Micronutrients have a major impact on immune response, through antioxidant activities and modulation of cytokine expression. Antioxidant enzymes, such as copper, zinc, and manganese superoxide dismutases, require trace metals for biological activity, and these enzyme reactions protect against oxidative damage caused by free radical formation during immune response and other biological reactions. Intracellular redox balance has a signaling role in immune cell development and function, and the antioxidant effects of micronutrients regulate cytokine production .
Iron deficiency anemia in children leads to impaired cell-mediated immunity, such as decrease of T cell number, abnormal delayed cutaneous hypersensitivity, IL-2 production, and reduced bactericidal activity of neutrophils [38, 65]. Vegetarian diet and Helicobacter pylori infection can be causes of iron deficiency anemia [8, 66]. Pangastritis is more common in children whose H. pylori infection is accompanied by anemia .
Zinc deficiency is associated with primary immune deficiency disorders such as common variable immune deficiency or hypogammaglobulinemia, Di George syndrome and IgA deficiency, as well as other conditions including fetal alcohol syndrome, sickle cell disease due to hyperzincuria, celiac disease, enteritis and diarrhea. Zinc deficiency due to loss occurs in epider-molysis bulosa and in p-thalassemia due to chelation protocols required to remove excess iron secondary to chronic blood transfusion for anemia. Zinc deficiency inhibits Th1 cytokine responses, thymic hormone activity, and lymphopoiesis [1, 58, 68]. Acrodermatitis enteropathica, a genetic defect in zinc absorption, presents in infancy as skin lesions (acute dermatitis or hyperkeratotic plaques), diarrhea, alopecia, and increased susceptibility to infection, and is resolved with zinc supplementation . Because zinc competes with copper for GI uptake, zinc supplements may induce copper deficiency, and may cause neutropenia .
Selenium is an important micronutrient for health  and is critical for antioxidant function acting via the selenium-dependent enzyme, glu-tathione peroxidase, to protect cellular membranes and organelles from peroxidative damage. Neither toxic nor deficient levels in soil are commonly found in Europe [71, 72], yet deficiency is fairly common due to variable bioavailability [72, 73]. Soil deficiencies of selenium and iodine are common in some countries such as New Zealand, Australia, Finland, and in parts of China . Some studies have suggested that risk of cancer is increased in selenium deficiency [75, 76]. Selenoproteins are an important component of the antioxidant host defense system affecting leukocyte and NK cell function . Selenium is emerging as a critical micronutrient in host defense against viral infection since selenium deficiency is associated with progression in HIV disease and in viral shedding [78, 79].
Vitamin A has long been appreciated as a significant factor in the severity of infection such as measles, rotavirus diarrhea, and HIV in the mal nourished host. Pure deficiency is uncommon, but neonates and children less than 5 years of age are at risk. Vitamin A deficiency, which affects 140 million pre-school children worldwide, is associated with severity of many infections including measles, rotavirus, and HIV [80, 81]. Low vitamin A levels are associated with the occurrence of chronic bacterial infections and splenomegaly, as well as high neopterin levels in common variable immune deficiency or hypogammaglobulinemia . In these patients supplementation in vivo led to improved immune function in vitro.
Vitamin C is a free radical scavenger that serves as an important antioxidant. Vitamin C concentrations in the plasma and leukocytes decline during infections and stress. Supplementation with antioxidant vitamins including vitamin C has been shown to improve immune response to group A streptococcal infection compared to penicillin alone . Supplementation may enhance phagocytosis and NK cell activity , increase levels of the antioxidant plasma glutathione levels, and inhibit Fas-induced apoptosis of monocytes. H. pylori infection is associated with a decrease in gastric juice ascorbic acid concentration, and this effect is greater in children with the CagA-positive strain A . Both vitamin C and astaxanthin, a carotenoid, show antimicrobial activity against H. pylori that may be mediated through immune mechanisms . Vitamin C is used to treat recurrent furunculosis in patients with deficient neutrophil function, and may lower the incidence of colds associated with acute physical stress. This may be related to the finding that vitamin C reduces muscle release of IL-6 . No substantial evidence supports the view that megadoses of vitamin C decrease the severity or frequency of respiratory infection. However, recent studies show that vitamin C selectively influences intracytoplasmic cytokine production in vitro. 
Current studies suggest that vitamin E deficiency is common in US toddlers . Vitamin E supplementation enhances proliferative response in vitro  and improves IL-2 cytokine response . Vitamin E deficiency causes reduced transferrin receptor internalization in the mouse, which suggests restriction of intracellular iron stores that would be needed for cellular function and proliferation . Vitamin E may influence T cell function by downmodulating PGE2. Improvement in eczema and reduction in serum levels of IgE in atopic subjects has recently been reported . A recent study has shown that antioxidant deficiency is common in a very large cohort of CF patients. Carotenoid and vitamin E deficiencies were found to occur early in the course of the disease and antioxidants were observed to decrease with bronchial infection .
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