The deterioration of immune function with advancing age contributes to the increased incidence of morbidity and mortality among the elderly from infectious disease and possibly cancer. The innate and adaptive arms of immunity are affected by the deleterious effects of aging, but it is adaptive immunity, and in particular T lymphocytes, that is most susceptible to these effects. The aging of the immune system, referred to as immunosenescence, is associated with a dramatic decline in responsiveness as well as functional dysregulation. Age-associated alterations in T cells are evident at all stages of its development, and it is these changes that contribute to the overall increased susceptibility to infection and possibly cancer. Although there is an enormous effort worldwide to develop vaccines, much of the research is performed with young animals. Because the immune system of the aged is different from that of the young, many of the findings cannot be extrapolated. In this review, we will discuss those differences in T cell immunity of the aged, relate how these differences influence the immune response of the aged to pathogens as well as to tumors, and describe the current approaches to rejuvenate the aged immune response. Although the majority of the conclusions on T cell immunity in the aged are based on studies in the murine model, many of these findings can be extended to the human model. Throughout this review, we have noted those findings that are specific to humans.
Lymphocyte function-associated antigen-1 (LFA-1, αLβ2, CD11a/CD18) plays a critical role in the complex and well-orchestrated molecular interactions responsible for cell adhesion events required for normal and pathologic functions of the immune system. This review focuses on the diseases from various etiologies (genetic, bacterial, viral, neoplastic, allergic, and autoimmune) that are associated to lymphocyte function-associated antigen-1 with a tremendous impact on human and animal health.
Lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, αLβ2) actively contributes to the molecular interactions responsible for normal functions of the immune system but is also associated to several diseases from various etiology (genetic, bacterial, viral, neoplastic, allergic, and autoimmune). In this way, the interaction between lymphocyte function-associated antigen-1 and its major ligand intercellular adhesion molecule-1 (ICAM-1 or CD54) has been extensively studied, leading to the development of therapeutic antibodies, peptides, and small inhibitory molecules.
A wide range of age-related alterations in immune system function have been reported and are referred to as immunosenescence. Much of the decline in immunoresponsiveness seen in elderly persons is due to changes within the T cell compartment because of the involution of the thymus. For this reason, infectious diseases are more frequent and severe in elderly persons, and the efficacy of vaccinations is low. Recently, scientific evidence has accumulated that chronic cytomegalovirus (CMV) infection may accelerate the aging of the immune system and may lead to a high chronic-inflammatory background in elderly persons. This may exacerbate the functional pathology and disease course of age-related disorders, such as atherosclerosis, rheumatoid arthritis, and Alzheimer's disease. Therefore, the present article will summarize the changes that occur in the immune system of elderly persons with and without chronic CMV infection and will highlight the impact of CMV infection on the immune response and efficacy of vaccinations in old age. It will also elucidate the mechanisms CMV uses to escape immune surveillance, the basis for life-long persistence in the host. Finally, current and future immunotherapeutic strategies to fight or prevent CMV infection will be reviewed.
The β2-integrin lymphocyte function-associated antigen-1 (LFA-1, αLβ2, CD11a/CD18) is made of the association of the CD11a and CD18 subunits that each possesses a large extracellular region and short transmembrane and cytoplasmic parts. A general comparison among species enlights the importance of especially conserved functional regions, as well as their role in folding and heterodimerization. This review also focuses on providing insights into structural aspects that lead to lymphocyte function-associated antigen-1 ability, central to its critical role in the molecular interactions responsible for leukocyte adhesion and migration in the immune system, to modulate dynamically its adhesiveness through avidity (affinity and valency)-based mechanisms.
