Human Immunology

General theories of aging have been postulated to explain the decline in immune function of older adults. Among these many theories, the free radical (a free radical is an atom, molecule, or compound with one or more unpaired electrons in its outer orbit. When oxygen is utilized during oxidative metabolism, oxygen intermediates, such as superoxides, hydrogen peroxide, and hydroxyP radicals, are formed due to the partial reduction of oxygen. Although most of these oxygen intermediates will react with hydrogen to form water, some will remain as free radicals. These free radicals can cause damage to cell membranes by reacting with nearby molecules in the cell.) theory of aging is one of the most popular and well documented. This theory states that the production of free radicals increases with age, and that these molecules permanently modify the structure of lipids, proteins, DNA, and cells; and thus impairs their function. Although this theory seems plausible, there is little direct evidence that the accumulation of free radicals is causally related to decreased immune responsiveness in humans. Reduction of free radical levels has improved some, but not all, indices of immune function, and the effects seemed to be indirect.

A second general theory of aging is that age-related changes in physiologic and biologic processes are due to changes in the composition of cell membranes, rendering them dysfunctional. Proponents of the free radical theory of aging believe that these alterations in membrane composition result from increased free radicals, which attack membrane phospholipids, increase the cholesterol to phospholipid ratio, and increase cell membrane rigidity. Although limited in scope, studies have shown that lymphocyte membranes of aged donors are more rigid and less fluid. Reports have also shown that a more rigid membrane impairs receptor movement within the cell membrane, and therefore inhibits activation and proliferation of lymphocytes and other immune cells. In addition, these changes in the cell membrane could affect cognate interactions between immune cells, or between immune cells with target cells. It is likely that a combination of several interrelated but independent theories of aging will ultimately explain the age-related decline in the immune response of elderly humans.