Kinomic Evaluation of the Complexities of Toll-like Receptor Signalling: Synergies, Specializations and Pathological Influences (Stress)

先天免疫系统是抵御微生物病原体的前线防御系统。天然免疫的激活是通过模式识别受体来实现的，模式识别受体检测病原体相关的分子模式，启动管理病原体所需的即时细胞反应，同时向适应性免疫系统传达这种威胁的发生，以及可能需要更高阶的反应。Toll样受体是天然免疫系统中最重要的模式识别受体之一。虽然不同的TLR被不同的配体激活，但随后的反应通常与一条保守的信号转导途径相关联，以达到共同的细胞反应。这一模型与先天免疫系统及其控制的反应通常是非特异性的信念是一致的。然而，新出现的证据挑战了这一观点，提出了单个TLR的信号和反应更加专业化的建议，以及不同TLR之间存在的协同作用，使得能够针对TLR激活的特定情况进行定制的反应。这就是说，与生俱来的免疫反应在其激活过程中不是二元的，而是能够根据其感官受体激活的特定性质而特化。同样，人们逐渐认识到，免疫和应激等生物过程不存在于封闭系统的功能隔离中，而是存在相当大的功能重叠和多方向影响。虽然公众和科学文献都普遍意识到压力和免疫之间的关系，但压力影响免疫的确切机制仍不清楚。TLR信号的失调可能代表了一种应激损害免疫力的机制。

The innate immune system serves as a front line defense against microbial pathogens. Activation of innate immunity occurs through pattern recognition receptors which detect pathogen-associated molecular patterns to the initiation of the immediate cellular responses required for management of the pathogen while communicating the occurrence of this threat, and potential need for higher-order responses, to the adaptive immune system. The Toll-like receptors (TLRs) are among the most important pattern recognition receptors of the innate immune system. While the various TLRs are activated by diverse ligands, the ensuing responses are classically associated with a conserved pathway of signal transduction to a common cellular response. This model is consistent with the belief that that innate immune system, and the responses that it governs, are generally non-specific. There is emerging evidence, however, that challenges this perspective with the suggestion of a higher degree of specialization of signalling, and responses, from individual TLRs as well as synergies that exist between different TLRs that enable responses that are customized to specific situations of TLR activation. That is to say that the innate immune response is not binary in its activation, but rather capable of specialization depending on the specific nature of activation of its sensory receptors. Similarly, there is emerging appreciation that biological processes, such as immunity and stress, do not exist in the functional isolation of closed systems but rather share considerable functional overlap and multidirectional influence. While there is general awareness among the general public, as well as within the scientific literature, of the relationship between stress and immunity, the precise mechanisms by which stress compromises immunity remain unclear. Dysregulation of TLR signalling may represent a mechanism by which stress compromises immunity.