The origin and development of the immune system with a view to stem cell therapy (Reprinted from Blood, Pure and Eloquent: A story of discovery of people and of ideas)

Careful study of the phylogeny and ontogeny of the three components of the immune system reveals that the macrophage, lymphatic, and hematopoietic systems originate independently of each other. Chronologically, the most ancient is the macrophage system, which arises in the coelomic cavity as mesenchymal ameboid cells having the properties to recognize self from non-self and to ingest foreign particles. The lymphatic system later develops from the endoderm of pharyngeal pouches, where the thymic anlage differentiates. The lymphocytes that originate here seed all lymphatic organs and retain the ability to divide and thereby form multiple colonies ( lymphatic nodules) in the respiratory and digestive tract; further diversification of lymphocytes follows after confrontation with antigens. The last component of the immune system to appear is the hematopoietic system, which originates from the splanchnic mesoderm of the yolk sac as hematogenic tissue, containing hemangioblasts. The hematogenic tissue remains attached to the outer wall of the vitelline vessels, which provides an efficient mechanism for introducing the hematogenic tissue into the embryo. In an appropriate microenvironment, the hemangioblasts give rise to sinusoidal endothelium and to hemocytoblasts - the bone marrow stem cells for erythrocytes, myeloid cells, and megakaryocytes. The facts and opinions presented in this article are not in agreement with the currently accepted dogma that a common "hematolymphatic stem cell" localized in the marrow generates all of the cellular components of blood and the immune system.