Stages of immune system development appear to be fairly conserved within mammals, so for the purposes of this review, when fundamental human data are unavailable, mouse data will be provided. A thorough review of the development of the immune system in mice is given in Chapter 1.

In humans, the development of the immune system begins with HSC formation in the yolk sac from 15 to 18 days through 6 weeks of gestation, with the HSC becoming undetectable by the 10th week (Tavassoli 1991). (Definitive HSC in the mouse appear in the AGM region at 9 to 11 days postcoitus [Muller et al. 1994; Nishikawa et al. 2001; Orkin and Zon 2002]). Between the 5th and 8th weeks of human gestation, the fetal liver becomes the center of hematopoiesis (Bellanti et al. 2003; Cooper et al. 1993; Holt and Jones 2000; Tavassoli and Yoffey 1983; West 2002), with some activity persisting until shortly before birth (Cooper et al. 1993). The spleen also transiently participates in blood formation from 10 to 12 weeks post conception until hematopoietic activity shifts to the bone marrow beginning around

11 to 12 weeks. It is also at this time (variably reported as between 8 to 9 or 11 to

12 weeks of gestation [Bellanti et al. 2003; Holt and Jones 2000]) that the thymus is seeded with precursor cells. By 20 weeks, essentially all hematopoiesis in human embryos occurs in the bone marrow (Cooper et al. 1993).

These waves of blood cell production from different organs have long fueled the concept that hematopoiesis is a migratory phenomenon (Holt and Jones 2000; Metcalf and Moore 1971; Tavassoli and Yoffey 1983). Although not definitive, there is some evidence to support this notion, including experiments in mice demonstrating that HSC fail to colonize fetal liver in the absence of p 1 integrin expression (Potocnik et al. 2000). Moreover, the tyrosine kinase receptor Flk-1 appears required for migration and expansion of HSC (Schuh et al. 1999).

How To Bolster Your Immune System

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