病毒的感染与致病机制ppt课件

Chapter 21 The infection and pathogenic mechanism of virus Viral infection Origin of viral infection Exogenous infection (1) patient (2) carrier (3) animal (zoonotic disease) The pathway of viral infection 1. respiratory tract 2. digestive tract 3. damaged skin or mucous membranes 4. blood 5. arthropod vector 6. contact: sex contact (STD) The mode of viral infections horizontal transmission horizontal transmission Viruses transmit from person-to-person or Viruses transmit from person-to-person or animal to person animal to person vertical transmission vertical transmission Viruses transmit from mother to offspring Viruses transmit from mother to offspring through placenta through placenta - fetus, congenital infection, - fetus, congenital infection, (congenital deformity)(congenital deformity) through birth canal through birth canal - - infection of newborninfection of newborn through through breast breast milkmilk - - from from virus-infected virus-infected mothersmothers The viruses which can result in congenital infection rubella virus (RV) cytomegalovirus (CMV) herpes simplex virus-I (HSV-I) hepatitis B virus (HBV) human immunodeficiency virus (HIV) congenital deformity (先天性畸形) caused by rubella virus congenital deformity (先天性畸形) caused by HCMV Viral dissemination in vivo local infection systemic infection viremia skin/mucous membrane cell to cell nervous systemblood system The type of viral infection I. inapparent or subclinical infection viruses enter the body , but cause no apparent clinical syndrome. II. apparent infection or infectious disease. viruses enter the body ,which can cause apparent clinical syndrome. acute viral infection: viruses exist in the bodies for a short time (6 month) persistent viral infection: viruses exist in the bodies for a long time (6 month) persistent viral infectionpersistent viral infection 1) chronic infection: virus can be continuously detected. 2) latent infection : virus is usually not detectable but patient may have periodic out-breaks of disease. Such as HSV, VZV 3) slow virus infection: with long incubation periods (years), subacute ,progressive HIV； prion 4) delayed complication after acute viral infection Subacute Sclerosing Panencephalitis (SSPE) HSV HSV The pathogenesis of viral infection cell virus receptor attachment protein cell virus tropism I. virus cell interactions:I. virus cell interactions: 1. cytocidal infection virus which infect and replicate within cells causing the cells to lyse when the progeny virions are released. CPE (cytopathic effect ) 2. steady state infection viruses are produced from the infected cells but the cells are not killed by the process. - cell fusion such as HCMV - integration of viral Ag in cell membranes such as influenza virus, HBV cytopathic effect (CPE): n-The presence of the virus often gives rise to morphological changes in the host cell. Any detectable morphological changes in the host cell due to viral infection are known as a cytopathic effect. n-Cytopathic effects (CPE) may consist of cell rounding, disorientation, swelling or shrinking, death, detachment from the surface, etc. 3. inclusion body round, oval, or irregular-shaped bodies occurring in the cytoplasm or nucleus of virus- infected cells, which can be seen under the microscope. 4. cell apoptosis virus or viral protein(e.g.HIV) 5. viral genome integration integration: integration of the viral genome into cellular DNA. ( e.g. HIV) cell proliferation and transformation morphological change immortalization e.g. oncogenic virus oncogenic virus HBV- hepatocellular carcinoma HCV- hepatocellular carcinoma HPV - cervical carcinoma EBV - Burkitt lymphoma , nasopharyngeal carcinoma HHV8 - Kaposi Sarcoma HTLV - T cell leukemia II II .virusimmune system .virusimmune system interaction:interaction: immunopathological reactions- Hypersensitivity : type II response (cytotoxic) type III response (immune complex) type IV response (cell-mediated or delayed ) the injury of immune system induced by virus infection: immunosuppressive Virus infect immunocyte kill the immunocyte auto-immunity can be induced by viral infections Immunity against viral infections Section III Non-specific immunity Specific immunity Non-specific or innate immunity anatomical barriers humoral factors phagocytic cellsNK cells Acquired immunity humoral immunity cell-mediated immunity IgEIgG IgDIgM IgA perforin granzyme IFN- IL-2、TNF- Mucosa immunity CD+4Th1CD + 8CTL SIgA 1. skin and mucosa barrier ： the intact skin and mucous membranes of the body afford a high degree of protection against pathogens. secrete bactericin , fatty acid, lactic acid， lysozyme，lactoferrin etc. normal flora 2.hemo-spinal fluid barrier 3. placental barrier Anatomical barriers natural killer cell NK cell： Recognize change on virus-infected cells and destroy them by an extracellular killing mechanism. Role in early viral infection or carcinogenesis before activation of acquired immunity. inherent barriers Skin, Mucus, Ciliated epithelium , Low pH NK cell humoral and cellular components interferon (IFN) complement cytokines: TNF-, IL-1 and IL-6 Non-specific immunity InterferonInterferon（ IFN） conceptconcept : : A class of A class of proteinprotein (glycoprotein ) produced (glycoprotein ) produced by by cellscells in response to viral infection or in response to viral infection or other interferon other interferon inducersinducers that protected that protected other cells of same species from attack by a wide other cells of same species from attack by a wide range of viruses.range of viruses. production of IFN:production of IFN: interferon inducers:interferon inducers: PolyI:C virus bacterial endotoxin, etc production of IFN:production of IFN: IFN inducer acts on cell receptors IFN gene activation IFN mRNA transcribe IFN synthesis IFN released Characteristics :Characteristics : 1）not act directly on virus 2) broad-spectrum antiviral activity 3) host species specific: inhibit viral replication only in the species in which it was produced 4)Immuno opsonization and anti-tumor classification of IFNs: classification of IFNs: Hu IFN; Mu IFN IFN- IFN- IFN- Gene chromosome 9 chromosome 9 chromosome 12 cell blood mononuclear cell fibroblasts Ag-activated T cell anti-viral + + + Activity Modify- immune + + + responses antiviral activity:antiviral activity: cannot act directly on virus, but through induction of antiviral proteins (AVP). IFN 抗病毒作用示意图 Mechanisms: IFN combines cell surface AVP gene activation AVP mRNA transcribe AVP synthesis. AVP consists of : protein kinase R 2,5-A synthetase Specific immunity humoral immunity neutralization antibody cell mediated immunity CD +8CTL CD+4Th1 1.neutralization antibody bind to envelope or capsid protein of virus, blocking the virus replication adsorption by the inhibition of penetration IgG IgM IgAIgG IgM IgA mechanism: