The human fetus and newborn: development of the immune response

Maturation of the immune system starts early in fetal life. Lymphocytes of the B series develop in the liver by 9 weeks' gestation and are present in the blood and spleen by 12 weeks. T lymphocytes start to leave the thymus from about 14 weeks' gestation and subsequently cells with helper and suppressor phenotypes are present in the spleen. The relative lack of development of secondary lymphoid tissues in healthy fetuses most probably reflects the lack of antigen stimulus. Newborn plasma contains adult levels of IgG which is acquired across the placenta from the mother. The small amounts of IgM (less than 20 mg/dL) which are normally present in healthy newborns have been reported to include antibody with specificity for maternal lymphocytes. IgA synthesis normally starts in the secretory immune system, about 2-3 weeks after birth. Poor antibody responses by newborns following immunization, especially with bacterial capsular polysaccharides, suggest that newborn immune responses are immature as compared with adults. The susceptibility of newborns to severe HSV and VZV supports this view. In vitro correlates of this immaturity include 1) deficiency of the response by newborn B cells to polyclonal activators, and 2) a lack of T cells which proliferate in HSV- or VZV-stimulated cultures. These characteristics more likely result from a lack of prior antigen stimulation and resulting clonal expansion than from intrinsic lymphocyte suppression. Antigen handling by newborn monocytes, in contrast, appears to be mature by the time of birth.