“自我”与“非我”免疫识别新机理与创新疫苗发展

New Immune Mechanism of“Self vs Non-Self”Discrimination and Its Implication in Designing Novel Vaccines

疫苗接种或者感染诱导保护性免疫的核心是刺激B、T淋巴细胞的特异性免疫应答。后者启动的关键在于免疫系统对“自我”与“非我”抗原正确的识别。1989年Janeway提出存在天然免疫受体识别病原分子模式的猜想。这个划时代的理念极大丰富了免疫识别的内涵并直接推动了对Toll样受体(Toll-like Receptor,TLR)的发现,也帮助确立了淋巴细胞活化的基本范式,即天然免疫信号决定适应性免疫应答的发生及类型。利用佐剂刺激天然免疫信号来增强免疫应答就是这个理论在疫苗设计中的成功应用。尽管如此,复杂多样的体内免疫应答现象显示我们对天然免疫信号的调控机制仍然还有许多未知。本文回顾了研究TLR信号增强蛋白抗原免疫应答机理的历史;介绍了B细胞TLR信号选择性增强病毒抗原抗体反应现象的发现,以及B细胞在启动抗病毒免疫应答中的关键作用;并在此基础上提出靶向B细胞免疫识别机理的一种全新疫苗设计思路。

Inducing the adaptive responses of B and T lymphocytes is the centerpiece of the immune protection caused by infection or vaccination.During the process,a determining step is to make correct recognition“self vs non-self”of the antigen by the immune system.In 1989,Janeway CA proposed the hypothesis of the existence of the innate immune receptors that are able to recognize the molecular patterns of pathogens,which led to subsequent discovery of innate immune receptors such as Toll-like receptors(TLR).This epoch-making discovery greatly enriched our understanding of molecular mechanism of immune recognition,and helped to establish the current immune activation paradigm in which the innate immune signaling critically regulates the adaptive immune responses.An exemplary application of this theory in vaccine design is using adjuvant to stimulate innate immune signals for the enhancement of immune response to vaccination.Nevertheless,the complex and diverse in vivo immune response demonstrated that the mechanism of natural immune signals is still unknown.In the review,we summarized the previous research on the topic of TLR signaling in promoting antibody response to protein antigen.In addition,we introduced the discovery of the selective use of B cell TLR signaling,and the critical function of B cell antigen presentation in the initiation of anti-viral adaptive immune responses.Finally,we proposed the concept that targeting B cell immune recognition can be used as a new strategy to design novel vaccines.