A discussion of the ontogeny of the immune system is not complete without mention of the 35+ plasma or membrane proteins that make up complement and that serve as an auxiliary defense system (Prodinger et al. 2003). The major complement component C3 appears in fetal tissues as early as 6 weeks of gestation, whereas C2 and C4 are not detected until 8 weeks of gestation (Adinolfi 1997). Regulatory proteins that protect the fetus from maternal complement such as decay-accelerating factor (DAF), membrane co-factor protein (MCP), and CD59 are expressed in the liver from at least 6 weeks of gestation (Simpson et al. 1993). Complement receptors CR1 and CR3 have been detected on monocytes and neutro-phils and on cells in the bone marrow, spleen, and thymus of 14-week-old fetuses (Adinolfi et al. 1988). Recently, Mastellos and Lambris have postulated that complement is crucial in ontogeny, not because of a role in immunity, but because of a role in modulating cellular responses and cell-cell interactions that are crucial to early development and cell differentiation (Mastellos and Lambris 2002).
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