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 are making progress.

Almost every mother has said it: "Wear a jacket or you'll catch a cold! Probably not, exposure to moderate cold temperatures doesn't increase your susceptibility to infection. There are two reasons why winter is "cold and flu season. Also the influenza virus stays airborne longer when air is cold and less humid.

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 performed experiments in which volunteers were briefly dunked in cold water or spent short periods of time naked 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.

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. 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 to boost your immune system naturally and keep it healthy? Just like a healthy diet, exercise can contribute to general good health and therefore to a healthy immune system.

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Can watching sports be bad for your health? Beyond the usual suspects for healthy resolutions. February 15, Helpful ways to strengthen your immune system and fight off disease How can you improve your immune system?

What can you do to boost your immune system? Photos courtesy of Michael N. Starnbach, Ph. 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: Don't smoke. Eat a diet high in fruits and vegetables.

Exercise regularly. Maintain a healthy weight. 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. Try to minimize stress. Keep current with all recommended vaccines.

Vaccines prime your immune system to fight off infections before they take hold in your body. Increase immunity the healthy way Many products on store shelves claim to boost or support immunity. Immune system and age As we age, our immune response capability becomes reduced, which in turn contributes to more infections and more cancer.

Diet and your immune system Like any fighting force, the immune system army marches on its stomach. Improve immunity with herbs and supplements?

Stress and immune function Modern medicine has come to appreciate the closely linked relationship of mind and body. Does being cold give you a weak immune system? Exercise: Good or bad for immunity? Share This Page Share this page to Facebook Share this page to Twitter Share this page via Email.

Print This Page Click to Print. Related Content. Staying Healthy. You might also be interested in…. This gating mechanism is called cationic Figure 2. The relationship between nutrition and the immune system.

Micronutrients like Vitamin A and Zinc can promote cell proliferation; inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells NF-κB pathway; decrease the pro-inflammatory cytokines IL-1β and tumor necrosis factor-α TNF-α ; regulate the Th17 and Th9 cell differentiation; initiate the growth Treg cell population.

Indoleamine 2,3-dioxygenase 1 IDO1 is a powerful immunosuppressive enzyme involved in the catalysis of the first and rate limiting step of L-tryptophan catabolism. IDO1 depletes L-tryptophan storage and induces the production of immunoregulatory molecules interferon-γ IFN-γ , tumor-necrosis factor TNF and IL-1 High IDO1 expression and catalytic activity occur in dendritic cells DCs — in response to IFN-γ In immune tolerance, arginine catabolism may determine the initiation of the nuclear factor kappa-light-chain-enhancer of activated B cells NF-κB pathway.

Arginine may also provide a substrate for the growth and survival of the cells and concomitantly exerts a key role in differentiation and appropriate gene expression The decline of protein metabolism that is related to the diminishing concentration of certain amino acids, leads to the endoplasmic reticulum ER stress.

As a result, the T cells which produce pro-inflammatory cytokines are activated The deficiency of Arg is correlated with reduced T cell ability to trigger tumor immunity Vitamins and minerals such as vitamin A and Zn in addition to their involvement in cell division and proliferation Figure 2 are involved in immune-modulation.

For example, the rate of antibody synthesis can be modified by these micronutrients Vitamin A Figure 2 , which is involved in biosynthesis of carotenoids and retinyl esters, molecules well known to affect appropriate immune function It can also exert a role as transcription factor if it is bound to retinoic acid receptors RARs.

As a result, it can be responsible for lipid homeostasis, cell division, growth, and specialization by regulating the expression of certain specific genes Vitamin A deficiency has repercussions on immune functions, such as impaired neutrophil function, suppressing the activity of natural killer NK cells, as well as a decline in their number, and damaged capacity of phagocytosing of macrophages.

In addition, it may affect the growth and differentiation of B cells 2. In this way, the predisposition for infection disease can increase Zinc represents another example of the micronutrient group. The transcription factor NF-κB 23 can be inhibited by Zinc Figure 2. Also, the pro-inflammatory cytokines IL-1β and tumor necrosis factor TNF-α production 24 may be repressed, as a result of modulation of the Toll-Like Receptor 4 TLR4 signaling pathway.

Moreover, the pro-inflammatory specific Th17 and Th9 cell differentiation pathway 25 , 26 can be moderated by Zn. Treg cell population can be increased after Zinc administration 27 , 28 thus Zn is considered an important factor for immune cell development.

Specific effects include impaired lymphocyte proliferation, Delayed-Type Hypersensitivity DTH response, and natural killer NK cell activity 29 — As we mentioned before, there are strong and dynamic relationships between nutrition and the immune system, which are important for maintaining good health.

We will discuss further in more details the role of specific nutrients in the mediation of pro-and anti-inflammatory responses. The immune system consists of cells belonging to the two types of immune responses, i. Once the pathogens enter the body, the first reaction is mediated by the cells belonging to the innate immunity system.

This system consists phagocytes, dendritic cells, eosinophils, neutrophils, mast cells, and some additional cells In this case, the immune response acts quickly. The difference between the innate immunity system and the adaptive response is that the former is unspecialized and less efficient In contrast, the adaptive response is capable to recognize each pathogen, and furthermore, remember if it has been encountered before, therefore T cells being the most important in antigen identification.

They are also involved in immune response regulation. Furthermore, in the function of type cytokines produce by them, there are some subtypes of T helper cells: Th1, Th2, Th17 13 , Th1 cells are responsible for fighting against bacteria and viruses. The main role of these cells is to produce Interferon γ IFNγ and IL IFNγ, like IL2, is a cytokine created by both immune adaptive and innate cells like Th1, T8 lymphocytes as well as innate lymphoid cells and NK At the same time, the immune function is activated by Th2 cells.

They are capable to produce other interleukins ILs Interestingly, the other immunity regulatory T cells are involved in the suppression or the blockage of cytokine secretion by the immune response In light of this information, they have a crucial role in peripheral tolerance through the initiation and continuance of this stage B lymphocytes, which also belong to the adaptive immune system are involved in the synthesis of antibodies.

Similar to T cells, they have the ability to specifically respond to each antigen Antigens can actually produce damage to the tissue that they attack.

It makes sense that the pathogens in the tissues and around this region promote an inflammatory response. Its main role is to repair the damage tissue in certain ways that can eliminate the antigens and their effects, and decrease their extension After that this process takes place, some physiological changes occur which are responsible for increasing the phagocytes number in the place where this process is happening.

As a result, pro-and anti-inflammatory cytokines, prostaglandins, and complements are delivered, especially through the activation of phagocytes. All these changes cause the growth of the inflammatory response 1.

Based on the knowledge of which cells are involved in each inflammatory response pathway, it is now feasible to shed light on the effects of specific nutrients on each of these processes.

To this end, we selected to discuss the influence of certain vitamins such as: A, B1, B2, B3, B12, C, and D, minerals like: Zinc, and Selenium as well as certain amino acids such as arginine and tryptophan and some fatty acids.

Vitamin A plays an essential role in the regulation of innate and cell-mediated immunity, and antibody responsiveness through the activity of either all-trans retinoic acid, 9-cis retinoic acid or other metabolites and nuclear retinoic acid receptors Vitamin A and associated retinoid metabolites exert an important regulatory function of the immune system.

This essential role is evidenced when Vitamin A is deficient and an augmented susceptibility to infections is evident Vitamin A deficiency affects processes related to appropriate cytokines release and antibody production. Additionally, vitamin A deficiency is associated with a reduced production of natural killer cells, monocytes or macrophages, and impaired maturation and proliferation of T- and β-lymphocytes.

Vitamin A deficiency impairs innate immunity by impeding normal regeneration of mucosal barriers damaged by infection, and by diminishing the function of neutrophils, macrophages, and natural kill cells.

Vitamin A supplementation cuts down morbidity and mortality in various infectious diseases In the case of vitamin A deficiency, the integrity of the mucosal epithelium is altered, resulting in enhanced accessibility to various pathogens to the gastrointestinal tracts and other organs, being children the most affected population In children, severe vitamin A deficiency causes almost the disappearance of goblet cells present in the upper layer of the epithelial line, therefore the production of mucus by these cells is compromised, and bacterial adherence to the epithelial lining is reinforced thus becoming the major factor for the development of the bacterial disease Additionally, vitamin A deficiency is associated with diminished phagocytic activity and macrophage oxidative breakdown that takes place during the process of inflammation along with a reduction in the number of natural killer NK cells It has been demonstrated that vitamin A Tab.

Thus, vitamin A is capable of promoting the Th2 anti-inflammatory response by repression of IL and IFNγ which are synthesized by Th1 lymphocytes In addition, some studies suggest a positive relationship between vitamin A and mitogen-induced pro-inflammatory cytokine IFN-γ and anti-inflammatory cytokine IL It is important to know that retinol, retinoic acid RA , and retinal are the three forms of vitamin A.

It has been shown that RA is involved in a lot of biological activities According to Rampal et al. When it comes to hypovitaminosis in children, vitamin A administration reduces mortality caused by diarrheal diseases Vitamin A might be responsible for antitumor effects on human pancreatic cell lines In metastasis of renal carcinoma, it seems that all-trans-RA ATRA have a similar effect ATRA represents a nutrient that is required in small quantities and it is synthesized in the human body from the A vitamin In acute promyelocytic leukemia APL , ATRA is utilized as a very efficient therapeutic agent.

Furthermore, together with arsenic trioxide ATO , they are able to increase life expectancy. As a result, vitamin A is capable of reducing some negative chemotherapy effects The next question worth asking would be whether there are more nutrients involved in mediating pro- and anti-inflammatory responses.

The group of B-vitamins comprise eight water soluble vitamins in charged to carry out essential, inter-related roles for appropriate cellular functioning.

These vitamins act as efficient co-enzymes in a vast array of catabolic and anabolic enzymatic reactions and they are essential cofactors for many important cellular metabolic pathways.

We therefore cannot refer to life or to cellular life without referring to the B vitamins. However, an important aspect to be considered in terms of B vitamins, is that when it comes to the human body, an important source of vitamins B is determined by the activity of the gut microbiota except for some that may be ingested by the diet.

The absorption of B vitamins takes place in two different intestinal locations, the large and small intestines. The large intestine represents the main absorption place for most bacterial-produced B vitamins.

At the same time, the small intestine represents the place where dietary B vitamins are absorbed. It is tentatively to surmise whether two specific immune responses result from the two different absorption places We surmise that the immune activities at the two specific locations are different since the population of gut immune cells are different Vitamin B1 or Thiamine Table 1 , exerts an anti-oxidative role due to its protective action on sulfhydryl groups from the surface of neutrophils.

As a result, the synthesis of cytokines from macrophages is blocked furthermore. The NF-κB pathway involved in the control of the oxidative stress, is prevented by Thiamine.

This role is highlighted by suppressing the phosphorylation and catabolism of inhibitory kappa B IκB , which subsequently inhibits the nuclear translocation of the transcription factor-sensitive redox NF-κB 58 , These properties are a result of its function in maintaining an equilibrium between glycolysis and the TCA cycle The TCA energy cycle represents the main source of naïve T cells, rest macrophages, and T-regulatory cells.

Interestingly, activated T helper cells need energy from aerobic glycolysis because the amount of energy from TCA is not sufficient Due to the significant effects of thiamine on these pathways, B1 deficiencies have so significant side effects.

One of the side effects is linked to the stimulation of IL-1, IL-6, and TNF-α pro-inflammatory cytokines expression and neuro-inflammation. Finally, neuronal death may occur due to the inhibition of CD 40 and CD 40L regulation It was observed that B1 could be used in the treatment of neurodegenerative diseases through its involvement in the suppression of the pro-oxidative activity of microglial cells Additionally, in regards to B vitamins, we should pay attention to their role in oncogenesis and more over is extremely important to clearly make a distinction between healthy and sick individuals.

Some speculations exist regarding the role of B1 in cancer due to its involvement as a cofactor in proliferation and energy pathways that are essential in the development of tumor cells.

Table 1. Vitamins with pro-and anti-inflammatory effects as well as pro-tumor and anti-tumor effects. Riboflavin, or vitamin B2 is crucial for energy metabolism through its function as a cofactor It also plays an important role as an anti-inflammatory and anti-oxidant modulator, especially in lungs 68 , Some specific aspects regarding the link between major histocompatibility complex MHC and B2 bacterial compounds are worth mentioning.

This function on the innate mucosal results in the stimulation of invariant T cells. Riboflavin and its precursors selectively activate mucosa-associated invariant T cells MAIT that represent the largest population of innate-like T cells in humans.

Their synthesis as well as the link with the major histocompatibility complex through the major histocompatibility complex-protein MR1 are not fully understood.

It was observed that the activation of MAIT cells is dependent on genes that encode enzymes responsible for the formation of intermediate compounds in the synthesis of bacterial riboflavin. These types of cells are known for their function in the inflammation and defense activity in gut mucosal due to their production of IL and IFN-γ The proliferation of neutrophils and monocytes as well as the stimulation of macrophages and neutrophils activities might be boosted by the activity of riboflavin 72 , The catabolism of inhibitory kappa B IκB is responsible for the activation of the pro-inflammatory factor Kappa B NF-κB.

Following this catabolic pathway, the inflammatory signaling pathway becomes activated. At the end of this signaling pathway, the activation of pro-inflammatory cytokines, such as TNF-α and ILs, takes place.

In this signaling process vitamin B2, act as an anti-inflammatory suppressor and it may block the activation of the NF-κB Furthermore, through the overexpression of catalase and nitric oxide synthase vitamin B2 could reduce oxidative stress Vitamin B3, niacin Table 1 is known as NADP and NAD precursor.

Similarly, to all B vitamins, it is a cofactor for a wide variety of enzymes involved in several metabolic pathways.

In contrast to other B vitamin groups, human cells can synthesize NADP and NAD cofactors through independent pathways. From a biochemical point of view, niacin and the resulting cofactors are involved in redox reactions. NAD is responsible for genomic equilibrium and epigenetic regulation may represent its mechanism of action Additionally, there is a positive correlation between high concentrations of NAD and the blockage of ROS synthesis Furthermore, NAD can be considered an anti-inflammatory micronutrient due to its inhibitory and deacetylation actions, which were observed in the NF-κB pathway Also, it has an inhibitory effect on inflammatory cytokines as well as on animal tumor cells NAD is also considered an efficient anti-inflammatory component since it induces the reduction of certain cytokines released from alveolar macrophages B12, cobalamin Table 1 affects pro- and anti-inflammatory responses.

A negative correlation has been observed between vitamin B12 and TNF-α It has been demonstrated that an increase of TNF-α induce the exhaustion of antioxidants involved in the defense against free radicals As a result, pro-inflammatory cytokines and some other pro-inflammatory compounds are activated Additionally, in these patients, the activity of NK cells is decreased Interestingly, hyperhomocysteinemia is the result of vitamin B12 deficiency 85 , leading to chronic diseases such as insulin resistance 86 and coronary heart disease 87 through the expansion of inflammatory processes.

Since vitamin B12 deficiency is associated with abnormal TNF-α activity, it can also lead to insulin resistance 88 , Regarding cancer activity, a study by Cheng et al. In the case of lung cancer, B12 administration was not considered a risk factor On the contrary, a higher intake of B12 was considered dangerous for many types of cancer as indicated in a big meta-analysis of cancer patients Vitamin C Table 1 , is considered an essential micronutrient 93 in humans since they cannot synthesize it.

Human absorption of vitamin C is higher compared to other species that are capable to synthesized it 94 , Vitamin C is involved in the modulation of a wide variety of immune functions and play a role as a regulator of cell-signaling. Vitamin C is also, involved in gene transcription as well as in hydroxylation reactions Through its main function as an antioxidant, it became capable to defend the body against reactive oxygen species that are the result of the activity of toxins and pollution Vitamin C is responsible for discontinuing the action of the pro-inflammatory cytokines and inhibiting the initiation of the NF-κB reaction In peripheral blood cultures that are stimulated with LPS lipopolysaccharide , after vitamin C administration, an enhancement of IL and a reduction of TNF-α and IFN-γ has been observed Moreover, as a result of ROS accumulation in microbial infections, vitamin C causes neutrophils displacement into infected sites Additionally, vitamin C might be useful as a cofactor in the synthesis pathways for vasopressin and norepinephrine in severe infections.

This has a noticeable effect on the infection response of the cardiovascular system when the pathological state represents a danger In this case, the effect is more pronounced if vitamin C is administrated in combination with vitamin E Ellulu et al. Vitamin C is also involved in the regulation of hypoxia-inducible factor 1-alpha HIF-1α activity, which makes neutrophil viability under hypoxic conditions possible , and in this way, neutrophil apoptosis is delayed Furthermore, it is thought that vitamin C is involved in the fight against tumor cells through the increase in the number of NK cells Vitamin D, Table 1 exerts many anti-inflammatory roles since receptors to this vitamin are expressed in different organs throughout the human body.

The best known and established effects are linked to mineral and bone metabolism Wöbke et al. Vitamin D binds its receptors VDR resulting in a complex of vitamin D-VDR that may contribute to the formation of homodimer with an additional VDR or formation of a heterodimer compound with the nuclear retinoid X receptor RXR.

Also, the nuclear role is demonstrated following the formation of heterodimers with steroid hormone receptors From the immunological regulatory aspect, vitamin D can block the secretion of the pro-inflammatory cytokines IL-6 or TNFα in monocytes Additionally, the same effect has been observed in prostate cells These effects are caused by the inhibition on P MAP kinase a subclass of mitogen-activated protein kinase as a response to pro-inflammatory cytokines The results are closely related to the specificity of cells, their response, and effects of triggering factors Thus, vitamin D may be considered an anti-inflammatory micronutrient as a result of these interactions.

The vitamin D bound VDR becomes active and thus exerts inhibitory effects on NF-κB, which is also a heterodimer compound Additionally, some studies suggest anti-inflammatory role of D vitamin is mediated also through the inhibition of specific pro-inflammatory Th1 cell cytokines such as TNF-α, IFN-γ, IL-6, IL-2, and IL , Additionally, vitamin D is capable of increasing the concentration of cytokines such as IL, IL-4, and IL-5 as a result of an increase in the activity of Th2 cells At the same time, it may induce the amplification of Treg cells as well as a reduction of the number of Th17 cells , From a medical perspective, vitamin D has an important effect on the lung defense system against microbial pathogens.

This function represents the result of the antimicrobial peptides activation expression in monocytes, epithelial cells lining the respiratory tract, monocytes, neutrophils, and NK cells Lower levels of vitamin D in the serum are correlated with higher infection risks Particularly, the administration of vitamin D induce a decline in acute respiratory infections The anti-cancer effect of vitamin D in tumor cells is mediated by calcitriol which is the biologically active molecule of vitamin D The stimulation of apoptosis, the suppression of cancer cell proliferation, and associated delayed tumor development in cancer are the main effects mediated by calcitriol , At a molecular level, through the suppression of pro-inflammatory cytokines and prostaglandins PG activity as well as by preventing the NF-κB signaling pathway, calcitriol is considered an anti-inflammatory nutrient From this point of view, calcitriol may be used as a preventive and therapeutic agent in cancer When inflammatory cytokines are maintained at a high level, chronic inflammation takes place This process is closely linked to the action of some minerals.

In this way, it is important to test what is the role of Zinc in this essential process. The process is mediated Table 2 by the activity of several signaling pathways that are triggered due to the action of some changes produced by antigens and their metabolites.

The main compound involved in inflammatory responses as a result of its role in cell proliferation, cell apoptosis, and the release of certain cytokines like IL-6, IL-8, and IL-1β are mediated by the activity of the NF-κB factor The role of Zinc in this regard is controversial.

In vitro studies demonstrate that the zinc effects can be either anti-or-pro- inflammatory From one side the apoptosis effect is evident following the binding of the chelator and heavy metals From the other side, other studies indicate a strong relationship between the initiation of LPS-induced NF-κB and zinc Moreover, after a decline in the release of IL-1β, zinc is able to inhibit pro-inflammatory actions Furthermore, it has been reported that cytokine synthesis is dependent on Zinc status and this is closely related to chronic inflammation.

In this regard, it has been observed that obese people having low zinc plasma concentrations over-express IL-1β, IL-1α and IL-6 genes Zinc exerts beneficial effects on the proliferation and differentiation of T lymphocytes The strong relation between a high number of cytokines and the decline in zinc plasma levels in infections and trauma-associated conditions has been demonstrated in cross-sectional studies.

In patients with severe head injuries, upregulated cytokine production genes have been observed In addition, the production of cytokines is elevated in patients that are in a critical state due to their decrease in plasma zinc concentration Moreover, zinc antioxidant effects help the body to defend against reactive nitrogen species RNS and reactive oxygen species ROS Zinc also can be capable to support the integrity of skin and the mucous membrane In this regard, it was observed that deficiency of this mineral negatively impacts health by decreasing resistance to infectious diseases, dermatitis, growth diseases, and genetic disorders Another crucial micronutrient is selenium Table 2 , which is involved in the functioning of the thyroid metabolism and the cardiovascular system as well as in ensuring a functional immune system and preventing cancer.

From the cellular point of view, there are still discrepancies regarding the exact dose that may be translated into deficiency or toxicity, even if these stages do not commonly take place in the human body , It is well known that when selenium is present within the amino acid selenocysteine is able to control certain metabolic reactions that may lead to lipoxygenase synthesis that finally, can be involved in the production of inflammatory mediators , In mice, selenium, due to stimulation of T cell receptor complexes TCR activity and conversion of Th1 from T0 cells, may improve the regulation of cellular immunity Selenium can also contribute to the defense against pathogens as a result of its effects on redox signaling activities It was recently demonstrated that in COVID patients, selenium together with zinc exert a protective role and they are associated with a higher chance of survival During vaccination against COVID, it has been demonstrated that the response may increase after selenium administration as well as the increase of titers antibodies.

It is assumed that selenium may act as a cofactor in immunity response that is mediated by the vaccine Additionally, in women that are infertile as a result of polycystic ovary syndrome, to whom fertilization in vitro has been recommended, a decline in IL-1 and TNF-α gene expression was observed as a result of selenium treatment This effect suggests that selenium has an anti-inflammatory role in the human body.

Furthermore, in patients with cancer, the supplementation of selenium increased antibody titers of IgA and IgG as well as the number of neutrophils Selenium is capable to enhance the immune response of Th1 cells and the stimulation of T cells.

Selenium has a positive relationship with the number of B cells. The innate immune system may be strengthened after selenium administration. A similar effect has been observed on cellular immunity Increased titers of antibodies were measured due to selenium supplements that can cause an enhancement of vaccine effects , In the brain, both neurogenesis and hippocampal neural precursor cells are increased after selenium infusion Besides micronutrients, macronutrients, such as proteins and amino acids, also play an important role in the activity of the immune system.

Proteins are formed from amino acids that are essential in the construction of other proteins among which antibodies and cytokines that are typical proteins belonging to the immune system Arginine Table 3 contribute with the production of nitric oxide in macrophage cells.

Nitric oxide NO resulting from arginine under the action of nitric oxide synthase iNOS determines the cytotoxicity of macrophages in the fight against antigens such as pathogenic bacteria and parasites.

Moreover, M1 macrophages use arginine to produce NO Even though that arginine was initially considered a non-essential amino acid , after one decade, some papers have proven that arginine is essential for embryonic outliving, ontogenetic fetal development, and for constant hemodynamics and vascular parameters Moreover, the induction of the NF-κB pathway has been linked to the arginine degradation pathway As we presented previously, arginine through cations dependent mechanism can improve the release of insulin from pancreatic β cells.

However, clinical evaluations have shown that the beneficial effects of arginine administration are limited, probably due to the fact that it is very quickly transformed into ornithine or citrulline in epithelial cells In addition, the polyamines, compounds which are also derived from arginine degradation, are involved in balanced levels of membrane, mRNA and DNA.

Thus polyamines are capable to control the proliferation of cells In vitro , polyamines can modify the inflammatory process Furthermore, it has been demonstrated that higher concentrations of intracellular polyamines may change the in vitro cytotoxicity regulated by macrophage cells The inflammation regulation and identification of pathogens are closely related to polyamines through their binding manner to receptor-ligand complexes In an in vitro intestinal system in Caco-2 cells, arginine is able to induce the inhibition of IL-1β-mediated NF-κB pathway However, the mechanism of reducing the inflammatory pathways is still unknown.

Perhaps, it is linked to the activity of Arginase-1 Arg-1 , which, in this case, is stimulated by L-arginine as a substrate. The arginase-1 is an enzyme involved in the end of the urea cycle with the aim of forming l-ornithine and urea from l-arginine Some studies suggest that the Arg-1 has positive effects in certain inflammatory diseases through an anti-inflammatory action , In contrast, there are studies which have shown that higher metabolism of arginine in tumors cells, together with their particular environment, create conditions that are intermediary, and at the same time, crucial for the maintenance and development of cancer cells.

The result of these actions is translated into proper immunosuppression , One thing is certain, that the relationship between arginine and cancer cells is controversial. On the one hand there is data suggesting that arginine deprivation is correlated with a delay in the development of some tumor cells On the other hand, arginine can have antitumoral actions which are observed through the enhancement of immune response Furthermore, Al-Koussa et al.

In this sense, some authors suggest that arginine deprivation may downregulate the migration of cancer cells.

In physiological conditions, the movement process is useful for embryonic growth and immune function. But when it comes to cancer cells, things are different. This happens since certain kinds of cancer cells can use this property with the aim to stimulate metastasis , Therefore, arginine deprivation in cancer cells is capable of reducing metastatic activity Unfortunately, the exact mechanism remains unknown.

Tryptophan Trp is clearly essential for the activity of the immune system Table 3. Since Trp is necessary for protein synthesis, it becomes to be indispensable for cell division and development Since Trp is not synthesized by the human body, it is required to be obtained from the diet Trp serves as a substrate for the biosynthesis and formation of serotonin 5-HT , kynurenine Kyn , and indoles The most useful and active Trp metabolism is the Kyn path which is related to the formation of nicotinamide adenine dinucleotide NAD and kynurenic acid.

Of course, similarly to all pathways, this type takes place due to the involvement of two types of enzymes indoleamine 2,3-dioxygenase IDO and IDO2 and tryptophan 2,3-dioxygenase TDO , Additionaly to the Trp metabolism, we brought information on its role in the regulation of inflammation through its initiators, starting with IDO, which exerts an insignificant effect on healthy and normal conditions.

Things are changed by some cytokines, including interferons which represent the result of the triggered inflammatory process The highly potent and amply used cytokine interferon-gamma IFN-γ.

It is linked to the promotor-region of IDO and it is capable to express itself in many types of cells. However, the highest expressive grade is found in dendritic cells and macrophages, but there are some other places where it was manifest such as epithelial and connective tissues — As we discussed before, inflammation and chronic immune tolerance are regulated by Trp biochemistry.

In tumor cells, an important step for metabolic reprogramming is represented by amino acids metabolism. Some authors suggest that, in the case of glioma, there is a strong link between the two because the metabolic amino acid pathway could be used as a predictor for survival as well as certain clinical characteristics As we mentioned before, amino acids and their metabolites are responsible for both controlling malignant cells as well as for changing the microenvironment.

In this way, the results are translated into the improvement of immunosuppression and malignancy state Kynurenine metabolism is capable of stimulating an oxidative stress resistance pathway, and, in this way, creating an opportunity to make changes in the tumor microenvironment that helps the development of the tumor However, another metabolite of tryptophan; 5-methoxytryptophan 5-MTP has the ability to suppress the development of tumors and the displacement of cancer cells in other tissues.

Wu et al. This type of inflammation-associated enzyme is very abundant in tumor cells and also contributes to development process of cancer Cholesterol has a key function on cellular membranes functionality, especially in the plasma membrane of the cell where it is found at higher concentrations.

Its special location at the lipid bilayer allows optimal interaction with other lipids and displays a significant role in membrane fluidity. Cholesterol points its structure mainly into the lipid bilayer leaving only the hydroxyl group facing the external environment.

Thus, the steroid rings are in close vicinity to the hydrocarbon chains of adjacent lipids Cholesterol is vital for the many physiological roles that the plasma membrane is involved. The cells keep their lipid bilayer appropriate functionality due to cholesterol molecules, otherwise, microenvironment, endocytosis, signaling pathways, as well as other functions, would be altered.

Cholesterol is involved in membrane integrity and it is responsible for receptors arrangement and bilayer fluidity , For a better understanding of the information provided later-on, we will describe the cholesterol synthesis and pathway in a schematic frame.

Cholesterol biosynthesis of is characterized by a complex pathway, nonetheless the pathways involved have been clearly elucidated Its synthesis involves more than 20 metabolic-specific actions, which include enzymatic reactions belonging to the mevalonate pathway of and additional synthesis pathway of cholesterol.

Enzymes involved in cholesterol biosynthesis are mainly detected in the membranes of the endoplasmic reticulum ER. These enzymes are the target of several molecular reactions which, closely controlled in order to not allow cellular damage , However, cholesterol is non-uniformly disseminated in the plasmalemma.

It has been observed that each pool is corresponded to an exclusive function in the plasma membrane physiology — It is clear that cholesterol equilibrium involves a transport mechanism by virtue of the concentration gradient from high concentration cholesterol places to regions where cholesterol has been lost or has a low level.

The transport of cholesterol is dependent on proteins due to its hydrophobic conformation, thus it cannot be transported through the blood. Thus cholesterol binds to different proteins and forms distinct lipoprotein compounds such as low-density LDL and high-density HDL.

As expected, regulatory mechanisms for the formation of each lipoprotein are specific The surplus of cholesterol can be transported through the efflux process or deposited as intracellular lipid droplets because of the incapacity of most human cells to efficiently degrade it.

The deposition of lipid droplet plaques in the bloodstream causes the release of inflammatory cytokines which create later an inflammatory process.

The consequence of this event is associated with inflammation triggered by the cytokine interleukin-1β IL-1β Furthermore, IL-1β is considered an important marker in the inflammatory process The cholesterol signaling pathway plays a role in the immune response we therefore will highlight these pathways.

Sterol response element-binding protein SREBP exerts an essential role in the signaling pathway of cholesterol Figure 3. Normally, these proteins are located in the membrane of the ER, which is capable of binding with additional two complex proteins such as the cleavage-activating protein and generating SCAP and the insulin-inducible genes INSIGs The shift of SCAP from ER to the Golgi apparatus plays a key role in its activity.

SREBPs proteins are composed of three variants SREBP1a, SREBP1c, and SREBP2, being the latter the most important SREBP2 is a protein complex structure that seems to be capable to regulate the expression of all the enzymes that are involved in cholesterol biosynthesis Its most important activity is its specific response to high concentration of sterols which are able to efficiently induce a decrease in cholesterol synthesis.

SREBP2 fulfills its function when the sterols concentration decrease. This change in sterol concentration due to SREBP2 activity will generate afterward the shifting the complex SCAP from ER to the Golgi apparatus In this organelle, the SCAP molecule is changed Once the SCAP reaches the Golgi apparatus, proteases sit 1 and 2 cut this complex Figure 3.

As a result, the transcription factor TF is created and stimulated Then the TF enters the nucleus where it is responsible for the regulation of the cholesterol synthetic pathway enzymes All these pathways may stimulate the flux of cholesterol biosynthesis , Figure 3.

Schematic frame of cholesterol biosynthesis. In the signaling pathway of cholesterol, sterol response element-binding protein SREBP2 has an essential role. SREBP2 is located in RE, where it forms a complex with the protein like cleavage-activating protein and generating SCAP ; Its most important activity is to reduce the cellular cholesterol concentration when this is higher.

Then, SCAP is shifted from ER to the Golgi apparatus. Once SCAP reaches the Golgi apparatus, proteases sit 1 and 2 digest this complex and subsequently, the transcription factor TF is formed and is activated Then, TF moves into the nucleus where it becomes active and control the transcription of the enzymes of cholesterol biosynthetic pathway.

Additionally, it is important to mention that all cholesterol associated pathways involving synthesis, influx, efflux, and esterification take place through mechanisms closely related to each other allowing well-adjusted whole mechanistic biochemical pathways.

All these tightly controlled mechanisms highlight the crucial role of cholesterol in life span, and clarify the potential risks when the concentrations are diverted from the optimal range. In this regards, Luo et al. Moreover, in several diseases such as various types of cancer, infections and allergies, cholesterol biochemical equilibrium is severely altered through inflammation-associated consequences.

Regarding the relationship between cholesterol and macrophages, counter-regulatory mechanisms oppose macrophage inflammation and at the same time cholesterol cellular accumulation. When the concentration of cellular cholesterol increases, specific sterols are formed.

With their help, the transcription factors liver X receptor LXR —retinoid X receptor RXR are activated. These heterodimers have anti-inflammatory roles, including controlling the expression of ATP-binding cassette transporters ABC transporters , which are ABC subfamily A member 1 ABCA1 and ABCG1.

They are also involved in stimulating the efflux of cholesterol from macrophages. In this way, they can suppress the activation of TLR signaling given by the increased intracellular cholesterol concentration. When TLRs are activated, LXR genes are inhibited, thus decreasing the cholesterol efflux from macrophages.

Activation of cholesterol efflux by ABCA1 and ABCG1 is via apolipoprotein A1 APOA1 , forming HDL and initiating the process of transporting cholesterol back to the liver via blood vessels and lymphatics.

Therefore, as a way of amplifying the inflammatory response, the immune system can alter cholesterol homeostasis When the control of cholesterol biosynthesis is disturbed resulting in high cholesterol levels it can be translated into metabolic diseases such as atherosclerosis and dyslipidemia Figure 4.

In some of these cases, both the innate and the adaptive immune functions have the ability to regulate this phenomenon In this way, ApoB-containing lipoproteins are originated immediately after atherosclerosis damages.

These are generated, developed and stored in the endothelial compartment Interestingly, these molecules exert pro-inflammatory effects through acetylation, oxidation, and especially induce aggregation with additional molecules The modifications provoked by the accumulation of ApoB-containing lipoproteins Figure 4 in endothelial location results in the growth of adherence, hold, and mobility in this place of immune cells In summary, the inflammation is supported through the generation of ROS and certain cytokines such as TNF α, IL6, and IL 1β , At the same time, Th17 and Th1 are involved in the pro-inflammatory process , Figure 4.

Cholesterol rate in the modulation of immune function. Polyunsaturated fatty acids PUFAs are essential fatty acids that contain more than one double bond in their backbone. PUFAs are divided into two main groups: omega-3 and omega The structural chemical difference between the two groups is represented by the location of the cis double bonds Together with cholesterol, PUFAs are essential for cell membrane integrity, development and maintenance in the homeostasis of cell function.

Moreover, they are used by certain structures in cells and they stimulate cell proliferation In this way, the sensitivity of the immune function can be modified The most representative polyunsaturated fatty acids are eicosapentaenoic acid EPA , alpha-linolenic acid ALA , and docosahexaenoic acid DHA , all defined as omega-3 fatty acids They are very intensively studied since they are involved in many essential vital activities and more interestingly in immunomodulation pathways.

In addition, the ALA is important due to the fact that it is a precursor of other fatty acids Omega-3 PUFAs have a role in immunomodulation by decreasing pro-inflammatory eicosanoids. They represent a substrate for AA cascade enzymes, in this way certain prostanoids and leukotrienes are produced.

Some lipid mediators such as maresins have omega-3 PUFAs as precursors. They promote the ending of the inflammatory process In human breast cancer cells ALA produce inhibition of cell proliferation and activate apoptosis In diabetic rats, ALA increases insulin sensitivity and restored lipid and glucose metabolic abnormalities ALA is considered essential because it cannot be synthesized by the human body.

In these regards, from the omega-6 group, an essential is considered linoleic acid LA. Following LA ingestion, this fatty acid is quickly converted into arachidonic acid ARA , which is responsible for the fluidity as well as the flexibility of the cell membrane.

Free ARA is involved in the modulation of ion channels, enzymes, and receptors through stimulation or suppression of their function Free unesterified ARA exerts antitumoral activity in vitro as well in vivo.

It can be used as an anti-cancer drug. Moreover, ARA can cause the death of tumor cells through the suppression of proliferation determining in this way, the death via stimulation of neutral sphingomyelinase nSMase mechanism Omega-3, as well as omega-6, participate in immunomodulation.

According to Simonetto et al. Omega-3 from the PUFAs group is involved in anti-inflammatory reactions through the inhibition of ARA from the membrane, which is the main precursor for pro-inflammatory eicosanoids They are capable to modulate immune and inflammatory responses through intensity and duration.

On the one hand, pro-inflammatory effects are linked to fever, vasodilatation and intensification of pain. On the other hand, they could have anti-inflammatory effects by blocking natural killer activity and lymphocyte proliferation.

Also, they are capable to inhibit IL-6, IL-2, and TNF-α However, most importantly is the ratio between the 2 groups of PUFAs. She additionally concluded that a lower ratio is associated with a general decrease in very common chronic diseases in the Western society As mentioned throughout all this review, there is a strong and dynamic link between nutrition and immune function, as a direct consequence of the modulation of the immune function through the pro-inflammatory and anti-inflammatory effects of certain nutrients including cholesterol who exerts a crucial impact in these complex biological settings and holds a great capacity to regulate immune function, tightly related to its concentration.

Certain micronutrients mentioned in this review: A, B1, B2, B3, B12, C, and D vitamins and minerals such as Zinc, and Selenium affect innate as well as adaptive immunity specifically through genetic, biochemical, and signaling pathways.

All these may be translated into the modulation of proliferation, cell division, cell mobilization, and physiology of immune cells.

Additionally, we provide evidence that some macro-nutrients such as tryptophan, arginine, cholesterol and PUFAs may be involved in the prevention and therapy of some immune-related diseases. Also, is very important to note that some vitamins such as A and D are fat soluble That is why when we consume fat-free light products, we are practically deprived of fat-soluble vitamins and the immune function can be affected.

So, western diets should contain the accurate class of healthy fats, such as PUFAs, in a correct ratio, otherwise the edible products become poor in nutrients.

A good example is the Mediterranean diet. In addition, the fats are much more satiating and give food a much better taste We highlight the difference in response to micro- and macro nutrients between healthy and sick population.

We provided evidence that the response in pathophysiologic stages are very different to normal physiologic stages additionally to interindividual variations. As a result, the immune response is different and variable 11 , , We also presented some evidences and speculations on the roles of some vitamins, as well as certain amino acids, in cancer patients, due to their involvement as cofactors in proliferation and energy-related pathways finally leading to the development of tumor cells.

We foresee that further research needs to be done in order to clearly distinguish the possible oncogenic effects of thiamin, cobalamin, and arginine 58 , We additionally provide evidence that the inflammatory responses in general, and the changes in immune functions are modified by the lack of an accurate cholesterol metabolism.

The alterations in the cholesterol biosynthetic pathway may have both positive and negative immune health-related repercussions. Alterations in the cholesterol biosynthetic pathway may directly impinge and interfere with antimicrobial responses, as well as with antiviral effects Thus, an immediate action is required in order to adjust the cholesterol metabolism.

Moreover, we refer to the bioavailability of macro- and micro nutrients from food. We ask whether foods contain enough amounts of macro- and micro nutrients. Does the soil and then the foods today still have the same nutritional value as before for example in fruits and vegetables?

These led us to question under what conditions can artificial supplementation with macro or micronutrients be done?

And how should be done? Should they be taken alone or as a complex? The question is the synergistic and complementary action of taking supplements of vitamin complexes, results in a better or worst outcome?

We surmise that the administration of nutrients micro and macro would exert distinct effects on each person. We know that each individual is different, and thus their immune responses will differ from each other.

To add more complexity, we referred also to the absorption capability of nutrients in the different compartments of the digestive system.

We finally provided evidence that for each stage of the immune process, both micro and macronutrients are needed for the proper functioning of this important system.

BS and CM wrote the manuscript after a rigorous investigation, interpretation, systematization, and conceptualization of current data. Both authors agreed to publish the present manuscript, contributed to the article, and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Gombart A, Pierre A, Maggini S. A review of micronutrients and the immune system—working in harmony to reduce the risk of infection.

doi: PubMed Abstract CrossRef Full Text Google Scholar. Maggini S, Pierre A, Calder P. Immune function and micronutrient requirements change over the life course.

Wu D, Lewis E, Pae M, Meydani S. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Front Immunol. Koithan M, Devika J. New approaches to nutritional therapy. J Nurse Practit. Mullero K. Malnutrition and health in developing countries.

Can Med Assoc J. World Health Organization. Joint Statement on the Management of Acute Diarrhoea. Geneva: World Health Organization Google Scholar. Adepoju A, Allen S. Malnutrition in developing countries: nutrition disorders, a leading cause of ill health in the world today.

Paediatr Child Health. CrossRef Full Text Google Scholar. Popkin B, Adair L, Ng S. Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev. Shi H, Walker W. Development and physiology of the intestinal mucosal defense. Mucosal Immunol. McDole J, Wheeler L, McDonald K, Wang B, Konjufca V, Knoop K, et al.

Tourkochristou E, Triantos C, Mouzaki A. The influence of nutritional factors on immunological outcomes. Walls J, Sinclair L, Finlay D e. Nutrient sensing, signal transduction and immune responses. Semin Immunol. Childs C, Calder P, Miles E. Diet and immune function. Sica A, Mantovani A.

Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. Szefel J, Danielak A, Kruszewski W. Metabolic pathways of L-arginine and therapeutic consequences in tumors.

Adv Med Sci. Grohmann U, Mondanelli G, Belladonna M, Orabona C, Pallotta M, Iacono A, et al. Amino-acid sensing and degrading pathways in immune regulation.

Cytokine Growth Fact Rev. Newsholme P, Brennan L, Rubi B, Maechler P. New insights into amino acid metabolism, β-cell function and diabetes. Clin Sci. Mellor AL, Munn DH.

IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol. Rubio-Patiño C, Bossowski J, De Donatis G, Mondragón L, Villa E, Aira L, et al.

Low-protein diet induces IRE1α-dependent anticancer immunosurveillance. Cell Metab. Li P, Yin Y, Li D, Kim S, Wu G. Amino acids and immune function. Br J Nutr. Al Tanoury Z, Piskunov A, Rochette-Egly C. Vitamin A and retinoid signaling: genomic and nongenomic effects: thematic review series: fat-soluble vitamins: vitamin A.

J Lipid Res. Prentice S. They are what you eat: can nutritional factors during gestation and early infancy modulate the neonatal immune response? Liu M, Bao S, Gálvez-Peralta M, Pyle C, Rudawsky A, Pavlovicz R, et al.

ZIP8 regulates host defense through zinc-mediated inhibition of NF-κB. Cell Rep. Brieger A, Rink L, Haase H. Differential regulation of TLR-dependent MyD88 and TRIF signaling pathways by free zinc ions. J Immunol. Kitabayashi C, Fukada T, Kanamoto M, Ohashi W, Hojyo S, Atsumi T, et al.

Zinc suppresses Th17 development via inhibition of STAT3 activation. Int Immunol. Maywald M, Wang F, Rink L. Zinc supplementation plays a crucial role in T helper 9 differentiation in allogeneic immune reactions and non-activated T cells. J Trace Elements Med Biol. Rosenkranz E, Maywald M, Hilgers R, Brieger A, Clarner T, Kipp M, et al.

J Nutr Biochem. Rosenkranz E, Metz C, Maywald M, Hilgers R, Weßels I, Senff T, et al. Mol Nutr Food Res. Haase H, Rink L. The immune system and the impact of zinc during aging. Immun Ageing. Prasad A. Effects of zinc deficiency on Th1 and Th2 cytokine shifts.

J Infect Dis. Zinc in human health: effect of zinc on immune cells. Mol Med. Marshall J, Warrington R, Watson W, Kim H. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. Jasenosky L, Scriba T, Hanekom W, Goldfeld AE. T cells and adaptive immunity to Mycobacterium tuberculosis in humans.

Immunol Rev. Romagnani S. T-cell subsets Th1 versus Th2. Ann Allergy Asthma Immunol. Hu X, Ivashkiv L. Cross-regulation of signaling pathways by interferon-γ: implications for immune responses and autoimmune diseases.

Haryanto B, Suksmasari T, Wintergerst E, Maggini S. Multivitamin supplementation supports immune function and ameliorates conditions triggered by reduced air quality. Vitam Miner. Zuniga E, Macal M, Lewis G, Harker J.

Innate and adaptive immune regulation during chronic viral infections. Annu Rev Virol. Romano P. Past, present, and future of regulatory T cell therapy in transplantation and autoimmunity. Schroeder H Jr. Structure and function of immunoglobulins. J Allergy Clin Immunol. Cañedo-Dorantes L, Cañedo-Ayala M.

Skin acute wound healing: a comprehensive review. Int J Inflamm.

However, prolonged inflammation can lead to tissue damage and may overwhelm the immune system. Autoimmune disorders like lupus, rheumatoid arthritis, or type 1 diabetes are partly hereditary and cause hypersensitivity in which immune cells attack and destroy healthy cells. Immunodeficiency disorders can depress or completely disable the immune system, and may be genetic or acquired.

Acquired forms are more common and include AIDS and cancers like leukemia and multiple myeloma. Eating enough nutrients as part of a varied diet is required for the health and function of all cells, including immune cells.

Certain dietary patterns may better prepare the body for microbial attacks and excess inflammation, but it is unlikely that individual foods offer special protection. Examples of nutrients that have been identified as critical for the growth and function of immune cells include vitamin C, vitamin D, zinc, selenium, iron, and protein including the amino acid glutamine.

Diets that are limited in variety and lower in nutrients, such as consisting primarily of ultra-processed foods and lacking in minimally processed foods, can negatively affect a healthy immune system.

It is also believed that a Western diet high in refined sugar and red meat and low in fruits and vegetables can promote disturbances in healthy intestinal microorganisms, resulting in chronic inflammation of the gut, and associated suppressed immunity. The microbiome is an internal metropolis of trillions of microorganisms or microbes that live in our bodies, mostly in the intestines.

It is an area of intense and active research, as scientists are finding that the microbiome plays a key role in immune function. The gut is a major site of immune activity and the production of antimicrobial proteins.

A high-fiber plant-rich diet with plenty of fruits, vegetables, whole grains, and legumes appear to support the growth and maintenance of beneficial microbes. Certain helpful microbes break down fibers into short chain fatty acids, which have been shown to stimulate immune cell activity. These fibers are sometimes called prebiotics because they feed microbes.

Therefore, a diet containing probiotic and prebiotic foods may be beneficial. Probiotic foods contain live helpful bacteria, and prebiotic foods contain fiber and oligosaccharides that feed and maintain healthy colonies of those bacteria.

Animal studies have found that deficiencies in zinc , selenium , iron , copper, folic acid , and vitamins A , B6 , C , D , and E can alter immune responses. Epidemiological studies find that those who are poorly nourished are at greater risk of bacterial, viral, and other infections.

Eating a good quality diet, as depicted by the Healthy Eating Plate, can prevent deficiencies in these nutrients. However, there are certain populations and situations in which one cannot always eat a variety of nutritious foods, or who have increased nutrient needs.

In these cases a vitamin and mineral supplement may help to fill nutritional gaps. Studies have shown that vitamin supplementation can improve immune responses in these groups.

The elderly are a particularly high-risk group. The immune response generally declines with increasing age as the number and quality of immune cells decreases. This causes a higher risk of poorer outcomes if the elderly develop chronic or acute diseases.

In addition, about one-third of elderly in industrialized countries have nutrient deficiencies. Diet variety may also be limited due to budget constraints or lower interest in cooking for one person; poor dentition; mental impairment; or lack of transportation and community resources to obtain healthy food.

Megadose supplements many times the RDA do not appear justified, and can sometimes be harmful or even suppress the immune system e. Remember that vitamin supplements should not be considered a substitute for a good diet because no supplements contain all the benefits of healthful foods.

Several herbal supplements have been suggested to boost immune function. What does the research say? Diet Review: Anti-Inflammatory Diet.

Food Safety, Nutrition, and Wellness during COVID Ask the Expert: The role of diet and nutritional supplements during COVID The contents of this website are for educational purposes and are not intended to offer personal medical advice. You should seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.

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What Is Our Immune System? These barriers include: Skin that keeps out the majority of pathogens Mucus that traps pathogens Stomach acid that destroys pathogens Enzymes in our sweat and tears that help create anti-bacterial compounds Immune system cells that attack all foreign cells entering the body Adaptive or acquired immunity is a system that learns to recognize a pathogen.

Other conditions that trigger an immune response Antigens are substances that the body labels as foreign and harmful, which triggers immune cell activity. What factors can depress our immune system?

Older age: As we age, our internal organs may become less efficient; immune-related organs like the thymus or bone marrow produce less immune cells needed to fight off infections. Aging is sometimes associated with micronutrient deficiencies, which may worsen a declining immune function.

Environmental toxins smoke and other particles contributing to air pollution, excessive alcohol : These substances can impair or suppress the normal activity of immune cells. Excess weight: Obesity is associated with low-grade chronic inflammation.

Fat tissue produces adipocytokines that can promote inflammatory processes. Chronic diseases: Autoimmune and immunodeficiency disorders attack and potentially disable immune cells. Chronic mental stress: Stress releases hormones like cortisol that suppresses inflammation inflammation is initially needed to activate immune cells and the action of white blood cells.

Lack of sleep and rest: Sleep is a time of restoration for the body , during which a type of cytokine is released that fights infection; too little sleep lowers the amount of these cytokines and other immune cells. Does an Immune-Boosting Diet Exist? Probiotic foods include kefir, yogurt with live active cultures, fermented vegetables, sauerkraut, tempeh, kombucha tea, kimchi, and miso.

Prebiotic foods include garlic, onions, leeks, asparagus, Jerusalem artichokes, dandelion greens, bananas , and seaweed. However, a more general rule is to eat a variety of fruits, vegetables , beans , and whole grains for dietary prebiotics.

Grill or broil 3 to 4 inches from heat for about 10 minutes, or until fish flakes easily with a fork. The fish should reach an internal temperature of F. Set aside. In a large bowl, toss together remaining ingredients, except for grapefruit and orange segments.

Divide salad between two plates. Top with cod and citrus pieces, and black pepper to taste. Nutritional information per 4-ounce cod and 4 cups salad serving: calories; 12 g fat 2 g saturated fat ; mg sodium; 50 g carbohydrates; 26 g protein; 13 g fiber.

Nutritional information per 3-tablespoon serving: 53 calories; 2 g fat 0 g saturated fat ; mg sodium; 7 g carbohydrates; 2 g protein; 2 g fiber. Recipes from mayoclinic. Jamie L. Pronschinske is a dietitian in La Crosse , Wisconsin.

Skip to main content. Posted By. Jamie Pronschinske, RDN, CD Nutrition. Recent Posts. Speaking of Health. Topics in this Post. A few key micronutrients have been identified as critical for the growth and function of immune cells, including: Iron Iron is a component of enzymes critical for immune cell function.

Sources include red meat, beans, nuts and fortified breakfast cereals. Vitamin A Vitamin A helps protect against infections by keeping skin and tissues in the mouth, stomach, intestines and respiratory system healthy.

Sources include orange and red fruits, and vegetables like carrots, apricots and bell peppers. Vitamin C Vitamin C stimulates the formation of antibodies, and the production, function and movement of white blood cells.

Sources include citrus fruits like oranges, grapefruit, strawberries and tomatoes. Vitamin D Vitamin D helps regulate antimicrobial proteins that can directly kill pathogens. Sources include sunlight; fatty fish, like salmon; egg yolks; and fortified dairy.

Vitamin E Vitamin E works as an antioxidant to protect the integrity of cell membranes from damage caused by free radicals. Sources include seeds, nuts, vegetables oils and peanut butter.