Ageing and the Immune System

Abstract

Recognising invading foreign organisms, preventing their spread and ultimately clearing them from the body throughout life is the central role of the immune system. In a healthy adult, the immune system is composed of approximately 1012 cells which interact with each other to produce both effector molecules and cells which defend the tissues of the body against potential pathogens.

Unfortunately, like all biological systems, there is normal wear and tear, and with advancing age, the immune system shows a gradual loss of function. However, because each individual differs in their genetic makeup and has been exposed to a different range of environmental factors, this functional decline is not uniform and predictable. There is no certain age at which this process begins and no defined pathway or identifiable sequence of loss of function. The result is considerable variation within the aged population in the ability of an individual to respond productively to potential pathogens and vaccines. Current work is directed at mapping the changes in the immune system with age with a view to identifying any common triggers of deterioration in function. This in turn might lead to an opportunity to reverse the degradation process and thus to extend the period of fully effective protection.

Key Concepts

  • Low‐grade systemic inflammation is a feature which characterises the ageing process in many individuals.
  • Evidence from epidemiology studies shows that the susceptibility to infectious diseases increases with age.
  • Studies on responses to vaccines reveal that many older individuals fail to produce the responses seen in younger individuals, which is associated with protection from the disease.
  • Some change in the function of cells of the innate immune system (NK cells, neutrophils, macrophages and dendritic cells) has been noted in a number of older individuals.
  • All older individuals show an accumulation of fat in the primary lymphoid organs, which is associated with functional decline and a reduction in their ability to produce new lymphocytes.
  • The thymus atrophies with age, and there is a reduction in the areas of active thymopoeisis and in the output of naïve T cells.
  • The area of active (red) bone marrow declines with age, and the number of naïve B cells emerging from the marrow shows a reduction with age.
  • A successful T cell‐mediated immune response results in the generation of both T and B memory cells, and as survival depends on successful responses, there is an increase in the number of memory cells with age.
  • Infections with persistent viruses such as the human herpes virus group can lead to the expansion of specific clones amongst which are cells at, or close to, their replicative limit.
  • The expansion of some clones within the memory cell pool may also be linked with the loss of other clones and the appearance of ‘holes’ in the repertoire.

Keywords: thymic involution; senescence; lymphocyte; immunotherapy

Figure 1.

The complex relationship between the thymus and the peripheral lymphoid pool as we age is shown above. On the left is the situation in young individuals where the thymus, shown at the centre, produces naïve T cells. Each cell has a different specificity represented here as a different colour and the naïve T‐cell pool is contained within the inner pentagon. Cells within the naïve T‐cell pool meet antigen, make a successful response cross the boundary into the outer pentagon and become part of the memory T‐cell pool.

Cells within a clone of memory; all have the same specificity and are shown here in the region between the pentagons. In order to survive, these cells have to divide. With age (seen on the right‐hand side of the diagram), the thymus atrophies and its output decline. Hence, the size of the naïve T‐cell pool diminishes and the size of the memory pool increases. Throughout this period, the total number of T cells in the pool remains within defined limits.

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Further Reading

Aspinall R and Lang PO (2013) The avalanche is coming… and it's starting to snow. Frontiers in Immunology 4: 165.

Chen WH, Cross AS, Edelman R, et al. (2011) Antibody and Th1‐type cell‐mediated immune responses in elderly and young adults immunized with the standard or a high dose influenza vaccine. Vaccine 29 (16): 2865–2873.

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Siegrist CA and Aspinall R (2009) B cell responses to vaccination at the extremes of age. Nature Reviews Immunology 9: 1–10.

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Aspinall, Richard, and Lang, Pierre Olivier(Sep 2015) Ageing and the Immune System. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0004031.pub2]