【作者】 吕梅励；

【导师】 张林；

【作者基本信息】 四川大学 ， 法医学， 2006， 博士

【摘要】 目的 自身免疫性疾病(autoimmune disease，AID)是由于各种原因导致机体免疫系统针对自身抗原发生免疫应答，产生自身抗体或自身致敏淋巴细胞，造成正常组织损伤而引起的一大类疾病，是公认的人类难治性重大疾病之一。目前临床上缺乏针对AID特效的治疗方案，常采用各种免疫抑制剂治疗AID，但这些制剂副作用大，会导致机体免疫功能的全面抑制。 人类多发性硬化(multiple sclerosis，MS)是一种主要累及中枢神经系统的炎症性、多发性AID，这种疾病具有症状复杂多变、缓解与复发交替进行、病程迁延不规律等特点，多年来一直困扰着患者。实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis，EAE)是一种由活化T细胞(主要是Th1细胞)介导的器官特异性自身免疫性疾病，主要病理特征为血管周围炎性细胞浸润和神经脱髓鞘反应，在临床症状、生化指标及病理等方面与MS具有相似的特征，因此EAE被认更多还原

【Abstract】 Objective There are no specific treatments for autoimmune disease in human currently, and multiple sclerosis(MS) is no exception. Experimental autoimmune encephalomyelitis(EAE) is T cell mediated demyelinating disease of the central nervous system(CNS) and serves as a well-established animal model for MS. The widely accepted pathogenetic process of EAE and MS is that activated T cells migrate to the CNS and develop inflammatory lesion, and some chemokines and their receptors preferentially expressed in T cells are involved in the pathogenesis. EAE can be induced by Myelin Basic Protein(MBP), Proteolipid Protein(PLP), Myelin Oligodendrocyte Glycoprotein(MOG) or Myelin Associated Glycoprotein(MAG), et al. In the study we prefered MBP to inducing mouse EAE model. It has been confirmed that many chemokine receptors are expressed in the membranes of activated T cells. CCR5 is over-expressed in the activated T cells membrane and might be an ideal target for the immunotherapy. In the study we choose MIP-1α, one of the ligand of CCR5, as the target moiety.更多还原