The aging immune system
Kanwal Razzaq and Gordon Dickinson
Introduction
Humans possess an elaborate array of host defenses against the many potential pathogens in their environment. Among these protective mechanisms are important mechanical and physiological guards such as skin and mucosal barriers, valvular structures like the epiglottis and the urethral valves, cleansing fluids (tears and respiratory tract mucus) and involuntary activities such as coughing. These defenses are, however, frequently breached and it is the immune response that is the final and most potent form of protection. ‘Immune response’ generally refers to internal cellular and humoral defense mechanisms, especially those that are acquired.
Innate and acquired immunity
Immunity can be categorized as innate or acquired. The components of innate immunity are generally present from birth and do not require exposure to a pathogen for their development. Innate immunity includes the macrophage/phagocyte cell lines, which act as nonspecific scavengers within the body, engulfing and killing invaders that have breeched the skin or mucosal barriers. To assist the macrophages, there are substances in the serum called complement and acute-phase reactants that facilitate the attachment and ingestion of pathogens. The macrophages, as well as the complement and acute-phase reactants, are poised to function as an immediate response system against virtually all bacteria; however, even in the presence of complement and acute-phase reactants, phagocytic cells often have difficulty promptly and efficiently ingesting pathogens. Some bacteria, for example Streptococcus pneumoniae and Haemophilus influenzae, form a polysaccharide capsule that shields them from these defenses. Moreover, many pathogens are either too large for ingestion by macrophages (e.g. parasites) or thrive in an intracellular location (e.g. viruses, mycobacteria and an assortment of other pathogens). To bolster these defenses, an acquired immune system has evolved, which is extremely potent and pathogen-specific, but which must be primed by a first-time exposure to the pathogen. Once in place, acquired immunity is permanent. The term ‘immunity’ generally refers to the activity of the acquired immune system.
T and B lymphocytes
The principal components of the acquired immune system are the T and B lymphocytes. All lymphocytes originate from progenitors in the bone marrow. Some evolve into B lymphocytes, so-called because in birds these cells originate in the bursa of Fabricius. The B lymphocytes become antibody factories when activated by helper/inducer T lymphocytes. T lymphocytes circulate through the thymus gland and develop the ability to recognize foreign matter (an antigen), retain memory of the antigen and influence B lymphocytes to produce antibodies against this antigen. These highly specific antibodies attach themselves to the invader, either killing it directly or facilitating the process of phagocytosis, and ultimately cause the destruction and clearance of the invader from the body. Because the lymphocytes retain a memory of the invader, the next exposure to this invader prompts a specific and immediate response. This ability of the immune system to develop and maintain a highly effective and specific response is the basis of vaccination.
When activated, natural killer cells, another subset of lymphocytes, have the ability to select and destroy abnormal host cells (i.e. malignant cells) and destroy intracellular pathogens such as viruses by destroying the cells harboring them. Other T lymphocytes, the T-suppressor lymphocytes, have the ability to downregulate and turn off the immune response once an invader is repelled. The macrophages and lymphocytes interact with one another by secreting soluble products known as cytokines. There are many unique cytokines, and presumably others remain to be discovered.
Immune function changes and risks of infection
The aging process is associated with changes in immune function, particularly in those functions directed or carried out by the lymphocyte system. Although some research has suggested that the aging process itself may be the result of the immune system turning against the body, at present such a theory remains speculative. Most observations of age-associated altered immune function concern failure of or deficiency in function. The increased incidence of malignancies results partly from a loss of the immune system’s surveillance and eradication of abnormal cells as they arise. Aging is also associated with increased activity or loss of control of some aspects of the immune system. For example, the incidence of monoclonal gammopathies (multiple myeloma) rises in the older population and the frequency of both anti-idiotypic (antibodies directed against other antibodies) and autoimmune antibodies increases as a person ages. Long before our understanding of the intricacies of the cellular immune system and the specialized properties of its various components began, it was known that the thymus gland progressively atrophies until it becomes virtually a vestigial organ in later life. Investigation of immune function suggests that the most dramatic changes occur within the cellular arm of the immune system (Akbar & Fletcher, 2005; Gomez et al., 2005; Goronzy & Weyand, 2005). B lymphocytes, the cells involved in the production of antibodies (‘humoral immunity’), function relatively well, even in the very old (Chen et al., 2009; Siegrist & Aspinall, 2009). Specific changes in immune function that have been described as being associated with aging are listed in Box 11.1.
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