ZAP)AssemblyGoff(2019,Mol.Cell)232425262728IFN?2930Adaptive immune response Effect/Injury via:?antibodyAntigens?cytotoxicity?cytokinesTissuedamageAPCIIgEIIIgGBIIIG+TCRCD4VIMHC IIC
10、D8+MHC I313233Immunological Memory34III)Viral escape mechanismsmAb35Escape by Hiding?Blood barrier:brain?Kidney36Escape by LatencyThe immune system remains ignorant to latently infected cells that do not express viral antigens.水痘水痘带状疱疹带状疱疹37Escape by antigenicity changesAntigenic drift and shift in
11、influenza virus38Antigenshifthuman virusH1N1cell infected withhuman and avian strains of influenza virusavian virus1900 H3N81918 H1N1(Spanish)1957 H2N2(Asian)1968 H3N2(Hong Kong)Mixture of viruses,includingH2N2 virusHA and HN genes from avian strain,kept five genes from circulating human strain39rea
12、ssortment of vRNAsEscape by Subverting Antigen Processing and Antigen Presentation40Escape by Destruction of Immune CellsHIV-1 virus,which infects and destroys CD4+TcellsHBV41Inhibition of Target Cell Lysis42Inhibition of Natural Killer Cell ActivityCMVUL18Inhibition of natural killer(NK)cell functi
13、ons.Viral products(gray outline)inhibitNK cell activity by providing class I major histocompatibility complex(MHC)decoys43Interference of Cytokine FunctionsInhibition of InterferonsHIV,EBAdenovirus(E3)TNF44Inhibition of Interleukin-18Molluscum contagiosum virus,as well as Orthopoxvirus species,secre
14、te IL-18binding proteinsCytokine MimeticsEBV produces an IL-10like molecule(212)that inhibits synthesis of IL-12 and thus the generation of Th1 immune responses.Receptor MimeticsHerpesviruses and poxviruses encode a number of secreted proteins that bind chemokines or cytokines45Inhibition of Complem
15、ent ActivationVCP binds C3b and C4b,thus inhibiting their function and causing their accelerated degradation46Crystallized Fragment(Fc)Receptor MimeticsMCMV encodes a crystallized fragment(Fc)?receptorlike molecule that subverts antibody-mediated lysis of infected cells47Immune tolerance48LCMVHBVVI)
16、病毒感染的致病机理病毒感染的致病机理immunopathology!49Viral infection and ImmunopathologyTissue damage by virus-induced immune responses:?Cellular immunity?Antibody and complement?Cytokines50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(2019)IP-10 expression after SARS virus infectionSARS patientControlIFNs influen
17、ce Eosinophil infiltrationWTIFN?R-/-IFN?b?R-/-EEJ Pathol.(2019)J Immunol.(2019)51Autoimmunity after viral infection?Molecular mimicry:a viral antigen shows sequence homology with a self-protein?Immune complexes?Abnormal regulation of T-cell responses52V)Immunological Prevention and Therapy 53Vaccina
18、tion5455BACTERIAL INFECTION55Septic shockBacterial infection induced acute inflammatory states LPS:an endotoxin in the outer membrane of Gram-negative bacteria.The mortality rate for septic shock still approaches 50%despite antimicrobial therapy and supportive care.56The LPS-induced TLR4 pathways57I
19、nflammatory cytokines and septic shockPro-inflammatory mediatorsTNF-interleukin 1interferon Innate Immunity:Anti-Infectious responseInflammationSevereDeleterious Organ effectsdysfunction581）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。
20、以肺结核最常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。592)Helicobacter pylori and Cancer?Helicobacter pylori:inhabits various areas of the stomach and duodenum.causes a chronic low-level inflammation of the stomach lining is strongly linked to the development
21、 of duodenal and gastric ulcers and stomach cancer.Over 80%of individuals infected with the bacterium are asymptomatic.Immunohistochemical staining of H.pylori from a gastric biopsy 6060Inflammation in the stomach(gastritis)as well as ulceration of the stomach or duodenum(peptic ulcer disease)is the
22、 result of an infection of the stomach caused by the bacterium Helicobacter pylori.6161In 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.p
23、ylori antigens by epithelial cells to gastric mucosal T cells,which are mainly of the T helper 1(TH1)-cell type.623）MYCOPLASMA INFECTION?Mycoplasmas are widespread in nature as conditional pathogen，which may be the unique prokaryote that can cohabit with eukaryote and interact permanently with mammalian 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
