Journal of Immunology Research

1. Introduction

Nutrition and Immunity: You Are What You Eat
Thus, a continual conversion of alanine carbon to glucose carbon occurs with acute infection. Zinc deficiency influences both lymphocyte and phagocyte cell functions and affects more than metalloenzymes that are zinc dependent [ 36 ]. Zinc and rehabilitation from severe protein-energy malnutrition: Vitamin, trace element and peroxide status in HIV seropositive patients: In adequately nourished children they are usually huge but are virtually undetectable in children with severe PEM. In vitamin C deficiency, phagocytic cells cannot produce tubulin, therefore, with impaired chemotaxis, microorganisms cannot be engulfed and destroyed [ 33 ]. Pediatric Infectious Disease Journal.

KEY POINTS

Effects of Malnutrition

Although there are many trials of nutrition interventions and their effect on infectious disease, trials that show a successful improvement in nutritional status and a subsequent effect on measures of immunological function are very few. In one of the studies in anorexia nervosa referred to above, nutritional rehabilitation returned the increased mitogen responsiveness towards normal Cytokine perturbations also returned to normal after re-feeding 13 , but in both of these instances it is not possible to dissect out the influence of macro- and micronutrients.

In a trial in which Kenyan school children were randomized to several different food supplementation foods meat-based, milk-based, vegetable oil-based or none , antibody titres to Helicobacter pylori , rotavirus, tetanus toxoid and malaria merozoite surface proteins showed very little change The effect of nutritional therapy on malaria has been unclear ever since the Murray team found in the s that undernutrition protected against morbidity and mortality This unexpected finding was borne out by studies in protein-deprived animals.

Subsequent work has not really supported this contention, and a recent WHO analysis has, characteristically, attempted to quantify the proportion of malaria attributable to malnutrition This more comfortable reading suggests that micronutrient deficiency plays a more significant role in immunity to malaria than macronutrient deficiency. It is well established that survival in AIDS is determined to a considerable degree by nutritional status both macronutrient and micronutrient , and if this is through an effect on immune function one would expect to see improvements in CD4 count if weight gain can be achieved.

Despite a careful search of several databases, no evidence for an effect of treatment using macronutrients on immune function in AIDS could be found see also Macallan For example, parenteral nutrition improved nutritional status body composition compared to controls, but no assessment was made of immune function There is no evidence that lipid supplementation is of benefit 56 , If there is a relationship between body composition and immune function, it might be mediated by leptin Leptin, produced by adipose tissue, acts as a satiety signal: The leptin receptor has structural similarities to the IL-6 family of cytokines and leptin signalling is inhibited by SOCS-3 that regulates other cytokines.

Macrophages from leptin-deficient mice are constitutionally activated and over-react in response to LPS, but their killing of Escherichia coli is impaired. Leptin-deficient mice also have lymphopenia and impaired delayed-type hypersensitivity DTH. However, this has not been shown in humans, and the link between macronutrient depletion and the immune dysfunction remains tentative.

It has been clear that vitamin A has important anti-infective properties since when it was shown that it reduced case fatality from measles.

Large studies in Ghana, Indonesia and elsewhere have confirmed that vitamin A has important effects in reducing adverse outcome from infectious disease in underdeveloped countries, particularly diarrhoea and measles There are also two relevant clinical trials of the effect of vitamin A supplementation on malaria.

Vitamin A supplementation may reduce placental infection However, the outstanding question is: In laboratory animals, vitamin A polarizes the immune response towards Th2 64 , 65 , acting through retinoic acid, its principal oxidative metabolite.

Retinoic acid also boosts the antitetanus antibody response However, evidence of an immune booster effect in humans is much less clear. This evidence has recently been thoroughly reviewed To summarize this evidence 67 , there is evidence that intestinal epithelial integrity is improved by vitamin A 68 , but not of improved antimicrobial properties in breast milk, and no evidence of improved barrier function in the vagina.

There is some evidence of a beneficial effect in raising CD4 counts in HIV-infected children but not in adults. Neither is there conclusive evidence of effects on cytokine production or lymphocyte function, but antibody responses to tetanus toxoid may be enhanced if the vitamin A is given before the vaccine When contrasted with the highly significant effects of vitamin A in reducing childhood morbidity and mortality, particularly from measles and diarrhoea, the very uncertain evidence of effects on immune competence is striking.

It seems likely on the basis of current evidence that epithelial or barrier integrity is an important part of the effect of vitamin A. Furthermore, addition of a vitamin A supplement to a supplement of vitamins B, C, and E given to HIV-infected pregnant women detracted from the benefit attributable to the supplement 69 so the effects of vitamin A, even if mediated by augmented cell-mediated immunity, are complex and can be disadvantageous.

There is abundant clinical evidence that zinc is a critically important nutrient for the proper functioning of the immune system. Zinc is effective in prevention of diarrhoea: Similar benefits were also found for pneumonia and malaria, though fewer trials are available for analysis.

Thus, it appears that zinc supplementation is clinically effective in reducing morbidity and mortality due to diarrhoeal disease and malaria in children. But is this an effect on immunity or host defence or something else? There are two lines of evidence that suggest that zinc deficiency adversely affects immune function and that supplementation improves it. First, in humans there are data from the s which, though not conclusive, support this contention.

Children with acrodermatitis enteropathica, a congenital defect of zinc absorption, have thymic atrophy, lymphopenia, reduced lymphocyte response to mitogens, reduced DTH, and reduced immunoglobulin responses Many other reports of immune defects in zinc-deficient patients are difficult to interpret because of comorbid processes e.

In terms of innate immunity, Paneth cells, which synthesize antimicrobial molecules for innate defence of the small intestine in humans, are also dependent on zinc 76 , Challenging zinc-deficient animals with low doses of Trypanosoma cruzi or intestinal nematodes resulted in death The deficiency state was associated with reduced numbers of lymphocytes due to impaired lymphopoiesis, but the production of antibody by each cell was not impaired.

Furthermore, while zinc deficiency had marked effects on lymphoid cells, there was no effect on myeloid cells, and this lead Fraker et al. This is that maintenance of lymphocyte populations is very expensive in terms of zinc and other nutrients, and that in the face of nutritional stress innate defence is maintained at the expense of adaptive immune responses. The Fraker theory is very attractive and deserves much further work. If true, the ramifications for management of infectious disease in malnourished patients could be considerable.

However, there is evidence that NK cell function and phagocytosis by macrophages are also impaired in zinc deficiency, and this may be a consequence of reduced oxidative burst capacity, for example in trypanosomiasis Zinc supplementation of mice during Plasmodium berghei infection reduced markers of oxidative stress 81 , but the significance of this is not clear. Early data suggest that zinc is important for maintenance of antimicrobial peptide delivery in the small intestine 77 , The most definitive evidence that zinc deficiency is critical for immune function in humans comes from experimental zinc deficiency induced by dietary restriction in human volunteers NK cell activity was also reduced in the volunteers on a zinc-deficient diet.

In studies in iron-deficient humans, iron deficiency has been associated with defects in both adaptive and innate immunity, and these are reversible with iron therapy Adaptive immune defects include reduced T-cell numbers, reduced T-cell proliferation, reduced IL-2 production by T cells, reduced MIF production by macrophages, and reduced tuberculin skin reactivity.

Innate immune defects include reduced neutrophil killing, probably due to reduced myeloperoxidase activity and impaired NK cell activity. However, the picture is far from simple. Lactoferrin in human milk chelates iron and inhibits bacterial proliferation by depriving the bacteria of an essential nutrient. The bacteriostatic effect of human milk is abolished by iron therapy 86 , so that iron therapy would be expected to increase neonatal intestinal infectious disease.

In milk-drinking nomads, iron therapy was associated with an increase in Entamoeba histolytica infection, possibly due to saturation of the milk transferrin that overcomes the protective effect The same group had previously noted recrudescence of malaria and schistosomiasis in nomads treated with iron An overview of iron supplementation studies in malarious regions included 11 trials Five of nine trials in which clinical malaria was assessed showed a deleterious effect, and no trials showed benefit.

Respiratory infections and other infectious morbidity were also, if anything, increased though diarrhoeal disease was not. This deleterious effect of iron supplementation on infectious disease has not been observed in clinical trials in nonmalarious regions 85 , though there is evidence that dialysis and multiply transfused patients with iron overload have immune defects In summary, it is difficult to draw a firm conclusion as to whether iron status contributes to the impaired immunity to parasites seen in malnutrition.

There is evidence of T-cell and innate immune impairment in iron deficiency, but supplementation i. Selenium is an important antioxidant that has been shown to have wide-ranging immunostimulant effects in macrophages and T and B cells in humans However the evidence for this rests on a very small number of primary publications 93 , The most compelling recent evidence is an example of the sort of functional immunological testing that is all too rare in this field They also showed more rapid clearance of the virus from stool.

The situation is very similar for vitamin E, in which there is much interest, but for which the evidence base is narrow. In one clear-cut study in elderly people, vitamin E supplementation for 4 months increased DTH responses and increased antibody titres to clinically relevant vaccines hepatitis B, tetanus but not immunoglobulin levels or T or B cell numbers There are no data to our knowledge of the effect of these micronutrients specifically on immune responses to parasites, but these data suggest that antioxidant nutrients are likely to be important in maintaining immunity.

There is evidence that malnutrition impairs elements of adaptive and innate immunity which would be important for defence against parasitic infections, although evidence of increased incidence or severity of parasitic infections in malnourished humans is fairly limited.

The evidence that this immune dysfunction is attributable to deficiency of protein or other macronutrients is weak; we find it unconvincing and conclude that it has been overstated in the past on the basis of poorly controlled studies. On the other hand, there is good evidence of links between micronutrient deficiencies and immune impairment. This evidence is strongest for zinc, deficiency of which leads to impairment of both innate and T-cell responses.

The evidence that antibody responses are impaired in any malnourished state is much less convincing. Given the very heavy burden of infectious disease around the world, and its massive contribution to illness and premature death, this field warrants much greater attention.

As primary malnutrition is usually associated with famine, conflicts and population displacement, and confounding factors in secondary malnutrition are inevitable, observational studies are difficult to interpret. Study of patients with anorexia nervosa could still give much useful information on the impact of macronutrient depletion. However, the most useful information will be derived from specific controlled interventions in volunteers and in patients.

National Center for Biotechnology Information , U. Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2. Received Feb 2; Accepted May 8. This article has been cited by other articles in PMC. Abstract KEY POINTS Clinical malnutrition is a heterogenous group of disorders including macronutrient deficiencies leading to body cell mass depletion and micronutrient deficiencies, and these often coexist with infectious and inflammatory processes and environmental problems.

There is good evidence that specific micronutrients influence immunity, particularly zinc and vitamin A. Iron may have both beneficial and deleterious effects depending on circumstances. There is surprisingly slender good evidence that immunity to parasites is dependent on macronutrient intake or body composition. Increased incidence or severity of infections. It should be noted that without evidence of increased susceptibility to, or severity of, infectious disease, abnormalities in laboratory assessments do not constitute an immunodeficiency.

Markers of immunodeficiency laboratory or clinical, some of these are well validated, others much less so. Table 1 Evidence for elements of immunodeficiency in cases of malnutrition. Open in a separate window. Macronutrients Clinical trials of nutritional rehabilitation and immune function are few. Vitamin A It has been clear that vitamin A has important anti-infective properties since when it was shown that it reduced case fatality from measles.

Zinc There is abundant clinical evidence that zinc is a critically important nutrient for the proper functioning of the immune system.

Iron In studies in iron-deficient humans, iron deficiency has been associated with defects in both adaptive and innate immunity, and these are reversible with iron therapy Other antioxidant molecules Selenium is an important antioxidant that has been shown to have wide-ranging immunostimulant effects in macrophages and T and B cells in humans Improved nutritional recovery on an elemental diet in Zambian children with persistent diarrhoea and malnutrition.

Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum -infected erythrocytes.

Helminth antigens modulate TLR-initiated dendritic cell activation. HIV or human immunodeficiency virus infection has assumed worldwide proportions and importance in just a span of 25 years. Continuous research is being done in many parts of the world regarding its treatment and vaccine development, and a lot of money has flown into this.

However, fully understanding the mechanisms of immune depletion has still not been possible. Malnutrition further reduces the capacity of the body to fight this infection by compromising various immune parameters. Knowledge of essential components of nutrition and incorporating them in the management goes a long way in improving quality of life and better survival in HIV-infected patients.

HIV accounts for significant immunosuppression in an infected individual. If the corroboratory indices of good health are satisfactory, the suppression of immune defences can be mitigated. One such index is nutrition. HIV, immune expression, and nutrition interactions are complex and related to each other. Once there is an infection with HIV, the patient's nutritional status declines further leading to immune depletion and HIV progression.

Acquired immune deficiency syndrome, or AIDS, is a disease caused by a retrovirus, the human immunodeficiency virus HIV , which attacks and impairs body's natural defence system against disease and infection. Nutrition and HIV are strongly related and complement each other. A malnourished person after acquiring HIV is likely to progress faster to AIDS, because his body is weak to fight infection whereas a well-nourished person can fight the illness better.

It has been proved that good nutrition increases resistance to infection and disease, improves energy, and thus makes a person stronger and more productive. Nutritional improvement measures must be initiated before a patient reaches this stage. One of the factors responsible for malnutrition in an HIV-infected person is reduced appetite, which could be due to difficulty in ingesting food as a result of infections like oral thrush or oesophagitis caused by Candida, a common opportunistic infection in HIV-infected people and fever, side effects of medicines, or depression.

Poor absorption of nutrients may be due to accompanying diarrhea which may be because of bacterial infections like Salmonella or Mycobacterium avium intercellular ; viral like CMV or parasitic infections like Giardia, C.

Gastrointestinal tract is the largest lymphoid organ in the body and is directly affected by HIV infection. HIV causes damage to the intestinal cells by causing villus flattening and decreased D-xylose absorption. This leads to carbohydrate and fat malabsorption thereby affecting fat soluble vitamins like vitamins A and E, which are important for proper functioning of immune system. Whereas larger amounts of nutrients are required during fever and infections that accompany an HIV infection, they are utilised poorly by the body.

This leads to loss of weight and lean muscle tissue, further causing damage to the immune system. Lack of iron in the diet and infections such as malaria and hookworm lead to anaemia.

Anaemia causes lethargy, further reduces food intake and nutrient absorption, and also causes disruption of metabolism, chronic infections, muscle wasting, or loss in lean body tissue [ 4 ]. AIDS-related dementia or neuropsychiatric impairment may make the patients unable to care for themselves, forget to eat, or unable to prepare balanced meals. Even in households with HIV-infected members, nutritional impacts can be seen if the infected adult becomes too sick to work and provide food for themselves and their families [ 5 , 6 ].

Dietary intake also varies inversely with level of virus, suggesting that viral replication directly or indirectly suppresses appetite [ 7 ]. Malnutrition is frequent and is considered a marker for poor prognosis among HIV-infected subjects [ 8 ].

Also, in acute viral infections such responses could be seen but they were generally not present in patients with chronic progressive infections. Antiviral immunity involves both the arms of the immune system.

The protective component of cell-mediated immunity involves the cytotoxic CD8 T-lymphocytes. Schmitz and colleagues had demonstrated the effects of CD8 T lymphocytes in monkeys experimentally infected with simian immunodeficiency virus SIV. Humoral immunity to HIV is expressed by neutralising antibodies. Anti-HIV antibodies are able to bind cell-free virus and potentially prevent established infection in the challenged host.

Neutralising antibodies attaching to CD4 binding site of HIV have been identified which appear to prevent the virus from attaching to and infecting T cells. Though HIV-specific humoral immune responses can be detected during primary infection, they mostly comprise low-avidity env specific IgG antibodies with little or no neutralising activity [ 12 ].

Significant neutralising titers are believed to take place after chronicity has set in. HIV evolves various strategies to establish chronicity in human body. Initial CTL responses cause downregulation of viremia and prevent disease progression, but later it induces the selection of virus mutants capable of escaping the immune response [ 14 ].

Immune activation in HIV is supported by an experiment by Pandrea et al. High T-cell turnover in chronic HIV infection is attributed to overlapping and nonsynchronized bursts of proliferation, differentiation, and death in response to T-cell receptor- TCR- mediated stimulation and inflammation [ 16 , 17 ].

Antiretroviral therapy ART results in a marked reduction of T-cell activation and apoptosis and helps to decrease naive T-cell consumption and restore their numbers [ 18 ]. Chronic HIV infection also causes immunological or direct virotoxic effects on gastrointestinal tract which shows blunted villi, crypt hyperplasia, and damaged epithelial barrier with increased permeability and malabsorption of bile acid and vitamin B12, microbial translocation, and enterocyte apoptosis.

There is a decrease of luminal defensins and massive CD4 T-cell depletion but high concentration of infected CD4 T cells [ 19 ].

Malnutrition is considered to be the most common cause of immunodeficiency worldwide [ 20 ]. Malnutrition, immune system, and infectious diseases are interlocked in a complex negative cascade [ 1 ]. Malnutrition elicits dysfunctions in the immune system and promotes increased vulnerability of the host to infections [ 21 ].

Every type of immunological deficiency induced by malnutrition can be included under the NAIDS umbrella. Protein-energy malnutrition PEM , now known as protein-energy undernutrition, is an energy deficit due to chronic deficiency of all macronutrients [ 22 ].

In children, PEM causes widespread atrophy of lymphoid tissues, particularly T-lymphocyte areas. The thymus involutes causing a reduction in the thymus-derived lymphocyte growth and maturation factors, arrest of lymphocyte development, reduced numbers of circulating mature CD4 helper cells, and impairment of antibody production to T-dependent antigens. Imbalance in Th1-Th2 activation occurs depending on nature of stimuli and altered regulatory pathways, including responses mediated by the nuclear factor-kB NF-kB [ 23 ], a major transcription factor involved in the development of innate and adaptive immunity.

Hence the patient's ability to ward off infections and show recovery is compromised. However, CD8 suppressor cells are relatively preserved. The lymphocytes not only get reduced in blood, but also impaired show T-lymphocyte mitogenesis and diminished activity in response to mitogens [ 24 ].

According to Chandra [ 25 ], in children with PEM, there is a decrease or reversal of the T-helper-suppressor cell ratio and total numbers of T-lymphocytes decrease due to reduced numbers of these T-cell subpopulations.

In malnourished children, changes such as dermal anergy, loss of delayed dermal hypersensitivity DDH reactions, and loss of the ability of killer lymphocytes to recognize and destroy foreign tissues were noted [ 20 ]. Necropsy studies on malnourished patients have also shown profound depletion of the thymolymphatic system and severe depression of cell-mediated immunity. Chronic thymic atrophy with peripheral lymphoid tissue wasting along with depletion of paracortical cells and loss of germinal centres was noted.

This was suggested to have led to various types of infections from which these patients actually died [ 26 ]. B-lymphocyte numbers and functions generally appear to be maintained though immunoglobulin concentrations get reduced including secretory IgA sIgA , which is responsible for mucosal immunity. This may be due to increased bacterial adherence to nasopharyngeal and buccal epithelial cells or altered expression of membrane glycoprotein receptors [ 27 ]. It has been speculated that the existing antibody production is conserved or even increased during generalized malnutrition but new primary antibody responses to T-cell-dependent antigens and antibody affinity are impaired [ 20 ].

The failure of antibody formation is reversed within a few days of protein therapy as amino acids become available for the synthesis of immune proteins [ 28 ]. It also reduces complement formation, and interferon and lower interleukin 2 receptors [ 26 ]. In patients with severe generalized malnutrition, functional status of the immune system should be assessed by simply looking at the tonsils in young children.

In adequately nourished children they are usually huge but are virtually undetectable in children with severe PEM. This would indicate atrophy in the child's thymus, spleen, and lymph nodes, and severely compromised cell-mediated immunity [ 24 ]. Deficiencies of other nutrients also adversely affect the immune mechanisms. Deficiencies of essential amino acids can depress the synthesis of proteins responsible for production of cytokines released by lymphocytes, macrophages, and other body cells, complement proteins, kinins, clotting factors, and tissue enzymes activated during acute phase responses [ 24 ].

Arginine deficiency diminishes the production of nitric oxide, and hence, the antioxidants, allowing damaging effects of free oxygen radicals [ 24 ].

Arginine has also been shown to enhance phagocytes of alveolar macrophages, depress T suppressor cells, and stimulate T helper cells [ 29 ]. Particularly the omega-3 fatty acids, serve as the key precursors for the production of eicosanoids like prostaglandins, prostacyclins, thromboxanes, and leukotrines that play a variety of host defensive roles.

Thus their deficiency in the diet can impair cytokine synthesis [ 30 ]. Vitamin A has an important role in nucleic acid synthesis, and its deficiency is also characterized by lymphoid tissue atrophy, depressed cellular immunity, impaired IgG responses to protein antigens, and pathologic alterations of mucosal surfaces.

Experimental animals with vitamin A deficiency have decreased thymus and spleen sizes, reduced natural killer cell, macrophage and lymphocyte activity, lower production of interferon, and weak response to stimulation by mitogens [ 31 ]. B-group vitamins like thiamin, riboflavin, pantothenic acid, biotin, folic acid, and cobalamin can influence humoral immunity by diminishing antibody production.

Chronic thymic atrophy with peripheral lymphoid tissue wasting along with depletion of paracortical cells and loss of germinal centres was noted. This was suggested to have led to various types of infections from which these patients actually died [ 26 ]. B-lymphocyte numbers and functions generally appear to be maintained though immunoglobulin concentrations get reduced including secretory IgA sIgA , which is responsible for mucosal immunity.

This may be due to increased bacterial adherence to nasopharyngeal and buccal epithelial cells or altered expression of membrane glycoprotein receptors [ 27 ]. It has been speculated that the existing antibody production is conserved or even increased during generalized malnutrition but new primary antibody responses to T-cell-dependent antigens and antibody affinity are impaired [ 20 ].

The failure of antibody formation is reversed within a few days of protein therapy as amino acids become available for the synthesis of immune proteins [ 28 ]. It also reduces complement formation, and interferon and lower interleukin 2 receptors [ 26 ]. In patients with severe generalized malnutrition, functional status of the immune system should be assessed by simply looking at the tonsils in young children.

In adequately nourished children they are usually huge but are virtually undetectable in children with severe PEM. Deficiencies of other nutrients also adversely affect the immune mechanisms. Deficiencies of essential amino acids can depress the synthesis of proteins responsible for production of cytokines released by lymphocytes, macrophages, and other body cells, complement proteins, kinins, clotting factors, and tissue enzymes activated during acute phase responses [ 24 ].

Arginine deficiency diminishes the production of nitric oxide, and hence, the antioxidants, allowing damaging effects of free oxygen radicals [ 24 ]. Arginine has also been shown to enhance phagocytes of alveolar macrophages, depress T suppressor cells, and stimulate T helper cells [ 29 ].

Particularly the omega-3 fatty acids, serve as the key precursors for the production of eicosanoids like prostaglandins, prostacyclins, thromboxanes, and leukotrines that play a variety of host defensive roles. Thus their deficiency in the diet can impair cytokine synthesis [ 30 ]. Vitamin A has an important role in nucleic acid synthesis, and its deficiency is also characterized by lymphoid tissue atrophy, depressed cellular immunity, impaired IgG responses to protein antigens, and pathologic alterations of mucosal surfaces.

Experimental animals with vitamin A deficiency have decreased thymus and spleen sizes, reduced natural killer cell, macrophage and lymphocyte activity, lower production of interferon, and weak response to stimulation by mitogens [ 31 ].

B-group vitamins like thiamin, riboflavin, pantothenic acid, biotin, folic acid, and cobalamin can influence humoral immunity by diminishing antibody production. Pyridoxine deficiency has also been associated with reduced cell-mediated immunity.

Folic acid and vitamin B are essential to cellular replication. Experimental deficiencies of these vitamins were shown to interfere with both replication of stimulated leukocytes and antibody formation.

In anemia due to folic acid deficiency, cell-mediated immunity is depressed [ 32 ]. In vitamin C deficiency, phagocytic cells cannot produce tubulin, therefore, with impaired chemotaxis, microorganisms cannot be engulfed and destroyed [ 33 ]. Vitamin D acts as an immunoregulatory and a lymphocyte differentiation hormone [ 34 ]. In vitamin E deficiency, leukocyte especially lymphocyte killing power gets reduced. In animals it was shown to interfere with antibody formation, plaque-forming cells, and other aspects of cell-mediated immunity.

At higher than recommended levels, it has been shown to enhance immune response and resistance to disease [ 35 ]. Zinc is also the fundamental component of thymic hormones and shares a similar role as vitamin A in nucleic acid synthesis. Zinc deficiency influences both lymphocyte and phagocyte cell functions and affects more than metalloenzymes that are zinc dependent [ 36 ]. During infections, reticuloendothelial cells sequester iron from the blood and phagocytes release lactoferrin with a higher iron binding capacity than bacterial siderophores.

The net effect is to deprive the infectious agent of iron for its replication and inhibit the spread of infection [ 34 ]. Iron deficiency results in impaired phagocytic killing, less response to lymphocyte stimulation, fewer natural killer cells, and reduced interferon production [ 37 ]. Selenium serves as an antioxidant and contributes to antibody responses and cytotoxicity of natural killer cells [ 38 ].

In children with HIV infection, selenium concentration in plasma appeared to correlate with their immune functions [ 39 ]. Similar changes were also seen in patients with copper deficiency [ 40 ]. Copper concentrations often increase during infection as a result of stimulation of the hepatic production of ceruloplasmin.

Conversely, plasma zinc concentration often declines due to internal redistribution to the liver. Antimicrobial systems in the neutrophils are affected by malnutrition. These include both oxygen-dependent systems responsible for the respiratory burst, and oxygen-independent systems, such as lactoferrin, lysozymes, hydrolase, and proteases [ 34 ].

Cytokines are substances that play an important role in coordinating inflammatory response of the body to various external and internal stimuli. They may be proinflammatory, which are essential to initiate defence against various pathogens, and anti-inflammatory, which downregulate the inflammatory process by suppressing production of the proinflammatory cytokines and balance the inflammatory response.

Excess production of both are counterproductive. Severe malnutrition alters the ability of T lymphocytes to respond appropriately to IL-1 rather than simply affecting synthesis of this monokine [ 42 ]. During catabolic states, interleukin 1 is released by leukocytes which causes endocrine changes that lead to amino-acid mobilization, primarily from skeletal muscle. These amino acids are used for gluconeogenesis in the liver, and the nitrogen released is excreted in urine [ 43 ].

Thus, a continual conversion of alanine carbon to glucose carbon occurs with acute infection. In malnourished Africans without overt infections, increased circulating levels of inflammatory mediators e.

Another cytokine, tumor necrosis factor has been suggested as a potential etiologic factor in HIV wasting syndrome as it has been incriminated as an appetite inhibitor [ 46 ].

Malnutrition and HIV form a vicious cycle and ultimately aim at reducing the immunity of the patient. In both malnutrition and HIV there is reduced CD4 and CD8 T-lymphocyte numbers [ 47 ], delayed cutaneous sensitivity, reduced bacteriocidal properties [ 24 ], and impaired serological response after immunizations. Some of the immunological parameters concerning these two entities have been listed in Table 1.

Whereas micronutrient deficiencies may affect replication of the invading virus, they also induce several metabolic alterations in the body.

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