Abstract

The concept that nutrients are cofactors in the development, maintenance, and expression of immune response is based on observations in many fields, including nutrition, immunology, epidemiology, infectious disease, perinatology, geriatrics, cancer, and genetics (1–10). Nutritional immunology, as a cross-disciplinary field, is emerging from widely ranging studies showing how specific nutrients regulate immune response (11–17). Mechanisms of nutrient action often involve several pathways and produce a range of phenotypic effects. For example, experimental vitamin B12 (cobalamin) deficiency causes megaloblastic anemia in humans and also reduces complement factor C3, immunoglobulin (Ig)M, and IgG and increases IgE by causing a shift from a T helper type-1 (Thl) to a T helper type-2 (Th2) response (2). Human B12 deficiency is associated with increased CD8+ T-cell number and natural killer (NK) activity (18). Vitamins A and D have been intensively studied as critical regulators of gene expression in both growth and immune development. Vitamin A deficiency impedes retinol dependent signals during embryonic development, whereas supplementation enhances the Th2 response to viruses, as shown for influenza (19–21). Vitamin D acts as a nuclear receptor for target genes and also has a regulatory influence on immune response by affecting immune cell differentiation (12,22,23). Studies such as these may illustrate basic elements of experimental design for studies of nutrients’ mechanisms of action on the immune system.

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