Neonates are particularly susceptible to various pathogens compared to adults, which is attributed in part to their immature innate and adaptive immunity. Natural killer cells provide first-line innate immune reactions against virus-infected cells without prior sensitization. This review updates phenotypic and functional deficiencies of neonatal cells compared to their adult counterparts and their clinical implications.

Genetics and environmental factors have important roles in autoimmune diseases but neither has given us sufficient understanding of these mysterious diseases. Therefore, we are now looking closer at epigenetics, an interface between genetics and environmental factors. Epigenetics can be defined as reversible heritable changes to chromatin that can alter gene expression without altering the gene's DNA sequence. Methylation of DNA and histones are primary means of epigenetic control. By adding methyl groups to DNA and histones, it can limit accessibility of the underlying gene thereby altering the amount of gene expression. The methyl group is derived from an essential molecule in the cell, S-adenosylmethionine (SAM). However, a group of small molecules called polyamines also require SAM for their synthesis. Polyamines are essential for many cellular functions and polyamine activity is increased in many autoimmune diseases. Presented here is the "polyamine hypothesis" in which increased polyamine synthesis competes with cellular methylation (epigenetic control) for SAM. It is proposed that increased polyamine activity can cause disruption of cellular methylation, which can lead to abnormal expression of previously sequestered genes and disruption of other methylation-dependent cellular processes.

\Natural killer (NK) cells that provide first-line innate immune reactions against virus-infected and tumor cells have different roles in different body sites and in different stages. From the beginning of life, NK cells participate in many aspects of development, especially in a successful pregnancy and a healthy neonatal stage. This article reviews recent advances regarding the role of NK cells in implantation, placentation and immune tolerance during pregnancy as well as in the neonatal immune defense. The interactions between NK cells and other immune cells in each developmental stage are discussed.

Dendritic cells (DC) are essential for the first-line innate defense against influenza infection. The greater susceptibility to severe influenza infection in young infants and neonates may be attributed in part to their defective DC function. We sought to investigate the effect of influenza A virus (IAV) infection on the maturation, apoptosis, and function of monocyte-derived dendritic cells (MoDCs) from umbilical cord blood (UCB) and compared this with responses from adult peripheral blood (APB). Our findings were as follows. First, MoDCs derived from UCB showed deficient CD40, CD80, CD86, and HLA-DR upregulation following IAV infection compared to APB MoDCs. Second, IAV induced a multiplicity of infection (MOI)-dependent increase of apoptosis in UCB MoDCs, similar to that observed with APB. Third, the ability of UCB MoDCs to uptake dextran is decreased following IAV infection. Fourth, deficient TNF-a, but not IL-6, IFN-a response was induced by IAV infection of UCB MoDCs. Fifth, the ability of UCB MoDCs to promote allogeneic CD3 T-cell proliferation is inhibited by IAV infection. Taken together, we demonstrated a differential response of UCB and APB MoDCs following IAV infection, which may contribute in part to the increased susceptibility to severe influenza infection observed in young infants and neonates.