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免疫衰老与老年人疫苗接种II. 恢复与年龄相关免疫损伤的新策略

Immunosenescence and vaccination of the elderly II. New strategies to restore age-related immune impairment.

作者信息

Ongrádi J, Stercz B, Kövesdi Valéria, Vértes L

机构信息

Institute of Public Health, Semmelweis University, Budapest, Hungary.

出版信息

Acta Microbiol Immunol Hung. 2009 Dec;56(4):301-12. doi: 10.1556/AMicr.56.2009.4.1.

Abstract

One of the greatest health-care challenges in the elderly is to ensure that vaccination against infections are optimally effective, but vaccination can only be effective if cells that are capable of responding are still present in the repertoire. The reversing of immunosenescence could be achieved by improving immune responses or altering vaccine formulation. Recent vaccination strategies in the elderly exert low effectiveness. Nutritional interventions and moderate exercise delay T cell senescence. Telomerase activity and expression of toll-like receptors 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 immunostimulatory and anti-inflammatory cytokines show the best practical approach. Reduced dendritic cell activity and co-receptor expression might be increased by interleukin (IL)-2 administration. IL-7 protects both B and T lymphocytes, but IL-2, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone also have a stimulatory effect on thymopoiesis. In animals, several strategies have been explored to produce more efficacious vaccines including high dose vaccines, DNA vaccines with immunostimulatory patch, virosomal vaccines and vaccines containing new adjuvants. Hopefully, one of these approaches will be translated into human therapy in a short time.

摘要

老年人面临的最大医疗保健挑战之一是确保抗感染疫苗发挥最佳效果,但只有当免疫系统中仍存在能够产生应答的细胞时,疫苗才能有效发挥作用。免疫衰老的逆转可以通过改善免疫反应或改变疫苗配方来实现。目前针对老年人的疫苗接种策略效果不佳。营养干预和适度运动可延缓T细胞衰老。化疗可提高端粒酶活性和Toll样受体的表达。胸腺移植、清除积累的功能失调的初始T细胞和疱疹病毒特异性耗竭记忆细胞可实现胸腺萎缩的逆转。免疫刺激和抗炎细胞因子的给药是最具实践意义的方法。给予白细胞介素(IL)-2可能会增加树突状细胞活性和共受体表达。IL-7可保护B淋巴细胞和T淋巴细胞,但IL-2、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对胸腺生成也有刺激作用。在动物实验中,已经探索了几种策略来生产更有效的疫苗,包括高剂量疫苗、带有免疫刺激贴片的DNA疫苗、病毒体疫苗和含有新型佐剂的疫苗。有望在短时间内将这些方法中的一种转化为人类治疗手段。

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