The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.

The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.

Subsequent T cells that depart from the thymus populate the lymphoid organs across the body. Early B cells created in the liver and bone marrow have IgM antibodies on their plasma membranes.

After the fourth month, the fetus can produce IgM antibodies when exposed to specific pathogens. However, the fetus generally does not produce antibodies due to the passive immunity it naturally acquires through maternal IgG antibodies, the only antibodies capable of crossing the placenta.

This includes antibodies related to Rh incompatibility issues. Problems due to ABO blood group incompatibilities are rare because anti-A and anti-B antibodies are IgM antibodies, which cannot cross the placenta. The maternal IgG's natural immunity may not adequately defend the fetus if a bacterial or viral infection overwhelms the maternal defenses.

Upon delivery, the maternal IgG supply is cut off. While the mother provides IgA antibodies through breast milk, the infant's passive immunity gradually diminishes. The maternal IgG in the infant's bloodstream rapidly declines in the first two months after birth, leaving the infant prone to infections that the maternal antibodies once protected against.