Pneumonia is the most common serious infectious disease of newborn infants. The inability of newborns to mount adequate resistance to respiratory infections may be due to macrophage immaturity, lack of accessory factors, special perturbing environmental factors such as lung surfactant as well as unknown immunoregulatory factors carried over from fetal development. During the current project period we have: 1) identified and partially purified and characterized migration enhancement factor (MEF) in neonatal serum and spleen cell supernatants, 2) prepared a synthetic MEF (L-fucosyl BSA), 3) determined lipid membrane changes of AM during neonatal development, 4) observed that 28d rabbits are down-regulated in their response to BCG, 5) determined that AM from neonatal animals are permissive for herpes simplex virus type 2 (HSV-2), whereas AM from adult animals are non-permissive. The main composite hypothesis to be tested is that AM from neonates and infants are functionally compromised because of special environmental conditions at birth such as endocytosis of excess surfactants by newly recruited AM causing them to become physiologically compromised and a down-regulation of the immune system by natural suppressor cells and/or their products present in neonatal and infant rabbits. During the renewal project period we will 1) determine the biochemical composition of surfactants and lipids in lung lavage from 7 day- and 90 day-old (d) rabbits. 2) Determine the functional capacity of AM from 7d, 28d and 90d rabbits in vitro in the absence and presence of crude and fractionated lavage components (from aim 1). 3) Determine the mechanisms responsible for nonpermissive replication of infectious HSV-2 in AM from adult (90d) as compared to permissive AM from neonatal (7d) and infant (28d) rabbits, and 4) evaluate the role of splenic natural suppressor cells and their products in the modulation of T cell proliferative responses with special reference to the down-regulation observed in AM from 28d rabbits vaccinated with BCG.
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