Immune System And The Elderly
Author: GO Oyeyinka
Department of Chemical Pathology and Immunology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria.
G.O Oyeyinka, College of Health Sciences,
University of Ilorin, PMB 1515, Ilorin, Nigeria E-mail: firstname.lastname@example.org
This article takes a cursory look at the immune system, describes its state in the elderly and examines possible mechanisms for its rejuvenation in old age.
The Immune System
The immune system is the body’s defensive network and protect s individuals a gainst billions of microorganisms in the environment. The system is complex, being made up of many types of cells and proteins that perform different functions in fighting foreign substances. Foreign substances are called antigens. The response of the immune system to the introduction of foreign substances is called the immune response. The immune response takes place within the peripheral lymphoid tissues. These include the lymph nodes, spleen and un-encapsulated tissues lining the respiratory, and genitor-urinary tracts. The lymph nodes filter off, and if necessary, respond to foreign materials entering body tissues. The spleen monitors the blood while un-encapsulated lymphoid tissues defend the mucosal surfaces. Communication between these tissues and the rest of the body is carried out by re- circulating lymphocytes which pass from the blood into the lymph nodes, spleen and other tissues; and back to the blood by the major lymphatic channels. The immune response can be innate or acquired.
Innate or natural immunity involves mechanisms that pre-exist the invasion of foreign substances. These include physical barriers like the skin and mucosal surfaces, chemical substances (e.g. complement proteins and lysozymes) that counteract microorganisms and other foreign particles; and specialized cells (phagocytes) that engulf and digest foreign particles. The mechanisms of innate immunity are non-specific, i.e., they treat different foreign substances alike. Complement proteins meet foreign invaders early on invasion. They flow in the blood and quickly reach the
site of invasion. They require activation to perform their functions which include the triggering of inflammation, attraction of phagocyte cells to the area of invasion and coating of intruders for easy access to them by phagocytes. They can also kill foreign bodies by cytolysis. Phagocytes are immune cells with char acteris tics of locating and engulfing of microorganisms and dead or injured body cells for destruction. Phagocytes include the granulocytes, macrophages and dendritic cells. Macrophages also play a key role in alerting the rest of the immune system to the presence of invaders. Like macrophages, dendritic cells help with the activation of the rest of the immune system. They also filter body fluids to rid them of foreign organisms and particles.
Acquired immunity is generated strictly in response to a given foreign agent. The immunity improves in Cytotoxic T cells specialize in attacking virus-infected cells and cancer cells. B cells are produced, and mature, in the bone marrow. They form plasma cells when activated by contact with antigen and help from helper T cells. Plasma cells produce antibodies which are capable of destroying the antigen type responsible for their production. Antibodies link foreign antigens that they coat to phagocytes and also to complement proteins. They also neutralize toxins and incapacitate viruses from infecting new cells.
The Immune System in the Elderly
Immune functions decline with age, i.e., immune competence declines as people grow old. Ageing affects the immune system at multiple levels including reduced B cell and T cell production in the bone marrow and
thymus. Furthermore, mature lymphocytes in peripheral lymphoid tissues are characterized by diminished function. As a result, elderly people do not respond to immune challenges as actively as do the young. For instance, individuals of 70 years of age and older people have increased vulnerability to influenza infection1.
One major change that occurs during ageing is the process termed thymic involution. The thymus naturally atrophies as humans age. Although T cells are produced throughout the life span, the progressive decay of the thymus causes significant decrease in the number of T cells and alters their sub-type distribution. The progressive loss of the thymus has profound effects on the immune system of the aged. Ageing affects the functions of T cells in many ways. This includes depletion of the population of naïve T cells since fewer T cells are produced as the thymus progressively deteriorates. Consequently, the aged immune system cannot respond as well as a young one to new antigens. The cell surface of all T cells undergo significant changes during ageing. When a T cell binds to an antigen, the stimulus must be communicated to the interior of the T cell for activation of the cell to take place. The process of transmitting the antigen-binding signal across the cell membrane into the cell is called signal transduction. Signal transduction is a cascade of chemical reactions involving many molecules. Aged T cells do not display the surface CD28 antigen, a molecule that is critical for signal transduction and T cell activation2. Such T cells remain quiescent and do not respond to foreign agents. A decrease in calcium is another defect of T cell activation in the elderly. Calcium is crucial for many biochemical reactions, including signal transduction. Calcium deficiency results in failure of stimulation of required enzymes that need it to function properly2. As T cells age, their capacity to produce or respond to the cytokine IL-2 is lost, thus greatly impairing T cell function.
Reduced function of T cells in old people affects B cell function as well since helper T cells are required for the activation of B lymphocytes. Activated B cells develop into plasma cells which produce antibodies. The presence of auto-antibodies (i.e., antibodies that react to self components, against normal principles), is more prevalent in the aged, even in healthy aged without auto- immune disease. Although the exact role of auto- antibodies in ageing is not fully elucidated, they may cause slowly progressive tissue damage which contributes to physical ageing.
The cellular and molecular changes that occur in the immune system during ageing have been defined and form the basis for the design of strategies to rejuvenate the immune system in the elderly. An increased mortality rate associated with impaired delayed hypersensitivity responses was obtained in old Australians3 indicating that modulation of cellular immune responses may lead to a prolonged life-span. There is correlation between age, immune competence and survival. However, the decline in immune response with age is not an invariable occurrence as about one-third of the healthy elderly have immunological function at levels seen in younger age groups4.
Also, studies have obtained significant positive correlation between circulating immune complexes concentrations (complexes of antigen and antibody) and age plus age-associated increase in auto-antibodies including anti-nuclear antibodies and rheumatoid factor5.
It would appear that auto-antibodies contribute to increased prevalence of circulating immune complexes in old individuals. It has been observed that caloric restriction in rodents leads to a decline in both circulating immune complexes and auto-antibodies6 and also to amelioration of overt auto-immune disease7 suggesting that the immune system can be manipulated to advantage during ageing. Elevated immune complex concentrations in sera from old subjects could result from the age-associated increase in the prevalence of auto-antibodies. Although immune complex disease is usually more likely to occur in chronic than in acute infections and in those who produce low affinity antibodies, auto-immunity is a chronic condition and elderly subjects produce antibodies with poor antigen avidity.
One approach to the care of the elderly is preventive health care through vaccination. Influenza and pneumonia are two infections to which the elderly are particularly vulnerable, and providing vaccination for these is a high priority. Reduced caloric intake is known to slow the ageing process and maintains higher naïve T cell count and increased levels of IL-22. Zinc in particular and vitamin E are important for the proper functioning of the immune system. In the elderly, long- term zinc deficiency leads to decreased cytokine production and impaired regulation of helper T cell activity. There are indicat ions that vitamin E supplementation may boost the immune system as a daily dose has been found to improve T cell function in cell mediated-immunity2. Vitamin E is also an anti- oxidant that can protect lymphocytes and other tissues from destructive free radicals.
Ageing affects many components of the immune system. A clear understanding of the immunological changes due to ageing is important for the designing of effective health care for the elderly.
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