1、Viral infection and immunity,Outline,Section I Viral pathogenesis Transmission routes Forms of viral infections Pathogenesis of viral infections Section II Antiviral immunity I. Innate immunity II. Specific immunity,Section 1 Viral pathogenesis,I. Transmission routes,The route of viral infectionA. H
2、orizontal transmissionB. Vertical transmission,A. Horizontal transmission,Respiratory tract Alimentary canal Skin and mucous membrane Genital tract Blood: Injection, transfusion, transplantation Arthropod-borne,civet cat,B. Vertical Transmission,Through placenta congenital infections, congenital def
3、ormityThrough birth canal infection of newborn,Vertical Transmission,The viruses which can result in congenital infections：rubella viruscytomegalovirus (CMV)herpes simplex virus (HSV)hepatitis B virus (HBV)human immunodeficiency virus (HIV),III. Virus Spread in the Host,Local Replication and Local S
4、pread Dissemination from the Portal of EntryMultiplication in Target Organs,A. Local Replication & Local Spread,B. Dissemination from the Portal of Entry,Dissemination through Bloodstream Viremia Dissemination through Nerves,Through Bloodstream,e.g. Poliovirus Measles virus Mumps virus,Through Nerve
5、s,e.g. Rabies virus Herpesvirus Poliovirus,II. Forms of viral infections,Acute viral infectionPersistent viral infection,Types of Viral Infection,Chronic infection Latent infection Slow infection,Natural history of acute and persistent human infections.,A. Chronic infection,Continued presence of inf
6、ectious virus following the primary infection and may include chronic or recurrent disease. Virus can be continuously detected. HBV, ect.,B. Latent infection,virus is usually not detectable but patient may have periodic out-breaks of disease. characterized by the lack of demonstrable infectious viru
7、s between episodes of recurrent diseaseHSV-1 in trigeminal ganglion HSV-2 in lumbar and sacral ganglia,Latency and recurrence in herpes simplex virus infections,Cold sores caused by herpes virus type 1 Recurrence of Latent virus infections,Shingles caused by varicella-zoster virus Recurrence of Late
8、nt virus infections,C. Slow virus infection,characterized by a long preclinical period extending for months or years from the time of exposure subacute progressive caused by ： Lentivirus (HIV) unconventional virus ( prion).,III. Pathogenesis of viral infections,Pathogenesis of viral infections,A. Di
9、rect damage to infected host cells B. Immunopathological injury,A. Direct damage to infected host cells,Cytocidal infection Steady state infection Integration and transformation,1. Cytocidal infection,Most productive infections are called cytocidal infection because they kill the host cells.,Cytopat
10、hic effect (CPE):,CPE are morphologic changes of host cells which infected by cytocidal virus, including cell swollen and round, cell lysis, or necrosis, and the formation of inclusion body, or polykaryocytes,CPE,CPE,Normal cells,Cytopathic effect, virus inclusion bodiesIn the some of virus-infected
11、 cells, round or oval patches with different color and structure can be observed at the light microscope.It is :Aggregation of virus particles Traces of the virus multiplication Virus induced cell reactants,Rabies virus inclusion bodies,negribody,Polykaryocytes,RSV infectec cells,Measels virus infec
12、ted cells,2. Steady state infection,Viral nucleic acid remain in specific host cells indefinitely; progeny virus may or may not be produced.Features : Commonly induced by enveloped virus Virus release by budding child virus New antigens may be produced-so, the infected cells may be attacked by host
13、immune system,3. Integration and transformation,Integration All or part of virus nucleic acid becomes integrated into the genome at specific or any site in host cells. Outcomes:is closely related to tumor formation.,B. Immunopathological injury,Hypersensitivity Inflammation cytokine Immune inhibitio
14、n Escape of immune response,Section II Antiviral immunity,Antiviral immunity,Innate Defenses,Adaptive defenses,IFN,Skin,Neutralizing antibody,I. Innate immunity,Innate immune factors against viral infection,Skin-mucous membrane Interferons Natural killer cell macrophages,a heterogeneous group of gly
15、coproteins produced by human and other animal cells after viral infection (or after exposure to other inducers.) Functions of IFNs:anti-virus, anti-tumor, immunomodulation,Interferon (IFN),Innate Defenses,principal source inducer IFN- leukocyte virus/dsRNAIFN- fibroblast virus/dsRNAIFN- lymphocyte a
16、ntigen / mitogen,Interferons,Innate Defenses,IFN genes normally are not expressed The strong inducers: Viruses and double-stranded RNAs Induction is not specific for a particularvirus,Induction IFN- /IFN- ,Interferon (IFN),one of the first lines of defense against viruses confer resistance to infect
17、ion to other cells. do not act directly on the virus, it acted on the cells to make them resistant to viral infection,NK cells or IFN,Nonspecific Defenses,Action of IFN- /IFN- ,act by induce the synthesis of three cell-encoded proteins 2,5-oligoadenylate synthetase Ribonuclease Protein kinase R,Inte
18、rferons,NK cell,Directly lysed virus infected cells no “lag phase” Effective Early No antigen-specific,NK cell,II. Adaptive immunity,Humoral immunity Neutralizing antibody,Antibodies which bind to the virus, usually to the peplomer and capsomer, and block the virus from binding and entering into hos
19、t cell,IgG, IgM, IgA can “neutralize” extracellular viruses,Neutralizing Antibody,IgA confers protection against viruses that enter through the respiratory and gastrointestinal mucosaIgM, IgG protect against virus enter or are spread through the blood,Virus infection without neutralizing Ab,Virus in
20、fection with neutralizing Ab,Cellular Immunity,Cellular ImmunityCytotoxic T lymphocytes (CTL),Features: MHC-restriction Viral specificity Highly effective Late phase Mostly important factor in recovery from the viral infection,Lysis of virus-infected cells by cytotoxic effector cells.,Questions,1.Types of virus infection 2. What is IFN? Features? How IFN is produced? what are the mechanisms of anti-viral effects of IFN? 3. What are adaptive defenses against viral infection?,
