Inadequate intake of zinc is a common human nutritional problem which can greatly compromise the immune system leaving the host vulnerable to disease and infection. The long term goal of this project is to characterize the effects of a moderate period of suboptimal zinc on the various branches of the immune system and immune ontogeny using the mouse as a model. There are four future objectives: I. Mononuclear phagocytes (MNP) from zinc deficient mice (ZD) were unable to kill associated parasites unless preincubated with zinc. It is probable that the mechanism of action of zinc was to restore the oxygen burst. Experiments are proposed to explore the effect of exogenously added zinc on several enzymatic and non-enzymatic reactions of the burst that may be zinc dependent. II. The rapid decline in mature, peripheral lymphocytes in ZD mice provides an opportunity to determine whether or not the bone marrow adjusts the rate of lymphopoiesis in such situations. Initially, experiments will focus on the rate of production of B-cells in the marrow of ZD mice. III. As a corollary, the residual splenic B-cells of ZD mice will be further characterized as to phenotypic distribution. Preliminary evidence suggests that ZD interferes with B-cell maturation not only in the young adult but fetal-neonatal mice as well. The possibility that zinc alters the quantity and distribution of histones, thereby altering gene expression associated with the maturational process will be considered. IV. Finallly, data will be presented which shows that dams receiving marginal zinc in utero gave rise to offspring which exhibited immune dysfunction postpartum that could not be readily corrected by nutritional repletion. The ability of such offspring to mount antibody and cell mediated responses will be investigated from birth to puberty to determine the degree and persistence of the immunodeficiency. Whether transmission of protective immunity from dam to offspring was impaired will also be determined. These experiments are of special significance to those concerned with the management of low birth weight infants, some of whom may have been marginally malnourished in utero.
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