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.