Nevinsky Georgy A, Buneva Valentina N
Institute of Chemical Biology and Fundamental Medicine of the Siberian Division of the Russian Academy of Sciences, Novosibirsk.
ScientificWorldJournal. 2010 Jun 29;10:1203-33. doi: 10.1100/tsw.2010.98.
In human patients with autoimmune, viral, and bacterial diseases, the generation of antibodies (Abs) to foreign antigens and/or autoantibodies to self-antigens usually occurs. Some Abs with different catalytic activities (abzymes, Abzs) may be induced spontaneously by primary antigens and can have characteristics of the primary antigen, including the catalytic activity of idiotypic and/or anti-idiotypic Abs. Healthy humans usually do not develop Abzs or their activities are low, often on the borderline of sensitivity of the detection methods. Detection of Abzs was shown to be the earliest indicator of development of different autoimmune diseases (ADs). At the early stages of ADs, the repertoire of Abzs is usually relatively narrow, but it greatly expands with the progress of the disease, leading to the generation of catalytically diverse Abzs with different activities and functions. Some Abzs are cytotoxic and can play an important negative role in the pathogenesis of ADs, while positive roles have been proposed for other Abzs. Abzs with some low activities can temporarily be present in the blood of patients in the course of viral and bacterial diseases, but their activity increases significantly if these infections stimulate development of ADs. A significant increase in the relative Abz activities associated with a specific reorganization of the immune system, including changes in the differentiation and proliferation of bone marrow hematopoietic stem cells and lymphocyte proliferation in different organs. Different mechanisms of Abz production can be proposed for healthy externally immunized and for autoimmune mammals during the development of pathology.
在患有自身免疫性、病毒性和细菌性疾病的人类患者中,通常会产生针对外来抗原的抗体(Abs)和/或针对自身抗原的自身抗体。一些具有不同催化活性的抗体(催化抗体,Abzs)可能由主要抗原自发诱导产生,并且可以具有主要抗原的特征,包括独特型和/或抗独特型抗体的催化活性。健康人通常不会产生催化抗体或其活性较低,往往处于检测方法灵敏度的临界值。催化抗体的检测被证明是不同自身免疫性疾病(ADs)发展的最早指标。在自身免疫性疾病的早期阶段,催化抗体的种类通常相对狭窄,但随着疾病的进展会大大扩展,导致产生具有不同活性和功能的催化多样性催化抗体。一些催化抗体具有细胞毒性,可在自身免疫性疾病的发病机制中发挥重要的负面作用,而其他催化抗体则被认为具有积极作用。活性较低的催化抗体在病毒和细菌性疾病过程中可暂时存在于患者血液中,但如果这些感染刺激自身免疫性疾病的发展,其活性会显著增加。与免疫系统的特定重组相关的催化抗体相对活性显著增加,包括骨髓造血干细胞分化和增殖以及不同器官中淋巴细胞增殖的变化。对于健康的外部免疫动物和自身免疫性哺乳动物在病理发展过程中,可以提出不同的催化抗体产生机制。