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

行为条件反射范式已经记录了大脑感知免疫源性信号或免疫状态的能力，将它们与同时相关的外部刺激相关联，并根据需要恢复这种免疫反应。我们最近可以证明行为条件免疫抑制作用的大鼠采用环孢素A作为一种非条件刺激。这种条件性免疫抑制作用与临床相关，因为它们延长了心脏移植物的存活并减弱了过敏反应。这些条件效应通过去甲肾上腺素和β-肾上腺素受体依赖性机制，经由岛叶皮质和杏仁核以及经由脾神经在外周传出臂上中枢介导。通过这项研究工作，我们打算分析行为条件免疫药理学反应的动力学以及免疫抑制条件效应的可恢复性。此外，我们将调查的传入通路之间的外周免疫系统和中枢神经系统的条件反射过程的背景下，并将特别分析何时以及如何在外周免疫系统的变化被检测到的中枢神经系统，以及确定参与中枢神经递质和/或细胞因子参与这个联想学习过程。这些实验将形成一个基础，用于评估是否可以利用条件范例，以补充免疫调节药物制度在临床情况下。

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.