Factors that may impact on immunosenescence: an appraisal.
Factors that may impact on immunosenescence: an appraisal.
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可能影响免疫衰老的因素：评估。
DOI：
10.1186/1742-4933-7-7
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发表时间：
2010-06-14
影响因子：
7.9
通讯作者：
Kovesdi, Valeria
中科院分区：
文献类型：
--
作者：
Ongradi, Joseph;Kovesdi, Valeria
人口老龄化比例的增加对医疗保健系统提出了新的挑战。老年人经常遭受严重的感染。接种疫苗可以保护他们免受几种传染病的侵害，但只有当能够做出反应的细胞仍然存在于库中时，它才能有效。由于年龄相关的免疫功能受损，老年人最近的疫苗接种策略可能会降低有效性。免疫衰老影响先天免疫和适应性免疫。除了遗传易感性的个体差异外，人类生命的整个过程中的表观遗传变化也发挥免疫调节作用。巨噬细胞源性细胞因子释放的紊乱和自然杀伤细胞介导的细胞毒性的减少导致感染频率增加。衰老会抑制B细胞产生针对新抗原的抗体的能力。耗尽的记忆B淋巴细胞亚群取代幼稚细胞。细胞介导的免疫力下降是多种变化的结果，包括胸腺萎缩、新T淋巴细胞输出减少、无反应性记忆细胞积累和细胞因子产生不足。持续的病毒和寄生虫感染导致免疫监视的丧失和T细胞的过早耗尽。化疗可改善端粒酶活性和Toll样受体表达的降低。通过胸腺移植、清除累积的功能失调的幼稚T细胞和疱疹病毒特异性耗竭的记忆细胞可以逆转胸腺萎缩。施用白细胞介素（IL）-2、IL-7、IL-10、角质形成细胞生长因子、胸腺基质淋巴细胞生成素以及瘦素和生长激素促进胸腺生成。在动物中，已经探索了几种策略来生产上级疫苗。其中，含有多肽抗原或DNA质粒的病毒体疫苗以及新的佐剂疫苗制剂在老年人中引起比常规疫苗更高的树突状细胞活性和更有效的血清学应答。希望在不久的将来，这些方法中至少有一部分可以转化为人类医学。
The increasing ratio of ageing population poses new challenges to healthcare systems. The elderly frequently suffer from severe infections. Vaccination could protect them against several infectious diseases, but it can be effective only if cells that are capable of responding are still present in the repertoire. Recent vaccination strategies in the elderly might achieve low effectiveness due to age-related immune impairment. Immunosenescence affects both the innate and adaptive immunity. Beside individual variations of genetic predisposition, epigenetic changes over the full course of human life exert immunomodulating effects. Disturbances in macrophage-derived cytokine release and reduction of the natural killer cell mediated cytotoxicity lead to increased frequency of infections. Ageing dampens the ability of B cells to produce antibodies against novel antigens. Exhausted memory B lymphocyte subsets replace naïve cells. Decline of cell-mediated immunity is the consequence of multiple changes, including thymic atrophy, reduced output of new T lymphocytes, accumulation of anergic memory cells, and deficiencies in cytokines production. Persistent viral and parasitic infections contribute to the loss of immunosurveillance and premature exhaustion of T cells. Reduced telomerase activity and Toll-like receptor expression can be improved by chemotherapy. Reversion of thymic atrophy could be achieved by thymus transplantation, depletion of accumulated dysfunctional naive T cells and herpesvirus-specific exhausted memory cells. Administration of interleukin (IL)-2, IL-7, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone boost thymopoiesis. In animals, several strategies have been explored to produce superior vaccines. Among them, virosomal vaccines containing polypeptide antigens or DNA plasmids as well as new adjuvanted vaccine formulations elicit higher dendritic cell activity and more effective serologic than conventional vaccines responses in the elderly. Hopefully, at least some of these approaches can be translated to human medicine in a not too far future.