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Regulation of B-cell responses by Toll-like receptors

机译:Toll样受体对B细胞反应的调节

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The discovery of host-encoded gene products that sense molecular patterns in infectious microbes, and the demonstration of their role in triggering innate and adaptive immune responses, has been a key milestone in our understanding of immunology. Twenty-three years after Janeway first outlined the fundamental concepts of the 'pattern recognition' model, and 15years since the identification of Toll-like receptors (TLRs) as pattern recognition receptors (PRRs), new insights continue to be revealed, and questions remain. For example, innate immune responses to microbes that are mediated by PRRs have historically been viewed as the domain of innate immune cell populations such as dendritic cells and macrophages. New evidence, however, has pointed to the role of B-cell-intrinsic TLR activation in shaping antibody responses. These studies have revealed that TLRs regulate a complex transcriptional network that controls multiple steps in the development of antigen-specific antibodies. This review covers these recent developments regarding the role of TLRs in B-cell gene expression and function in vitro and in vivo, and highlights the remaining challenges in the field, with particular emphasis on the role of TLRs in antibody responses to viral infection. A more complete understanding of how TLRs regulate antibody responses will lead to improved vaccine design.
机译:发现宿主编码基因产物以检测传染性微生物中的分子模式,并证明它们在触发先天性和适应性免疫反应中的作用已成为我们对免疫学理解的关键里程碑。珍妮威(Janeway)首次概述“模式识别”模型的基本概念已有23年,距将Toll样受体(TLR)识别为模式识别受体(PRR)已有15年了,新的见解不断被揭示,问题仍然存在。例如,历史上已将由PRR介导的对微生物的先天免疫应答视为先天免疫细胞群体(例如树突细胞和巨噬细胞)的域。但是,新证据指出了B细胞内在性TLR激活在塑造抗体应答中的作用。这些研究表明,TLR调控着复杂的转录网络,该网络控制着抗原特异性抗体开发中的多个步骤。这篇综述涵盖了有关TLR在体外和体内B细胞基因表达和功能中的作用的最新进展,并强调了该领域中尚存的挑战,尤其着重于TLR在抗体对病毒感染的应答中的作用。对TLR如何调节抗体反应的更完整的了解将导致改进的疫苗设计。

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