rapid and are not antigen specific. Cell types and mechanisms typically considered vital to innate immunity include complement activation, phagocytosis by macrophage, and lysis by natural killer (NK) and natural killer T (NKT) cells and possibly by TCR γδ+ T cells (see below).
Acquired immune responses, in contrast, are antigen specific and are largely mediated by T cells and B cells. Acquired responses can be further divided into primary (response associated with initial antigen contact) and secondary (rapid and powerful amnestic responses associated with subsequent contact to the same antigen).
Antigen specificity is generally regulated by two sets of genes in the major histocompatibility complex (MHC), located on chromosome 6 in humans. MHC class I molecules (HLA-A, -B, and -C) are present on the surface of nearly every cell in the human body and are important in defense against intracellular pathogens, such as viral infection and oncogenic transformation. MHC class I molecules act as important ligands for both the T-cell receptor on CD8+ cytotoxic/suppressor T cells and for a variety of receptors on NK cells (122). MHC class II molecules (HLA-DR, HLA-DP, and HLA-DQ), in contrast, are present on the surface of a limited number of antigen-presenting cells, including dendritic cells, macrophage and monocytes, B cells, and tissue-specific cells such as the Langerhans cells in the skin. These molecules are important in defense against extracellular pathogens, such as bacterial invaders. The major ligand for MHC class II is the T-cell receptor on CD4+ T-helper cells.
One very important concept in immunology that has particular application to pregnancy is that of immune tolerance. The passage of bone marrow–derived T cells through the fetal thymus during early development has been well described. During this developmental interval, the T cells encounter a process termed thymic education. During thymic education, T cells that express either the CD4 or the CD8 coreceptor are chosen, and autoreactive cells are effectively eliminated. In short, this education promotes T-cell tolerance, allowing selection and survival only of those T cells that recognize non-self and will not react against self. Recently, a subpopulation of CD4+ T cells has been described that, like all activated lymphocytes, strongly express CD25 on their cell surface (123). These CD4, CD25+ cells are more specifically identified by the intracellular presence of the forkhead box P3 (Fox P3) transcription factor and have been called regulatory T lymphocytes (Treg cells). Treg cells, when activated by autoantigens, can suppress activated inﬂammatory cells. They secrete regulatory cytokines, including interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) (123–125). They may have particular importance in avoidance of tissue destruction associated with inﬂammation, possibly with applications to tolerance. In an abortion-prone murine model, adoptive transfer of Treg cells from normal pregnant mice into abortion-prone animals prevented immune-mediated pregnancy wastage (126). In pregnant women, Treg cells suppress autologous peripheral blood mononuclear cell (PBMC) secretion of the inﬂammatory cytokine, interferon-γ (IFN-γ) when challenged by paternal or unrelated PBMCs (127).