EXERCISE, STRESS AND IMMUNITY--PHYSIOLOGICAL MECHANISMS

描述(申请人摘要)：文献表明 活跃的生物体不太容易受到压力的有害后果的影响 关于疾病和免疫功能。使用已建立的压力动物模型，我的 实验室已经调查了急性应激源暴露对 一种良性蛋白--锁孔帽状蛋白特异性抗体的研制 运动与久坐大鼠的血蓝蛋白(KLH)。测量 KLH激发后血液中的特异性抗体水平提供了一种 体内免疫反应的极佳衡量标准，并减少了 对细菌、病毒或可溶性毒素的特异性抗体反应可使 对该病原体引起的疾病更敏感的有机体。久坐不动 用KLH免疫并暴露于单次尾部休克的大鼠 应激时，对KLHIg(抗KLHIg)的抗体反应降低。在……里面 与之形成对比的是，被允许在暴露于 急性应激源，不会遭受免疫有害后果 压力的影响。这项提案的中心主题是确定 应激缓冲作用的免疫-神经内分泌-脑机制(S) 体力活动。初步数据表明，体力活动可以调节 大脑和神经内分泌对应激源暴露的反应。与.相比 久坐应激大鼠、体力活动大鼠暴露于尾部应激 C-Fos免疫反应(神经元激活标记物)增加较少 在几个应激反应的大脑区域，这些区域对激活 交感神经下行通道。这些变化可能是导致 应激诱导的交感神经系统输出减少(血浆和 脾去甲肾上腺素(NE)在体力活动和久坐状态下的分布 动物。重要的是，有证据表明，暴露于应激水平的NE 升高一氧化氮(NO)，导致抗KLHIg降低。封锁 压力诱导的交感神经输出可以阻止这些影响。这是合理的 因此，假设运动大鼠对 应激对免疫功能的负面影响，因为它们在 交感神经系统输出导致免疫抑制减少 不，并预防抑制的抗KLHIg。

DESCRIPTION (Applicant's abstract): The literature indicate that physically active organisms are less susceptible to the deleterious consequences of stress on illness and immune function. Using an established animal model of stress, my laboratory has investigated the effect of acute stressor exposure on the development of a specific antibody response to a benign protein, keyhole limpet hemocyanin (KLH) in physically active versus sedentary rats. Measurement of specific antibody levels in the blood after challenge with KLH provides an excellent measure of the in vivo immune response, and a reduction in the specific antibody response to a bacteria, virus or soluble toxin, could render the organism more susceptible to disease caused by that pathogen. Sedentary rats that are immunized with KLH, and exposed to a single session of tail shock stress, have a reduction in the antibody response to KLH (anti-KLH Ig). In contrast, rats that are allowed to live with a running wheel before exposure to an acute stressor, do not suffer the immunologically deleterious consequences of stress. The central theme of this proposal is to determine the immune-neuroendocrine-brain mechanism(s) of the stress-buffering effect of physical activity. Preliminary data suggest that physical activity modulates the brain and neuroendocrine responses to stressor exposure. Compared to sedentary stressed rats, physically active rats exposed to tail shock stress have a smaller increase in c-Fos immunoreactivity (neuronal activation marker) in several stress reactive brain areas that are important for activation of sympathetic descending pathways. These changes may be responsible for the reduction in stress-induced sympathetic nervous system output (plasma and splenic norepinephrine (NE)) found in physically active versus sedentary animals. Importantly, there is evidence that exposure to stress levels of NE elevates nitric oxide (NO) which leads to a reduction in anti-KLH Ig. Blockade of stress-induced sympathetic output prevents these effects. It is reasonable to hypothesize, therefore, that physically active rats are resistant to the negative effects of stress on immune function because they have a reduction in sympathetic nervous system output leading to a reduction in immunosuppressive NO, and prevention of suppressed anti-KLH Ig.