How to boost your immune system

Excerpted from The Truth About Your Immune System, a Special Health Report from Harvard Health Publications

What can you do?

On the whole, your immune system does a remarkable job of defending you against disease-causing microorganisms. But sometimes it fails: A germ invades successfully and makes you sick. Is it possible to intervene in this process and make your immune system stronger? What if you improve your diet? Take certain vitamins or herbal preparations? Make other lifestyle changes in the hope of producing a nearperfect immune response? The idea of boosting your immunity is enticing, but the ability to do so has proved elusive for several reasons. The immune system is precisely that a system, not a single entity. To function well, it requires balance and harmony. There is still much that researchers dont know about the intricacies and interconnectedness of the immune response. For now, there are no scientifically proven direct links between lifestyle and enhanced immune function. But that doesnt mean the effects of lifestyle on the immune system arent intriguing and shouldnt be studied. Quite a number of researchers are exploring the effects of diet, exercise, age, psychological stress, herbal supplements, and other factors on the immune response, both in animals and in humans. Although interesting results are emerging, thus far they can only be considered preliminary. Thats because researchers are still trying to understand how the immune system works and how to interpret measurements of immune function. The following sections summarize some of the most active areas of research into these topics. In the meantime, general healthy-living strategies are a good way to start giving your immune system the upper hand.

Immunity in action. A healthy immune system can defeat invading pathogens as shown above, where two bacteria that cause gonorrhea are no match for the large phagocyte, called a neutrophil, that engulfs and kills them (see arrows). Photos courtesy of Michael N. Starnbach, Ph.D., Harvard Medical School

Adopt healthy-living strategies

Your first line of defense is to choose a healthy lifestyle. Following general good-health guidelines is the single best step you can take toward keeping your immune system strong and healthy. Every part of your body, including your immune system, functions better when protected from environmental assaults and bolstered by healthy-living strategies such as these: Dont smoke. Eat a diet high in fruits, vegetables, and whole grains, and low in saturated fat. Exercise regularly. Maintain a healthy weight. Control your blood pressure. If you drink alcohol, drink only in moderation. Get adequate sleep. Take steps to avoid infection, such as washing your hands frequently and cooking meats thoroughly. Get regular medical screening tests for people in your age group and risk category.

Be skeptical
Many products on store shelves claim to boost or support immunity. But the concept of boosting immunity actually makes little sense scientifically. In fact, boosting the number of cells in your body immune cells or others is not necessarily a good thing. For example, athletes who engage in blood doping pumping blood into their systems to boost their number of blood cells and enhance their performance run the risk of strokes. Attempting to boost the cells of the immune system is especially complicated because there are so many different kinds of cells in the immune system that respond to so many different microbes in so many ways. Which cells should you boost, and to what number? So far, scientists do not know the answer. What is known is that the body is continually generating immune cells. Certainly it produces many more lymphocytes than it can possibly use. The extra cells remove themselves through a natural process of cell death called apoptosis some before they see any action, some after the battle is won. No one knows how many cells or what kinds of cells the immune system needs to function at its optimum level. Scientists do know more about the low end of the scale. When the number of T cells in an HIV/AIDS patient drops below a certain level, the patient gets sick because the immune system doesnt have enough T cells to fight off infection. So there is a bottom number below which the immune system cant do its job. But how many T cells is comfortably enough, and beyond that point, is more better? We dont know. Many researchers are trying to explore the effects of a variety of factors from foods and herbal supplements to exercise and stress on immunity. Some take measures of certain blood components like lymphocytes or cytokines. But thus far, no one really knows what these measurements mean in terms of your bodys ability to fight disease. They provide a way of detecting whether something is going on, but science isnt yet sufficiently advanced to understand how this translates into success in warding off disease. A different scientific approach looks at the effect of certain lifestyle modifications on the incidence of disease. If a study shows significantly less disease, researchers consider whether the immune system is being strengthened in some way. Based on these studies, there is now evidence that even though we may not be able to prove a direct link between a certain lifestyle and an improved immune response, we can at least show that some links are likely.

Age and immunity

Earlier in this report (see Cancer: Missed cues), we noted that one active area of research is how the immune system functions as the body ages. Researchers believe that the aging process somehow leads to a reduction of immune response capability, which in turn contributes to more infections, more inflammatory diseases, and more cancer. As life expectancy in developed countries has increased, so too has the incidence of age-related conditions. Happily, investigation into the aging process can benefit us all no matter what our age. While some people age healthily, the conclusion of many studies is that, compared with younger people, the elderly are far more likely to contract infectious diseases. Respiratory infections, influenza, and particularly pneumonia are a leading cause of death in people over 65 worldwide. No one knows for sure why this happens, but some scientists observe that this increased risk correlates with a decrease in T cells, possibly from the thymus atrophying with age and producing fewer T cells to fight off infection. Thymus function declines beginning at age 1; whether this decrease in thymus function explains the drop in T cells or whether other changes play a role is not fully understood. Others are interested in whether the bone marrow becomes less efficient at producing the stem cells that give rise to the cells of the immune system. Researchers at the University of Arkansas are looking at another aspect of why the immune system seems to weaken with age. They studied cell death in mice. They conducted an experiment to compare the lifespan of memory T lymphocytes in older mice with those of younger mice and found that the lymphocytes in older mice die sooner. This suggests that as the lymphocytes die off, the elderly immune system loses its memory for the microbes it is intended to fight and fails to recognize the microbes when they reappear. The body thus becomes less able to mount a vigorous immune response. A reduction in immune response to infections has been demonstrated by older peoples response to vaccines. For example, studies of influenza vaccines have shown that for people over age 65, vaccine effectiveness was 23%, whereas for healthy children (over age 2), it was 38%. But despite the reduction in efficacy, vaccinations for influenza and S. pneumoniae have significantly lowered the rates of sickness and death in older people when compared with nonvaccination. Yet other researchers are looking at the connection between nutrition and immunity in the elderly. A form of malnutrition that is surprisingly common even in affluent countries is known as micronutrient malnutrition. Micronutrient malnutrition, in which a person is deficient in some essential vitamins and trace minerals that are obtained from or supplemented by diet, can be common in the elderly. Older people tend to eat less and often have less variety in their diets. One important question is whether dietary supplements may help older people maintain a healthier immune system. Older people should discuss this question with a physician who is well versed in geriatric nutrition, because while some dietary supplementation may be beneficial for older people, even small changes can have serious repercussions in this age group.

What about diet?

Like any fighting force, the immune system army marches on its stomach. Immune system warriors need good, regular nourishment. Scientists have long recognized that people who live in poverty and are malnourished are more vulnerable to infectious diseases. Whether the increased rate of disease is caused by malnutritions effect on the immune system, however, is not certa in. There are still relatively few studies of the effects of nutrition on the immune system of humans, and even fewer studies that tie the effects of nutrition directly to the development (versus the treatment) of diseases. There are studies of the effects of nutritional changes on the immune systems of animals, but again there are few studies that address the development of diseases in animals as a result of changes in immunity. For example, one group of investigators has found that in mice, diets deficient in protein reduce both the numbers and function of T cells and macrophages and also reduce the production of immunoglobulin A (IgA) antibody.

There is some evidence that various micronutrient deficiencies for example, deficiencies of zinc, selenium, iron, copper, folic acid, and vitamins A, B6, C, and E alter immune responses in animals, as measured in the test tube. However, the impact of these immune system changes on the health of animals is less clear, and the effect of similar deficiencies on the human immune response has yet to be assessed. But the research at this stage is promising, at least for some of the micronutrients. So what can you do? If you suspect your diet is not providing you with all your micronutrient needs maybe you dont like vegetables or you choose white bread over whole grains taking a daily multivitamin and mineral supplement brings health benefits of many types, beyond any possibly beneficial effects on the immune system. Taking megadoses of a single vitamin does not. More is not necessarily better. Researchers are investigating the immune boosting potential of a number of different nutrients. Selenium. Some studies have suggested that people with low selenium levels are at greater risk of bladder, breast, colon, rectum, lung, and prostate cancers. A large-scale, multiyear study is currently in progress to look at the effects of combining selenium and vitamin E on prostate cancer prevention. Vitamin A. Experts have long known that vitamin A plays a role in infection and maintaining mucosal surfaces by influencing certain subcategories of T cells and B cells and cytokines. Vitamin A deficiency is associated with impaired immunity and increased risk of infectious disease. On the other hand, according to one study, supplementation in the absence of a deficiency didnt enhance or suppress T cell immunity in a group of healthy seniors. Vitamin B2. There is some evidence that vitamin B2 enhances resistance to bacterial infections in mice, but what that means in terms of enhancing immune response is unclear. Vitamin B6. Several studies have suggested that a vitamin B6 deficiency can depress aspects of the immune response, such as lymphocytes ability to mature and spin off into various types of T and B cells. Supplementing with moderate doses to address the deficiency restores immune function, but megadoses dont produce additional benefits. And B6 may promote the growth of tumors. Vitamin C. The jury is still out on vitamin C and the immune system. Many studies have looked at vitamin C in general; unfortunately, many of them were not well designed. Vitamin C may work in concert with other micronutrients rather than providing benefits alone. Vitamin D. For many years doctors have known that people afflicted with tuberculosis responded well to sunlight. An explanation may now be at hand. Researchers have found that vitamin D, which is produced by the skin when exposed to sunlight, signals an antimicrobial response to the bacterium responsible for tuberculosis, Mycobacterium tuberculosis. Whether vitamin D has similar ability to fight off other diseases and whether taking vitamin D in supplement form is beneficial are questions that need to be resolved with further study. Vitamin E. A study involving healthy subjects over age 65 has shown that increasing the daily dose of vitamin E from the recommended dietary allowance (RDA) of 30 mg to 200 mg increased antibody responses to hepatitis B and tetanus after vaccination. But these increased responses didnt happen following administration of diphtheria and pneumococcal vaccines. Zinc. Zinc is a trace element essential for cells of the immune system, and zinc deficiency affects the ability of T cells and other immune cells to function as they should. Caution: While its important to have sufficient zinc in your diet (1525 mg per day), too much zinc can inhibit the function of the immune system.

Herbs and other supplements

Walk into a store, and you will find bottles of pills and herbal preparations that claim to support immunity or otherwise boost the health of your immune system. Although some preparations have been found to alter some components of immune function, thus far there is no evidence that they actually bolster immunity to the point where you are better protected against infection and disease. Demonstrating whether an herb or any substance, for that matter can enhance immunity is, as yet, a highly complicated matter. Scientists dont know, for example, whether an herb that seems to raise the levels of antibodies in the blood is actually doing anything beneficial for overall immunity. But that doesnt mean we should discount the benefits of all herbal preparations. Everyones immune system is unique. Each persons physiology responds to active substances differently. So if your grandmother says shes been using an herbal preparation for years that protects her from illness, whos to say that it doesnt? The problem arises when scientists try to study such a preparation among large numbers of people. The fact that it works for one person wont show up in the research data if its not doing the same for a larger group. Scientists have looked at a number of herbs and vitamins in terms of their potential to influence the immune system in some way. Much of this research has focused on the elderly, children, or people with compromised immune systems, such as AIDS patients. And many of the studies have had design flaws, which means further studies are needed to confirm or disprove the results. Consequently, these findings should not be considered universally applicable. Some of the supplements that have drawn attention from researchers are these: Aloe vera. For now, theres no evidence that aloe vera can modulate immune response. Because many different formulations and compounds have been used in studies, comparing the results is difficult. However, there is some evidence that topical aloe vera is helpful for minor burns, wounds, or frostbite, and also for skin inflammations when combined with hydrocortisone. Studies have found aloe vera is not the best option for treating breast tissue after radiation therapy. Astragalus membranes. The astragalus product, which is derived from the root of the plant, is marketed as an immune-system stimulant, but the quality of the studies demonstrating the immune-stimulating properties of astragalus are poor. Furthermore, it may be dangerous. Echinacea. An ocean of ink has been spilled extolling echinacea as an immune stimulant, usually in terms of its purported ability to prevent or limit the severity of colds. Most experts dont recommend taking echinacea on a long-term basis to prevent colds. A group of physicians from Harvard Medical School notes that studies looking at the cold prevention capabilities of echinacea have not been well designed, and other claims regarding echinacea are as yet not proven. Echinacea can also cause potentially serious side effects. People with ragweed allergies are more likely to have a reaction to echinacea, and there have been cases of anaphylactic shock. Injected echinacea in particular has caused severe reactions. A well-designed study by pediatricians at the University of Washington in Seattle found echinacea didnt help with the duration and severity of cold symptoms in a group of children. A large 2005 study of 437 volunteers also found that echinacea didnt affect the rate of cold infections or the progress and severity of a cold. Garlic. Garlic may have some infection-fighting capability. In laboratory tests, researchers have seen garlic work against bacteria, viruses, and fungi. Although this is promising, there havent been enough well-designed human studies conducted to know whether this translates into human benefits. One 2006 study that looked at rates for certain cancers and garlic and onion consumption in southern European populations found an association between the frequency of use of garlic and onions and a lower risk of some common cancers. Until more is known, however, its too early to recommend garlic as a way of treating or preventing infections or controlling cancer.

Ginseng. Its not clear how the root of the ginseng plant works, but claims on behalf of Asian ginseng are many, including its ability to stimulate immune function. Despite the claims of a number of mainly small studies, the National Center for Complementary and Alternative Medicine (NCCAM) considers there have been insufficient large studies of a high enough quality to support the claims. NCCAM is currently supporting research to understand Asian ginseng more fully. Glycyrrhiza glabra (licorice root). Licorice root is used in Chinese medicine to treat a variety of illnesses. Most studies of licorice root have been done in combination with other herbs, so its not possible to verify whether any effects were attributable to licorice root per se. Because of the potential side effects of taking licorice and how little is known about its benefits if any for stimulating immune function, this is an herb to avoid. Probiotics. There are hundreds of different species of bacteria in your digestive tract, which do a bangup job helping you digest your food. Now researchers, including some at Harvard Medical School, are finding evidence of a relationship between such good bacteria and the immune system. For instance, it is now known that certain bacteria in the gut influence the development of aspects of the immune system, such as correcting deficiencies and increasing the numbers of certain T cells. Precisely how the bacteria interact with the immune system components isnt known. As more and more intriguing evidence comes in to support the link that intestinal bacteria bolster the immune system, its tempting to think that more good bacteria would be better. At least, this is what many marketers would like you to believe as they tout their probiotic products. Probiotics are good bacteria, such as Lactobacillus and Bifidobacterium, that can safely dwell in your digestive tract. Youll now find probiotics listed on the labels of dairy products, drinks, cereals, energy bars, and other foods. Ingredients touted as prebiotics, which claim to be nutrients that feed the good bacteria, are also cropping up in commercially marketed foods. Unfortunately, the direct connection between taking these products and improving immune function has not yet been made. Nor has science shown whether taking probiotics will replenish the good bacteria that get knocked out together with bad bacteria when you take antibiotics. Another caution is that the quality of probiotic products is not consistent. Some contain what they say they do; some do not. In a 2006 report, the American Academy of Microbiology said that at present, the quality of probiotics available to consumers in food products around the world is unreliable. In the same vein, the FDA monitors food packages to make sure they dont carry labels that claim the products can cure diseases unless the companies have scientific evidence to support the claims. Does this mean taking probiotics is useless? No. It means the jury is still out on the expansive health claims. In the meantime, if you choose to take a probiotic in moderation, it probably wont hurt, and the scientific evidence may ultimately show some benefit.

The stress connection

Modern medicine, which once treated the connection between emotions and physical health with skepticism, has come to appreciate the closely linked relationship of mind and body. A wide variety of maladies, including stomach upset, hives, and even heart disease, are linked to the effects of emotional stress. But although the relationship between stress and immune function is being studied by a number of different types of scientists, so far it is not a major area of research for immunologists. Studying the relationship between stress and the immune system presents difficult challenges. For one thing, stress is difficult to define. What may appear to be a stressful situation for one person is not for another. When people are exposed to situations they regard as stressful, it is difficult for them to measure how much stress they feel, and difficult for the scientist to know if a persons subjective impression of the amount of stress is accurate. The scientist can only measure things that may reflect stress, such as the number of times the heart beats each minute, but such measures also may reflect other factors.

Most scientists studying the relationship of stress and immune function, however, do not study a sudden, short-lived stressor; rather, they try to study more constant and frequent stressors known as chronic stress, such as that caused by relationships with family, friends, and co-workers, or sustained challenges to perform well at ones work. Some scientists are investigating whether ongo ing stress takes a toll on the immune system. But it is hard to perform what scientists call controlled experiments in human beings. In a controlled experiment, the scientist can change one and only one factor, such as the amount of a particular chemical, and then measure the effect of that change on some other measurable phenomenon, such as the amount of antibodies produced by a particular type of immune system cell when it is exposed to the chemical. In a living animal, and especially in a human being, that kind of control is just not possible, since there are so many other things happening to the animal or person at the time that measurements are being taken. Despite these inevitable difficulties in measuring the relationship of stress to immunity, scientists who repeat the same experiment many times with many different animals or human beings, and who get the same result most of the time, hope that they can draw reasonable conclusions. Some researchers place animals into stressful situations, such as being trapped in a small space or being placed near an aggressive animal. Different functions of their immune systems, and their health, are then measured under such stressful conditions. On the basis of such experiments, some published studies have made the following claims: Experimentally created stressful situations delayed the production of antibodies in mice infected with influenza virus and suppressed the activity of T cells in animals inoculated with herpes simplex virus. Social stress can be even more damaging than physical stress. For example, some mice were put into a cage with a highly aggressive mouse two hours a day for six days and repeatedly threatened, but not injured, by the aggressive mouse a social stress. Other mice were kept in tiny cages without food and water for long periods a physical stress. Both groups of mice were exposed to a bacterial toxin, and the socially stressed animals were twice as likely to die. Isolation can also suppress immune function. Infant monkeys separated from their mothers, especially if they are caged alone rather than in groups, generate fewer lymphocytes in response to antigens and fewer antibodies in response to viruses.

Many researchers report that stressful situations can reduce various aspects of the cellular immune response. A research team from Ohio State University that has long worked in this field suggests that psychological stress affects the immune system by disrupting communication between the nervous system, the endocrine (hormonal) system, and the immune system. These three systems talk to one another using natural chemical messages, and must work in close coordination to be effective. The Ohio State research team speculates that long-term stress releases a long-term trickle of stress hormones mainly glucocorticoids. These hormones affect the thymus, where lymphocytes are produced, and inhibit the production of cytokines and interleukins, which stimulate and coordinate white blood cell activity. This team and others have reported the following results: Elderly people caring for relatives with Alzheimers disease have higher than average levels of cortisol, a hormone secreted by the adrenal glands and, perhaps because of the higher levels of cortisol, make fewer antibodies in response to influenza vaccine. Some measures of T cell activity have been found to be lower in depressed patients compared with nondepressed patients, and in men who are separated or divorced compared with men who are married. In a year-long study of people caring for husbands or wives with Alzheimers disease, changes in T cell function were greatest in those who had the fewest friends and least outside help.

Four months after the passage of Hurricane Andrew in Florida, people in the most heavily damaged neighborhoods showed reduced activity in several immune system measurements. Similar results were found in a study of hospital employees after an earthquake in Los Angeles.

In all of these studies, however, there was no proof that the immune system changes measured had any clear adverse effects on health in these individuals.

Does being cold make you sick?

Almost every mother has said it: Wear a jacket or youll catch a cold! Is she right? So far, researchers who are studying this question think that normal exposure to moderate cold doesnt increase your susceptibility to infection. Most health experts agree that the reason winter is cold and flu season is not that people are cold, but that they spend more time indoors, in closer contact with other people who can pass on their germs. But researchers remain interested in this question in different populations. Some experiments with mice suggest that cold exposure might reduce the ability to cope with infection. But what about humans? Scientists have dunked people in cold water and made others sit nude in subfreezing temperatures. Theyve studied people who lived in Antarctica and those on expeditions in the Canadian Rockies. The results have been mixed. For example, researchers documented an increase in upper respiratory infections in competitive cross-country skiers who exercise vigorously in the cold, but whether these infections are due to the cold or other factors such as the intense exercise or the dryness of the air is not known. Theyve found that exposure to cold does increase levels of some cytokines, the proteins and hormones that act as messengers in the immune system, but how this affects health isnt clear. A group of Canadian researchers that has reviewed hundreds of medical studies on the subject and conducted some of its own research concludes that theres no need to worry about moderate cold exposure it has no detrimental effect on the human immune system. Should you bundle up when its cold outside? The answer is yes if youre uncomfortable, or if youre going to be outdoors for an extended period where such problems as frostbite and hypothermia are a risk. But dont worry about immunity.

Exercise: Good or bad for immunity?

Regular exercise is one of the pillars of healthy living. It improves cardiovascular health, lowers blood pressure, helps control body weight, and protects against a variety of diseases. But does it help maintain a healthy immune system? Just like a healthy diet, exercise can contribute to general good health and therefore to a healthy immune system. It may contribute even more directly by promoting good circulation, which allows the cells and substances of the immune system to move through the body freely and do their job efficiently. Some scientists are trying to take the next step to determine whether exercise directly affects a persons susceptibility to infection. For example, some researchers are looking at whether extreme amounts of intensive exercise can cause athletes to get sick more often or somehow impairs their immune function. To do this sort of research, exercise scientists typically ask athletes to exercise intensively; the scientists test their blood and urine before and after the exercise to detect any changes in immune system components such as cytokines, white blood cells, and certain antibodies. While some changes have been recorded, immunologists do not yet know what these changes mean in terms of human immune response. No one yet knows, for example, whether an increase in cytokines is helpful or has any true effect on immune response. Similarly, no one knows whether a general increase in white cell count is a good thing or a bad thing.

But these subjects are elite athletes undergoing intense physical exertion. What about moderate exercise for average people? Does it help keep the immune system healthy? For now, even though a direct beneficial link hasnt been established, its reasonable to consider moderate regular exercise to be a beneficial arrow in the quiver of healthy living, a potentially important means for keeping your immune system healthy along with the rest of your body. One approach that could help researchers get more complete answers about whether lifestyle factors such as exercise help improve immunity takes advantage of the sequencing of the human genome. This opportunity for research based on updated biomedical technology can be employed to give a more complete answer to this and similar questions about the immune system. For example, microarrays or gene chips based on the human genom e allow scientists to look simultaneously at how thousands of gene sequences are turned on or off in response to specific physiological conditions for example, blood cells from athletes before and after exercise. Researchers hope to use these tools to analyze patterns in order to better understand how the many pathways involved act at once.

Sumber: http://www.health.harvard.edu/flu-resource-center/how-to-boost-your-immune-system.htm

Vitamin D: its role and uses in immunology

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1. 2.

HECTOR F. DELUCA and MARGHERITA T. CANTORNA* +Author Affiliations 1. Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA; and 2. *Department of Nutrition, Pennsylvania State University, University Park, Pennsylvania 16802, USA Correspondence: 2Correspondence: Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Dr., Madison, WI 53706-1544, USA. E-mail:deluca@biochem.wisc.edu Next Section

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Abstract
In recent years there has been an effort to understand possible noncalcemic roles of vitamin D, including its role in the immune system and, in particular, on T cell-medicated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. However, its highest concentration is in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D compounds as selective immunosuppressants is illustrated by their ability to either prevent or markedly suppress animal models of autoimmune disease. Results show that 1,25-dihydroxyvitamin D3 can either prevent or markedly suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, and inflammatory bowel disease. In almost every case, the action of the vitamin D hormone requires that the animals be maintained on a normal or high calcium diet. Possible mechanisms of suppression of these autoimmune disorders by the vitamin D hormone have been presented. The vitamin D hormone stimulates transforming growth factor TGF-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity. In support of this, the vitamin D hormone is unable to suppress a murine model of the human disease multiple sclerosis in IL-4-deficient mice. The results suggest an important role for vitamin D in autoimmune disorders and provide a fertile and interesting area of research that may yield important new therapies. DeLuca, H. F., Cantorna, M. T. Vitamin D: its role and uses in immunology. autoimmune diseases

vitamin D as immunomodulator inflammatory disease

vitamin D and immunity

UNTIL 1980, NO ONE had imagined that vitamin D might play a role in the functioning of the

immune system. The function of vitamin D was largely considered to be in the area of calcium, phosphorus, and bone metabolism. It prevents rickets in children, osteomalacia in adults, and

hypocalcemic tetany. The major thrust of research until 1980 was to determine how vitamin D functions in these important processes of mineral metabolism regulation. In 1968, the idea appeared that vitamin D itself is biologically inactive and must be metabolically activated before it can function (1, 2). This led to the isolation and chemical identification of the active forms of vitamin D in 19681971 (3). Continued pursuit of the metabolism of vitamin D resulted in the understanding that vitamin D must first be hydroxylated in the liver to form 25-hydroxyvitamin D3 (25-OH-D3), the major circulating form of the vitamin. This form of vitamin D was subsequently found to be metabolically inactive and must be further converted to a final active form, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (3, 4). This last step occurs predominantly if not exclusively in the proximal convoluted tubule cells of the kidney to produce the metabolically active form of vitamin D, 1,25-(OH)2D3. This major calcium mobilizing hormone then functions directly on the enterocyte of the small intestine to markedly increase the absorption of calcium and phosphorus from the lumen into the plasma compartment. It also plays a major role in the mobilization of calcium from bone when parathyroid hormone is present. Together with parathyroid hormone, it markedly improves the renal reabsorption of calcium in the distal tubule (3, 4). These actions result in the elevation of plasma calcium and phosphorus levels to supersaturating conditions that are necessary to support mineralization of the skeleton on the one hand and prevent hypocalcemic tetany on the other (3, 4). The production of the vitamin D hormone is regulated by the need for calcium and phosphorus (456). Slightly low levels of plasma calcium will stimulate the parathyroids to produce and secrete the parathyroid hormone. This hormone binds to osteoblasts of bone and the entire length of the nephron of the kidney (345). In the kidney, parathyroid hormone stimulates the 1-hydroxylase enzyme that produces the final vitamin D hormone. If calcium in plasma rises to very high levels, calcitonin is secreted from the c cells of the thyroid gland. This peptide hormone binds to the osteoblasts and osteoclasts to prevent the mobilization of calcium from bone; thus causing a reduction in plasma calcium levels. The exact details of this elegant endocrine system are reported elsewhere (12345) The attempt to understand how the active form of vitamin D carries out its functions led to the discovery of the vitamin D receptor (VDR) in 1974 and 1975 (6, 7). Before this, however, synthesis of radiolabeled 1,25-(OH)2D3 of high specific activity allowed for frozen section autoradiography of physiological doses of this hormone. It became clear that this hormone localized almost entirely in the nucleus in a specific fashion in target tissues. This localization was also found in other tissues not previously considered targets (8, 9). For example, keratinocytes of skin, islet cells of the pancreas, lymphocytes, and promyelocytes showed specific nuclear localization of 1,25-(OH)2D3 and the presence of the VDR. The discovery of the VDR in these tissues resulted in the idea that the vitamin D hormone had functions beyond calcium and phosphorus metabolism, which prompted investigations into the noncalcemic actions of the vitamin D hormone (10). Perhaps the most important was the discovery of the VDR in the parathyroid glands (9, 11, 12) and the demonstration that the vitamin D hormone functions through its receptor to suppress the preproparathyroid gene (13) and parathyroid cell proliferation (14). This, then, is the basis of the treatment of secondary

hyperparathyroidism found in the dialysis patients and constitutes a major therapeutic application of 1,25-(OH)2D3and its analogs. Noting VDR in promyelocytes, Abe et al. and Tanaka et al. demonstrated that the vitamin D hormone can suppress proliferation of promyelocytes and cause their differentiation into the monocyte (15, 16). Similar effects of the vitamin D hormone on several cancerous cell lines ensued (17). A role for the vitamin D hormone in cellular differentiation thus became known. These findings prompted a search to use vitamin D analogs to treat cancer and underscored the idea that the vitamin D hormone has functions beyond calcium, phosphorus, and bone. Table 1 provides a list of possible target cells of the vitamin D hormone including the classical sites of intestine, kidney, and bone. The work of Manolagas and his group provided the first strong evidence that activated lymphocytes contain significant quantities of the VDR (181920). Numerous in vitro studies followed in which the vitamin D hormone could be shown to increase proliferation or suppress proliferation, depending on the experiment and how it was conducted (21) . It is undeniable that peripheral lymphocytes, macrophages, and thymus tissue contain the VDR. In fact, calf thymus proved to be an excellent source of the VDR to be used for competitive binding assays in the measurement of the vitamin D hormone (22). These findings then raised the question of what effect vitamin D might have on the immune system. In our own laboratory we determined which cells of the lymphocyte population contain the largest amounts of the VDR (21). By purifying lymphocytes to homogeneity, we were able to demonstrate that the CD-8 lymphocytes have the highest concentrations of the VDR, whether or not they were activated. Most important, the presence of 1,25-(OH)2D3 increases the amount of measurable receptor, probably because it improves the longevity and stability of the receptor in vivo as well as in vitro (23).The CD4 lymphocytes and macrophages contain relatively small but significant amounts of the VDR. Figure 1 illustrates the VDR levels in cells of the immune system. The next important advance in the role of vitamin D in the immune system came from studies of vitamin D-deficient mice (24). Making mice vitamin D deficient proved not to be a trivial matter, and two generations of mice reproducing under low vitamin D conditions were required. Having accomplished this, S. Yang in my group demonstrated that delayed hypersensitivity response to dinitrobenzene is impaired under conditions of vitamin D deficiency (24) . This same response was also suppressed with supplemental 1,25-(OH)2D3 (25). It became evident, therefore, that T cell-mediated immunity is under modulatory control of 1,25-(OH)2D3. In its absence, T cell-mediated immune responses were blunted; with high doses of the vitamin D hormone, the same response could also be blunted. Similar immunosuppression was reported with interesting analogs of the vitamin D hormone including 22-oxa-1,25-(OH)2D3 (26) and the 16-ene-23-yne-1,25-(OH)2D (27). These vitamin D compounds began to be known as immunosuppressants. Based on the reported immunosuppressant activities of the vitamin D hormone, we decided to test the idea that certain autoimmune diseases involving hyperactive T cell-mediated immunity might be suitable for further study (28). We focused on the disease, experimental autoimmune encephalomyelitis (EAE) in mice. We selected B10.PL mice as the model because the sequence of

neural degenerative symptoms that result in these mice after myelin basic protein injection is similar to human multiple sclerosis (MS). We succeeded in establishing EAE and showed there was an incidence of 100% in B10.PL mice fed a 0.87% calcium diet containing dietary vitamin D. However, the provision of 1,25-(OH)2D3 at 50200 ng/day could prevent the appearance of the EAE lesions. If the vitamin D compound was given postimmunization, it prevented further development of the disease (28). By now we have carried out extensive experiments on this experimental model of autoimmune disease and have found that the vitamin D compounds (including some important potent analogs) are extremely effective in blocking the development of EAE. In our attempt to reduce the hypercalcemic effects of 1,25-(OH)2D3, we provided this compound to animals maintained on a very low calcium diet (29). To our surprise, the low calcium diet produced a lower incidence of disease that was resistant to treatment with the vitamin D hormone (29) (see Fig. 2 ). On the other hand, when similar examinations were followed in the high calcium diet, the vitamin D compounds were effective (Fig. 3 ). Thus, it became clear that calcium is required for the vitamin D suppression of the autoimmune disease, EAE. Our initial clinical trial with the analog 19-nor-1,25-(OH)2D2 (30) revealed little effectiveness in preventing new MS lesions primarily because we failed to simultaneously provide a normal to high calcium intake. The results, therefore, imply that a high calcium diet is required for the vitamin D hormone to be effective in the treatment of EAE. The success with EAE suggested that vitamin D compounds could be used to treat other autoimmune disorders. Rheumatoid arthritis proved to be another example of an autoimmune disorder that can be largely prevented by the administration of the 1-hydroxylated vitamin D compounds, including 1,25-(OH)2D3 (31). Two autoimmune models of rheumatoid arthritis were used. One is the disorder caused by Lymes disease or the organism Borrelia burgdorferi; the other is collagen-induced arthritis. An example of collagen-induced arthritis and its prevention by the administration of 1,25-(OH)2D3 is illustrated in Fig. 4 . Although little more was done in studying this disorder, high calcium intakes were not required for vitamin D compounds to prevent the lesions. Another example not yet reported in the literature from our group is systemic lupus erythematosus (SLE). In 1992, Lemire et al. described an attenuation of this disorder by 1,25(OH)2D3 injected three times a week to MRL mice (32). However, they were unable to attenuate the rising proteinuria characteristic of this disorder and reduced the dietary calcium level in the group of mice receiving 1,25-(OH)2D3. Therefore, it is unclear whether the low calcium diet, the 1,25-(OH)2D3, or both caused the minimal improvement reported. In our research group, MRL mice were placed on either a 0.87% calcium, 0.3% phosphorus diet or a 0.02% calcium, 0.3% phosphorus-purified diet. As shown in Fig. 5 , nearly 75% of the MRL mice developed proteinuria by 17 wk on the 0.87% calcium, 0.3% phosphorus diet; 50 ng/day of 1,25(OH)2D3 incorporated into the diet prevented the proteinuria. As shown in Fig. 5 , the severity of the MRL symptoms was also markedly prevented by the administration of 1,25-(OH)2D3. In the 0.02% calcium diet, however, the animals receiving 1,25-(OH)2D3 developed SLE symptoms earlier and appeared to be more severely affected than animals on the 0.02% calcium diet alone (Fig. 6 ). Again, the results illustrate that a high calcium background is required for the vitamin

D hormone to prevent the development of this autoimmune disorder in the MRL mice. This, then, agrees with the results obtained with EAE. The laboratory of Margherita Cantorna has investigated the possible treatment or prevention of inflammatory bowel disease (IBD) by vitamin D (33). Vitamin D deficiency accelerated the appearance of symptoms and increased the severity of IBD in interleukin 10 (IL-10) knockout (KO) mice. Vitamin D-deficient IL-10 knockout mice developed symptoms of IBD within 68 wk (Fig. 7 ). This was essentially prevented by the administration of 1,25-(OH)2D3, again under conditions of high calcium intakes. In our own laboratory, we have investigated the development of type I diabetes in the nonobese diabetic (NOD) mouse model (34). These experiments were performed with animals on a 0.87% calcium, 0.3% phosphorus diet. Vitamin D deficiency markedly accelerated the appearance and increased the incidence of type I diabetes in the NOD mice (Fig. 8 ). Administration of ordinary vitamin D partially protected the mice from developing diabetes but the rate of incidence was still on the order of 3040%. Addition to the diet of 1,25-(OH)2D3 at 50 ng/day for females and 200 ng/day for males prevented the appearance of the diabetic lesions. Mathieu et al. also studied the appearance of diabetes in NOD mice and have reported some partial benefit by the injection of 1,25-(OH)2D3three times a week together with a low calcium diet (35). It is not clear whether the improvement was due to the vitamin D or due to the low calcium diet from these studies. Furthermore, the protection appeared minimal. Another major difference was that we incorporated 1,25-(OH)2D3 into the diet at all meals vs. three times a week. With a halflife of between 2 and 4 h in animals, it seems unlikely that i.p. dosing three times/wk is sufficient. In any case, the autoimmune disorder in the NOD mice can be prevented by the administration of 1,25-(OH)2D3 if animals are receiving a normal to high calcium diet. Hypercalcemia continues to be a problem and so there is an ongoing search for a true in vivo noncalcemic analog that is still able to prevent the autoimmune disorders. So far, this has not been successful but we are only now beginning to try to prepare true noncalcemic analogs that are effective in vivo. It is possible that the calcemic action of 1,25-(OH)2D3 is also required for treatment of these autoimmune disorders. Another important development has been the use of vitamin D compounds to suppress or prevent transplant rejection (36, 37). The work of Lemire et al. with a low calcium diet and 1,25-(OH)2D3 three times a week showed some improvement in maintaining transplanted organs (38). We have used the ear/heart transplant model to look at the effects of vitamin D compounds on transplant rejection. The donor mice differed from the recipient mice by two major histocompatability complex differences (allografts). After transplantation, the heart tissue in this model begins to beat at 7 days. In the isografts, no rejection took place in any of the animals; within 27 days, allograft rejection was complete. Cyclosporin A at relatively low doses appeared not to protect whereas 1,25-(OH)2D3 at 50 ng/day in the diet (again, along with 0.87% calcium) protected the animal for as long as 100 days. Vitamin D compounds may be useful in preventing transplant rejection. The sum of these findings in whole animals clearly illustrates that T cell-mediated immunity can be regulated by exogenous administration of 1-hydroxylated vitamin D compounds. The

absence of vitamin D from the diet might also increase the incidence and severity of autoimmune diseases, pointing to important regulatory actions of the vitamin D hormone. The action of 1,25-(OH)2D3 as an immunosuppressant appears to be specific since it does not appear to interfere with the ability of the animal to act defensively against opportunist infection (37). We have tested whether vitamin D treatment of mice makes them more susceptible to two infectious diseases. One was an infection caused by the fungal pathogen Candida albicans, a common infection found in transplant patients; the other was susceptibility to a viral herpes infection. In both cases, no interference by the vitamin D compounds was found in the disease course brought about by these organisms, whereas identical vitamin D doses were fully effective in preventing transplant rejection. It is also important to realize that vitamin D does not appear to act on the B lymphocyte, primarily because the B lymphocyte does not contain VDR in appreciable amounts (21). There have been numerous studies of in vitro behavior of a variety of T cells and macrophages, all actors in the immune system. Although these have been contradictory and difficult to interpret, we are beginning to see some progress in understanding the mechanism whereby vitamin D acts as an immunosuppressant in vivo. We have measured the mRNAs encoding cytokines in the lymphocytes found in the lymph nodes of control mice and those treated with 1,25-(OH)2D3(39). As illustrated in Fig. 9 and Fig. 10 , vitamin D administration markedly increases TGF-1 and IL-4 transcripts whereas there is a reduction, if anything, in interferon and tumor necrosis factor gene expression. These r esults do not differentiate between the direct effects of vitamin D on cytokine gene expression and the indirect effects of vitamin D as regulators of other cells and genes that result in a net change in cytokine expression. With the availability of the IL-4 KO mice, we bred IL-4 KO mice onto the EAE susceptible B10.PL background. In the absence of IL-4, EAE was more severe. IL-4 KO mice with EAE are also resistant to treatment with 1,25-(OH)2D3 (40). Clearly, we are just beginning to probe the mechanisms whereby vitamin D hormone and its analogs can act as selective immunosuppressants. We do not understand the mechanism whereby the vitamin D hormone can act as an immunosuppressant especially of T cell-mediated inflammatory responses. Despite reports to the contrary, there are no in vivo analogs that seem to act without hypercalcemia. Suppression of autoimmune disease requires not only the active form of vitamin D and its analogs, but also adequate or high calcium intakes. Further complicating the picture, little has been done to understand how vitamin D deficiency influences delayed type hypersensitivity. It is not clear whether the suppression of delayed type hypersensitivity response seen during vitamin D deficiency is due to the secondary effect of hypocalcemia or is a direct action of vitamin D on certain components of the immune system. This is a complicated and fertile area of investigation, from which may emerge important new therapies for autoimmune disease.
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Table 1. 1,25-(OH)2D3 target cellsa

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Figure 1. Vitamin D receptor (VDR) levels in the immune cells from mice. Mice were fed the Purina chow 5008 diet; lymphocytes were harvested from the spleen and separated into 95% plus pure cells as described by Veldman et al. (21).

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Figure 2. Female B10.PL mice were fed the 0.02% calcium, 0.3% phosphorus-purified diet and immunized with myelin basic protein together with pertussis toxin. The animals simultaneously received a daily intake of 1,25-(OH)2D3 or vehicle. Even 200 ng/day of 1,25-(OH)2D3 does not markedly reduce the incidence of EAE under low dietary calcium conditions.

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Figure 3. 1,25-(OH)2D3 is fully effective in preventing EAE in mice fed a 1% calcium, 0.3% phosphorus diet. A detailed description of the methods is found in Cantorna et al. (27).

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Figure 4. 1,25-(OH)2D3 prevents collagen-induced arthritis. Male DBA/1LacJ mice were fed a 0.02% calcium, 0.3% phosphorus diet. Following the immunization procedure with bovine collagen type II, animals were treated with either vehicle or vehicle containing 50 ng/day of 1,25-(OH)2D3 mixed in the diet. Mice were observed daily and began to show symptoms 30 days postimmunization. Treated animals showed no symptoms (see Cantorna et al., ref 30).

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Figure 5. MRL/MJP mice were fed the 0.87% calcium, 0.3% phosphorus-purified diet throughout. Controls received vehicle incorporated into the diet or the indicated dose of 1,25-(OH)2D3 dissolved in the vehicle and added to the diet to provide 50 ng/day/mouse or 100200 ng/day. Symptoms of lupus and proteinuria were prevented by this treatment.

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Figure 6. MRL/MJP mice fed a 0.02% calcium diet were not protected by treatment with 1,25-(OH)2D3 at 100 ng/mouse/day. This treatment in fact accelerated the appearance of lesions.

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Figure 7. IL-10 knockout mice were fed the 0.87% calcium, 0.3% phosphorus diet for 10 wk and the small intestine was weighed at the end of the experiment. The data are supported by histology scores and declines in body weight. The results illustrate that 1,25-(OH)2D3 prevents the enterocolitis produced by a deficiency of IL-10.

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Figure 8. Incidence and severity of type I diabetes developed in NOD mice. Weanling NOD mice were fed the purified 0.87% calcium, 0.3% phosphorus diet for the entire period and, where indicated, were supplemented with either vitamin D3 at 625 ng/day or 1,25-(OH)2D3 at 50 ng/day. Type I diabetes was diagnosed by blood glucose rising above 300 mg/100 ml. The results illustrate that vitamin D administration reduces the incidence and severity of the disease, whereas 1,25-(OH)2D3 essentially blocks diabetes in these susceptible mice (33).

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Figure 9. 1,25-(OH)2D3 treatment of B10.PL mice immunized with myelin basic protein and pertussis toxin were given either vehicle added to the diet or vehicle with 1,25-(OH)2D3 (50 ng/day for females and 200 ng/day for males). Upon the appearance of EAE symptoms in the control group, the animals were killed and lymph nodes were removed for measurement of TGF-1 transcripts.

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Figure 10. 1,25-(OH)2D3 supplementation markedly increases the transcripts for IL-4 in the lymph nodes of B10.PL mice immunized with myelin basic protein and pertussis toxin as described in Fig. 9 legend.

In a study published in the journal Nature Immunology, researchers from the University of Copenhagen found that when a variety of white blood cells known as a T-cell comes across a pathogen in the bloodstream, it extends a receptor in search of vitamin D. If it encounters the vitamin, the T cell becomes "activated." If there is not enough vitamin D in the blood, the cell remains passive and no immune response occurs. The body produces vitamin D upon exposure to sunlight. It can also be found in eggs, fatty fish, fortified milk and in supplement form. Once activated, a T-cell transforms into one of two kinds of cells. One type seeks out and destroys all traces of the infectious agent, while the other records information about the pathogen and transmits it to other parts of the immune system. These latter ("helper") cells help the immune system respond quickly should infection with a similar pathogen occur at a later date. In addition to providing new information about the importance of vitamin D, the study provides hope for better understanding -- and perhaps prevention -- of the unhelpful immune responses that result in autoimmune disorders like allergies or Type 1 diabetes, as well as those that cause the body to reject transplanted organs. The researchers were able to determine what chemical steps occur to transform a T-cell from active to inactive, suggesting the possibility that doctors may eventually be able to initiate or block this process, depending on the patient's need. Sources for this story include: http://news.ku.dk/all_news/2010/2010.3/d_vitamin/; http://www.dailymail.co.uk/health/article1256149/Sunshine-play-vital... .

Vitamin A and Its Effects on Immune System

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Vitamin A is one of the major vitamins that play a crucial role in the health of the eyes. It also helps in formation and maintenance of teeth, soft tissues, and skin. Its role in the immune system is being widely researched.
Vitamin A play a crucial role in the health of the eyes
It has been noted to function in coordination with other vitamins and minerals in the regulation of the immune system. Some of the areas where vitamin A plays a vital role in the immune system are discussed in the below sections.

Action against Measles Virus

A study performed in Canada evaluated the ability of vitamin A to reduce the death rate associated with the measles virus. The measles virus replicates by affecting the cell signaling in our body wherein the affected cells are not able to send warning signs.Administration of vitamin A was noted to block this effect of the measles virus by strengthening the immune cells. Vitamin A improves the functioning of the uninfected cells and makes them resistant to the viral replication. This effect of vitamin A can help to augment the effects of the vaccinations or antiviral drugs being administered to counter viral infections. Boosting of the cells ability to resist an infection and improving the cell signaling mechanisms helps in reducing the virulence (infective capability) of a virus.1

Vitamin A Promotes T-lymphocytes and Associated Cells

Administration of vitamin A helps the progression of certain components of the T- lymphocytes. It was noted that the concentration of certain proteins related to the T-cells was significantly increased following administration of vitamin A supplements. The functioning of other immune cells known as monocots was also increased. Furthermore, the concentration of natural killer (NK) cells and T-helper cells in the blood were noted to increase as levels of vitamin A increased. These cells play a vital role

in

maintaining

the

anticancer

and

antiviral

ability

of

the

immune

system.2

Several other studies have reported that vitamin A has a role in the regulation of the genes and proteins controlling the activation of T-cells and the production of cytokines. Adequate amounts of vitamin A in the body helps in better functioning of these processes and thereby improves the immunity of an individual.2, 3

Retinoic Acid and Phagocytes

Retinoic acid is a derivative of vitamin A which helps in the growth and development of the bone and skin cells. Retinoic acid is required for the production and regulation of B- lymphocytes by the cells present in the cells lining the digestive tract . Further role of vitamin A has also been noted in the maturation of the phagocytes in the bone marrow. A deficiency of vitamin A can hamper these functions leading to decreased accumulation of B- lymphocytes and production of immature phagocytes that would weaken the immune response .

Vitamin B6 Strengthens Immune Response

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Vitamins are among the most essential nutrients required for the optimalfunctioning of our body, and adequate intake of vitamins and other micronutrients are essential for the efficient functioning of the immune system.
Deficiencies of several vitamins includingvitamin B6 are associated with a number of disorders related to immune function.

Strengthening Immune Responses

Vitamin B6 works along with other vitamins and micronutrients to support the protective activities being undertaken by the immune cells. Deficiency of essential vitamins such as B6 has been

associated with suppression of the immunity function which predisposes individuals to infectious disorders. This may be beneficial in individuals falling under the high risk category for immune disorders. Children, older adults, individuals suffering immune disorders are noted to have a weakened

immune system and are considered under the high risk category. Such individuals are highly prone to develop severe infections and administration of vitamin supplements can boost their immune system.

Benefits in Critically Ill Patients

Critically ill patients are prone for secondary infections that occur as a result of suppression of the immune system. A study conducted in Taiwan evaluated the benefits of vitamin B6supplementation in critically ill patients. An overall improvement in the immune status was noted following vitamin B6 supplementation for 2 weeks. The cells of the immune system that comprised of T-lymphocytes, Thelper cells and others displayed increased activity following daily injections of 50mg vitamin B6. In the other group who were administered 100mg ofvitamin B6 it was noted that the number of Tlymphocytes and other subsets of T- cells had significantly improved over the two week period. It was concluded that administration of larger doses of vitamin B6 in critically ill patients could boost their immunity and protect them against secondary infections.

Vitamin Supplementation for Older Adults

Older individuals are known to suffer from

deficiencies of various nutrients and are also at an increased risk of developingsevere infections. It may be beneficial to provide vitamin supplements in such cases to strengthen the immune system and decrease the severity of infections. Several studies have reported the enhancement in immune status following supplementation of vitamins and other nutrients. Although the benefits of vitamin supplementation in prevention of infectious disorders in the elderly population have not been studied widely, it may prove to be beneficial in future studies.3

Improves Proliferation of Lymphocytes

A result similar to that of the Taiwan study discussed before was noted in young women. A daily administration of about 2.1 mg of vitamin B6 resulted in about 35% improvement in the production of lymphocytes. The study concluded that administration of vitamin B6 at slightly higher dosages than recommended levels can improve the immunity by increasing the number and activity of the lymphocytes.

Vitamin C and Its Effect on Immune System

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Vitamin C or ascorbic acid is necessary for the formation of bones, muscles, blood vessels and other supporting cells and tissues. Its role in disorders such as asthma, diabetes or cancer is being widely researched.
Vitamin C has also been presented as a treatment modality in cases of common cold and infections of the lung. The role of vitamin C in the immune system has been studied for many years and has been reported to control certain regulatory

functions. The administration of vitamin C along with other micro and macronutrients is advised in individuals who are suffering from vitamin Cdeficiency and are at high risk of developing infections related to the lungs.

Vitamin C and Immune Cells

The role of vitamin C in the functioning of immune cells is well proven. Vitamin C is especially required for the functioning of the phagocytes and T-lymphocytes. The major role of vitamin C is the protection of the immune cells against free radicals formed during the interaction of the immune cells with harmful microorganisms. The T-cells and other phagocytes engulf the microorganisms and employ oxygen in the form of superoxides to destroy them. These superoxides can be harmful to the phagocytes themselves. Vitamin C protects them against the free radicals and thereby maintains the integrity of these cells. A deficiency of vitamin C hampers the function and results in early destruction of the T-cells and phagocytes. Deficiency of vitamin C is associated with increased duration of the common cold and infections of the lung, signifying its role in protection against these conditions. The effect has been more pronounced in elderly individuals who tend to suffer from multiple deficiencies owing to their altered dietary pattern and the ability of the body to absorb the essential nutrients from the diet being consumed.1, 2

Vitamin C and Flu

Administration of vitamin C was noted to improve the concentration of immune proteins and certain components of the complement system. These proteins and the complement system have a vital role in maintaining the immunity of the body. The effects of vitamin C has been particularly been emphasised against infections such as the common cold and flu. Vitamin C when administered with other medications for flu and common cold significantly reduced the duration of these infections. Vitamin C supplementation is therefore advised along with regular medications in order to reduce the severity and duration of infectious disorders.2, 3

General Functions
Vitamin C along with other micronutrients has a role in the ability of the skin to fight against infectious microorganisms. Vitamin C enhances the functioning of the skin cells and helps them form an effective barrier against the harmful microorganisms. Deficiency of vitamin C and other nutrients reduces the ability of the skin to prevent infections.

Vitamin E - Potent Antioxidant with an Ability to Regulate the Immunity

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Vitamin E supplements have been generally advised to improve the antioxidant status and prevent the occurrence of numerous disorders.
Effects on Cells
Aging is one of the factors that tend to slow down

thefunctioning of various organs in our body. This hampers the ability of the body to function at the same rate and vigour as during early and middle adulthood. Similar changes are noticed in the organs involved in regulating the immune system. Studies conducted on elderly individuals have proven the effect and it was noted that vitamin E supplementation in these individuals significantly improved the functioning of the cells and tissues of the immune system. Vitamin E had an impact on the genes that are responsible for the progression of cell cycles. The supplementation of vitamin E resulted in

increased functioning of the cells of the immune system. Furthermore, it was also reported that vitamin E has a role in the regulation of the cell membrane and interactions between individual cells.

Effects on Thymus and T-cells

The T-lymphocytes (T-cells) carry out the function of destroying the microorganisms recognised by the immune system. The immature cells of T-lymphocytes are formed in the bone marrow. These immature cells then travel to the thymus gland where they undergo differentiation and maturation to form the T-lymphocytes. The function of the thymus gland is critical as improper functioning can affect the formation of T- lymphocytes. Vitamin E plays a vital role in the maturation process of the T-cells in the thymus gland. A deficiency of vitamin E affects the maturation of T-cells resulting in the decrease of the immune resistance. Further, vitamin E also has a role in the recovery of the thymus gland from injuries. A study conducted in China also revealed that vitamin E protects the T-cells against oxidative stress that tends to destroy the T-cells prematurely.

Aging and Vitamin E

One of the effects of aging on the immune system is decrease in the functioning of the T- cells. It has been noted that a decline in the T-cell function is one of causes for the progression of immune related disorders such as arthritis and cancer. Further, a deficiency in immune function also makes the elderly individuals more prone to infections. The decrease in the ability of the T-cells to perform well has been attributed to the deficiency of vitamin E. It was noted that administration of vitamin E supplements in elderly individuals significantly improved the T-cell functioning and also decreased the risk of progression of numerous age related disorders.

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