AUTOIMMUNITY TO NEURAL ACETYLCHOLINESTERASE

借助抗脑乙酰胆碱酯酶的单抗 胆碱能功能障碍的一种新的自身免疫模型(AChE) 在老鼠身上产生的。一种抗体有惊人的蓄积趋势 在中枢神经系统(CNS)中有可能引起 广泛存在的异常现象。建议研究以下因素： 促进这种抗体与大脑中的靶点接触，并 描述它所介导的结构和化学异常 那里。这项工作可能会提炼我们关于血脑屏障的概念 与免疫球蛋白的关系。该实验系统还具有 有可能提供与神经退行性疾病相关的数据 中枢胆碱能系统，包括阿尔茨海默病。另一套 的实验将使用不能产生AChE的抗体 中枢神经系统中的表位。当系统注射时，这些抗体 引起一种新的节前交感神经紊乱，但 对其他胆碱能系统的明显影响最小。按照计划， 节前神经节破坏机制的探讨 并绘制出交感神经末梢的细胞分布 免疫损伤。AChE抗体对小鼠的影响较小 运动和副交感神经系统也将在 细节。将特别关注防止一种 抗体中交感神经末梢的正常再生反应 治疗大鼠，并导致永久性自主神经障碍。最后，尝试 将确定几种类型的人类中的哪一种 自主性障碍可能有类似的自身免疫机制。

With the aid of monoclonal antibodies to brain acetylcholinesterase (AChE), a new autoimmune model of cholinergic dysfunction has been created in rats. One antibody with a surprising tendency to accumulate in the central nervous system (CNS) has the potential to cause widespread abnormalities. It is proposed to study the factors that facilitate the access of this antibody to targets in the brain and to characterize the structural and chemical abnormalities that it mediates there. This work may refine our concepts of the blood brain barrier in relation to immunoglobulins. The experimental system also has the potential to provide data relevant to neurodegenerative diseases of central cholinergic systems, including Alzheimer's disease. Another set of experiments will utilize antibodies that do not have access to ACHE epitopes in the CNS. When injected systemically, these antibodies induce a novel disorder of preganglionic sympathetic nerves but have minimal apparent effects on other cholinergic systems. It is planned to investigate the mechanisms of destruction of the preganglionic sympathetic terminals and to map out the cellular distribution of the immunologic damage. The more modest effects of AChE-antibodies on the motor and parasympathetic nervous systems will also be examined in detail. Special attention will be focused on the factors that prevent a normal regenerative response of sympathetic terminals in antibody treated rats and result in permanent dysautonomia. Finally, attempts will be made to determine which of the several types of human dysautonomias might have a similar autoimmune mechanism.