Infants and the elderly share a high vulnerability to infections and therefore have specific immunization requirements. Inducing potent and sustained B-cell responses is as challenging in infants as it is in older subjects. Several mechanisms to explain the decreased B-cell responses at the extremes of age apply to both infants and the elderly. These include intrinsic B-cell limitations as well as numerous microenvironmental factors in lymphoid organs and the bone marrow. This Review describes the mechanisms that shape B-cell responses at the extremes of age and how they could be taken into account to design more effective immunization strategies for these high-risk age groups.

Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation.

The increased susceptibility of the elderly to infection presents a major challenge to public health services. An aging immune system is well documented as the cause of increased infection rates in elderly people. Such immunosenescence is multi-factorial and incompletely understood. Immunosenescent changes include malfunctioning of innate immune system cellular receptors; involution of the thymus, with consequent reduction of the naïve T cell population; alteration of the T cell population composition; modified phenotypes of individual T cells; and replicative senescence of memory cells expressing naïve markers. Unfortunately, immunosenescence also renders vaccination less effective in the elderly. It is therefore important that the vaccines used against common but preventable diseases, such as influenza, are specifically enhanced to overcome the reduced immune responsiveness of this vulnerable population.

SUMMARYThe thymus undergoes age-associated involution, with studies showing thymic size decreasing from birth at a rate of approximately 3% per year until middle age, and at a rate of 1% per year thereafter. The aim of this study was to determine the effect of thymic atrophy on T-lymphocyte production by the thymus, and to clarify the ongoing uncertainty regarding gender differences in thymic function. We quantified recent thymic emigrants (RTEs) in blood through the measurement of signal joint T-cell receptor rearrangement excision circles (sjTRECs), and showed that the decline in the number of RTEs in the blood with increasing age is gender-linked. Peripheral blood from females contained significantly higher levels of sjTRECs per CD3 1 T cell than blood from males (P 0´002), despite there being no significant gender difference in the absolute number of CD3 1 T cells in the populations analysed (P . 0´10). Our findings suggest better thymic function in females compared with males, providing females with a higher number of recent thymic emigrants for longer periods of life. Such a finding provides a plausible explanation for the immunological gender differences observed in previous studies and possibly, for the general longer life expectancy in females compared with males.

Interaction with the immune system is one of the most recently established nonclassic effects of vitamin D (VitD). For many years, this was considered to be limited to granulomatous diseases in which synthesis of active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or calcitriol is known to be increased. However, recent reports have supported a role for 1,25(OH)2D3 in promoting normal function of the innate and adaptive immune systems. Crucially, these effects seem to be mediated not only by the endocrine function of circulating calcitriol but also via paracrine (i.e., refers to effects to adjacent or nearby cells) and/or intracrine activity (i.e., refers to a hormone acting inside a cell) of 1,25(OH)2D3 from its precursor 25(OH)D3, the main circulating metabolite of VitD. The ability of this vitamin to influence human immune responsiveness seems to be highly dependent on the 25(OH)D3 status of individuals and may lead to aberrant response to infection or even to autoimmunity in those who are lacking VitD. The potential health significance of this has been underlined by increasing awareness of impaired status in populations across the globe. This review will examine the current understanding of how VitD status may modulate the responsiveness of the human immune system. Furthermore, we discuss how it may play a role in host resistance to common pathogens and how effective is its supplementation for treatment or prevention of infectious diseases in humans.