C24 Viral infection and immunity

1. C24Viral infection and immunity 樊晓晖 教授

2. 第24章 病毒的感染与免疫 Section I Mode of viral infection Direct person-to-person spread. Horizontal Transmission vertical infection Relies on PERSISTENCE of the agent to transfer infection from parents to offspring.

3. Transmission and portal of entry • Vertical transmission • Horizontal transmission

4. Several forms of vertical transmission can be distinguished: • 1.Neonatal infection at birth, e.g. gonorrhorea, AIDS. • 2.Infection in utero e.g. syphilis, CMV, Rubella (CRS), AIDS. • 3. Germ line infection - via ovum or sperm.

7. 第24章 病毒的感染与免疫 Section II Types of viral infection Inapparent infection ( Subclinical infection) . 1、 Apparent infection Acute infection 2、 Chronic infection 3、 PersistentInfection chronic latent Slow virus infections

8. 第24章 病毒的感染与免疫 PersistentInfection • ① Chronic Infection：Virus can be continuously detected ; mild or no clinical symptoms may be evident. • ② Latent infection：The Virus persists in an occult, or cryptic, from most of the time. There will be intermittent flare-ups of clinical disease , Infectious virus can be recovered during flare-ups . Latent virus infections typically persist for the entire life of the host • ③ Slow virus infection： A prolonged incubation period, lasting months or years, daring which virus continues to multiply. Clinical symptoms are usually not evident during the long incubation period .

10. 带状疱疹(水痘病毒感染后潜伏在脊髓后跟N节)

11. Mechanism of PersistentInfection • Immunity is weak； • Viral antigenicity is weak； • Viruses is in protective position； • Viral variation； • Viral genes integration.

12. 第24章 病毒的感染与免疫 Processes and fates of infections • local Infection processes： 2. systemic 1. die 2. Subclinical infection Infection fates： 3. Abortive infection 4. Recover • Animal model

13. 第24章 病毒的感染与免疫 Section III Pathogenicity of viruses

14. I. Effects of viral infection on cells • According to the interaction between host cells and viruses cytocidal effect include Steady state infection Apopotosis Transformation Integrated viral infection Formation of inclusion body

15. Cytocidal infection • Severe，cells lyse and die • Occur in non-enveloped virus • Cause Cytopathological effects(CPE) Cells rounding Degeneration, Aggregation Loss of attachments to substrate

16. 上皮细胞epithelial cells –腺病毒adenovirus uninfected early infection late infection slides from CDC

17. 上皮细胞epithelial cells –呼吸道合胞病毒respiratory syncytial virus uninfected respiratory syncytial virus slides from CDC

18. 纤维母细胞fibroblastic cells –单纯疱疹病毒herpes simplex virus uninfected late infection early infection slides from CDC

19. 纤维母细胞fibroblastic cells –脊髓灰质炎病毒poliovirus uninfected early infection late infection slides from CDC

20. Viral early protein Pathogenicity: • Blocking synthesis of cellular protein and nucleic acid • Toxicity of viral protein • Affect cellular lysosome • Alter the cellular organ 。 Some capsid destroy injury

21. 稳定状态感染Steady state infection • Enveloped viruses, • Without lyses of cells • Release by budding • Change of cell membrane • Formation of auto antigen and fusing of cells

22. Fig A multinucleate giant cell

23. 细胞凋亡apoptosis HIV

24. Cell transformation, SV40

25. Integration of viral genes • DNAviruses and retro-viruses • The viral genetic information may become integrated as DNA in the cellular genome or may persist as episomal DNA in these surviving cells. • Oncogenic transformation occur • New antigen appears.

26. Interaction between viruses and hosts • Types of infection. • HBV: steady and integration infection • Herpesviruses: Cytocidal,steady and integration infections. • Most viruses, only one type infection

27. 二、 Effects of virus infection on immune system • Inhibit or destroy immune system • Pathological effects caused by humorol immunity • Pathological effects caused by cellular immunity

28. Inhibit or destroy immune system • HIV • Measle virus

29. Pathological effects caused by humorol immunity • Viruses infect cells, new Ag present on cell membrane →typeⅡhypersensitivity damage cells • Viral Ag combines with Ab, precipitate on basic membrane of blood vessel→type III型 hypersensitivity damage cells.

30. Pathological effects caused by cellular immunity • Viruses infect cells, new Ag present on cell membrane →recognized by specific CTL) typeIVhypersensitivity kills cells

31. Section 4 Anti-virus immunity IFN Innate immunity （ nonspecific） NK cells Humorol immunity Adaptive immunity （ specific） Cellular immunity

32. IFN • Interferons are proteins produced by cells infected with viruses, or exposed to certain other agents, which protect other cells against virus infection or decrease drastically the virus yield from such cells. Interferon itself is not directly the anti-viral agent, but it is the inducer of one or many anti-viral mechanisms

33. Interferon inducing agents • (1) Viruses. • (2) dsRNA is a potent inducer, both viral intermediates, and synthetic polyI-C.   • (4) Certain Bacterial infections, and the production of endotoxin.   • (5) Metabolic activators/inhibitors. Mitogens for gamma induction, also a variety of tumor promoters induce IFNs. , in particular PTA-phorbol tetradecanoate acetate, butyrate, dexamethasone

34. Kinds and sources IFNs Kinds Principal cell source INF-αEpithelium and leukocytestype I IFN IFN-βFibroblasts IFN-γT lymphocytestypeⅡIFN

35. Mechanism of action • Release from an initial infected cell occurs • IFN binds to a specific cell surface receptor on an other cell • IFN induces the “antiviral state” : synthesis of protein kinase, 2’5’ oligoadenylate synthetase, and ribonuclease L • Viral infection of the cell activates these enzymes • Inhibition of viral and cellular protein synthesis occurs

37. Application of IFNs • Anti viral infection • Anti tumor treatment • Immuoregulation。

38. Diseases currently treated withIFN-alpha and IFN-beta • hepatitis C • hepatitis B • papilloma warts and early trials with cervical carcinoma • Kaposi sarcoma of AIDS, • colon tumors • kidney tumors ( usually in combination with other drugs). • Basal cell carcinoma • Breast cancer combined with tamoxifan.

39. Nature killer/ NK cell NK cells are Activated by IFN-alpha/beta NK cells are Activated by IFN-alpha and IL-2 and Activate macrophage NK cells target and kill virus infected cells

40. NK cell

41. Macrophages • Macrophagesfilter ciral particles from blood • Macrophages inactivate opsonized virus particles • Macrophages present viral antigen to CD4 T cells

42. Complement • Enhancing neutralization of Antibody • Enhancing phagocytosis of virus particles • Lysis

43. 二 Specific anti-viral immunity • humorol • cellular

44. Overview of Specific immunity • specific recognition and selective elimination of foreign molecules. • Involves specificity, diversity, memory, and self/nonself recognition.

45. Humorol immunity • Abs against viruses • NeutrolizationAb:IgG、IgM、IgA • nonneutrolizing: otherantibody • Extracellular viral infections

46. Antibody

47. Antibody

48. Neutralization antibody • Neutralization ： Neutralization antibody binds virus to terminate the viral infectivity

49. Mechanism of neutralization Ab: • Block viruses to attach and penetrate • Virus combine with Ab to immune complex, facilitate the phygocytosis of macrophage • Ab combines with enveloped virus, activate complement to lyse virus

50. Cellular immunity • Intracellular viral infection • CTL • DTH