Psychological stress, cortisol, and B lymphocyte decrements

描述（由申请人提供）：癌症疫苗正在成为癌症治疗和预防的重要工具。不幸的是，最终将从疫苗中受益最多的人群，那些患癌症风险较高的人群，可能会受到压力。慢性压力会损害免疫功能，包括对疫苗的免疫反应。对疫苗的反应不充分可能会削弱其保护作用;1然而，压力对疫苗反应产生影响的机制尚不清楚。一种机制可能涉及应激相关的皮质醇增加，导致B淋巴细胞数量减少。B淋巴细胞对于疫苗应答是重要的。免疫系统对入侵的病原体（和疫苗）作出反应，其具有涉及多种免疫细胞的精心策划的级联事件，并最终导致由B淋巴细胞谱系的成熟浆细胞产生抗体。我们小组以前的工作表明，高水平的学业压力与外周血B淋巴细胞数量非常低有关。有大量的体外和体内证据表明，高水平的糖皮质激素导致小鼠B淋巴细胞减少。有充分的证据表明，高水平的压力与人类皮质醇水平升高有关，但皮质醇导致人类B淋巴细胞减少的证据有限。只有体外数据表明，骨髓培养物中高水平的皮质醇与早期B淋巴细胞减少有关。据我们所知，没有体内人体研究报告由于心理应激导致皮质醇增加与B淋巴细胞数量急剧减少相关。本生物行为研究的目的是填补这一空白的纵向研究的影响，学术压力对唾液皮质醇和B淋巴细胞的数量在40名比较参与者和40名学生在他们的研究生院的第一年，最终与资格考试。这些数据将为研究心理压力、皮质醇、B淋巴细胞数量和疫苗抗体反应提供良好的初步数据。目前研究与公共卫生的相关性：癌症疫苗正在成为癌症治疗和预防的重要工具。但是心理压力会削弱对疫苗的免疫反应，而那些从癌症疫苗中受益最多的人，那些有癌症遗传风险的人，很可能会受到压力。本研究将开始阐明心理应激损害疫苗免疫应答的机制。

DESCRIPTION (provided by applicant): Cancer vaccines are emerging as important tools for cancer treatment and prevention. Unfortunately, the cohorts that ultimately will benefit most from the vaccines, those at elevated risk for cancer, are likely to be stressed. Chronic stress can impair immune function, including immune response to vaccines. An inadequate response to vaccines can weaken their protective effect ;1 however, the mechanism by which stress exerts its effect on vaccine response is not known. One mechanism may involve stress-related increases in cortisol leading to decrements in B lymphocyte number. B lymphocytes are important for vaccine response. The immune system responds to invading pathogens (and vaccines) with a well-orchestrated cascade of events that involve a variety of immune cells and ultimately result in the production of antibodies by mature plasma cells of the B lymphocyte lineage. Previous work by our group has shown that high levels of academic stress are associated with very low numbers of peripheral blood B lymphocytes. There is ample in vitro and in vivo evidence that high levels of glucocorticoids cause reductions in B lymphocytes in mice. There is ample evidence that high levels of stress are associated with elevated cortisol levels in humans, but the evidence regarding cortisol causing reductions in B lymphocytes in humans is limited. There are only in vitro data to suggest high levels of cortisol in bone marrow cultures are associated with reductions in early B lymphocytes. To our knowledge, there are no in vivo human studies reporting increases in cortisol due to psychological stress are associated with dramatic decrements in B lymphocyte number. The purpose of the present biobehavioral research is to fill this gap with a longitudinal study of the effects of academic stress on salivary cortisol and B lymphocyte number among 40 comparison participants and 40 students over the course of their first year of graduate school which culminates with the qualifying examinations. These data will provide excellent preliminary data to support a larger grant application studying psychological stress, cortisol, B lymphocyte number, and antibody response to vaccine. Relevance of the present research to public health: Cancer vaccines are emerging as important tools for cancer treatment and prevention. But psychological stress can impair immune response to vaccine, and the people who will benefit most from cancer vaccines, those at genetic risk for cancer, are likely to be stressed. The present study will begin to elucidate the mechanism by which psychological stress impairs immune response to vaccines.