Immunosenescence is the consequence of the continuous attrition caused by chronic antigenic stress. The most important characteristics of immunosenescence (accumulation of memory and effector T cells, reduction of naive T cells, shrinkage of T cell repertoire, reduction of the immunological space) are compatible with this assumption. Immunosenescence can be taken as proof that the beneficial effects of the immune system, devoted to the neutralization of harmful agents early in life, become detrimental late in life, in a period not foreseen by evolution. This perspective could explain the mechanisms of the ageing process as well as the pathogenesis of age-related diseases. Keywords: Antigenic load; Inflamm-ageing; Ageing rate; Immunosenescence; Age-related diseases Evolutionary-based immunosenescenceImmunosenescence is a recent phenomenon, related to the extraordinary and linear improvements in survival and lifespan that began around the 19th century and are still occurring. It is possible to speculate that the role of immunosenescence was indeed negligible in the past, when the human lifespan was 40-50 years, and that its impact on morbidity and mortality has emerged in combination with the extension of lifespan [1]. The changes associated with immunosenescence, such as inflamm-ageing, shrinkage of the T cell repertoire and filling up of the immunological space with memory/effector cells, are playing a more and more important role in the emergence of a series of age-related pathologies, conditioning the present epidemiology of old people [2].The ageing of the immune system (IS) is not a random process without rules or directions, but rather is subject to evolutionary constraints [3]. The IS has been probably selected to serve individuals living until reproduction. The trend of thymic ontogenesis and involution likely supports this hypothesis [4]. Our ancestors lived until 30-50 years of age. Nowadays, the IS must serve the soma of individuals living 80-120 years, an enormous amount of time longer than that predicted by evolutionary forces. Therefore, old people have to cope with a lifelong antigenic burden encompassing several decades of evolutionary unpredicted antigenic exposure. This chronic antigenic stress and the subsequent inflammatory burden have a major impact on survival and frailty. The quality of ageing and the peculiar remodeling of the IS in more advanced age are the results of the individual immunological history, which therefore heavily influences both longevity and successful ageing [5]. Individual immunological history derives from the interaction between genetic background and specific lifelong antigenic burden [6,7]. This latter depends on historical period where you live, on geography (poor/dirty or reach/hygienized countries) and on social/economic status and education. Indeed, since the genetic pool of humans remained almost constant in the last century, the recent spectacular improvement in survival can be largely attributed to improved life conditions and hygiene [8]. Chronic an...

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Conclusions-Quantitative determination of CD19 and CD20 may provide useful diagnostic information for the study of B lymphoproliferative disorders. (J Clin Pathol 1998;51:364-369)

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Osteoporosis is a condition characterized by low bone mass and increased bone fragility, putting patients at risk of fractures, which are major causes of morbidity substantially in older people. Osteoporosis is currently attributed to various endocrine, metabolic and mechanical factors. However, emerging clinical and molecular evidence suggests that inflammation also exerts significant influence on bone turnover, inducing osteoporosis. Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as important risk factor. Chronic inflammation and the immune system remodelling characteristic of ageing, as well as of other pathological conditions commonly associated with osteoporosis, may be determinant pathogenetic factors. The present article will review the current perspectives on the interaction between bone and immune system in the elderly, providing an interpretation of osteoporosis in the light of inflamm-ageing.

The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy all over the world and manifestations of food allergy appear increasingly frequent also in elderly subjects. Environmental and nutritional changes have partly changed the epidemiology of allergic reactions to foods and new food allergic syndromes have emerged in recent years. The deepening of the study of the intestinal microbiota has highlighted important mechanisms of immunological adaptation of the mucosal immune system to food antigens, leading to a revolution in the concept of immunological tolerance. As a consequence, new prevention models and innovative therapeutic strategies aimed at a personalized approach to the patient affected by food allergy are emerging. This review focuses on these new perspectives and their practical implications in the management of food allergy, providing an updated view of this complex pathology.

Osteoporosis is a condition characterized by low bone mass and increased bone fragility, putting patients at risk of fractures, which are major causes of morbidity substantially in older people. Osteoporosis is currently attributed to various endocrine, metabolic and mechanical factors. However, emerging clinical and molecular evidence suggests that inflammation also exerts significant influence on bone turnover, inducing osteoporosis. Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as important risk factor. Chronic inflammation and the immune system remodelling characteristic of ageing, as well as of other pathological conditions commonly associated with osteoporosis, may be determinant pathogenetic factors. The present article will review the current perspectives on the interaction between bone and immune system in the elderly, providing an interpretation of osteoporosis in the light of inflamm-ageing.