Passive and active components of neonatal innate immune defenses

Abstract

Innate immune defenses are crucial for survival in the first days and weeks of life. At birth, newborns are confronted with a vast array of potentially pathogenic microorganisms that were not encountered in utero. At this age, cellular components of the adaptive immune system are in a naive state and are slow to respond. Antibodies received from the dam are essential for defense, but represent a finite and dwindling resource. Innate components of the immune system detect pathogen-associated molecular patterns (PAMPs) on microorganisms (and their products) by means of pattern-recognition receptors (PRRs). Soluble mediators of the innate system such as complement proteins, pentraxins, collectins, ficolins, defensins, lactoferrin, lysozyme etc. can bind to structures on pathogens, leading to agglutination, interference with receptor binding, opsonization, neutralization, direct membrane damage and recruitment of additional soluble and cellular elements through inflammation. Cell-associated receptors such as the Toll-like receptors (TLRs) can activate cells and coordinate responses (both innate and adaptive). In this paper, accumulated knowledge of the receptors, soluble and cellular elements that contribute to innate defenses of young animals is reviewed. Research interest in this area has been intermittent, and the literature varies in quantity and quality. It is hoped that documentation of the limitations of our knowledge base will lead to more extensive and enlightening studies.

Effectiveness of Intraoral Chlorhexidine Protocols in the Prevention of Ventilator-Associated Pneumonia: Meta-Analysis and Systematic Review

“…Plasmatic levels of complement components and other multifunctional soluble immune proteins are significantly lower in newborns compared with adults. 33 Moreover, existing evidence based on animal models indicates that a post-natal impairment of TLR2 and TLR4 expression negatively affects inflammatory responses following intratracheal administration of Gram-negative bacteria early in life. 34 Likewise, a strong bias against T helper cell type 1 polarization of the immune response is also thought to make infants more susceptible to microbial infections.…”

Hyper innate responses in neonates lead to increased morbidity and mortality after infection

“…However, in neonates, the immune system has yet to fully mature, potentially leaving newborns susceptible to either infection or inappropriate activation. Lacking a fully developed adaptive immune system, newborns must rely on the innate immune response for protection against pathogens (29,30). However, intrinsic deficiencies in the capability of neonatal innate immunity lead to inefficient clearance of pathogens (9).…”

Supplementation of Merino ewes with cholecalciferol in late pregnancy improves the vitamin D status of ewes and lambs at birth but is not correlated with an improvement in immune function in lambs

“…However, even at the optimal birthweight of 4.5-5.5 kg (Oldham et al 2011;Hinch and Brien 2014), lamb survival to weaning rarely exceeds 90% for singles, 75% for multiples and 60% for triplets (Paganoni et al 2014), suggesting that factors independent of birthweight must also influence lamb survival. Functional innate and adaptive immune deficiencies in neonatal mammals are known to predispose them to infections, and the associated inflammation may cause tissue damage and/or dysfunction and death, particularly in the perinatal period (Firth et al 2005;Futata et al 2012). However, the role of immune competency in the survival of lambs is poorly understood.…”