Ontogeny of early life immunity

Abstract

The human immune system is comprised of cellular and molecular components designed to coordinately prevent infection while avoiding potentially harmful inflammation and auto-immunity. Immunity varies with age, reflecting unique age-dependent challenges including fetal gestation, the neonatal phase and infancy. Herein, we review novel mechanistic insights into early life immunity, with emphasis on emerging models of human immune ontogeny, which may inform age-specific translational development of novel anti-infectives, immunomodulators and vaccines.

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

“…Although the ontogenesis of the immune system starts well before birth, a detailed description of prenatal events is beyond the scope of this review and was covered by previous comprehensive reviews (Dowling and Levy, 2014;Ygberg and Nilsson, 2012). Here we provide a brief overview of the key postnatal maturational events influencing the ontogenesis of the two arms of the immune system-the innate immune system and the adaptive (acquired) immune system (Delves and Roitt, 2000a, b;Medzhitov and Janeway, 2000).…”

“…Key elements of the immune system (eg, Toll-like receptors) have been shaped through natural selection and provide newborns with the ability to recognize, right from the first contact, conserved patterns (pathogen-associated molecular patterns, or PAMPs) on pathogens that have been common in the environment throughout evolutionary times (Janeway and Medzhitov, 2002). Although newborns have an innate ability to recognize common pathogens, their ability to process such antigens and to respond to them through non-specific innate defense mechanisms is insufficient at birth and develops throughout childhood and adolescent years (Dowling and Levy, 2014;Ygberg and Nilsson, 2012). For example, newborns have fewer and less functional antigen-presenting cells, leading to the impaired stimulation of subsequent innate and adaptive responses.…”

IL-36–Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells

“…1). First, neonatal innate responses to danger signals are anti-inflammatory rather than proinflammatory (2,3). This leads to the preferential differentiation of CD4 + Th cells toward Th2 cells, antagonizing Th1 and cytotoxic responses (4).…”

Ready to benefit from training: heterologous effects of early life immunization

“…However, the high susceptibility to infection in early life is partially due to distinct immunity, including suppressive soluble (plasma) and cellular factors, 2,3 which also result in sub-optimal vaccine responses. 4 Thus, while the neonatal immune system is adapted to early life needs, including avoidance of over-exuberant responses to initial colonization with the microbiome, it is distinct from the later in childhood and adulthood immunity. There is subsequent age-dependent maturation of immunity over the first years of life.…”

“…There is subsequent age-dependent maturation of immunity over the first years of life. 4 A number of approaches suggest that safe and effective immunization at birth is possible despite distinct neonatal immunity. A key example of this approach is the administration of bacille Calmette-Gué rin (BCG), a live attenuated strain of Mycobacterium bovis, which is given at birth to reduce the risk of disseminated TB in infancy in TB-endemic countries.…”