ThlTh2 Balance in Normal Human Pregnancy

Thl-dependent effector mechanisms such as cytotoxic T lymphocyte (CTL) activity play a central role in acute allograft rejection. The production of Th2-type cytokines or regulatory cytokines such as TGF-(3 and IL-10 may be central to the induction and maintenance of allograft tolerance. Based on these findings, Wegmann et al16 hypothesized that physiological protection from maternal rejection is due to aTh2-type response at the materno-fetal interface. In mouse models, Thl-type cells and CTL...

Apoptosis and Implantation

During implantation, the uterine endometrium undergoes morphological and physiological changes to accommodate the embryo. This process of accommodation implies that the embryo has to degrade the endometrial extracellular matrix (ECM) to invade the uterus in species with hemochorial placentation. Apoptosis has been observed in endometrial epithelial cells at the embryo implantation site, and it is believed to be due to loss of contact with ECM. Those apoptotic cells are removed either by...

Placentas and Placentation

The most primitive and presumably ancestral placentation is choriovitelline, formed by fusion of the yolk sac and chorion. Placental structural evolution proceeded towards the generation of a larger surface area, which facilitated metabolic exchange accompanying changes in more aggressive invasion of the maternal host. The production of growth factors, cytokines and hormones encourages increased blood flow and nutrient delivery to the feto-placental unit. Interspecies comparisons again...

Infections and the Innate Immune

The innate immune system represents the immunological first line of defense against invading pathogens through is its ability to distinguish between what is non-infectious self and infectious nonself.12 One way in which the innate immune system achieves this is through an evolutionary conserved system of pattern recognition.13 Cells of the innate immune system express a series of receptors known as pattern recognition receptors PRR which recognize and bind to highly conserved sequences known as...

Macrophages at the Maternal Fetal Interface

Histological analysis of normal placental beds shows the presence of large number of macrophages which, in the majority of cases, are localized to the vicinity of apoptotic cells. Indeed, macrophages are one of the major cell types in both the maternal and fetal compartments of the uteroplacental unit.38 In humans, during the first weeks of implantation, macrophages are found in high numbers in the maternal decidua and in tissues close in proximity to the placenta.39 Similarly, in rodents...

Preface

Immunology of Implantation An General Concepts of Maternal Immune Response to the The Role of the Innate Immune System in Apoptosis and 1. Evolution of the Mammalian Reproductive Tract and Placentation 7 Susan Richman and Frederick Naftolin Mammalian Secondary Use of Immune Mechanisms for Reproduction 8 The Role of the Endometrial Placental Contribution and Graft 12 2. Toll-Like Receptors and Toll-Like Receptor Toll-Like Receptor Signaling in Trophoblast Toll-Like Receptors and Infection,...

Recurrent Spontaneous Abortion

Recurrent spontaneous abortion RSA is defined as the occurrence of three or more spontaneous abortions and occurs in about 2-4 of women.1 About 50 of RSA cases can be attributed to chromosomal anomalies, endocrine disorders, or anatomical abnormalities.7,37'73 Immunological explanations have been sought to explain the remaining 50 unexplained RSA. Recent evidence in humans suggests that perturbations in the balance of pro- and anti-inflammatory cytokine expression is associated with RSA. Women...

Trophoblast Apoptosis and Complicated Pregnancies

A greater incidence of villous912 as well as extravillous13, 4 trophoblast apoptosis has been detected in placentas from pregnancies complicated by preeclampsia or IUGR. This increase in trophoblast cell death might explain the insufficient trophoblast invasion often found in abnormal pregnancies. If increased trophoblast apoptosis occurs early in pregnancy, it may limit interstitial and endovascular invasion by extravillous trophoblasts.1 14,11 However, a recent study by Kadyrov et al,...

Cytokines Th1 and Th2 Type

Immune cells mediate their effects by releasing cytokines and thus establishing particular microenvironments. T helper lymphocytes Th that originate from the thymus play a major role in creating a specific microenvironment for a particular organ or tissue. Following an immune challenge, immune cells produce cytokine, the type of which determines their differentiation into T helper-1 Th-1 or T-helper 2 Th-2 lymphocytes. For example, Th-1 lymphocytes secrete interleukin-2 IL-2 and interferon-y...

Cytokine Shift

The proliferation, invasion and differentiation of trophoblast cells during implantation is a tightly controlled process coordinated by a system of intercellular signals mediated by cytokines, growth factors and hormones.13,14 An extensive array of cytokines is produced at the tropho-blast-maternal interface that contributes to the well being of the feto-placental unit. Furthermore, these cytokines to a great extent regulate maternal immune responses, which play an important role for a...

Pregnancy Represents an Allograft

Cases of recurrent abortions, preeclampsia or babies born with hemolytic diseases of the newborn still puzzle us with the of 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, with surprise and admiration the question now becomes Why didn't your mother reject you Medawar, in the early 1950s, recognized for the first time the unique immunology of the maternal-fetal interface and...

Defining Immunology of Pregnancy

Colbern and Main in 1991 redefined the conceptual framework of reproductive immunology as maternal-placental tolerance instead of maternal-fetal tolerance, focusing the interaction of the maternal immune system on the placenta and not on the fetus.1 The embryo in early development divides into two groups of cells, an internal, the inner cell mass, which give rise to the embryo and an external layer, the embryonic trophoblast that becomes trophoblast cells and later the placenta. The cells from...

The Pregnant Uterus as an Immune Privileged Site

Implantation is the process by which the blastocyst becomes intimately connected with the maternal endometrium decidua. During this period, the semi-allogenic fetus is in direct contact with the maternal uterine and blood-borne cells however, as I pointed above, fetal rejection by the maternal immune system, in the majority of the cases, is prevented by mechanism s yet undefined. A number of mechanisms have been proposed to account for the immune-privileged state of the decidua. The different...

Gil Mor MD PhD

Department of Obstetrics and Gynecology Reproductive Immunology Unit Yale University School of Medicine New Haven, Connecticut, U.S.A. Springer Science Business Media New York, New York U.S.A. Landes Bioscience Eurekah.com Springer Science Business Media, Inc. ISBN 0-387-30612-9 Printed on acid-free paper. Copyright 2006 Eurekah.com and Springer Science Business Media, Inc. All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the...

5 The Regulation of Human Trophoblast Apoptosis and Survival

Straszewski-Chavez and Gil Mor Death Receptor-Mediated The Extrinsic The Intrinsic The Apoptotic Cascade in Trophoblast Endogenous Regulators of Trophoblast Exogenous Regulation of Trophoblast Trophoblast Apoptosis and Complicated Pregnancies 56 The Future of Trophoblast 6. Macrophages and Gil Mor, Roberto Romero and Vikki M. Abrahams Apoptosis and in Pregnancy-Associated 7. Potential Role of Glucocorticoids in the Pathophysiology of Intrauterine Growth Restriction Seth Guller,...