The Centers for Disease Control predicted death and disease from immune decline to reach epidemic proportions by 1990. Not only is HIV/AIDS affecting ever greater numbers of people.....an estimated 42 million are now infected....but about half of those living with HIV are now women. A new report, AIDS Epidemic Update 2002,adds that the epidemic is rapidly expanding in Eastern Europe and Asia and is fueling a famine in southern Africa. Everyone is at risk. If you practice what you preach, you may fare better than the rest. But there are no guarantees. This covers the spectrum from HIV-induced AIDS and chronic fatigue syndrome virus in the young and middle-aged, to premature senility in the elderly.
The current consensus from the medical establishment is that there is no cure. Prevention is the only hope. The question is-how do we prevent immune decline if we dont even know what causes it? Not everyone exposed to HIV gets AIDS. Why not? Is it because some people have better immune function? We dont test normal peoples immune function-so we can only theorize.
Free-Radical Influences on Immune Function
We do know that radiation, environmental toxins, air pollution, smoking, alcohol, high caloric diets, sugar, fat (particularly polysaturated fatty acids (PUFAs) recreational drugs and aerobic activity in unconditioned subjects lead to generation of toxic oxygen radicals and impaired immune function. Again, hard clinical data are slow in coming forth from basic science research. They are further obscured because they seldom have direct clinical application.
For example, a study reported in April 10, 1986 issue of the New England Journal of Medicine found that when neutrophils from patients with burns are examined in vitro, they are found to have functional alterations, which include depressed chemotaxis, impaired bactericidal activity, depressed phagocytosis, decreased oxygen consumption and loss of lysosomal enzymes; all of which have been interpreted as reflecting an in vivo exposure of neutrophils to stimuli that are abnormal in magnitude, creating systemic rather than localized activation due to unmeasured agents.
The principle therapeutic implication of that study was that the apparent source of neutrophil activating substances, the burn wound, should be excised as early as clinically feasible to free the patient of the burden of systematically activated neutrophils-demonstrating a recognition that the trauma site was producing "an unknown substance" or "the unmeasured agent" [Moore 1986].
Another study in the same journal by different investigators concerning lymphocyte subsets and NK activity in growth hormone (GH) [Click here for information on Human Growth Hormone] deficiency, chronic deficiency of GH or GH-releasing factor leads to decrease in NK activity-"demonstrating the close relationship of neuroendocrine systems and the immune system" [Kiess 1986]. The first study demonstrated free-radical damage from the trauma site, but did not measure free-radical damage from stress-related factors-another aspect of the neuroendocrine systems interrelation with the immune system.
Inflammation and Immunity
Prostaglandins, important cell regulatory molecules, have been shown to contribute to the impaired proliferative responses of lymphocytes from aged persons. Healthy humans over the age of 70 have found to have increased sensitivity to exogenous prostaglandin E2 [Goodwin 1979]. It has also been reported that macrophages from old mice secrete more prostaglandins of the E series than do macrophages of young mice [Rosenstein 1980]. These data suggest that depressed response seen with age may be due to the "down" regulation of the immune response by prostaglandins.
Prostaglandins are produced when PUFAs such as arachidonic acid are released from membrane phospholipids and converted by the cyclooxygenase pathway to form potent mediators of inflammation. Prostaglandin E2 has marked proinflammatory effects and can potentiate other mediators of inflammation such as histamine, bradykinin, and the leukotrienes to intensify the pain and edema of inflammation.
Calcium ions have been shown to play an important role in cell activation. With divalent cation chelators, lymphocytes from old subjects were found to be more sensitive to increased amounts of chelating agents such as EDTA, and they required greater amounts of ionic calcium supplements to restore their proliferation after inhibition [Jebbes 1981]. Another study using verapamil, a calcium channel blocker, supported the conclusion that the calcium ion dependent portion of lymphocyte activators is impaired with age [Blitstein-Willinger 1978].
Oral doses of b -carotene (180mg/day) given for two weeks to normal human volunteers significantly increased the proliferation of T4 helper lymphocytes after seven days [Alexander 1985]. Proliferation of lymphocytes is essential for the generation of a normal immune response. Normal cell surface receptor function and nucleic acid fidelity are essential for cell replication. For these reasons, changes in the number, affinity, or mobility of cell surface determinants and the increased sensitivity of nucleic acid to damage may be the most important factors contributing to impaired immune response.
Cellular Aging and Immunity
Cell surface determinants on lymphocytes change with age. Recently, it has been found that the decrease in T-lymphocyte function in elderly humans and old animals can be, in part, related to their decreased capacity to produce and bind T-cell growth factor [Gillis 1981]. In addition, when the proliferative response of T cells and B cells are compared, the T-cell defect is, in most reports, greater than the B-cell defect. The defect in T-cell response following immunizations is reduced in old animals, and yet the total immunoglobulin response and serum immunoglobulin concentration are little affected by age.
In the past decade, many of the changes in the immune system that accompany aging have been defined and related to the involution of the thymus gland. Involution of the thymus gland is still believed to be genetically pre-determined. However, the age associated changes in the immune system do not distinguish between thymic-dependent immune system impaired by age and an immune system compromised by the environment.
For example, during the last one third of the lifespan, significant suppressor T-cell activity occurs. Suppressor activity contributes to, but does not account for, the immune deficiency of aging. The impairment of antibody response develops before this rise in suppressor cells can be demonstrated, and elimination of suppressor T cells does not reverse the impaired response of B cells to thymic-dependent antigens [Dekruyff 1980]. In addition, cell surface determinants on T cells, as well as the density of surface immunoglobins on B cells, decrease with age. Furthermore, the rate of capping these surface determinants decreases with age.
These data suggest the phospholipid bilayer membrane composition and the cytoskeleton are altered in lymphocytes from aged animals. Capping of membrane protein was found to be closely related to the lateral mobility of glycoproteins in the lipid bilayer [Schreiner 1977]. Viscosity of these membranes increases. Preliminary studies using fluorescence polarization suggest that there is a small age-related increase in macroviscosity in both murine splenic and lymph node cell membranes [Rivany 1979]. This change in viscosity appears to be due to an increase in the cholesterol-to-phospholipid molar ratio. This ratio changes with age and is influenced by free-radical activity.
In the 1980, Anderson and Grabow [reported in Adv. Nutr. Res., Vol. 6, 1984] pointed out that free-radical activity from the myeloperoxidase-hydrogen peroxide-halide system is an important component of the phagocytic intracellular defense system. Free-radicals are also released extracellularly during phagocytosis, and can autoxidize the neutrophil membrane, this causing loss of respinse to leukoattractants and sulfhydryl groups (membrane sulfhydryl components). Ascorbate protected the chemotactic responsiveness of neutrophils and activation of the oxidative-respiratory bursts of leukocytes and the excessive/chronic release of hydrogen peroxide causing oxidation of membrane receptor sites, endothelial linings, and synovial membranes.
Finally, a number of enzymes found in lymphocytes change with age as well as certain immunodeficiency states. Lymphocytes from both elderly experimental animals and humans are more susceptible to free-radical damage induced by ionizing radiation, UV light, and mutagenic drugs. These findings reflect not only differences in proliferative potential, but also increased sensitivity to ionizing radiation in aged lymphocytes. Such findings suggest free-radical damage to DNA molecules and altered DNA repair enzymes also contributes to immune decline.