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In humans the immune system develops early during fetal life, most immune cells being detectable by mid-gestation. This early developmental process prepares the fetus for the challenge of controlling a large diversity of infectious pathogens at birth while establishing regulated interactions with non-pathogenic commensals. Following congenital infections with viruses, bacteria, or protozoa, the fetal immune system is challenged to generate antimicrobial effector functions. The immune system of the fetus has long been considered as non-reactive or prone to tolerance to foreign antigens. Recent clinical studies have demonstrated that immune effector functions can develop during fetal life. This chapter first provides an overview of the immune system and describes current knowledge of its development during fetal life. The capacity of the fetal immune system to respond to infectious pathogens is then summarized, focusing on the most studied congenital infections.
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