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The human body has been bombarded by environmental insults since conception. The prenatal immune system facilitates the generation of tissues and organs and is a versatile medium for communication with the outside world, which largely constitutes endogenous maternally-derived solutes. As the fetus matures, characterized by an elaboration of physical and chemical barriers, this prepares the postnatal exposure to exogenous environmental antigens and insults. These early life impressions leave epigenetic footprints that may dictate how the immune system senses and responds to pathogens later in adult life. Here, we illustrate the crosstalk between immune system components in prenatal versus postnatal life, and the impact of the environmental transformation in this critical developmental process.
Prenatal Exposures
- Maternal diet and metabolites
- Maternal illness
- Maternal antibodies
Prenatal exposures, including maternal nutrition, illnesses, and immune factors can impact fetal development. Deficiencies in essential nutrients like zinc, iron, and retinoic acid can disrupt immune development. Maternal infections, including ToRCH (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex virus) viruses, and recently, Zika and Dengue viruses, also pose significant risks to fetal development. Additionally, maternal antibodies and their transfer across the placenta contribute to the developing fetal immune responses and overall health.
Prenatal Immune Development
Development of the immune system begins in waves, with the earliest macrophages observed at 4 weeks of gestation, followed by T cell development between 8-12 weeks of gestation. Mature neutrophils are present at the end of the first trimester, and increase in number until shortly before birth. Most immune cells have functional defects in early life, for instance, reduced adherence and chemotaxis, that will mature as they encounter new antigens and stimuli postnatally.
Postnatal Exposures
- Breastfeeding
- Food and environmental antigens
- Vaccinations
Postnatal exposures, such as breast milk, environmental antigens, and vaccination play a key role in postnatal immune development. Breast milk provides essential bioactive molecules, bacteria, and antibodies that shape humoral immunity and gut colonization while oral feeding and exposure to food antigens aid in mucosal immune maturation. Furthermore, childhood vaccinations are crucial for acquiring immunity against infectious diseases.
Postnatal Immune Development
The immune system undergoes profound changes across all tissues from neonate to adulthood. Neonates initially exhibit high white blood cell counts and neutrophilia, with impaired immune responses and altered cytokine profiles characterized by increased anti-inflammatory cytokine production. As mucosal membranes develop prenatally and mature postnatally, the mucosal barrier continues to evolve, with ongoing specialization and adaptation in response to increased microbial exposure.
Zi Yan Chen
