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Soups and stews (which provide immune-boosting amino acids and minerals) can feel soothing, while the heat helps open up congestion. This hypothesis was supported by a later study showing that EGCG-mediated inhibition of IL-2R involves all three IL-2R subunits: To characterize interactions between nutrition and immunity, we discussed the effects of multiple food components on immune functions. Blueberries, blackberries, strawberries, pomegranate, plums, red cabbage, cherries, cranberries — all are loaded with anthocyanidins and are a great nutrient-rich addition to your diet. It helps to make skin healthy and may even provide some protection against skin damage from ultraviolet (UV) rays. 7 smoothie ingredients to reboot your immune system. Vitamin C helps protect you from infection by stimulating the formation of antibodies and boosting immunity.

(87) of autoimmune disease patients were significantly lower compared to the controls. It is believed that probiotics play a role in maintaining homeostasis in the gut that is exposed to many foreign substances, including both harmful and harmless, by balancing the pro-inflammatory and anti-inflammatory/regulatory immune response (201). Nutrition as a modifiable factor in impacting immune function has been studied for several decades, and the research in this field has developed into a distinguished study subject called nutritional immunology. Flavonoids are substances found in plants that can protect your body from disease. It’s a fat-soluble vitamin, meaning it requires the presence of fat to be absorbed properly. Try to minimize stress. Vitamin D can also significantly influence the adaptive immune response. Yet look at websites of reputable high street retailers, chemists as well as health food stores, and you’ll find hundreds of products that promise to boost, tune, support or enhance your immune system.

Clearly, young children require a higher caloric intake relative to body size to facilitate physical and mental development as compared to the elderly [216–218].

This important vitamin — part of nearly 200 biochemical reactions in your body — is critical in how your immune system functions. So, if you aren’t getting enough through your diet, your body can’t make enough antibodies to help you fight whatever germs you pick up throughout the day. Ohta M, Okabe T, Ozawa K, Urabe A, Takaku F. These numerous animal models allowed a growing understanding and characterization of the immunological disturbances triggered by under-nutrition. Incorporating specific foods into the diet may strengthen a person’s immune response. Particularly for zinc, vitamin E, n-3 PUFA and probiotics, clearly there is need to establish the optimal doses for maximum clinical benefits, which may likely differ depending on the age, genetic background, and nutritional and health status of the population of study. Four weeks of supplementation with a multi-species probiotic formulation (Lactobacillus, Bifidobacterium and Streptococcus) reduced markers of gut permeability and symptoms of gastrointestinal discomfort during exercise heat stress (Shing et al. )

Foods rich in vitamin C are: In clinical trials in humans, dietary supplementation with n-3 PUFA appears to beneficially affect histological and clinical parameters of IBD (167, 168). In a subsequent larger, double-blind, placebo-controlled trial, this group found that the elderly nursing home residents (>65 y) receiving vitamin E supplementation (200 mg/d) for 1 year had lower incidence of upper respiratory infection (RI) and common cold compared to those receiving the placebo (55). This is not an indication of a security issue such as a virus or attack. 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. Zinc deficiency is prevalent in children under 5 y of age in developing countries (100), and a systemic review reported that preventive zinc supplementation was associated with reduction in diarrhea and pneumonia morbidity and mortality in children (3 mo to 5 y) of developing countries (101).

The changes in the immune system are associated with decreased responses in the skin hypersensitivity test, lower production of IL-2, reduced response to mitogens and antigens, and lower-titer antibodies after vaccination. As with other bodily systems, the immune system depends on adequate nutrients to function properly. Third, correction of nutritional deficiencies does improve immune responses even in old age. Consuming turmeric may improve a person’s immune response. But these subjects are elite athletes undergoing intense physical exertion. However, a Cochrane systematic review (169) and meta-analysis (170) concluded that data was insufficient to suggest n-3 PUFA as a primary treatment for IBD suggesting that further research needs to be done regarding the efficacy of n-3 PUFA on disease progression and remission of IBD. Second, with diminished food intake there is less diet-induced thermogenesis; third, activity lessens, particularly with disability. The immune nature of chronic inflammatory disease has often been documented without being connected with VAT obesity (SI Appendix, Appendix 12).

  • Epigenetic genomic effects may be involved, as they appear to connect some effects of nutrition with the metabolic syndrome (150, 151).
  • A healthy gut is your strongest ally when it comes to fending off viruses and the not-so-good bacteria.
  • There is of course a way you can speed up this process and thereby boost your immunity.
  • Water is of the utmost importance, whether you are trying to avoid getting sick or already fighting a cold.
  • Many foods provide vitamin E, including nuts, seeds, and vegetable oils—all associated with healthy fats and dietary patterns.

Tea Time

Medzhitov(2020). The area of discussion on nutrition, immune and aging relationship is much extensive, wide and varied that this is beyond the scope of a single review. How to boost your immune system by eating the right foods, lastly, you might want to swap your morning coffee for a green tea -- McGrice said it has antiviral effects. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist.

Include strength training and stretching along with aerobic exercise to build muscle and increase flexibility. And as that’s a fairly difficult thing to show off at a dinner party, it’s probably not worth the investment. The impact of micronutrients on immunocompetence has been explored extensively, albeit mostly by experiments on laboratory animals using diets deficient in micronutrients resulting in the development of clinical symptoms of diseases of the immune system. Here are some tips for getting the top vitamins and minerals your immune system needs to perform. Further, data from the first National Health and Nutrition Examination Survey (NHANES), a US national survey, indicate that raised iron levels may be a risk factor for cancer and death, especially in men [85]. Everyday preventive measures—such as handwashing, avoiding contact with sick individuals, and good hygiene—can go a long way in reducing your risk for viruses, bacteria, and other pathogens.

These shortfalls are more conspicuous in preterm infants, which also have lower serum IgG and complement. Hyperpermeability of the gut barrier (“leaky gut”), which can occur with high-fat and high-fructose diets and in extreme childhood malnutrition (see below), can lead to pathogen-induced endotoxemia, (typified by presence of LPS in the blood), which activates immune responses of the mesenteric FALCs (25), as well as stimulating an inflammatory response in the omentum (26). And, let me tell you, our prospects aren’t looking particularly good. The main protein food sources are meats and seafood, so chicken, poultry, fish and shellfish. As found in the above-mentioned study, simply taking a break with junk food for a few weeks can do a great deal to calm inflammation and balance the immune system. Falling short of your calorie requirements can compromise your immune system, as can poorly planned and low-calorie diets, especially those low in protein. Zinc dyshomeostasis during polymicrobial sepsis in mice involves zinc transporter Zip14 and can be overcome by zinc supplementation. Inflammation is an essential response of a host to infection which helps destroy invading pathogens.

However, obvious differences were noted between the two studies, such as the fact that the study by Graat et al.

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All of these nutrients are normally used within a clinical setting to supplement the food given to sick people experiencing a high degree of physical stress due to their illnesses and/or the treatment they are receiving. Keep this in mind: Some immune cells may even deplete the microenvironment of certain nutrients, to manipulate the activation of mTOR. Effects of aging on nutrition The relation between aging and nutrition is complex one as what affects what is difficult to decide. It is suggested that zinc may influence CD4+ T cell polarization in favor of Th1, which involves increasing IFN-γ production through upregulation of IL-12 signaling and transcription factor T-bet activity (98).

Probiotics support the growth of the good bacteria which in turn play an important role in balancing your body's good bacteria and are stored in the gut. 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. Urashima, and C. For now, there are no scientifically proven direct links between lifestyle and enhanced immune function. Click here to learn more. While there are many other members in each of above-mentioned categories that are also known to affect immune function, we have included only a few as representatives in the current review mainly based on the fact that they are relatively more intensively studied and their immuno-modulating properties are widely accepted although it is clearly acknowledged that discrepancy is far from resolved for the nature and magnitude of their actions, as well as in the efficacy and translational value of their potential application.

My Favorite Books on Nutrition

In particular, vitamin D inhibits production of IL-2 and IFN-γ, two key T cell cytokines (13). Fill your plate with fatty fish (salmon, herring, and tuna), fortified foods (dairy, breads, cereals, and orange juice), eggs, and supplements. Certainly it produces many more lymphocytes than it can possibly use. Vitamin E is important in regulating and maintaining immune system function. But we should bear in mind that it is a vitamin which is destroyed by heat and so cooking damages its structure. Examples of autoimmune disorders include lupus and inflammatory bowel disease (IBD).

A high-performance liquid chromatographic method for the determination of tocopherol in plasma and cellular elements of the blood. For adult men, it’s 11 milligrams (mg), and for women, it’s 8 mg. As logic would dictate, support for nutritional supplements to improve immune resistance (and thus decrease pathogen burden) comes largely from studies in those with impaired immunity, such as the frail elderly and clinical patients, particularly in those with poor nutritional status (Bermon et al. )They are also specialized to respond to immune-related signals (e. )Eat regularly through the day, every 4-6 hours.

Since our body’s fluid needs increase when we’re fighting infection, drinking an extra two cups of water plus your daily minimum can fuel regeneration of immune-fighting lymphatic cells to get your body feeling stronger. For example, 30 to 60 minute walk most days per week is considered moderate exercise. Aging changes in immunity: medlineplus medical encyclopedia, chemotherapy and other cancer drugs are prime examples, along with immunosuppressant drugs used to treat autoimmune diseases. Similarly, a short period (7 d) of L. Liam O’Mahony is a molecular immunologist at the Swiss Institute of Allergy and Asthma Research in Davos. Anthocyanidins are actually responsible for the purple color in your favorite fruits and vegetables. Morton (2020). But the extensively documented correlations with intrauterine nutritional variation indicate that variation in nutritional factors usually overwhelms the influence of genetic variation within the populations involved.

“By exercising you keep them out looking for potential problems rather than sitting around waiting for problems to happen.

Gallery: The best of the new foods available at Allianz Field this season

Healthy protein foods, like fish, poultry, lean meats, soy foods and low-fat dairy products provide the building blocks that your body needs to make these specialised proteins. Children with low gestational weight plus atrophy may exhibit reduced thymus size and display attenuated cellular immunity. Grab wheat germ instead—1/4 cup provides approximately 25 percent of your daily needs. Salt causes high blood pressure, irritates the stomach and retains fluid. The underlying mechanisms of the immunomodulatory effects of vitamin E have been largely elucidated using animal models combined with the cell-based approaches. Instead, obese VAT is diseased VAT; it turns against the organism with what appears to be a prolonged and low-level immune response characterized by chronic inflammation and increasing insulin resistance, signal characteristics of CVD (45) and T2DM (46). Macrophages appeared as crown-shaped aggregates, similar to those observed in other known inflammatory conditions, such as rheumatoid arthritis, and grew larger with increasing degrees of obesity.

Although gelatin is not a complete protein, it contains several essential and nonessential amino acids, including arginine, glycine, and proline. Another area of uncertainty is whether regular high-dose vitamin C supplementation (1 g/day) blunts some of the adaptations to endurance training. In a recent prospective clinical trial, Iovino et al. Nutrients like protein, zinc and vitamins A, C and E are important. Viewed in a larger picture, authors of a recent systematic review and meta-analysis investigated relationship between zinc status and autoimmunity using data from 62 studies that met their inclusion criteria (111).

Inside Children's Health:

The immune system can be broadly split into two parts, the innate and the acquired response. These limit the proinflammatory effect of Omega-6, and their use in nutritional formulas has demonstrated positive results of various kinds, among them, an improved immune response. Including pre-biotic food such as leeks, Chicory root, Jerusalem artichoke, onions, oats and bananas in your diet will strengthen your gut defence system. After injury, illness (primarily respiratory but also gastrointestinal) was the second most common reason for an elite athlete to seek medical attention either during training or when competing at the summer or winter Olympic Games. (1) innate immune responses which are specific for shared microbial factors not found in mammals, respond rapidly via non-polymorphic cell surface receptors and do not mediate immune memory; 2) adaptive immune response (also called acquired immunity), able to recognize myriads of short peptides derived from target cells detected by highly specific polymorphic cell surface receptors and mediating immune memory. Research has shown that people who consume large amounts of fruit and vegetables have less genetic damage which is one of the precursors to cancer. There’s even a word for it:

Think of free radicals as bulls in a china shop destroying things left and right. In the chronic systemic inflammation of obesity VAT responds with adipocyte multiplication and (permanent) fat-depot enlargement (12). Naturally occurring compounds like vitamins and minerals modulate immune responses. Nevertheless, the so called Westernized, Educated, Intelligent, Rich, and Democratic (WEIRD) societies also suffer from age-associated malnutrition in one way or the other. Sreeramkumar V, Fresno M, Cuesta N.

Vitamins: The Basics

Eat a variety of protein foods including seafood, lean meat, poultry, eggs, beans and peas, soy products and unsalted nuts and seeds. It is proposed that vitamin E can enhance T cell-mediated function by directly promoting membrane integrity and positively modulating the signaling events in T cells while also protecting T cell function indirectly by reducing production of T cell-suppressing factors such as PGE 2 from macrophages as previously reviewed (38, 39). Inflammation and Immunity: Mocchegiani E, Santarelli L, Muzzioli M, Fabris N.

Probiotics are considered the “good” bacteria in your gut.

Nutrients are always most bioavailable in their natural food form. Weight reduction schemes using diets with less than 1200 kcal per day can also reduce immune function, an excellent reason to avoid unhealthy "crash diets". 3 herbs that may help strengthen your immune system. But the concept of boosting immunity actually makes little sense scientifically. The omentum has been called “the abdominal policeman” [see ref.

Activation of genes for most of the pro-inflammatory mediators is controlled by nuclear factor-kappa B (NF-κB), a transcription factor ubiquitous in almost all cell types. A healthy immune system is one more reason to follow an overall healthy lifestyle. Zinc helps the immune system work properly and may help wounds heal. Read more about the benefits of quitting smoking and how to quit on the Smoking Cessation page. A germ invades successfully and makes you sick. So call in the troops! In the last 100 years, humanity has made more progress than anyone could ever have imagined. Future research will need to focus on how these pathways interact with each other and explore nutrient allocation strategies of the body, and the effects of aging thereon.

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Help protect yourself against infection and boost your immunity by incorporating the following top 6 recommendations: Too much exposure to the sun can cause skin cancer. I always have a reusable water bottle on me that I fill up at every opportunity. In a subgroup of five placebocontrolled trials in heavy exercisers (n=598), including marathon runners, skiers and soldiers, vitamin C (0. )It is suggested that in future the following areas of research may be addressed:

Despite its potential benefits, dark chocolate is high in calories and saturated fat, so it is important to eat it in moderation.

Furthermore, anomalous immune responses in the aged can aggravate inflammation, conceivably contributing to other diseases of old age: Well, the answer to this question is both yes and no. Foods high in vitamin B6 include bananas, lean chicken breast, cold-water fish such as tuna, baked potatoes and chickpeas.

Maintaining a healthy weight can also benefit the immune system.

List of Abbreviations

While it is agreed that nutritional deficiency or insufficiency needs to be corrected to ensure that the immune system functions properly, mounting evidence suggests that for certain nutrients, increased intake above currently recommended levels may help optimize immune function including improving defense function and thus resistance to infection, while maintaining tolerance. The same is true for normal aging. In their study, Musselman et al. Europe PMC requires Javascript to function effectively. If it works for flu infections, it may help your immune system against coronavirus (COVID-19) infection. They probably owe their origin to the advantage, in poorly nourished individuals, of prioritized investment in fat tissue that fuels defenses against abdominal bacterial and parasitic infections, beginning with a fetal allocation decision that reflects maternal nutritional state.

Watch Your Sugar Intake

Zhang P, Smith R, Chapkin RS, McMurray DN. Your digestive tract is home to trillions of bacteria that have numerous functions in promoting health. In this review, several aspects of this complexity have been explored. You can increase your intake through foods such as fatty fish (salmon, mackerel, tuna and sardines) and fortified foods such as milk, orange juice and cereals. Clearly, pathogenic obesity is not selectively advantageous so it must arise from some advantageous process gone awry. The association is less reliable for refined-grain intake, with some cross-sectional studies recording a positive association and others no relation [92]. This system is responsible for providing our bodies with the necessary defence mechanisms.

You may need to work up to a 150 minutes per week goal or set a goal adjusted for your needs.

Frozen is fine. There is considerable heterogeneity among individuals in the vigor of their immunological function, largely owing to factors such as genetics, environment, lifestyle, nutrition, and the interaction of these factors. 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression.

Despite the challenges, scientists are actively studying the relationship between stress and immune function. The protein you consume is broken down into smaller pieces, known as amino acids. However, the amounts of needed nutrients change as an individual passes from one stage of life to the next. 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. Garlic is a common home remedy for the prevention of colds and other illness.


In contrast, cortisol and adrenalin prompt thymic atrophy in mice [209, 210], and cortisol is high in children with malnutrition and other forms of stress. Vitamin C protects you from infection by stimulating the formation of antibodies and boosting immunity. We further emphasize the fact that both nutrition and immunity are complex and multi-dimensional traits. Whole grains and leafy root vegetables are good plant sources of zinc. Probiotics include a wide variety of species and they in turn are composed of many strains, either naturally occurring or intentionally modified, which have been used in different studies. Am J Clin Nutr. Research also indicates that flavonoids may help to prevent the common cold in otherwise healthy people. Evidence for a serum-factor secreted by the human thymus.

The innate immune system offers an early first line of defense against assaulting pathogens. For example, this model helps to explain why nutritional supplements with tolerogenic effects may reduce the burden of infection in otherwise healthy athletes (e. )As we have said, there are a variety of nutrients directly involved in the working of the immune system. Despite this, many phytochemicals and functional foods have been shown to have beneficial effects on immune function. When the immune system is overactive, the body damages its own tissues. Facts (and myths) about boosting your immune system, remember, however, that excessive exercise, such as training for a marathon or competing in an intense sporting event, actually puts stress on your immune system, reducing its efficiency. What vitamins can boost my immune system?

The authors of one study caution against high-dose antioxidant supplementation during endurance training to avoid blunting cellular adaptations (Paulsen et al.

NUTR625: Nutrition and the Immune Response

Mature single CD4 and CD8 positive T cells are first identified in the thymus at week 15 and are numerous in the periphery well before birth [21, 22]. “The key with curcumin is making sure it is combined with a phytosome to enhance its absorption into the blood stream. According to a review, ginger has anti-inflammatory and antioxidative properties and is likely to offer health benefits. In contrast to its effect on the innate immunity, vitamin D is in general inhibitory on both T and B cells (9). Recent studies have revealed that EGCG differentially impacts development of CD4+ T cell subpopulations. Overview of immunodeficiency disorders, try to minimize stress. In only the past decade, with genetic sequencing technologies becoming more affordable, scientists have begun to learn not only how invading pathogens shape and strengthen our immune system, but also about how it interacts with the communities of microbes that live in and on our bodies.

While it's highly unlikely you'll get too much in the way of vitamins from food sources, fat-soluble vitamins — vitamin A, D, E, and K — can be harmful in high doses. How can diet boost our immune system? Exercise can also boost your body's feel-good chemicals and help you sleep better. Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: Additionally, the immune system develops appropriate tolerance to avoid unwanted response to healthy tissues of self or harmless foreign substances.

Imbedded in immune cell physiology are metabolic pathways and metabolites that not only provide energy and substrates for growth and survival, but also instruct effector functions, differentiation, and gene expression [91]. Once pathogens have traversed this first barrier, the immune system is responsible for defence mechanisms that can be divided into two categories: Mocchegiani E, Muzzioli M, Giacconi R, Cipriano C, Gasparini N, Franceschi C, et al. Guatemalan children (6–9 mo) treated with 10 mg of zinc/d as sulfate for 7 mo had decreased diarrhea by 22% but had no effect on RI incidence (102). For these reasons, it is a good choice of vegetable to eat regularly to support immune system health. 11) and plasma (mean effect:


Vitamin C can be found in parsley, peppers, broccoli, Brussels sprouts, kiwi, papaya, strawberries, lemon, etc. Inadequate sleep has also been linked to suppressed immune function. Just like a healthy diet, exercise can contribute to general good health and therefore to a healthy immune system. 86; see also refs. Regular exercise promotes good cardiovascular (heart) health, too. Second, nutritional deficiencies are quite common in this old age; a large proportion of the elderly show evidence of PEM or selected nutrient deficiencies. The influence of PEM on immune function has been reviewed extensively [52–58] and also studied widely, particularly in the context of effects of PEM on viral susceptibility [59, 60], PEM and supressed immunity, PEM and impaired immune organ growth [61] and PEM and thymic atrophy [62].

Interestingly, this study also found that participants in the probiotic group had increased percentage of B cells, NK cells, APC, CD4+CD25+, and CD8+CD25+ phenotypes in peripheral blood cells, and most of these changes lasted 12 wk after probiotic discontinuation (221). Soy products are also good at preventing heart disease. The immune system and psoriasis, the second aspect is to stratify the patients into subgroups, and each subgroup should be biologically and clinically plausible based on the systematic collection of a relevant and known biological basis. One study found that diets rich in fiber and low in saturated fat can lead to deeper, more restorative sleep. For cancer prevention, the American Institute for Cancer Research recommends not to drink alcohol.

On the one hand, malnutrition has a well-described negative influence on immunity and resistance to infection, but on the other, the widely reported increase in energy requirements during infection paradoxically coincides with reduced appetite (anorexia) and nutrient malabsorption; hitherto, a poorly described phenomenon. Research done at the University of Bonn showed that junk food is correlated with a strong inflammatory response in the body, which resulted in an overly active immune system, as well as changes in our genetic coding. This might not just affect infections but could also strengthen the type of immune cells, which can fight tumour cells. N-3 PUFA have been shown to inhibit APC function of spleen cells (148), monocytes/macrophages (149, 150) and dendritic cells (151–153), such as suppressing expression of MHC-II and co-stimulation molecules, activation of cognate T cells, and production of related cytokines.

Key Points

Like vitamin C, vitamin E can be a powerful antioxidant that helps your body fight off infection. Moreover, a particular nutrient may alter the whole immune constellation as deficiency of one nutrient may affect the proper metabolism of another nutrient and elicit a chain reaction of secondary malnutrition. This age-associated decline in nutritional status may be more obvious in societies with low economy, literacy rate and lack of nutrition-related awareness. It may not be a coincidence that cold and flu season coincides with the dark, cold days of winter. Next, they aimed to determine what component of the food was responsible for this lethal effect.

Whether probiotics and prebiotics can prevent travelers’ diarrhea remains unclear as prophylaxis may be dependent upon the strain of probiotic given. Probiotics for eczema: why use them, and do they work? In 1981, the British general practitioner and celebrated epidemiologist, R. Staying up-to-date on immunizations is another important part of a strong immune system.

Similar to the results in the animal studies mentioned above (80, 81), zinc supplementation increased circulating levels of active thymulin in the elderly (66, 89, 90).

Conclusion And Future Outlook

Examples of foods that have these nutrients are: As mentioned previously, the therapeutic effects of zinc lozenges for treating the common cold, although principally considered to reduce the pathogen burden (improved resistance), may also be attributed to antioxidant and anti-inflammatory (tolerogenic) properties of zinc. Erdener, and L. But growing evidence indicates that for some nutrients there are times when intake above recommended levels may have beneficial effects on immunity, likely by optimizing the delicate balance between resistance and tolerance. Older people tend to eat less and often have less variety in their diets. Individuals subject to fetal nutritional stress, as indicated by low birth weight (LBW), are especially susceptible to infection as infants and children (27, 28). Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J, et al. Even if you do not feel hungry, try to have a snack or mini meal.

In a later trial with similar design but larger sample size and more comprehensive outcome measures, the same group found difference between probiotics and control groups in several immunologic parameters suggesting favorable effect of probiotics on allergy, however, they once again failed to detect difference in primary effect on clinical endpoints (223). Unlike lymph nodes, milky spots are unencapsulated, and they enlarge and become more numerous during pathogen-induced endotoxemia, sepsis, and chronic inflammation (18). In this respect, T cells appear to be more affected than B cells, and the microbicidal activity of neutrophils and macrophages as well as the cytolytic activity of NK cells is reduced; hypersensitivity and antibody production in vitro in response to mitogens is also affected under these conditions [89].