Immune system: development and acquisition of immunological competence

Abstract

Objectives: To describe the ontogeny of the immune system and the adaptive mechanisms of the immune system in the neonatal period, with an emphasis on transplacental antibody transport and breastfeeding.

Source of data: Non-systematic literature review in the PubMed database.

Summary of the findings: The last two decades have witnessed a great advance in the knowledge of the immune system since conception. Several investigation tools have provided insight on phenomena that were previously inadequately understood. Still expanding, the functional and molecular investigation of various aspects of the immune system will make it possible to understand how intra-uterus maternal-fetal exchanges, the maternal microbiota interacting with the fetus and newborn, and the acquisition of immunological competence occur in healthy and disease scenarios.

Conclusions: In-depth knowledge of the development of the immune system and of the adaptive mechanisms that allow a safer transition to the extrauterine environment are fundamental components of optimizing maternal and young infant vaccination, as well as the strategies associated with full postnatal development, and the early diagnosis and treatment of innate errors of immunity.

Keywords: Breastfeeding; Host-pathogen interactions; Immune system; Immunocompetence; Maternal-fetal relations; Vaccination.

Figure 1

Immune system ontogeny. Adapted from Ygberg and Nilsson.

Figure 2

Function of neonatal human monocytes and antigen-presenting cells at different stages of intracellular signaling pathways. a, High concentrations of adenosine in neonatal blood plasma act through adenosine A3 receptors in neonatal mononuclear cells to induce high intracellular concentrations of cyclic AMP (cAMP). Dependent and independent protein kinase A (PKA) pathways can inhibit the tumor necrosis factor mediated by the Toll-like receptor 2 (TLR2), which preserves the production of interleukin-6 (IL-6). b, Neonatal monocytes have decreased expression of MyD88, a key adapter molecule for TLR-mediated signaling. c, Failure in the nucleosome remodeling of the Il12p35 gene promoter contributes to the decrease in TLR-mediated IL-12 p35 production by neonatal dendritic cells (DCs), an example of distinct regulation of neonatal cytokine production at the chromatin level. d, The lipopolysaccharide (LPS)-induced association of interferon (IFN) with regulatory factor 3 (IRF3) with cAMP-responsive element-binding protein (CREB) - binding protein (CBP) and DNA IRF3 binding are reduced in human neonates, resulting in impaired IFN receptor expression. Adapted from Levy.