Immune System: Early Ontogeny


The development of immunity in humans starts within a few days of conception and proceeds over a few years before it reaches full maturity. Maturation of the immune system during gestation occurs through waves of cellular production and turnover. Unlike the adult immune system, the foetal one shows reduced antigenic diversity and attenuated pathogen recognition receptor function. Current models suggest that this state is well adapted to the foetal environment. However, this physiological state can prove to be detrimental for infants born prematurely. Consequently, given the high burden of neonatal morbidity and mortality due to infections, understanding of the foetal and neonatal immune system is important to improving health outcomes in this age group. In this article, we review the developmental changes in the immune system during human gestation and highlight its impact on the risk of neonatal infections.

Key Concepts

  • The development of the immune system takes place in sequential waves during gestation.
  • The foetal immune system is biased towards immunological tolerance to the mother.
  • Macrophages play a broad role in embryonic organ development.
  • Foetal lymphoid cells show more limited antigenic diversity and an increased proportion of innate‐like lymphoid cells.
  • This developmental immaturity of the immune system is responsible for a high health burden, especially in neonates born prematurely.

Keywords: foetal immune ontogeny; postnatal immune response; embryonic and foetal monocytes; foetal T cells; innate‐like lymphocytes; invariant natural killer T cells; human immunology

Figure 1. Embryo haematopoietic sites and the emergence of lymphopoiesis in mid‐gestation embryos. The transversal view depicting AGM region includes sub‐aortic and intra‐aortic haematopoietic cell clusters. Foetal liver (FL) is likely colonised by both YS‐ and Sp/AGM‐derived progenitors (1, 2). The embryo thymus is engrafted with Sp/AGM‐ and FL‐derived pre‐committed precursors (3, 4). Whether haematopoietic progenitors migrate between both YS and Sp/AGM is unclear (5, 6). In red, embryo haematopoietic sites (except the lymphopoietic thymus). Neural tube, blue; dorsal aorta, green; mesonephros, brown; gonads, orange.
Figure 2. Differentiation routes from the haemangioblast/haemogenic endothelium up to mature blood cells. Full arrows indicate the scheme based on the existence of a primordial CLP/CMP (common myeloid progenitor) branching. Dotted arrows show alternative roads of lymphoid differentiation. The cellular stages and pathways predominating in embryo are labelled in blue. ETP, early T‐cell progenitors; GMP, granulocyte‐macrophage progenitors; LTR, long‐term reconstituting; MEP, megakaryocyte‐erythrocyte progenitors; MMP, multipotential progenitors; MZ, marginal zone; STR, short‐term reconstituting; other abbreviations, in the main text.


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Further Reading

Cumano A and Godin I (2007) Ontogeny of the hematopoietic system. Annual Review of Immunology 25: 745–785.

De Kleer I, Willems F, Lambrecht B, et al. (2014) Ontogeny of myeloid cells. Frontiers in Immunology 5: 423.

Dzierzak E and Speck NA (2008) Of lineage and legacy: the development of mammalian hematopoietic stem cells. Nature Immunology 9: 129–136.

Krow‐Lucal ER and McCune JM (2014) Distinct functional programs in fetal T and myeloid lineages. Frontiers in Immunology 5: 314.

Mold JE and McCune JM (2012) Immunological tolerance during fetal development: from mouse to man. Advances in Immunology 115: 73–111.

Vermijlen D and Prinz I (2014) Ontogeny of innate T lymphocytes – some innate lymphocytes are more innate than others. Frontiers in Immunology 5: 486.

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Sharma, Ashish A, and Lavoie, Pascal M(Oct 2015) Immune System: Early Ontogeny. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001132.pub2]