中文摘要：细菌肠毒素、霍乱毒素和大肠杆菌不耐热肠毒素都是可以诱导粘膜免疫反应的佐剂。他们共同的A链能够通过诱导G蛋白ADP糖基化介导产毒机理，并提高靶细胞内cAMP浓度。混合抗原(Ag)能够诱导产生大量IgA 和 IgG抗体反应的一个标志就是这些佐剂存在的标志，且这种作用与他们的A链活性相关。先前关于这些佐剂机理的研究报道表明，在佐剂发生作用的过程中会出现Ag特异性B细胞和T细胞增多、T细胞细胞因子浓度变化和调控性T细胞浓度变化的现象。这些毒素的B链衍生物也可以微弱地增强免疫反应，尤其是当其与Ag形成共价化合物并通过鼻咽部进行免疫的情况下。重要的是，这些毒素或其B链衍生物能够改变正常的免疫调控过程，从而产生口服免疫耐受现象，表明他们可以调控粘膜与系统性免疫的之间的代谢过程。体外模型中CT或者LT活性与佐剂在机体内显示的活性还存在一些差异。目前，对粘膜B细胞和T细胞与系统性淋巴样组织进行互作的机理还不是完全清楚，因此对已获得的试验数据进行机体内机理模拟还存在障碍，反之亦然。更重要的是，毒素对局部和引流粘膜淋巴样组织的作用还不是十分清晰。但可以肯定的是，T细胞和B细胞激活、细胞因子产生是抗原呈递的关键。
外文摘要：The bacterial enterotoxins, cholera toxin and the heat labile toxin of E, coli, are well known adjuvants for mucosal immune response. Their common A chain mediates the toxigenic mechanism by causing ADP ribosylation of G proteins and subsequent elevation of cAMP in target cells. A large IgA and IgG antibody response to admixed protein antigen (Ag) is the hallmark of these adjuvants and is clearly associated with the A chain activity. Expansion of Ag-specific B and T cells, alteration of T cell cytokine production, and changes in regulatory T cells have been reported as adjuvant mechanisms. The B chain derivatives of these toxins can also weakly enhance immune response, especially if covalently associated with Ag and used for nasophyrangeal immunization. Importantly, these toxins or their B chain derivatives can alter the normal immune regulation that produces oral tolerance. This indicates that they modulate mechanisms operative between the mucosal and systemic immune systems. There are some discrepancies between in vitro models of CT or LT activity and in vivo manifestations of their adjuvant activities. Interpretation of current data regarding in vivo mechanism is hampered by an incomplete understanding of how mucosal B and T cells can interact with systemic lymphoid tissue and vice versa. More important, there is no clear understanding of the early effects of the toxins on the local (and draining) mucosal lymphoid tissues. This is especially true in the critical areas of antigen presentation, T and B cell activation, and cytokine production.
外文关键词：cholera toxin； heat-labile toxin； mucosal immunity； cAMP
作者：Snider, DP
作者单位：美国麦克马斯特大学
期刊名称：CRITICAL REVIEWS IN IMMUNOLOGY
期刊影响因子：2.327
出版年份：2018
出版刊次：6
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