Abstract
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.
Highlights
The global population, especially in the developed countries, is ageing
Concluding remarks Frequent and severe microbial infections influence the quality of life of elderly individuals and their families, and have a deleterious financial impact onto the health-care system
Several types of infectious diseases might be prevented by vaccinating old people
Summary
The global population, especially in the developed countries, is ageing. The percentage of the population that is elderly (≥60 years of age) represents a larger proportion than ever before: it has increased from 8% in year 1950 to 10% in 2000, and this trend is expected to continue, to reach 21% of the population by 2050 [1]. Sex steroid ablation in men undergoing therapy for prostate cancer is reported to result in increased numbers of circulating naive T lymphocytes, but this approach is obviously not generally applicable to the majority of elderly people [7] It has been known since ancient times that eunuchs live longer than normal males, perhaps due to preserved immune functions. Strategies to reduce the chronic infectious antigenic load would seem to offer a reasonable approach to restoring appropriate immune functions and might benefit naive T cell production Targeting these viruses and any other infectious agents that have established a persistent infection may be of clinical benefit both directly by reducing the pathological consequences of the infections and in terms of improving responses to vaccinations. Authors' contributions Both authors drafted the manuscript and approved the text
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