AIDS & IMMUNOLOGY

1. AIDS & IMMUNOLOGY Immunopathogenesis of AIDS Chief speaker: 董玉雷 郑 瑞

2. Basic conception • AIDS Acquired Immuno -deficiency Syndrome • HIV Human Immuno -deficiency Virus • HIV-1 : worldwide • HIV-2 : west Africa & India

3. The problem we will mention: the structure of HIV 1 . Brief introduction the gene group of HIV replication period and mutation rate classical way mediated by gp120 binding to CD4 2. How does HIV infect cells other ways HIV enter into cells

4. The problem we will mention: HI to HIV 3.Immune response CD4+ T immune CMI to HIV response CD8+ T immune response

5. The problem we will mention: CD4+ T cell decrease other abnormal immune functions 4.Immuno -pathogenesis peripheral lymph tissue damage disorders of CNS gastrointestinal damage tumor genesis

6. 1.1 The structure of HIV

7. 1.2 The gene group

8. 1.3 The replication and mutation • HIV的复制周期为1．2～2．6 d。 • 在每个复制周期中，HIV的每个位点发生变异的概率是3．4×105。 • 这使HIV成为一种高变异率的病毒，为HIV逃避免疫监视，产生耐药性提供基础，并为疫苗的制备带来困难。

9. 1.4 Target cells • The HIV chiefly attack CD4 cells,including CD4+T cell,Mφ,DC,etc • CD4 is the specific affinity receptor of gp120 • Coreceptors: CCR-5&CXCR-4

10. 2.1 第一次亲密接触

11. Contact

12. fusion The cycle of HIV

13. 3. Immune response to HIV 3. Immune response to HIV

14. 3.1 Specific humoral immunity to HIV • 3～12weeks later from HIV enter into the host，all kinds of specific Ab to the structure Pr of HIV will be produced by the immune system. • However,except the neutralizing Ab to GP120 which has the anti-virus function ,others have little protection function,so they are the markers of HIV infection.In A word ,specific HI plays a quite limited role in anti HIV infection.

15. Specific HI to HIV

16. 3.2 Specific CMI to HIV • CD4+Tcell immune response： As the central cells of immune system, CD4+T cells plays a vital role in specific immunity to HIV

17. 目前，如何保留和重新恢复这些CD4+T细胞的功能,已成为HIV抗病毒治疗研究的重点。目前，如何保留和重新恢复这些CD4+T细胞的功能,已成为HIV抗病毒治疗研究的重点。

18. CD8+Tcell & CTL is the most important immune cell to HIV. • 90％以上处于原发感染期的HIV感染者．体内能检测出特异性的抗HIV CTL，急性感染期HIV血浆病毒载量的减少与这类细胞的产生具有密切关系。这些抗HIV的CD8+T细胞不能完全清除HIV，可能与HIV的高度变异、HIV抗原的特异性CD4+T细胞的丧失有关。

19. CMI to HIV

20. 4 . Immunopathogenesis

21. 4.1 CD4 T lymphocyte decrease • Theprofoundimmunosuppression seen in AIDS is due to the depletion of CD4+Thelper lymphocytes.

22. In the immediate period following exposure, HIV is present at a high level in the blood (as detected by HIV Antigen and HIV-RNA assays). ↓ • It then settles down to a certain low level (set-point) during the incubation period. During the incubation period, there is a massive turnover of CD4+Tcells, whereby CD4+T cells killed by HIV are replaced efficiently. ↓ • Eventually, the immune system succumbs and AIDS develop when killed CD4+T cells can nolonger bereplaced (witnessed by high HIV-RNA, HIV-antigen, and low CD4 counts).

23. CD4 T lymphocyte decrease caused by HIVinfection is the central part in AIDS.

24. Mechanisms on decrease of CD4+T • 1. Virus destroys the cell membrane as a result of budding • 2. Syncytium(合胞体）Formation • 3. Cytotoxic T cell-mediated lysis • 4. Binding of soluble Gp120 to CD4 Ag makes uninfected CD4+cell look like an infected cell by complement-mediated lysis

25. 5. Involvement of a precursor CD4+T cell population. • 6. Autoimmunity. We can detect self-antibody to CD4 during HIV infection • 7. Replication of HIV may interfere the synthesis of CD4 T cell protein

26. 4.2 Abnormal of other immune function • HIV inhibit the activity of bone marrow. • Persistent lymphadenopathy of the whole body. • Function of NK cell come down. • Count of DC decease & function deficiency.

27. 4.3 peripheral lymph tissue damage 在长期的无症状期，淋巴结(特别是外鞘区)内含有大量病毒感染的CD4+T淋巴细胞. 可造成CD4+T淋巴细胞和滤泡样树突状细胞的破坏，淋巴结会逐渐失去正常结构，晚期可出现萎缩。

28. 4.4 Disorder of CNS • 大脑的病毒是通过外周血中感染的巨噬细胞和CD4+T淋巴细胞所带入，诱导产生高水平毒性细胞因子和病毒蛋白，导致中枢神经系统病变。

29. 4.5．Gastrointestinal damage • HIV感染数年后可出现慢性吸收不良、营养不良和腹泻，多数研究认为，是由于免疫缺陷所致机会性感染的后果，但也有研究发现，这些胃肠道病变可能与HIV的直接作用有关。

30. 4.6 Tumor genesis • 在HIV感染者中，恶性肿瘤的发生率明显增加，这与HIV感染所致免疫功能紊乱和免疫监视功能缺陷有关。常见的伴发肿瘤有卡波济肉瘤、霍奇金病、宫颈癌和肛门癌等。

31. Summary HIV感染所致的CD4+T淋巴细胞的进行性减少，细胞免疫功能的严重受损是导致艾滋病的关键环节，对HIV发病机制的深入研究是临床治疗艾滋病和疫苗开发的基础，虽然目前还没有一种方法可以完全有效地治疗艾滋病，并且距安全高效的疫苗制备也还有相当长一段距离，但是随着对HIV发病机制的深入研究，相信人类在不久的未来终将战胜这一疾病。

32. AIDS in China • 首例AIDS 4例 感染者 • 149例感染者 • 492例感染者 AIDS 5例 • 50000左右感染者 • 2005 840000感染者 AIDS 80000 • 更多感染者未知 • Now 每天增加190例感染者 • ··········· • 2010 Maybe 10，000，000 • But we hope ……Zero • Let’s fight！ • STAFF 制作组 资料搜集郭庆 徐荣建 资料整合 贾正虎 孙素和 PPT 制作 杜阳 任华亮 Thank you for your listening!