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 near-perfect 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 don't 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 doesn't mean the effects of lifestyle on the immune system aren't intriguing and shouldn't 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. That's 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:
Eat a diet high in fruits, vegetables, and whole grains, and low in saturated fat.
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.
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 doesn't have enough T cells to fight off infection. So there is a bottom number below which the immune system can't do its job. But how many T cells is comfortably enough, and beyond that point, is more better? We don't 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 body's ability to fight disease. They provide a way of detecting whether something is going on, but science isn't 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 people's 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 malnutrition's effect on the immune system, however, is not certain. 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 don't 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 didn't 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 don't 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 didn't 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 it's important to have sufficient zinc in your diet (15–25 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 don't 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 doesn't mean we should discount the benefits of all herbal preparations. Everyone's immune system is unique. Each person's physiology responds to active substances differently. So if your grandmother says she's been using an herbal preparation for years that protects her from illness, who's to say that it doesn't? The problem arises when scientists try to study such a preparation among large numbers of people. The fact that it works for one person won't show up in the research data if it's 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, there's 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 don't 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 didn't 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 didn't 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 haven't 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, it's too early to recommend garlic as a way of treating or preventing infections or controlling cancer.
Ginseng. It's 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 it's 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 bang-up 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 isn't known. As more and more intriguing evidence comes in to support the link that intestinal bacteria bolster the immune system, it's 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. You'll 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 don't 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 won't 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 person's 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 one's work. Some scientists are investigating whether ongoing 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 Alzheimer's 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 Alzheimer's 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.
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Does being cold make you sick?
Almost every mother has said it: "Wear a jacket or you'll catch a cold!" Is she right? So far, researchers who are studying this question think that normal exposure to moderate cold doesn't 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. They've 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. They've 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 isn't 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 there's no need to worry about moderate cold exposure — it has no detrimental effect on the human immune system. Should you bundle up when it's cold outside? The answer is "yes" if you're uncomfortable, or if you're going to be outdoors for an extended period where such problems as frostbite and hypothermia are a risk. But don't 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 person's 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 hasn't been established, it's 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 genome 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.