BEHAVIORALLY CONDITOINED IMMUNE RESPONSES

行为调节的免疫反应

• 批准号: 3381050
• 负责人: ROBERT ADER
• 金额: $ 34.41万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3381050
• 关键词: AIDS; antigen antibody reaction; autoimmune disorder; behavioral medicine; cellular immunity; conditioning; humoral immunity; immunopharmacology; immunoregulation; immunosuppression; immunosuppressive; interferon inducers; laboratory mouse; morphine; natural killer cells; neuroendocrine system; poly IC; psychoneuroimmunology; psychophysiology; stress; taste

As one means of studying CNS-immune system interactions, our goal continues to be the elaboration and mediation of behaviorally conditioned alterations in immunologic reactivity. We will investigate the possibility of conditioning an enhancement of natural killer (NK) cell and immune responses, the conditions under which one observes conditioned suppression or enhancement of immune responses, and the extent to which these depend upon conditioned behavioral responses. Thus, conditioned changes in NK cell activity will be studied using interferon-inducers (e.g. Poly I:C and morphine as a unconditioned stimuli (UCSs) in multiple-trial conditioning paradigms that will enable the detection of possible conditioned compensatory responses. In the case off morphine, conditioned changes in NK activity will be related to behavioral responses in a taste aversion situation and in a learning paradigm in which morphine has positively reinforcing effects. Conditioning studies that do not involve immunomodulating drugs will also be undertaken. In one instance, the decreased antibody response to an antigenic stimulus administered after repeated exposures to ip injections of saline will be examined as a conditioning phenomenon . Particular emphasis will be directed to enhanced antibody responses to an immunologically neutral (conditioned) stimulus previously paired with an antigen (the UCS). Distinctively flavored drinking solutions will serve as conditioned stimuli (CSs) and antigens (e.g., keyhole limpet hemacyanin, KLH) will serve as UCSs. Conditioned C3H/Hej mice would receive multiple CS-UCS pairings at intervals of 3 weeks. On the test day, one group would be reexposed to the CS and one group would not. These groups will be further subdivided into those that are and those that are not given a low- dose ("booster") injection of KLH on the test day. Nonconditioned and Placebo-treated control groups would be similarly manipulated. We will establish the generality of conditioned antibody responses by using different antigens as UCS and, in a series of studies, assess the specificity of the conditioned response (i.e., determine if the conditioned changes responsible for the enhanced production of antibody are a consequence of immunologic reactions specific to the antigen used as the UCS or are mediated by nonspecific immunologic or neuroendocrine reactions induced by exposure to antigenic stimuli). In pursuing the mediating mechanisms, the effects of conditioning on B and T cell functions and on cytokines (interleukin-1 and -2), and on norepinephrine changes in spleen and in specific regions of the hypothalamus will be examined. The proposed research will increase our understanding of the means by which behavior can serve an immunoregulatory function and provide an experimental foundation for and new approaches to the study of adaptive processes in health and in a variety of disease processes such as autoimmune diseases, infectious diseases, and AIDS which involve disordered regulation of the immune system.

作为研究CNS-免疫系统相互作用的一种手段，我们的目标继续 成为行为条件改变的阐述和调解 在免疫反应性中。我们将调查的可能性 调节自然杀手（NK）细胞的增强和免疫 反应，一个人观察到条件抑制的条件 或增强免疫反应，以及这些依赖的程度 有条件的行为反应。因此，NK单元的条件变化 将使用干扰素诱导者研究活动（例如Poly I：C和 吗啡作为多次试验条件的无条件刺激（UCSS） 可以检测可能的条件的范例 补偿性反应。在吗啡的情况下，NK的条件变化 活动将与味觉厌恶中的行为反应有关 形态和吗啡的学习范式 增强效果。 不涉及免疫调节药物的调节研究也将 进行。在一个例子中，抗体对一个的抗体反应降低 重复接触IP注射后，给予抗原刺激 盐水将被检查为一种调节现象。特别的 重点将针对增强对 免疫学上中立（条件）刺激先前与A 抗原（UCS）。风味鲜明的饮酒解决方案将作为 条件刺激（CSS）和抗原（例如，钥匙孔的limpet hemacyanin， KLH）将用作UCSS。条件C3H/HEJ小鼠将获得多个 CS-UCS配对以3周的间隔。在测试日，一组会 重新公开CS，一个组不会。这些小组将是 进一步细分为那些，以及那些没有给出的那些 测试当天的剂量（“助推器”）注射KLH。无条件和 安慰剂处理的对照组将类似地操纵。 我们将通过使用条件抗体反应的一般性 不同的抗原作为UCS，在一系列研究中，评估了 条件响应的特异性（即确定条件是否 负责增强抗体产生的变化是 与用作抗原特有的免疫反应的结果 UCS或由非特异性免疫或神经内分泌反应介导 暴露于抗原刺激）。追求调解 机制，调节对B和T细胞功能的影响以及 细胞因子（白介素-1和-2），以及脾脏的去甲肾上腺素变化 并将检查下丘脑的特定区域。 拟议的研究将提高我们对这种手段的理解 行为可以发挥免疫调节功能并提供实验性 研究适应过程的基础和新方法 健康和各种疾病过程，例如自身免疫性疾病， 传染病和涉及无序调节的艾滋病 免疫系统。