Neuroimmune Modulation of Virus Immunity In Aging

衰老过程中病毒免疫的神经免疫调节

• 批准号: 6881753
• 负责人: Raymond Preston Stowe
• 金额: $ 3.24万
• 依托单位: MICROGEN, LLC
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6881753
• 关键词: Epstein Barr virus; Herpesviridae disease; T lymphocyte; age difference; aging; cellular immunity; clinical research; cytotoxic T lymphocyte; developmental immunology; enzyme linked immunosorbent assay; flow cytometry; human middle age (35-64); human old age (65+); human subject; latent virus infection; neurohormones; neuroimmunomodulation; patient oriented research; questionnaires; stress; virus infection mechanism; virus load

This proposal is responsive to topic #I 1, Psychoneuroimmunology. Herpesviruses commonly establish infections in humans. These infections are usually characterized by an acute phase associated with minor morbidity and mortality followed by a chronic latent phase reflecting a balance between viral replication and the host immune response. Control over herpesvirus reactivation is primarily mediated by cellular immunity which declines with advancing age. As a result, herpesvirus infections are important pathogens in the elderly and result in considerable cost to the health care system. Another factor associated with herpesvirus reactivation is stress, and there has been considerable speculation linking stress and the appearance, duration, and intensity of herpesvirus infections. The immunological decrements associated with stress are of particular concern in the elderly because they already have age-related reductions in cellular immunity. Preliminary analysis of three elderly subjects has demonstrated lytic replication of Epstein-Barr virus (EBV), a member of the herpesvirus family. Therefore, the applicant will test the hypothesis that aging will decrease EBV-specific cellular immunity and increase reactivation of latent EBV. Furthermore, stress will result in higher viral load. Importantly, little is known about the immunobiology of EBV in aging. Studies outlined in this proposal will provide preliminary data regarding age-related declines in herpesvirus-specific T-cell immunity and subsequent latent virus reactivation. These data will subsequently be used to support an R01 application to develop a mechanistic investigation on how neuroendocrine hormones modulate herpesvirus-specific immunity in the elderly.

该建议对主题#I 1，PsychOneuromummummummummummyology做出了反应。疱疹病毒通常在人类中建立感染。这些感染通常以与较小的发病率和死亡率相关的急性相，然后是慢性潜伏期，反映了病毒复制与宿主免疫反应之间的平衡。对疱疹病毒重新激活的控制主要是由随着年龄增长而下降的细胞免疫介导的。结果，疱疹病毒感染是老年人的重要病原体，并为医疗保健系统带来了巨大的成本。与疱疹病毒重新激活相关的另一个因素是应力，并且存在相当大的猜测，将压力以及疱疹病毒感染的外观，持续时间和强度联系起来。在老年人中，与压力相关的免疫学减少特别关注，因为他们已经与年龄相关的细胞免疫降低。对三个老年受试者的初步分析表明，疱疹病毒家族的成员爱泼斯坦 - 巴尔病毒（EBV）的裂解复制。因此，申请人将检验以下假设，即衰老将降低EBV特异性细胞免疫力 并增加潜在EBV的重新激活。此外，应力将导致较高的病毒载荷。重要的是，关于EBV在衰老中的免疫生物学知之甚少。该提案中概述的研究将提供有关与年龄相关的特异性T细胞免疫和随后的潜在病毒重新激活的初步数据。这些数据随后将用于支持R01应用，以开发有关神经内分泌激素如何调节老年人中疱疹病毒特异性免疫的机械研究。