Multiple Sclerosis （ MS ） And Immunology

1. Multiple Sclerosis （MS）And Immunology 04级临六2班 赵逾涵（主讲人） 马洪鑫 刘瑾 张玉娇 董瑞芬 杨宁宁 刘丹丹

2. Multiple Sclerosis（MS）And Immunology CASE • 申某，男，28岁，01年3月份一次感冒后出现体力下降，下肢痿软无力，视力下降，复视，眩晕，小便潴留，平衡失调。对症治疗后好转。02年7月份复发，到省级医院检查，MRI显示脑部和脊髓白质均有多处脱髓鞘病变，视觉、脑干、体感诱发电位均异常，CSF寡克隆带（＋），被确诊为多发性硬化症。 • Mr. Shen,male,28 years old, he caught a cold in march, 2001.Then he got a descended physical strength, weak lower limbs, vision breakdown, diplopia , giddiness, urine retention ,dysequilibrium .He improved after symptomatic treatment. • On July,2002, the disease recurred. After examination, it shows multiple demyelinating disease in the white matter of the brain and the spinal cord on MRI. And the disorder in VEP,BAEP,SEP appeared. The OCB of CSF showed positive (+), his final diagnosis was multiple sclerosis.

3. Definition: MS is a mulifocality, demyelinating disease. It is charactered with recurrence and relieve. Typical signs and symptoms: affection of white matter transduction bundle of spinal cord, optic nerve, periventriclular white matter, brain stem and cerebella . Mainstay of clinical diagnosis: the affection of CNS white matter,the multiple refers to the multiple location and times. 定义：中枢神经系统炎性、多灶性、脱髓鞘性疾病。虽有20％病人自起病后进行性加重，但多数是以复发、缓解为特征。 典型的症状和体征：脊髓的白质传导束、视神经、脑室周围白质、脑干和小脑的病变。 临床诊断的主要依据是：有中枢神经系统白质病变的证据，且有其部位及时间上的多发。 Multiple Sclerosis, MS多发性硬化

4. Etiological factor And Pathogenesis of MS (一)Etiological Factor *viral infection and autoimmune reaction *genetic factor *environmental factor (二)Pathogenesis some individual hereditary factor easily infected environment ( virus, cold)autoimmune reaction 病毒与MBP可能有共同抗原---- IL、Ab也与髓鞘交叉反应----脱髓鞘----致病

5. 【Pathogenesis of Immunology】 • MBP（myelin basic protein）a kind of protein on the sheath cell in CNS. • In normal condition，as the existence of anatomy barrier, the autoreactive lymphocyte couldn’t react on MBP. When the virus with the common antigen of MBP invade the human body, barrier will break down. • When the virus infect the body, the T/B cells are activated ,then the cellular and humoral immunity are initiated. The immunological products (effective T cell and Ab ) react with MBP, the sheath cells are killed and cause the demyelin, then it is multiple sclerosis.

6. MS is mainly a T cell disease 髓鞘碱性蛋白(myelin basic protein，MBP)，MBP是髓鞘中抗原性最强的蛋白质； 实验性变态反应性脑脊髓炎(experiment allergic encephalo．myelitis，EAE)

7. Detailed Immunological Mechanism IgG IgA IgE IgM Plasma B2 cell Ab 辅助 TD-Ag Th2 CD4+ T Th1 Innate immunity 辅助 Target cell APC T cell CD8+ T CTL TI-Ag B1 cell Plasma Ab：IgM

8. Sensitization Stage—APC presentation • Endogenous -MHC I • Exogenous -MHC II

10. Reaction stage：sheath cells and virus infected cells

12. Activation of B2 cells

13. ADCC

14. CLASSICAL PATHWAY OF COMPLEMENT ACTIVATION

15. 抗体能够通过几种主要的机制引起脱髓鞘 • (1)细胞调理作用和吞噬作用； • (2)补体和Fc受体介导的炎症和组织损伤； • (3)与生理学上重要的分子或细胞受体结合的抗体对正常细胞功能的干扰。

16. MS • cellular immunity：MBP has the common antigen with virus, the immune tolerance can be broken by the invasion of virus. The CTL attack both the sheath cells and the virus infected cells. • Humoral immunity: play a part in the formation and the perpetual existence of impairment. • The study of the detailed mechanism is undergoing

17. Treatment & Prognosis Treatment: Principle：improve the quality Drug treatment: 1. hormonal therapy：大剂量冲击 + 少量维持甲基强的松龙ACTH 2. plasmapheresis 3. immune depressant：环磷酰胺、硫唑嘌呤 CsA, FK506 4.IFN-β 5. prevention and cure: antibiotics 6. rehabilitation care Prognosis good ,however ,it has death rate

18. Thank You