Sanne Hoeks

General Introduction 15 1 ◀ FIGURE 3. Ontogeny of Fetal, Neonatal, and Infant Host Defense. Host-protective barrier functions include physical, chemical, and functional components of the epithelial of skin and mucous membrane of the fetus, neonate (birth to 28 days of age), and infant (1 month – 1 year of age). These have to be understood in the context of age-specific developmental challenges as outlined near the top of the figure. A, Skin: While physical and chemical barriers are reduced early in life, especially in the preterm, the vernix caseosa and skin epithelia of full-term newborns robustly expresses antimicrobial proteins and peptides (APPs). B, Mucous membranes: In parallel with and induced by an increasingly complex microbiota, the newborn intestinal mucosal epithelium rapidly changes structurally with increase in crypts, and crypt-based Paneth cells, as well as functionally with increasing APP expression. C, Blood: The composition of neonatal blood is distinct, with relatively low concentrations of complement components and APPs and high concentrations of the immunosuppressive purine metabolite adenosine. Plasma also contains maternal antibodies transferred beginning mid-gestation, and supplemented by postnatal factors derived from breastmilk. Innate immunity is detectable from the end of the first month of gestation, with changes driven largely by the increasing exposure to environmental microbes. Neonatal APCs such as blood monocytes express pattern recognizing receptors (PRRs) (e.g., TLRs) with distinct functional responses including limited T H 1-polarizing cytokine production to most stimuli. Age-dependent differences in activity of interferon response factor (IRF) transcription factors as well as epigenetic changes contribute to this cytokine ontogeny. Adaptive immunity develops from 4 weeks of gestation onwards, with changes driven by an evolving chimerism reflecting fetal (liver-derived, shaded cells) Treg-rich lymphocytes and more adult-like (bone marrow- derived, not shaded cells) lymphocytes with distinct epigenetically encoded functional programs. Adapted from: Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny Immunity 2017;46:350-63; Kollmann TR, Kampmann B, Mazmanian SK, Marchant A, and Levy O