Chapter Category: Reproductive Biology

From the book Immunology of Pregnancy

The Eutherian Fetoembryonic Defense System Hypothesis: An Update

Gary F. Clark, Anne Dell, Howard Morris and Manish S. Patankar

All sexually reproducing organisms produce gametes that must be protected from immune challenge. Recent data indicates that the majority of the carbohydrate sequences that coat the murine zona pellucida are also upregulated on activated lymphocytes, and some participate in gamete binding. This overlap indicates that there may be a “species recognition system” (SRS) that is employed to identify both immune cells and gametes in the context of “species” rather than “self ”. In eutherians, histoincompatible progeny must also be protected from the maternal immune response. The composite data indicates that several glycoconjugates produced in the pregnant can modify immune responses in vitro. We have previously referred to these collective factors as the “eutherian fetoembryonic defense system” or eu-FEDS. Based on the available results, it is very likely that these glycoconjugates are utilizing specific carbohydrate sequences as functional groups to mediate these activities. Many different persistent pathogens and tumor cells also either mimic or acquire these carbohydrate functional groups, indicating that they may be able to evoke similar effects. We outline new data that clearly implicate glycobiological subterfuge in the pathological effects associated with infection with lentiviruses like HIV-1 and simian immunodeficiency virus (SIV). In addition, recent data showing that the uterine mucin CA125 and the major surface glycoprotein of HIV-1 (gp120) express the same N-glycans suggests a linkage to the pregnant uterus. Complete integration of this protective effect associated with eu-FEDS could also explain why the natural hosts of SIV (sooty mangabees and African green monkeys) are able to completely accommodate this virus without pathological effects. In summary, the requirements for accommodation of the germ cells and different stages of developing progeny could provide a very substantial “Achilles heel” for exploitation by pathogens and tumor cells. These more recent finding should provide a great impetus to further investigate the eu-FEDS hypothesis and its strong linkages to pathogenesis.

Taken from the book

Immunology of Pregnancy

Edited by: Gary F. Clark, Anne Dell, Howard Morris and Manish S. Patankar

More chapters from the book:

Th1/Th2 Balance of the Implantation Site in Humans
Shigeru Saito, Satomi Miyazaki and Yasushi Sasaki

Successful embryo implantation requires the synchronization of embryo development and uterine preparation. The embryo must have developed to the blastocyst stage and the endometrium must be in a receptive phase. Wilcox et al1 have estimated that 65% of conceptions end in unrecognized losses....


During pregnancy some cells traffic between the fetus and mother and recent studies indicate low levels persist in the respective hosts decades later. Microchimerism (Mc) refers to a small population of cells or DNA harbored by one individual that derive from a genetically distinct individual....


The Role of Corticotropin-Releasing Hormone (CRH) on Implantation and Immunotolerance of the Fetus
Sophia N. Kalantaridou, Antonis Makrigiannakis, Emmanouil Zoumakis and George P. Chrousos

The hypothalamic neuropeptide corticotropin-releasing hormone (CRH), as well as its receptors, have been identified in several reproductive organs, including the endometrial glands, the decidualized endometrial stroma and the placental trophoblast, synctiotrophoblast and decidua.1-9...


Characterization of Human Dendritic Cells at the Maternal-Fetal Interphase
U. Kammerer, L. Rieger, A. Honig and E. Kampgen

The unusual tolerance against fetal antigens is still one of the greatest miracles of pregnancy. Dealing with reproductive immunology, the question arises as to how the maternal immune system handles the foreign fetal antigens leading to that tolerance. Focussing on the various subsets of...


The mechanisms of acceptance of the fetus by the maternal immune system are mediated in part by immunomodulatory proteins expressed by placental cells. The recent discovery of novel members of the B7 family of immunomodulators has prompted much excitement among the scientific community because...


Interleukin-1 and Implantation
Jan-S. Krussel, Jens Hirchenhain, Andrea Schanz, Alexandra P. Hess, Hong-Yuan Huang, Carlos Sim—n and Mary Lake Polan

Infertility and pregnancy wastage affect one of every nine couples in Western Europe and in the United States. The molecular events of embryonic attachment to the endometrial epithelium and subsequent invasion and nidation into the stroma have long been of interest, scientifically to...


Mamamalian Reproductive Tract and Placentation
Susan Richman and Frederick Naftolin

Phylogenetic analysis suggests that the internalization of reproduction and the develop ment of hemochorial placentation have been accompanied by conservation of primitive genitourinary genes. The products include the renin-angiotensin system and the innate immune system. This explains what...


Immunology and Pregnancy Losses: HLA, Autoantibodies and Cellular Immunity
Joanne Kwak-Kim, Joon Woo Kim and Alice Gilman-Sachs

Pregnancy loss is the one of the most common obstetrical complications. The majority of pregnancy losses are random or isolated incidences that in many cases are related to genetic abnormalities. However, 2-5 % of reproductive age women experience recurrent miscarriages.1,2 Recurrent pregnancy...


Toll Like Receptors and Pregnancy
Vikki M. Abrahams and Gil Mor

The maternal-fetal interface represents an immunologically unique site that must promote tolerance to the allogenic fetus, whilst maintaining host defense against a diverse array of possible pathogens. Clinical studies have shown a strong association between certain pregnancy complications and...


Apoptosis occurs in the villous trophoblast of normal placentas throughout pregnancy, but with higher frequency near term in comparison to the first trimester. In pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR), a greater incidence of villous and extravillous...


Macrophages and Pregnancy
Gil Mor, Roberto Romero, Vikki M. Abrahams

During implantation, apoptosis is critical for the appropriate tissue remodeling of the maternal decidua and invasion of the developing embryo. Yet the regulation of apoptosis is also imperative for a successful pregnancy. The quick and effective removal of apoptotic cells by tissue...


Although the etiology of intrauterine growth restriction (IUGR) and preeclampsia (PE) remains unclear, most investigators attribute the initial “insult” to poor utero-placental perfusion due to defective trophoblast invasion that ultimately compromises fetal well-being.1-3 The resultant...


The Role of Regulatory T Cells in Materno-Fetal Tolerance
Varuna R. Aluvihare and Alexander G. Betz

Maternal immune tolerance to paternal allo-antigens expressed by the fetus is a precondition of successful pregnancy in viviparous mammals. This occurs despite exposure of the maternal immune system to potentially immunogenic fetal tissue. Local immune evasion mechanisms are thought to prevent...


The Eutherian Fetoembryonic Defense System Hypothesis: An Update
Gary F. Clark, Anne Dell, Howard Morris and Manish S. Patankar

All sexually reproducing organisms produce gametes that must be protected from immune challenge. Recent data indicates that the majority of the carbohydrate sequences that coat the murine zona pellucida are also upregulated on activated lymphocytes, and some participate in gamete binding. This...


The Nature and Role of the Decidual T Cells
Lucia Mincheva-Nilsson and Vladimir Baranov

The immunological paradox of mammalian pregnancy is the acceptance of the fetus, a semiallogeneic allograft that normally should provoke an immune response of the maternal T cells leading to fetal rejection. In this chapter the current understanding of decidual T-cell immunobiology is...


MHC Molecules of the Preimplantation Embryo and Trophoblast
Martina Comiskey, Carol M. Warner and Danny J. Schust

The mechanisms of protection of the allogeneic fetus from the maternal immune response during pregnancy remain mysterious more than fifty years after the paradox of maternal tolerance was first raised by Peter Medawar. Preimplantation embryos express paternal antigens early in development....


IL-10 and Pregnancy
Shaun P. Murphy and Surendra Sharma

Soon after the principles of nonself immunological recognition were discovered, it was realized that the state of pregnancy seemingly presents a paradox. In an outbreed popula tion, half of the fetal genes are paternal, thus the fetus may be considered a semi-allograft. Yet, unlike the outcome...


Leukemia Inhibitory Factor in Reproduction
Levent M. Senturk and Aydin Arici

To describe the clinical findings and implications of leukemia inhibitory factor (LIF) in human reproduction. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin-6 family and has different biological actions in various tissue systems. Although named for its ability to...


Actions of Seminal Plasma Cytokines in Priming Female Reproductive Tract Receptivity for Embryo Implantation
Sarah A. Robertson, John J. Bromfield, Danielle J. Glynn, David J. Sharkey and Melinda J. Jasper

Embryo implantation is critically dependent on a supportive uterine environment. Uter ine receptivity is the culmination of a cellular and molecular transformation mediated locally by paracrine signals under the governance of ovarian steroid hormones, with cells and cytokines of the immune...


Indoleamine 2,3 Dioxygenase dependent T cell Suppression and Pregnancy
Babak Baban, Phillip R. Chandler and Andrew L Mellor

Viviparity remains an immunological paradox despite increased knowledge of immunological processes that occur during mammalian pregnancy. The maternal immune system protects both mother and fetus from invading pathogens during gestation, but also has to maintain immunological tolerance towards...


NK Cells and Pregnancy
Mikael Eriksson, Satarupa Basu and Charles L. Sentman

Natural killer cells are found in large numbers in the endometrium and decidua, and data suggest that NK cell functions and interactions with fetal-derived trophoblasts can have a profound impact on pregnancy. Altered NK cell numbers and activity have been associated with a variety of clinical...


Inherited Thrombophilias and Early Pregnancy Loss
Jens Langhoff-Roos, Michael J. Paidas, De-Hui Ku, Yale S. Arkel and Charles J. Lockwood

Inherited thrombophilias are a heterogeneous group of conditions which have been associated with a variety of pregnancy complications, including early and late fetal loss, intrauterine growth restriction, abruptio placentae, and preeclampsia.1 As the functional significance of the burgeoning...


Cases of recurrent abortions, preeclampsia or babies born with hemolytic diseases of the new born, still puzzle us with the question “Why did your mother reject you?” Although, after looking at the complexity of the maternal-fetal immune interaction and the cases of successful pregnancies,...


Advertisements