Behaviorally conditioned changes in peripheral immune functions: kinetics, affernet pathways and central processings

行为条件反射范式记录了大脑感知免疫信号或免疫状态的能力，将它们与同时相关的外部感受性刺激联系起来，并根据需要恢复这种免疫反应。我们最近在使用环孢素A作为非条件刺激的大鼠身上展示了行为条件性免疫抑制效应。这种条件性免疫抑制作用具有临床意义，因为它们延长了同种异体心脏移植物的存活时间，并减轻了过敏反应。这些条件性效应通过去甲肾上腺素和β肾上腺素受体依赖的机制，通过岛叶皮质和杏仁核的中枢以及通过脾神经的外周传出臂来传递。通过这项研究工作，我们打算分析行为条件性免疫药理反应的动力学以及免疫抑制条件性效应的可逆性。此外，我们将在条件反射过程的背景下研究外周免疫系统和中枢神经系统之间的传入通路，特别是分析中枢神经系统何时以及如何检测到外周免疫系统的变化，以及确定中枢神经递质和/或细胞因子参与这一联合学习过程。这些实验将为评估条件化范例是否可用于补充临床情况下的免疫调节药物方案奠定基础。

Behavioral conditioning paradigms have documented the brain’s abilities to sense immune-derived signals or immune status, associate them with concurrently relevant extereoceptive stimuli, and reinstate such immune responses on demand. We could recently demonstrate behavioral conditioned immunosuppressive effects in rats employing cyclosporine A as an unconditioned stimulus. Such conditioned immunosuppressive effects are clinically relevant since they prolong heart allograft survival and attenuate allergic responses. These conditioned effects are mediated centrally via the insular cortex and the amygdala as well as on the peripheral efferent arm via the splenic nerve, through noradrenaline and β-adrenoceptor-dependent mechanisms. With this research work we intend to analyze the kinetics of the behavioral conditioned immunopharmacological response together with the reconditionability of the immunosuppressive conditioned effect. In addition, we will investigate the afferent pathways between the peripheral immune system and the CNS in the context of the conditioning process and will in particular analyze when and how the changes in the peripheral immune system are detected by the CNS as well as determine the involvement of central neurotransmitters and/or cytokines involved in this associative learning process. These experiments will form a basis for the evaluation of whether conditioning paradigms can be utilized to complement immunomodulatory drug regimes in clinical situations.