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An Introduction to Immunotoxicology - J. Descotes (Taylor and Francis, 1999) WW PDF

196 Pages·1999·1.54 MB·English
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An Introduction to Immunotoxicology An Introduction to Immunotoxicology JACQUES DESCOTES Lyon Poison Centre and Department of Pharmacology, Medical Toxicology and Environmental Medicine, INSERM U999, Lyon-RTH Laennec Faculty of Medicine, Lyon, France UK Taylor & Francis Ltd, 1 Gunpowder Square, London, EC4A 3DF USA Taylor & Francis Inc., 325 Chestnut Street, Philadelphia, PA 19106 This edition published in the Taylor & Francis e-Library, 2003. Copyright © Taylor & Francis 1999 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, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. Every effort has been made to ensure that the advice and information in this book is true and accurate at the time of going to press. However, neither the publisher nor the author can accept any legal responsibility or liability for any errors or omissions that may be made. In the case of drug administration, any medical procedure or the use of technical equipment mentioned within this book, you are strongly advised to consult the manufacturer’s guidelines. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library. ISBN 0-203-36254-3 Master e-book ISBN ISBN 0-203-37514-9 (Adobe eReader Format) ISBN 0-7484-0306-x (cased) ISBN 0-7484-0307-8 (paperback) Library of Congress Cataloguing-in-Publication Data are available Cover design by Hybert Design and Type This book is dedicated to Christiane. Jérôme and Aurélie vii Contents Preface page xi PART I Immunotoxic Effects and their Clinical Consequences 1 1 Definition and History of Immunotoxicology 3 Definition 3 History 4 Scope of immunotoxicology 7 References 9 2 Overview of the Immune System 11 Immunocompetent cells 12 The lymphoid system 14 Immune responses 15 External influences on the immune system 17 Conclusion 19 References 19 3 Immunosuppression and Immunodepression 21 Impaired resistance against microbial pathogens 21 Increased incidence of cancer 25 Other adverse consequences of immunosuppression 27 Immunosuppression and immunodepression 28 References 29 4 Immunostimulation 31 Flu-like reactions 31 Exacerbation of underlying diseases 32 Dormant diseases 32 Autoimmune diseases 33 Immuno-allergic reactions 34 Contents viii Inhibition of hepatic drug metabolism 34 Immunostimulation and immunosuppression 35 References 35 5 Hypersensitivity 37 Immunogenicity 38 Immuno-allergic reactions 40 Pseudo-allergic reactions 44 References 47 6 Autoimmunity 51 Organ-specific autoimmune reactions 51 Systemic autoimmune reactions 55 Isolated auto-antibodies 60 References 61 7 Major Immunotoxicants 63 Medicinal products 63 Industrial and environmental pollutants 69 References 73 PART II Immunotoxicity Evaluation 77 8 Guidelines 79 US Environmental Protection Agency 79 Council of the European Communities 82 The Japanese authorities’ drug antigenicity requirement 83 OECD guideline 407 83 The US FDA Red Book II 84 Other guidelines 85 Perspectives 85 References 86 9 Histopathology 89 Organisation of the lymphoid tissue 90 Histopathology of the lymphoid tissue 90 Non-histological, non-functional endpoints 92 References 95 10 Assays of Humoral Immunity 97 Antigenic stimulation 97 Measurement of specific antibody levels 99 The plaque-forming cell assay 100 B lymphocyte proliferation assay 101 References 102 11 Assays of Cell-Mediated Immunity 103 In vivo assays of cell-mediated immunity 103 In vitro assays of cell-mediated immunity 105 References 108 Contents ix 12 Assays of Non-Specific Defences 111 Assays of phagocytosis 111 Natural killer cell activity 115 References 115 13 Host Resistance Assays 117 Experimental infection models 118 Implanted tumours 121 Other experimental diseases 123 References 123 14 Strategies for the Evaluation of Immunosuppression 125 Tiered protocols 125 Practical considerations 131 Good Laboratory Practice 134 References 134 15 Identification of Chemical Sensitisers 137 Anaphylaxis models 137 Contact sensitisation assays 140 Evaluation strategies 142 References 143 16 Prediction of Autoimmunity 145 Predictability of organ-specific versus systemic autoimmune reactions 145 The popliteal lymph node assay 146 Auto-antibodies in conventional toxicity studies 148 Animal models of autoimmune diseases 149 References 150 PART III Trends and Perspectives in Immunotoxicology 153 17 Immunotoxicity Risk Assessment 155 Toxicity risk assessment 155 Approaches in immunotoxicity risk assessment 156 References 157 18 New Methods in Immunotoxicology 159 In vitro methods for immunotoxicity evaluation 159 New animal models 161 Perspectives 162 References 162 19 Human Immunotoxicology 165 Identification of immunotoxicants in human beings 165 Surveillance of exposed populations 168 Validation of non-clinical results 169 Biomarkers of human immunotoxicity 169 References 171

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