Stress, immune alterations and neurochemical change

应激事件可能促进心理疾病和免疫疾病的发展和恶化。虽然心理变化可能涉及中枢递质活动的改变，但身体疾病可能源于应激源的短暂免疫和神经内分泌作用，从而影响生物体对抗病原体的能力。有趣的是，似乎不仅压力源或中枢神经系统事件影响免疫功能，而且免疫改变可能会影响中枢神经递质活动。事实上，免疫激活可能深刻地影响中枢神经化学功能（包括对去甲肾上腺素、血清素和多巴胺的影响，以及促皮质释放激素及其受体亚型的影响），这种影响可能与压力源相互作用。鉴于抗原攻击后观察到的神经化学和激素变化的特征，这表明免疫系统可能作为一种感觉器官告知中枢神经系统病毒或细菌攻击的存在（这可能被翻译为应激源）。拟议的研究将评估应激源对免疫功能影响的情况，特别是应激源引起的变化的时间过程，以及慢性、不可预测的应激源（中等严重程度）明显增加适应负荷的影响。免疫变化将与应激源引起的神经内分泌和神经递质变化（包括单胺和神经肽）有关，研究将评估特定神经化学操作对应激源引起的免疫改变的影响。此外，实验将评估应激源的主动效应（行为和神经化学功能方面的致敏效应），以应对后续应激源或免疫挑战。最后，鉴于免疫激活可能影响情感状态，应激源和免疫挑战的影响将在模仿焦虑和抑郁疾病的行为测试中进行评估。再一次，影响CRH或单胺功能的操作效果将决定这些操作是否会改变免疫引起的行为障碍。

Stressful events may promote the development and exacerbation of psychological, as well as immunologically based illnesses. While the psychological changes may involve alterations of central transmitter activity, physical illnesses may stem from transient immunological and neuroendocrine effects of the stressor, thereby influencing the organism's ability to contend with pathogens.  Interestingly, it seems that not only do stressors or CNS events influence immune functioning, but immunological alterations may come to affect central neurotransmitter activity. Indeed, immune activation may profoundly affect central neurochemical functioning (including effects on norepinephrine, serotonin and dopamine, as well as corticotropic releasing hormone, and its receptors subtypes), and such effects may interact with stressors. Given the profile of neurochemical and hormonal changes observed following antigenic challenge, it was suggested that the immune system may act as a sensory organ informing the CNS of the presence of viral or bacterial challenge (which may be translated translated as a stressor).  The proposed studies will assess the conditions wherein stressors impact on immune functioning, with particular reference to the time course of the changes induced by stressors and the influence of chronic, unpredictable stressors (of moderate severity) that appreciably increase allostatic overload. The immune changes will be related to stressor provoked neuroendocrine and neurotransmitter changes (including monoamines and neuropeptides), and studies will assess the effects of specific neurochemical manipulations on stressor provoked immune alterations. In addition, experiments will assess the proactive effects of the stressors (sensitization effects with respect to behavior and neurochemical functioning) in response to later stressor or immune challenges. Finally, given that immune activation may influence affective state, the effects of stressors and immune challenges will be assessed in behavioral tests thought to mimic anxiety and depressive illness. Once again the effects of manipulations that affect CRH or monoamine functioning will be determine whether these modify immune-provoked behavioral disturbances.