STRESSOR-INDUCED MODULATION OF ANTIGEN SPECIFIC IMMUNITY

厌恶应激源改变大鼠的细胞和体液免疫指标 老鼠。使用暴露于急性(一次性)足电击应激源的大鼠， 以霍乱毒素(CT)为抗原，初步数据得出结论 即(I)抗原特异性的体外记忆脾细胞增殖和 只有在初次免疫时，血清抗体水平才会被抑制 紧随应激源之后发生(但不是在24小时后)；(Ii) 抗原致敏大鼠免疫后7天应激源暴露 结果增强了抗原特异性脾细胞的记忆增殖， 但抑制非特异性有丝分裂原诱导的增殖。在追求 这些应激源诱导效应的免疫学机制，重点是 所提议的实验将是关于辅助细胞的研究 应激后即刻的功能和T细胞对抗原的反应性 曝光。因为对CT的免疫反应只有在足部电击时才会改变 接近免疫，应激可能会改变辅助细胞 功能。因此，具体目标1将解决急性呼吸道感染的影响 足部电击(I)抗原提呈细胞(APC)的抗原提呈， 巨噬细胞产生IL-1、IL-6、肿瘤坏死因子、转化生长因子和前列腺素E_2。 此外，钼在体内介导应激源诱导的作用 淋巴细胞功能的抑制，将被调查。特定目标 2将研究压力对T淋巴细胞抗原反应性的影响 紧接在应激源暴露之后。因此，未激活的脾T细胞将 被检测为(I)对抗原特异性和非特异性的增殖活性 体外特异性信号，(Ii)Th1 CD4+T细胞 分泌IL-2和干扰素-γ，以及Th2 CD4+T细胞，以阐明IL-4和 IL-6和(Iii)CD4+和CD8+T细胞辅助性和抑制性调节 函数。这些措施代表了主要的相互作用 T淋巴细胞抗原特异性免疫反应的组成部分，可以 也调节B细胞功能，如上所述，这是被抑制的 免疫时的足部电击。增殖、细胞因子和 对T细胞反应性的监管措施也将构成 针对特定目标的最后一系列调查人员3.这些实验将 测试急性足底电击是否会不同程度地改变 幼稚和记忆T细胞对抗原特异和非特异信号。 这将通过将脾T淋巴细胞从 应激和非应激抗原刺激的大鼠，进入OX-22(记忆)和 OX-22+(幼稚)种群，并评估在 具体目标2.总的来说，这些研究将产生重要的 急性呼吸窘迫综合征改变基本免疫机制的研究途径 应激源暴露，并有助于了解环境 压力等因素会影响对病毒的免疫反应。 感染，如艾滋病毒。

Aversive stressors alter cellular and humoral immune measures in rats and mice. Using rats exposed to an acute (one time) footshock stressor, a cholera toxin (CT) as antigen, preliminary data has led to the conclusion that (i) antigen-specific in vitro memory spleen cell proliferation and serum antibody levels are suppressed only when primary immunization occurs immediately after the stressor (but not > 24 hrs later); (ii) stressor exposure of antigen-primed rats 7 days after immunization results in enhanced antigen-specific spleen cell memory proliferation, but suppressed non-specific mitogen-induced proliferation. In pursuing the immunological mechanisms of these stressor-induced effects, the focus of the proposed experiments will be on the study of accessory cell function and T cell reactivity to antigen immediately following stressor exposure. Since the immune response to CT is altered only when footshock is in close proximity to immunization, stress may alter accessory cell function. Therefore, Specific aim 1 will address the effects of acute footshock on (i) antigen presentation by antigen-presenting cells (APC), and (ii) macrophage (Mo) production of IL-1, IL-6, TNF, TGF, and PGE2. In addition, the in vivo role of Mo in mediating stressor-induced suppression of lymphocyte function, will be investigated. Specific aim 2 will examine the effect of stress on T lymphocyte reactivity to antigen immediately after stressor exposure. Thus, unprimed splenic T cells will be assayed for (i) proliferative activity to antigen-specific and non- specific signals in vitro, (ii) the ability of Th1 CD4+ T cells to secrete IL-2 and IFN-gamma, and Th2 CD4+ T cells to elaborate IL-4 and IL-6, and (iii) CD4+ and CD8+ T cell helper and suppressor regulatory function, respectively. These measures represent the major interacting components of T lymphocyte antigen-specific immune responses, that can also regulate B cell function, which, as stated above, was suppressed by footshock at the time of immunization. The proliferative, cytokine, and regulatory measures for T cell reactivity will also form the basis of the final series of investigators in Specific Aim 3. These experiments will test whether acute footshock differentially alters the reactivity of naive and memory T cells to antigen-specific and non-specific signals. This will be accomplished by dividing splenic T lymphocytes, from stressed and non-stressed antigen-primed rats, into OX-22- (memory) and OX-22+ (naive) populations, and assessing the parameters studied in Specific Aim 2. Collectively, these studies will generate important avenues for the investigation of basic immune mechanisms altered by acute stressor exposure, and facilitate understanding of how environmental factors, such as stress, can influence the immune response to viral infections, such as HIV.