Introduction to Ageing of the Adaptive Immune System
Like other somatic tissues and organs, the vertebrate immune system manifests age-associated alterations to its components and their functions. Unlike in invertebrates, in addition to the innate arm, vertebrates also possess adaptive immunity mediated by
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Introduction to Ageing of the Adaptive Immune System Ludmila Müller and Graham Pawelec
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Introduction
Like other somatic tissues and organs, the vertebrate immune system manifests ageassociated alterations to its components and their functions. Unlike in invertebrates, in addition to the innate arm, vertebrates also possess adaptive immunity mediated by both cellular and humoral components. This chapter reviews data on age-associated alterations to adaptive immunity specifically in humans, mostly originating from cross-sectional studies (i.e., comparing young with old people). We summarise what is known about the effects of age on the different components of the adaptive immune system, particularly T cells, which appear most obviously different in the elderly. We consider the serious limitations inherent in cross-sectional studies, and discuss the crucial requirement to perform longitudinal studies (i.e., following the same individuals over time). Despite the logistical and financial constraints, longitudinal follow-up has provided the most biologically meaningful information about which of the many biomarkers apparently changing with age are actually relevant to medical parameters and for late-life health and longevity, and which, in contrast, may change with age but without clinical relevance. Given the lack of consistent data currently available, as a result of performing studies on heterogeneous populations using different analytical techniques, we emphasize the necessity for more numerous, more extensive and more detailed studies including assessments of the impact of psychosocial, nutritional and other thus-far rarely considered parameters on immunological and other biomarkers in longitudinal studies. We consider the mechanisms responsible for the disparate age-associated changes observed, beginning at the level of hematopoiesis, where alterations in the stem cell niches and the stem cells themselves contribute to G. Pawelec () Center for Medical Research, University of Tübingen, Waldhörnlestr. 22, 72072 Tübingen, Germany e-mail: [email protected] L. Müller Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany
J. A. Bosch et al. (eds.), Immunosenescence, DOI 10.1007/978-1-4614-4776-4_2, © Springer Science+Business Media New York 2013
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L. Müller and G. Pawelec
age-associated differences in the constantly self-renewing immune system. Thereafter, because T-cell progenitors require further processing in the periphery, thymic involution at puberty also results in a severely decreased production of naïve T cells in later life. This helps to explain why the observed alterations in peripheral T cells seem more extreme than in B cells, which do not require such further processing after their release from the bone marrow. We consider T cells and B cells separately, and describe the constellations of biomarkers, which we term “immune signatures” that may associate with age and/or disease. Determining which of the many potential biomarkers that can be measured no
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