Immunology of Pregnancy and its Disorders PDF
Preview Immunology of Pregnancy and its Disorders
Immunology of Pregnancy and its Disorders IMMUNOLOGY AND MEDICINE SERIES Immunology of Endocrine Diseases Editor: A. M. McGregor Clinical Transplantation: Current Practice and Future Prospects Editor: G. R. D. Catto Complement in Health and Disease Editor: K. Whaley Immunological Aspects of Oral Diseases Editor: L. Ivanyi Immunoglobulins in Health and Disease Editor: M. A. H. French Immunology of Malignant Diseases Editors: V. S. Byers and R. W. Baldwin Lymphoproliferative Diseases Editors: D. B. Jones and D. Wright Phagocytes and Disease Editors: M. S. Klempner, B. Styrt and J. Ho HLA and Disease Authors: B. Bradley, P. T. Klouda, J. Bidwell and G. Laundy Immunology of Sexually Transmitted Diseases Editor: D. J. M. Wright Lymphocyes in Health and Disease Editors: G. Janossy and P. L. AmIot Mast Cells, Mediators and Disease Editor: S. T. Holgate Immunodeficiency and Disease Editor: A. D. B. Webster Immunology of Pregnancy and its Disorders Editor: C. M. M. Stern Immunotherapy of Disease Editor: T. J. Hamblin __ ______ IMMUNOLOGY~ • SERIES· SERIES· SERIES· SERIES AND SERIES· SERIES· SERIES· SERIES, MEDICINE Immunology of Pregnancy and its Disorders Edited by C. M. M. Stern Department of Paediatrics St Thomas's Hospital, London Series Editor: Professor W. G. Reeves KLUWER ACADEMIC PUBLISHERS DORDRECHT-BOSTON-LONDON Distributors for the United States and Canada: Kluwer Academic Publishers, PO Box 358, Accord Station, Hingham, MA 02018-0358, USA for all other countries: Kluwer Academic Publishers Group, Distribution Center, PO Box 322, 3300 AH Dordrecht, The Netherlands British Library Cataloguing in Publication Data Immunology of pregnancy and its disorders. 1. Pregnant women. Interactions with foetuses. Immunological aspects I. Stern, C.M.M. II. Series 618.3 ISBN-13: 978-94-010-7053-9 e-ISBN-13: 978-94-009-1247-2 DOl: 10.1007/978-94-009-1247-2 Copyright © 1989 by Kluwer Academic Publishers Softcover reprint of the hardcover 1s t edition 1989 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission from the publishers, Kluwer Academic Publishers BV, PO Box 17,3300 AA Dordrecht, The Netherlands. Published in the United Kingdom by Kluwer Academic Publishers, PO Box 55, Lancaster, UK. Kluwer Academic Publishers BV incorporates the publishing programmes of D. Reidel, Martinus Nijhoff, Dr W. Junk and MTP Press. Contents Series Editor's Note Vll List of Contributors IX Introduction Xl The nature of the feto-maternal physiological relationship M. Young 2 New and old aspects of the ontogeny of immune responses 33 M. Adinolfi 3 Human trophoblast antigens 61 Y. W. Loke 4 Pregnancy proteins and hormones in the immune response of 91 pregnancy A. Klopper 5 Maternal immune response to the fetus in human pregnancy 115 l. L. Sargent and C. W. G. Redman 6 The immunology of diseases of pregnancy 143 G. M. Stirrat 7 Immunotherapy in reproductive disorders 165 A.E. Beer 8 Genetics of reproduction 197 C. M. M. Stern Index 215 v Series Editor's Note The modern clinician is expected to be the fount of all wisdom concerning conventional diagnosis and management relevant to his sphere of practice. In addition, he or she has the daunting task of comprehending and keeping pace with advances in basic science relevant to the pathogenesis of disease and ways in which these processes can be regulated or prevented. Immunology has grown from the era of anti-toxins and serum sickness to a stage where the study of many diverse cells and molecules has become integrated into a coherent scientific discipline with major implications for many common and crippling diseases prevalent throughout the world. Many of today's practitioners received little or no specific training in immunology and what was taught is very likely to have been overtaken by subsequent developments. This series of titles on IMMUNOLOGY AND MEDICINE is designed to rectify ths deficiency in the form of distilled packages of information which the busy clinician, pathologist or other health care professional will be able to open and enjoy. Professor W. G. Reeves, FRCP, FRCPath Department of Immunology University Hospital, Queen's Medical Centre Nottingham vii List of Contributors M. ADINOLFI C. W. G. REDMAN Paediatric Research Unit Nuffield Department of Obstetrics and Division of Medical and Molecular Gynaecology Genetics John Radcliffe Hospital United Medical & Dental Schools of Headington Guy's & StThomas's Hospitals Oxford OX39DU 7th Floor, Guy's Hospital Tower, UK London Bridge London SE1 9RT I. L. SARGENT UK Nuffield Department of Obstetrics and Gynaecology John Radcliffe Hospital Headington, A. E. BEER Oxford OX39DU University of Health Sciences UK The Chicago Medical School 3333 Green Bay Road North Chicago, IL 60064-3095 C. M. M. STERN USA Department of Paediatrics St Thomas's Hospital London SE1 7EH UK A. KLOPPER Department of Obstetrics and G. M. STIRRAT Gynaecology, Phase II Department of Obstetrics and Royal Infirmary Gynaecology Foresterhill University of Bristol Aberdeen AB9 2ZB UK Bristol BS28EG UK M. YOUNG Y.W. LOKE 4 Preston Close Division of Cellular and Genetic Miller's Road Pathology Toft Department of Pathology Cambridge CB3 7RU University of Cambridge (lately, StThomas's Hospital Tennis Court Road Medical School Cambridge CB21 QP London UK UK) ix Introduction The purpose of this book is to describe the nature of the materno-fetal immunobiological relationship and to suggest the direction in which the management of reproduction and its failure in man is moving. The several authors, who have written about their special fields of interest, need to be read within a framework designed to blend their contributions into a whole. This preamble provides a part of that framework, by describing the early development of the embryo, that of the placenta and its membranes and their anatomical relationship with maternal tissues: in other words, the stage upon which this materno-fetal dialogue takes place. Professor Maureen Young's 'tour de force', encapsulating the whole of fetal physiology into a single chapter, completes the background information. After Maureen Young's summary of fetal physiology, Matteo Adinolfi describes the development of the immune system in the fetus, including new information that allows more accurate speculation concerning the gestational age at which fetal immune responses of various kinds may begin. Charles Loke examines the nature of antigens which are found in the placenta, concentrating on those which occur on syncytiotrophoblast and suggesting roles for them in fetal development. Arnold Klopper covers the wide range of proteins and hormones which have been studied during pregnancy and found to vary in a potentially significant way. He has been careful to distinguish between observation and hypothesis, as far as any immunomodulating action is concerned, and his analysis is a model of scientific scepticism. Ian Sargent and Chris Redman have dissected the immune reactions which seem to be most important during pregnancy. While their underlying premise is that these responses are in some way critical to fetal survival, their infor mation should be considered within the context of the succeeding chapters. Gordon Stirrat has covered the pathology of pregnancy and describes those diseases which one might expect to show at least some variation if the immune response of pregnancy had a general impact upon the immune system. xi IMMUNOLOGY OF PREGNANCY AND ITS DISORDERS Alan Beer's chapter summarizes the present situation with respect to reproductive failure and the impact of immunotherapy. He has managed to show how such patients can be classified in a more therapeutically useful way and to suggest what may lie ahead in our understanding of the relationship between reproduction, infertility and the immune system. The final chapter, on the genetics of reproduction, is an attempt to describe a way in which major histocompatibility complexes may be important in speciation and postulates that their role as immune responses genes and ih certain diseases may be epiphenomena. THE DEVELOPING CONCEPTUS AND ITS MEMBRANES This description is only a sketch, principally because I cannot pretend to more than a tyro's grasp of the subject. However, there is some advantage in its naivete, as I hope that it will allow the reader to turn back and refresh a distant memory of the relationships between different maternal and fetal structures. Some of the contributors, notably Charles Loke and Matteo Adinolfi, have been limited to particular tissues. Others, such as Ian Sargent and Chris Redman, require an awareness of histological detail. Each chapter, however, gains lucidity when the reader can visualize fetal growth and development clearly. Only the development of the embryo to the end of the second week is described here, as Mateo Adinolfi includes relevant subsequent embryology. After the early implantation phase has been detailed, the differentiation and histology of the placental and the fetal membranes are dealt with. The text has been deliberately kept simple for the sake of clarity and it is intended that the introduction be used as a template for the rest of the book. (a) Embryonic Development The ovum may be fertilized at one of several distinct locations in the female reproductive tract. Fertilization may occur within the peritoneal cavity, at any point within the Fallopian tube from the fimbria to its opening into the uterus, or in the uterus itself. The contributions in this book are concerned solely with intra-uterine post-implantation pregnancy, so pre-implantation development and ectopic implantation have been excluded. At the time of implantation, the blastocyst has developed into a hollow sphere of cytotrophoblast cells, one pole containing the inner cell mass, which is destined to become the fetus. There is a large blastocyst cavity, but no amniotic cavity yet. The amniotic cavity develops between the inner surface of the trophoblast and the inner cell mass. The inner cell mass becomes a flattened disc of two cell layers, the epiblast, which will give rise to virtually all the cells of the fetus and is the next to the amniotic cavity, and the hypoblast, which primarily differentiates into the extra-embryonic mesoderm and is next to the blastocyst cavity. As the amniotic cavity enlarges, it acquires a thin epithelial roof called the amnion. xii INTRODUCTION Some eccentric hypoblastic cells become thickened and columnar, forming the prochordal plate, which indicates the future site of the mouth, giving rise to the mesenchyme of the head region and the endoderm of the oropharyngeal membrane. lacuna eXira-embryonic somaliC mesoderm Syncytiotrophoblast Maternal AmniO\lc cavlly Co SIK:onrlarv yol Figure 1 Implanted human embryo at 14 days During this time, cells from the cytotrophoblast separate to form the exocoelomic membrane around the primary yolk sac, which develops within the blastocyst cavity, next to the hypoblast. The 'space' between the cyto trophoblast, on the outside, and the amnion and exocoelomic membranes, on the inside, is filled with loosely associated cells derived from the trophoblast, called the extra-embryonic mesoderm. The extra-embryonic coelom is formed by the fusion of the isolated spaces that have appeared in the extra-embryonic mesoderm. This cavity surrounds the whole of the amnion and yolk sac, save where they are joined together by the connecting stalk, and has the effect of dividing the extra-embryonic mesoderm into an outer, somatic layer and an inner, splanchnic one. The extra-embryonic mesoderm and the trophoblast together form the chorion and the extra-embryonic coelom becomes the chorionic cavity. Concurrently, xiii
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