Immunosenescence: the importance of considering age in health and disease

Abstract

This special issue of Clinical and Experimental Immunology is dedicated to immunosenescence. It covers a wide range of topics related to immunosenescence, from basic research and animal models to applied topics such as vaccines for elderly people and interventions to rejuvenate the immune system. The reviews in this issue highlight some of the topics discussed at the Satellite Symposium ‘Immunosenescence: Hot Topics and Interventions’, which took place on 5–6 September 2015 in Vienna, Austria, preceding the 4th European Congress of Immunology. The symposium was organized by Birgit Weinberger, Beatrix GrubeckLoebenstein (both University of Innsbruck, Innsbruck, Austria), Daniela Frasca, Bonnie Blomberg (both University of Miami, Miami, FL, USA), Arne N. Akbar (University College London, London, UK), Graham Pawelec (University of T€ ubingen, T€ ubingen, Germany), Rebecca Fuldner (National Institute on Aging, Bethesda, ND, USA) and Elizabeth J. Kovacs (Loyola University, Chicago, IL, USA). The world is undergoing a substantial shift in demographics, as the number of individuals aged more than 60 years is increasing dramatically. The immune system undergoes typical age-related changes, which are collectively termed ‘immunosenescence’. The incidence and severity of various infections increases with age; concomitantly, the immunogenicity and efficacy of many vaccines is lower in elderly people, making protection of this vulnerable population a challenge. With increasing age, the innate immune system exhibits a diminished ability to respond to and clear infections. The incidence of lung infections is high in older adults and severe disease is observed frequently. A more detailed understanding of local and systemic immune responses to pneumonia and the impact of age is essential in order to design age-specific therapies. Alveolar macrophages and neutrophils are the first line of defence against bacterial pneumonia, but alterations in Toll-like receptor signalling, cytokine and chemokine production and defects in effector functions, such as clearance of cell debris and bactericidal activity, limit their effect in elderly people. Dendritic cells and natural killer cells in the lung play an important role in the defence against viral infections such as influenza and respiratory syncytial virus, but migration to lymph nodes and stimulation of T cells by dendritic cells as well as the capacity of natural killer cells to eliminate infected cells are diminished in old age [1]. Cell-intrinsic defects of aged T cells have been investigated extensively. The review by Kim et al. [2] summarizes the details of vaccine-induced T cell responses, including activation, expansion, differentiation into effector cells and generation of T cell memory, and highlights the importance of these findings for vaccine development. Most approaches to improve vaccination responses in old age concentrate on activating the innate immune system by adjuvants in order to improve the induction of an adaptive immune response, but strategies to target T cells directly should also be considered [2]. During recent years it has become evident that metabolic regulation in lymphocytes plays an important role in immune responses and immune regulation. A short commentary by Arne Akbar highlights the interplay of nutrient sensing by adenosine 5 monophosphate activated protein kinase (AMPK), intracellular adenosine triphosphate (ATP) levels and ageing processes in T cells [3]. Age-related defects of B cells include alterations in the generation of B cells during OTHER ARTICLES PUBLISHED IN THIS REVIEW SERIES The convergence of senescence and nutrient sensing during lymphocyte ageing. Clinical and Experimental Immunology 2017, 187: 4-5. Immune senescence: significance of the stromal microenvironment. Clinical and Experimental Immunology 2017, 187: 6-15. Innate immune responses in the ageing lung. Clinical and Experimental Immunology 2017, 187: 16–25. Age-related alterations in immune responses to West Nile virus infection. Clinical and Experimental Immunology 2017, 187: 26–34. Intracellular signalling pathways: targets to reverse immunosenescence. Clinical and Experimental Immunology 2017, 187: 35–43. Ageing and inflammation in patients with HIV infection. Clinical and Experimental Immunology 2017, 187: 44–52. Considerations for successful cancer immunotherapy in aged hosts. Clinical and Experimental Immunology 2017, 187: 53–63. Ageing and obesity similarly impair antibody responses. Clinical and Experimental Immunology 2017, 187: 64–70. The life cycle of a T cell after vaccination – where does immune ageing strike? Clinical and Experimental Immunology 2017, 187: 71–81. Herpes zoster and the search for an effective vaccine. Clinical and Experimental Immunology 2017, 187: 82–92. Adult vaccination against tetanus and diphtheria: the European perspective. Clinical and Experimental Immunology 2017, 187: 93–99.