Department of Neurology, University of Regensburg, Universitaetsstrasse 84, 93053 Regensburg, Germany.
J Neuroimmune Pharmacol. 2013 Sep;8(4):857-66. doi: 10.1007/s11481-013-9467-3. Epub 2013 May 10.
Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that leads to changes of nerve conduction due to damage of CNS- resident cells, primarily oligodendrocytes and neurons. CD4+ T cells are of primary importance in the immune cascades leading to tissue damage, but also CD8+ T cells, NK cells and B cells and antibodies contribute to tissue damage. In addition, the innate immune response and mainly microglial cells participate in the events leading to lesions. There are different types of MS and possibly this is due to different underlying immune mechanisms. The current treatment options mainly affect the immune response but have not much influence on secondary signaling changes in astrocytes and neurons which contribute to constant disease progression. The immune response in MS must be seen in the systemic context and there are strong indications that the gut and lung immunity affect MS disease precipitation. The strongest genetic influence in MS is mediated by the HLA class II genes and in Western Europeans and North Americans the disease is associated with HLA-DR2b. Possibly this is due to presentation of a set of specific antigens in context of this HLA allele. Novel data indicates that the immune response in MS is not only focused on certain myelin proteins like myelin basic protein (MBP) but to additional astrocytic and neuronal proteins, which is also mirrored in the pathology. While in the past the disease has been considered as mainly a white matter disease, nowadays it is clear that also grey matter is affected by the aberrant immune response. Still much needs to be learned regarding the underlying events in MS. This expanded knowledge is important to finally discover curative therapies.
多发性硬化症是一种中枢神经系统（CNS）的自身免疫性疾病，由于中枢神经系统固有细胞（主要是少突胶质细胞和神经元）的损伤，导致神经传导发生变化。CD4+T 细胞在导致组织损伤的免疫级联反应中起着主要作用，但 CD8+T 细胞、NK 细胞和 B 细胞以及抗体也有助于组织损伤。此外，先天免疫反应和主要的小胶质细胞参与导致病变的事件。多发性硬化症有不同的类型，这可能是由于不同的潜在免疫机制。目前的治疗选择主要影响免疫反应，但对星形胶质细胞和神经元的二次信号变化影响不大，这些变化有助于持续的疾病进展。多发性硬化症中的免疫反应必须从全身角度来看待，并且有强烈的迹象表明肠道和肺部免疫会影响多发性硬化症的发病。多发性硬化症最强的遗传影响是由 HLA Ⅱ类基因介导的，在西欧人和北美人群中，该疾病与 HLA-DR2b 相关。可能这是由于在这个 HLA 等位基因的背景下，呈现出一组特定的抗原。新的数据表明，多发性硬化症中的免疫反应不仅集中在某些髓鞘蛋白（如髓鞘碱性蛋白，MBP）上，还针对额外的星形胶质细胞和神经元蛋白，这在病理学上也有反映。虽然过去该疾病被认为主要是一种白质疾病，但现在很清楚，异常的免疫反应也会影响灰质。关于多发性硬化症的潜在事件，还有很多需要了解。这些扩展的知识对于最终发现治疗方法非常重要。
