Immune responses in neonates

Abstract

Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in the understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in the neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents.

Keywords::

• adaptive immunity
• B cell
• BCR
• B-reg cell
• CD103 dendritic cell
• CD5 cell
• CD71 erythroid cell
• chemokines
• cord blood
• dendritic cell
• IL-27 macrophages
• innate immunity
• neonates
• neutrophils
• NK-cell
• RTE
• T follicular cell
• T cell
• TCR
• Th 17
• toll-like receptor
• Treg cell
• γδ-T cell

Acknowledgements

The authors would like to thank Zagursky R for his critical reading and valuable discussions.

Financial & competing interests disclosure

The authors were supported by the National Institutes of Health R0108671. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The immune system of neonates makes them highly vulnerable to viral, bacterial, fungal and parasitic diseases, often associated with a high mortality. Understanding the molecular regulation of the innate and adaptive immune systems as well as their molecular signatures is a key issue.

• Maternal infections (HIV, malaria, TB) during pregnancy shape neonatal immune development and it is important to consider maternal vaccinations that can generate protective immunity in neonates.

• The low precursor cell frequency and quantity, and quality of innate immune response have been shown to impede a stronger adaptive immune response in neonates. Future efforts to improve antigen presenting cells response by using new-generation adjuvants/toll-like receptors agonists are a key priority.

• Multiple factors influence the neonatal adaptive immune responses such as proliferation of T lymphocytes, T-cell help to B-cell immunity and B-cell antibody production. All of these should be considered in enhancing vaccine efficacy.

• Other factors that affect neonatal immunity include maternal nutrition, allergens, infections, maternal antibodies and plasma factors.

• Neonates and infants receive multiple priming doses of vaccines to achieve immunity. Yet, 19.3 million neonates and infants throughout the world do not receive the multiple recommended doses of vaccines required to achieve optimal immunity (UNICEF). These data strongly argue for additional research to better understand exploitable mechanisms to achieve more robust and prolonged immunity with fewer primary and booster vaccinations.

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