Experimental models and mechanisms of immune deficiencies of nutritional origin

The complex interactions between nutrition, infection and immunity are still poorly understood and the precise role of each factor is difficult to ascertain. Infection itself induces profound metabolic alterations resulting in negative nitrogen balance. Protein energy malnutrition, whatever its origin, results in an immune deficiency characterized by impaired delayed cutaneous hypersensitivity, low production of lymphokines, low T cell counts, decreased T cell responses to specific or non specific mitogenic stimuli. Serum immunoglobulin levels are normal or elevated and antibody responses to most vaccines are normal or slightly altered. Secretory IgA levels, number of IgA plasma cells in jejunal mucosa and specific IgA antibody levels are depressed. Neutrophil chemotaxis and serum opsonic activity are normal but bacterial killing capacity is markedly reduced. C3 levels are usually reduced as a consequence of low hepatic synthesis and increased consumption but most other complement proteins remain within the normal range. Such alterations of immunological parameters can be induced by malnutrition itself but they are commonly observed in populations also exposed to a heavy load of infectious agents from birth. Various types of immunodeficiencies can be achieved by selective deficiencies of minerals trace elements and several vitamins. Several experimental and clinical studies showed that overnutrition could alter T cell immune responses and accelerate the development of spontaneous auto-immune diseases in selected strains. Conversely low calorie or low fat diets as well as supplementation in fish oil markedly enhanced survival in these models. Despite much controversy as regards the mechanisms of immune alterations of nutritional origin, the clinical and experimental data already available provide a framework for the design of further investigations and for prophylactic action.