Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders.
Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders.
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DOI：
10.3389/fimmu.2017.00336
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发表时间：
2017
影响因子：
7.3
通讯作者：
Weissert R
中科院分区：
文献类型：
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作者：
Weissert R
不同类型的自身免疫性疾病如多发性硬化症(MS)、视神经脊髓炎谱系障碍(NMOSDs)、自身免疫性脑炎(AE)以及中枢神经系统副肿瘤性炎症性疾病之间有共同的方面和机制。据我们目前所知，根据疾病的不同，T和B细胞以及抗体在发病机制的不同方面起作用。可能导致不同疾病之间打破耐受性的事件具有很大的相似性，到目前为止，人们对此只有部分了解。除了内源性因素(遗传学、基因组学、表观遗传学、恶性肿瘤)外，外源性因素(维生素D、日光照射、吸烟、肠道微生物群、病毒感染)也是此类疾病的易感性因素。这些疾病之间的不同之处在于免疫攻击的目标分子。对于T细胞，这些靶分子作为主要组织相容性复合体(MHC)结合的配体出现在MHC分子上。B细胞通过利用其表面免疫球蛋白捕获抗原并将其呈递给T细胞，从而放大T细胞的免疫反应，从而发挥重要作用。从B细胞分化而来的浆细胞分泌的抗体具有高度的结构特异性，可以具有重要的效应功能，导致功能损害或/和病变的演变。在MS中，靶分子主要是髓鞘和神经元/轴突来源的蛋白；在NMOSD中，主要是星形胶质细胞上表达的水通道蛋白-4；在AE中，主要是神经元和轴突表达的各种蛋白质。
There are common aspects and mechanisms between different types of autoimmune diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), and autoimmune encephalitis (AE) as well as paraneoplastic inflammatory disorders of the central nervous system. To our present knowledge, depending on the disease, T and B cells as well as antibodies contribute to various aspects of the pathogenesis. Possibly the events leading to the breaking of tolerance between the different diseases are of great similarity and so far, only partially understood. Beside endogenous factors (genetics, genomics, epigenetics, malignancy) also exogenous factors (vitamin D, sun light exposure, smoking, gut microbiome, viral infections) contribute to susceptibility in such diseases. What differs between these disorders are the target molecules of the immune attack. For T cells, these target molecules are presented on major histocompatibility complex (MHC) molecules as MHC-bound ligands. B cells have an important role by amplifying the immune response of T cells by capturing antigen with their surface immunoglobulin and presenting it to T cells. Antibodies secreted by plasma cells that have differentiated from B cells are highly structure specific and can have important effector functions leading to functional impairment or/and lesion evolvement. In MS, the target molecules are mainly myelin- and neuron/axon-derived proteins; in NMOSD, mainly aquaporin-4 expressed on astrocytes; and in AE, various proteins that are expressed by neurons and axons.