w6感染與免疫

1、Infection and Immunity,（Anti-viral immunology）,1,2,由病原體引起，在人與人、動物與動物或人之間相互傳播的一類疾病病原體：微生物或寄生蟲（寄生蟲?。?。,1、甲類傳染病 甲類傳染病也稱為強制管理傳染病，包括：鼠疫、霍亂。 對此類傳染病發(fā)生后報告疫情的時限，對病人、病原攜帶者的隔離、治療方式以及對疫點、疫區(qū)的處理等，均強制執(zhí)行。 2、乙類傳染病 乙類傳染病也稱為嚴格管理傳染病，包括：

2、傳染性非典型肺炎、艾滋病、病毒性肝炎、脊髓灰質(zhì)炎、人感染高致病性禽流感、麻疹、流行性出血熱、狂犬病、流行性乙型腦炎、登革熱、炭疽、細菌性痢疾、阿米巴性痢疾、肺結(jié)核、傷寒和副傷寒、流行性腦脊髓膜炎、百日咳、白喉、新生兒破傷風(fēng)、猩紅熱、布魯氏菌病、淋病、梅毒、鉤端螺旋體病、血吸蟲病、瘧疾、甲型H1N1流感（原稱人感染豬流感）。 對此類傳染病要嚴格按照有關(guān)規(guī)定和防治方案進行預(yù)防和控制。其中，傳染性非典型肺炎、炭疽中的肺炭疽、人感染高致病性禽

3、流感和甲型H1N1流感這四種傳染病雖被納入乙類，但可直接采取甲類傳染病的預(yù)防、控制措施。 3、丙類傳染病 丙類傳染病也稱為監(jiān)測管理傳染病，包括：流行性感冒、流行性腮腺炎、風(fēng)疹、急性出血性結(jié)膜炎、麻風(fēng)病、流行性斑疹傷寒、地方性斑疹傷寒、黑熱病、包蟲病、絲蟲病，除霍亂、細菌性和阿米巴性痢疾、傷寒和副傷寒以外的感染性腹瀉病。 對此類傳染病要按國務(wù)院衛(wèi)生行政部門規(guī)定的監(jiān)測管理方法進行管理。2008年5月2日，衛(wèi)生部已將手足口病列入傳染病防

4、治法規(guī)定的丙類傳染病進行管理。,傳染病〔Infectious Diseases〕簡介,,手足口病皮疹分布: 1. 頰粘膜和手指 2. 手掌 3. 足底 4. 唇粘膜 5.咽峽炎。個別患者可引起心肌炎、肺水腫、無菌性腦膜腦炎等并發(fā)癥!,HFMD,3,A human syndrome caused by intestinal viruses of the Picornaviridae family. The most commo

5、n 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 protei

6、n primer for transcription by RNA polymerase,Picornavirus (small RNA virus),5,手足口病的流行病學(xué),HFMD的流行：1957年新西蘭首發(fā)，全球性傳染病2008年在中國CoxA16 和EV71 共循環(huán)引發(fā)HFMD傳染源和傳播途徑：糞-口途徑傳播呼吸道傳播接觸傳播（皰疹液中含大量病毒）易感人群：嬰幼兒和免疫力低下的人易感,6,9,I) Co

7、mmon 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“,

8、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 

9、; 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,,,IKKα/β/?/,,IRF3/7,,,NF-κB,,,,MAPKs,,,,IFN-α/β

10、,,,,Inflammatory cytokines,,,ATFs,AP-1,,,TLR3,Endosome,virus,dsRNA,,,,,TLR7/8,,ssRNA,,,TLR9,,CpGDNA,,,,,,,,,,,,,,,,,RIG-I,,,,病毒感染過程中的病原識別受體,19,Viral infection and early host responses,20,Course of Immune Response durin

11、g 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,I

12、II) 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,帶狀皰疹,Escape

13、 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

14、 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

15、 ( 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)

16、 TNF,44,Cytokine Mimetics,Receptor Mimetics,EBV produces an IL-10–like molecule ( 212 ) that inhibits synthesis of IL-12 and thus the generation of Th1 immune responses.,Herpesviruses and poxviruses encode a number of

17、secreted proteins that bind chemokines or cytokines,Molluscum contagiosum virus, as well as Orthopoxvirus species, secrete IL-18–binding proteins,Inhibition of Interleukin-18,45,Inhibition of Complement Activation,VCP bi

18、nds C3b and C4b, thus inhibiting their function and causing their accelerated degradation,46,MCMV encodes a crystallized fragment (Fc) ? receptor–like molecule that subverts antibody-mediated lysis of infected cells,Crys

19、tallized Fragment (Fc) Receptor Mimetics,47,Immune tolerance,LCMV,HBV,48,immunopathology!,VI) 病毒感染的致病機理,49,Cellular immunityAntibody and complementCytokines,Viral infection and Immunopathology,Tissue damage by virus-

20、induced immune responses:,50,細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 infectio

21、n,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% despi

22、te 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-

23、αinterleukin 1interferon γ…Inflammation,Innate Immunity:Anti-Infectious response,,,Deleterious effects,,Organ dysfunction,Severe,58,59,1）結(jié)核分支桿菌,結(jié)核病(tuberculosis)是由結(jié)核桿菌(tubercle bacillus)引起的一種慢性肉芽腫性炎。以肺結(jié)核最常見，但可見于全

24、身各器官。典型病變?yōu)榻Y(jié)核結(jié)節(jié)形成伴有不同程度干酪樣壞死。,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

25、 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,Inf

26、lammation 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 bacterium Helicobacter pylori.,61,In susceptible hos

27、ts, 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 epit

28、helial cells to gastric mucosal T cells, which are mainly of the T helper 1 (TH1)-cell type.,62,3）MYCOPLASMA INFECTION,Mycoplasmas are widespread in nature as conditional pathogen， which may be the unique prokaryote that