W6感染与免疫医学PPT

Infection and Immunity,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。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Infectious Diseases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,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).,Hand, foot and mouth disease (HFMD)手-足-口病,4,Non-enveloped, positive-stranded RNA viruses with an icosahedral (20) capsid Genome RNA has a protein primer for transcription by RNA polymerase,Picornavirus (small RNA virus),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2008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,Aims for studies in the field of“Infection and Immunity”,MechanismPreventionTherapies,垃圾猪养殖场,7,8,Avian influenza （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.,Avian flu: Asia, low hygiene conditions and close quarter.Spreading: poultry trades or wild bird migrations?,9,I) Common pathogens,10,Adenovirus,Herpesvirus,Papillomavirus,Hepatitis B Virus,Parvovirus,Pockenvirus,DNA-Viren,11,RNA-Viren,Paramyxovirus,Rotavirus,Enterovirus,Influenza-Virus,Retrovirus,Mumps, Masern“,Coronavirus,SARS“,12,13,- a novel coronavirus,SARS - Severe Acute Respiratory Syndrome,Outbreak in March 2003,14,Human Immunodeficiency Virus (HIV),RetrovirusMacrophagesCD4+ T cells,gp120,15,II) Host defense system,16,Fusion of a virus with the plasma membrane after attachment to a cell surface receptor,Fusion of a virus with the membrane of an endosome,17,Receptors,18,TBK1,IKKj,IKK/,IRF3/7,NF-B,MAPKs,IFN-/,Inflammatory cytokines,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,Viral infection and early host responses,20,Course of Immune Response during Influenza Infection,Upper respiratory infection,Subbarao et al. 2006, Immunity,21,22,Goff (2004, Mol. Cell),宿主限制性因子的抗病毒作用,?,23,24,25,26,27,28,IFNg,29,30,Adaptive immune response,31,32,33,Immunological Memory,34,III) Viral escape mechanisms,mAb,35,Escape by Hiding,Blood barrier: brain,Kidney,36,Escape by Latency,The immune system remains ignorant to latently infected cells that do not express viral antigens.,37,水痘,带状疱疹,Escape by antigenicity changes,38,Antigenshift,1900 H3N8,1918 H1N1 (Spanish),1957 H2N2 (Asian),1968 H3N2 (Hong Kong),39,Escape by Subverting Antigen Processing and Antigen Presentation,40,Escape by Destruction of Immune Cells,HIV-1 virus, which infects and destroys CD4 + Tcells,HBV,41,Inhibition of Target Cell Lysis,42,Inhibition of Natural Killer Cell Activity,Inhibition of natural killer (NK) cell functions. Viral products ( gray outline) inhibitNK cell activity by providing class I major histocompatibility complex (MHC) decoys,CMVUL18,43,Inhibition of Interferons,Interference of Cytokine Functions,HIV,EB,Adenovirus (E3) TNF,44,Cytokine Mimetics,Receptor Mimetics,EBV produces an IL-10like molecule ( 212 ) that inhibits synthesis of IL-12 and thus the generation of Th1 immune responses.,Herpesviruses and poxviruses encode a number of secreted proteins that bind chemokines or cytokines,Molluscum contagiosum virus, as well as Orthopoxvirus species, secrete IL-18binding proteins,Inhibition of Interleukin-18,45,Inhibition of Complement Activation,VCP binds C3b and C4b, thus inhibiting their function and causing their accelerated degradation,46,MCMV encodes a crystallized fragment (Fc) ? receptorlike molecule that subverts antibody-mediated lysis of infected cells,Crystallized Fragment (Fc) Receptor Mimetics,47,Immune tolerance,LCMV,HBV,48,immunopathology!,VI) 病毒感染的致病机理,49,Cellular immunityAntibody and complementCytokines,Viral infection and Immunopathology,Tissue damage by virus-induced immune responses:,50,细胞因子在感染免疫病理中的作用,51,Molecular mimicry: a viral antigen shows sequence homology with a self-proteinImmune complexesAbnormal regulation of T-cell responses,Autoimmunity after viral infection,52,V) Immunological Prevention and Therapy,53,Vaccination,54,BACTERIAL INFECTION,55,55,Septic shock 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.,56,The LPS-induced TLR4 pathways,57,Inflammatory cytokines and septic shock,Pro-inflammatory mediatorsTNF-interleukin 1interferon Inflammation,Innate Immunity:Anti-Infectious response,Deleterious effects,Organ dysfunction,Severe,58,59,1）结核分支杆菌,结核病(tuberculosis)是由结核杆菌(tubercle bacillus)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。,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 of duodenal and gastric ulcers and stomach cancer.,60,2) Helicobacter pylori and Cancer,Immunohistochemical staining of H. pylori from a gastric biopsy,Over 80% of individuals infected with the bacterium are asymptomatic.,60,61,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 st