Emerging Infections and Pregnancy

Denise J. Jamieson; Regan N. Theiler; Sonja A. Rasmussen


Emerging Infectious Diseases. 2006;12(11) 

In This Article

Immunology of Pregnancy

One of the most intriguing puzzles in modern immunology involves the "paradox of pregnancy," in which immunologic tolerance to paternally derived fetal antigens is achieved despite an apparently adequate maternal defense against infection. With 50% of its genetic material derived from its father, the fetus's susceptibility to rejection by the maternal immune system is similar to the susceptibility of a transplanted organ. Evidence indicates that the maternal immune system may tolerate fetal antigens by suppressing cell-mediated immunity while retaining normal humoral immunity. These changes are known to occur locally at the maternal-fetal interface but may also affect systemic immune responses to infection. Although pregnant women are not immunosuppressed in the classic sense, immunologic changes of pregnancy may induce a state of increased susceptibility to certain intracellular pathogens, including viruses, intracellular bacteria, and parasites.

Maternal-Fetal Interface

The fetal allograft is exposed to the maternal immune system at the placenta and fetal membranes (the amnion and chorion), collectively described as the maternal-fetal interface. On the fetal side of the interface, the placenta and membranes enclose the fetus and are derived entirely from fetal tissue. Forming a specialized epithelial surface within the placenta, fetal syncytiotrophoblast cells directly contact maternal blood for nutrient exchange. On the maternal side of the interface, the uterine tissue in contact with the placenta and fetal membranes, the decidua, is rich in specialized maternal immune cells including lymphocytes and macrophages.[2] Despite the prolonged direct exposure of decidual leukocytes and maternal blood to fetal antigens, the immune system does not recognize the fetus as foreign. Several mechanisms underlie this maternal tolerance of fetal tissues.

Humoral Immunity

Also known as antibody-mediated immunity, humoral immunity results from recognition of pathogens by specific antibodies. Most effective against extracellular pathogens, humoral immunity is essential for fighting many bacterial infections. The bacteria become coated in antibodies, which then mediate uptake of the pathogens by phagocytic cells, including neutrophils and macrophages. Presentation of the bacterial antigens on the surface of the macrophage then stimulates B lymphocytes specific to the pathogen, and the B cells produce more antibodies to control the infection. This humoral immune response is augmented by T-helper type II (Th2) lymphocytes, which provide costimulation and induce replication of the B cells. The Th2 response during pregnancy results in vigorous antibody-mediated immunity to pathogens.[2]

Cell-Mediated Immunity

Essential for controlling intracellular pathogens, cell-mediated immunity involves lymphocyte recognition of cell-associated foreign antigens, followed by destruction of the infected host cells. In contrast to humoral immunity, this arm of the immune response is stimulated by T-helper type I (Th1) lymphocytes and the cytokines they release. The most important effectors of the cell-mediated immune response, cytotoxic T lymphocytes, are the main immune cells that recognize foreign antigens on the surface of infected "self" cells. Cells infected with viruses or other intracellular pathogens are cytotoxic T lymphocytes' most common targets. The cell-mediated immune response is critical for controlling such pathogens because their intracellular location shelters them from antibody binding.

T-Helper Cells and the Th1-Th2 Shift

Emphasis on cell-mediated immunity versus humoral immunity changes according to the type of T-helper lymphocytes responding to an infectious threat. Multiple factors, including the cytokine environment and costimulatory molecules present during activation of the T-helper cell, determine the development of either Th1- or Th2-helper phenotype. One hypothesis is that, in addition to hormonal factors that affect the Th1-Th2 balance, macrophages present at the maternal-fetal interface release predominantly Th2-stimulating cytokines and contribute to the overall dominance of humoral immunity during pregnancy.[3] In addition to stimulating B lymphocytes, Th2 cells suppress the cytotoxic T lymphocyte response, decreasing the robustness of cell-mediated immunity. In the uterine decidua, the Th2 cytokine environment favors activation of B lymphocytes, resulting in stimulation of antibody secretion and suppression of cell-mediated immunity.[3] This phenomenon is often referred to as the Th1-Th2 shift of pregnancy and is thought to contribute to maternal tolerance of the fetus by suppressing the antifetal cell-mediated immune response.

Systemic Immune Changes

An evolving model of pregnancy-associated immune changes suggests that the hormonal environment of pregnancy contributes to local suppression of cell-mediated immunity at the maternal-fetal interface while mediating a systemic change toward Th2 dominance. That the local Th1-Th2 shift may also influence the systemic maternal immune response during pregnancy is evidenced in pregnant patients with autoimmune disorders. Women with rheumatoid arthritis, a predominantly cell-mediated autoimmune disorder, tend to experience remissions during pregnancy.[4] Similarly, patients with multiple sclerosis have fewer exacerbations while pregnant but worsening symptoms during the postpartum period.[5] Systemic lupus erythematosis, however, a predominantly antibody-mediated autoimmune disorder, often worsens during pregnancy, perhaps due to increased immunoglobulin synthesis and decreased clearance of immune complexes resulting from robust Th2 activity.[3,6] These well-studied changes in severity of autoimmune disorders during pregnancy illustrate systemic immune alterations that occur in conjunction with the Th1-Th2 shift. Systemic suppression of cell-mediated immunity may contribute to increased susceptibility to some intracellular pathogens—including viruses, bacteria, and parasites—during pregnancy.


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