EXERCISE, STRESS AND IMMUNITY--PHYSIOLOGICAL MECHANISMS

描述（申请人摘要）：文献表明， 活跃的有机体对压力的有害后果不太敏感 疾病和免疫功能。使用一个建立的动物模型的压力，我的 实验室研究了急性应激暴露对 对一种良性蛋白质，匙孔帽贝产生特异性抗体反应 血蓝蛋白（KLH）在体力活动与久坐大鼠。测量 用KLH攻击后血液中的特异性抗体水平提供了 体内免疫应答的极好测量，以及免疫应答的减少。 对细菌、病毒或可溶性毒素的特异性抗体反应， 生物体更容易受到病原体引起的疾病的影响。久坐 用KLH免疫大鼠，并暴露于单次尾部电击 应激时，对KLH（抗KLH IG）的抗体应答降低。在 相比之下，在暴露于水之前， 急性应激源，不会遭受免疫学上有害的后果， 压力该提案的中心主题是确定 免疫-神经内分泌-脑机制的压力缓冲作用 体力活动。初步数据表明，身体活动调节 大脑和神经内分泌对应激源暴露的反应。相比 久坐应激大鼠、运动应激大鼠 c-Fos免疫反应性（神经元激活标记物）增加较小 在几个应激反应脑区，这是重要的激活 交感神经下行通路这些变化可能是导致 应激诱导的交感神经系统输出（血浆和 脾去甲肾上腺素（NE）），发现在体力活动与久坐 动物重要的是，有证据表明，暴露于压力水平的NE 升高一氧化氮（NO），导致抗KLH IG减少。封锁 压力诱导的交感神经输出阻止了这些效应。是合理 因此，假设体力活动的大鼠对 压力对免疫功能的负面影响，因为它们减少了免疫功能。 交感神经系统的输出导致免疫抑制的减少， NO，以及抑制抗KLH IG的预防。

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.