The Reticuloendothelial

System A COMPREHENSIVE TREATISE

Volume 9 Hypersensitivity

The Reticuloendothelial System A COMPREHENSIVE TREATISE

General Editors: Herman Friedman, University of South Florida, Tampa, Florida

Mario R. Escobar, Medical College of Virginia, Richmond, Virginia and Sherwood M. Reichard, Medical College of Georgia, Augusta, Georgia

MORPHOLOGY Edited by Ian Carr and W. T. Daems

BIOCHEMISTRY AND METABOLISM Edited by Anthony J. Sbarra and Robert R. Strauss

PHYLOGENY AND ONTOGENY Edited by Nicholas Cohen and M. Michael Sigel

IMMUNOPATHOLOGY Edited by Noel R. Rose and Benjamin V. Siegel

CANCER Edited by Ronald B. Herberman and Herman Friedman

IMMUNOLOGY Edited by Joseph A. Bellanti and Herbert B. Herscowitz

PHYSIOLOGY (In two parts) Edited by Sherwood M. Reichard and James P. Filkins

PHARMACOLOGY Edited by John Hadden and Andor Szentivanyi

HYPERSENSITIVITY Edited by S. Michael Phillips and Mario R. Escobar

INFECTION Edited by John P. Utz and Mario R. Escobar

The Reticuloendothelial

System A COMPREHENSIVE TREATISE

Volume 9 Hypersensitivity

Edited by

S. MICHAEL PHILLIPS The University of Pennsylvania

Philadelphia, Pennsylvania

and

MARIO R. ESCOBAR Medical College of Virginia

Richmond, Virginia

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data

(Revised for vol. 9)

The Reticuloendothelial system.

Includes bibliographies and indexes. Contents: v. 1. Morphology-v. 2. Biochemistry and metabolism-[etc.]-v. 9. Hypersen­

sitivity. I. Reticuloendothelial system-Collected works. 2. Macrophages-Collected works. I.

Friedman, Herman, 1931- . II. Reichard, Sherwood M. [DNLM: I. Reticuloendothelial system. WH650 R437] QPII 5.R47 599'.029 79-25933

ISBN 978-1-4684-5160-3 ISBN 978-1-4684-5158-0 (eBook) DOI 10.1007/978-1-4684-5158-0

©1986 Plenum Press, New York Softcover reprint ofthe hardcover 1st edition 1986

A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013

All rights reserved

No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

Contributors

PHILIP W. ASKENASE • Department of Medicine, Yale University School of Medicine, New Haven, Connecticut

MICHAEL K. BACH • Department of Hypersensitivity Diseases Research, The Upjohn Company, Kalamazoo, Michigan

ANDRE CAPRON • Centre d'Immunologie et de Biologie Parasitaire, INSERM U-167, CNRS 624, Institut Pasteur, Lille Cedex, France

MICHAEL D. CLAYMAN • Renal Electrolyte Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

MARION C. COHEN • Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut

STANLEY COHEN • Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut

JEAN-PAUL DESSAINT • Centre d'Immunologie et de Biologie Parasitaire, IN­SERM U-167, CNRS 624, Institut Pasteur, Lille Cedex, France

RICHARD L. EDWARDS • Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, and the Veterans Admin­istration Medical Center, Newington, Connecticut

VEETA A. EWAN • Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, and the Veterans Administration Medical Center, Newington, Connecticut

STEPHEN J. GALLI • Departments of Pathology, Beth Israel Hospital and Har­vard Medical School, and the Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts

v

vi CONTRIBUTORS

CARL S. GOLDSTEIN • Renal Electrolyte Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

JANICE K. GUTOWSKI • Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut

JUDITH HEAD • Departments of Cell Biology, Pathology, and Internal Medi­cine, University of Texas Health Science Center, Dallas, Texas

MICHEL D. KAzATCHKINE • INSERM U-28 and Unite d'Immunopathologie, Hopital Broussais, Paris, France

JAMES W. KAzURA • Division of Geographic Medicine, Department of Medi­cine, Case Western Reserve University and University Hospitals, Cleve­land, Ohio

ANTHONY KULCZYCKI, JR. • Department of Internal Medicine, Division of Al­lergy and Immunology, Washington University School of Medicine, St. Louis, Missouri

GRAHAM F. MITCHELL • Immunoparasitology Unit, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia

ERIC G. NEILSON • Renal Electrolyte Section, Department of Medicine, Uni­versity of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

URS E. NYDEGGER • Central Hematology Laboratory Inselspital, Bern, Switzerland

FREDERICK R. RICKLES • Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, and the Veterans Admin­istration Medical Center, Newington, Connecticut

MICHAEL R. SIMON • Medical and Research Services, Veterans Administra­tion Medical Center, Allen Park, Michigan, and Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan

JOAN STEIN-STREILEIN • Departments of Cell Biology, Pathology, and Internal Medicine, University of Texas Health Science Center, Dallas, Texas

CONTRIBUTORS vii

J. WAYNE STREILEIN • Departments of Cell Biology, Pathology, and Internal Medicine, University of Texas Health Science Center, Dallas, Texas

LEON WEISS • Laboratory of Experimental Hematology and Cell Biology, Uni­versity of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania

PAUL R. WOOD • Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia

BURTON ZWEIMAN • Allergy and Immunology Section, University of Pennsyl­vania School of Medicine, Philadelphia, Pennsylvania

Foreword

This comprehensive treatise on the reticuloendothelial system is a project jointly shared by individual members of the Reticuloendothelial (RE) Society and bio­medical scientists in general who are interested in the intricate system of cells and molecular moieties derived from those cells which constitute the RES. It may now be more fashionable in some quarters to consider these cells as part of what is called the mononuclear phagocytic system or the lymphoreticular sys­tem. Nevertheless, because of historical developments and current interest in the subject by investigators from many diverse areas, it seems advantageous to present in one comprehensive treatise current information and knowledge con­cerning basic aspects of the RES, such as morphology, biochemistry, phylogeny and ontogeny, physiology, and pharmacology as well as clinical areas including immunopathology, cancer, infectious diseases, allergy, and hypersensitivity. It is anticipated that, by presenting information concerning these apparently het­erogeneous topics under the unifying umbrella of the RES, attention will be focused on the similarities as well as interactions among the cell types constitut­ing the RES from the viewpoint of various disciplines. The treatise editors and their editorial board, consisting predominantly of the editors of individual vol­umes, are extremely grateful for the enthusiastic cooperation and enormous task undertaken by members of the biomedical community in general and especially by members of the American as well as European and Japanese Reticuloen­dothelial Societies. The assistance, cooperation, and great support from the editorial staff of Plenum Press are also valued greatly. It is hoped that this unique treatise, the first to offer a fully comprehensive treatment of our knowl­edge concerning the RES, will provide a unified framework for evaluating what is known and what still has to be investigated in this actively growing field. The various volumes of this treatise provide extensive in-depth and integrated infor­mation on classical as well as experimental aspects of the RES. It is expected that these volumes will serve as a major reference for day-to-day examination of various subjects dealing with the RES from many different viewpoints.

Herman Friedman Mario R. Escobar

Sherwood M. Reichard

ix

Preface

All of the immunologic phenomena observed by the end of the 19th century supported the view that they were related to defense mechanisms of the host. This view was, however, being disputed by experimental tests which brought about a short period of confusion. Karl Landsteiner's findings and, especially, the discovery of anaphylaxis by Charles Richet and Paul Portier in 1902 heralded in the very beginning of this century the birth of the domain which we now call Hypersensitivity. This triggered a series of clinical investigations which, not infrequently, generated a number of misconceptions. However, the crescendo of progress that has ensued in the general field of immunology during the last 25 years has brought forth new understanding and pragmatic approaches to the patient with allergic disease. Indeed, one working in the field of immunology senses a major revolution of immunobiologic thinking, much of which has rele­vance to the area of Hypersensitivity.

In the present volume of this comprehensive treatise on the Reticuloen­dothelial System (RES) we strive to bring together relevant contributions from experts in the field. The further understanding of those mechanisms that have been elucidated by in vitro experiments and the use of appropriate animal mod­els, has in numerous instances paved the way towards a better interpretation of results from human studies and has reached the point of clinical application.

Dr. Weiss, in the first chapter of this volume, reviews the numerous ac­tivities of the hematopoietic system, which include diverse migratory pathways, cell sorting, cell recognition, cell differentiation, and cell functions. These ac­tivities require a complex regulation at every level of organization and function. Dr. Zweiman elaborates on the leukocyte-vascular endothelium interactions which are important to the understanding of the circulation of leukocytes and their role in localized immune and inflammatory responses. Drs. Streilein, Stein­Streilein, and Head show how the so-called regional spheres of immunologic influence, including the gastrointestinal, skin, lung, and reproductive systems, may prove to be crucial to our understanding of specific types of immune reac­tions and the pathogenesis of certain human inflammatory disorders. These first three chapters permitted tracing the origin and fate of various constituents of the RES in terms of structural distribution.

Dr. Kukzycki describes the role of the IgE receptor in the release and/or production of mediators from mast cells, and basophils, and Fc receptors of high and lower affinity, and/or less specificity for IgE. Drs. Dessaint and Capron lucidly present their own in vitro experiments on anaphylactic antibody-depen-

Xl

XII PREFACE

dent eosinophil or macrophage cytotoxicity as they relate to receptor-mediated mechanisms of activation. These observations were made not only in human and experimental schistosomiasis, but also in several models of experimental filariasis. Confirmation was obtained by the direct evidence of the in vivo rele­vance of anaphylactic antibodies complexed to parasite antigens. They show how the interaction of phagocytic cells (e.g., macrophages and eosinophils) with anaphylactic antibodies in human defense against helminth parasites, reveals that anaphylactic antibodies in the form of immune complexes, besides their well-known function in immediate hypersensitivity, can also have an alternate function in protective immunity. Dr. Simon recounts the multiplicity of immu­nologic abnormalities associated with specific human allergic diseases and their relation to mediators of immediate hypersensitivity. Dr. Kazatchkine and Nydegger expand the concept of immune complexes and other effector compo­nents through an examination of mechanisms of complement activation. These authors discuss effector events both in the circulation and at the site of the tissue lesion. Dr. Kazura addresses another aspect of effector function, effector cells and antibody classes participating in antibody-dependent cell-mediated cytotoxicity reactions (ADCC) and potential clinical applications. Drs. Cohen, Gutowski, and Cohen discuss the multiple biological properties of the inflam­matory lymphokines both in vitro and in vivo. Drs. Edwards, Ewan, and Rickles highlight the importance of coagulation in inflammation with particular refer­ence to monocyte/macrophage pro coagulants (PCA's) and their regulation. This regulation is dependent upon a complex network of interacting pathways. Dr. Bach reviews the areas of active research involving the leukotrienes and their role in human disease. Drs. Galli and Askenase focus on the current under­standing of the mechanisms regulating the cutaneous basophil hypersensitivity (CBH) and other delayed onset reactions containing large numbers of basophils. In this connection, they present a valid argument for the need to reassess the nomenclature of CBH.

The topics which we have introduced above have dealt mainly with the cellular components and the specific release of mediators of hypersensitivity reactions, their distribution, role and mechanisms of action, as well as their interactions. The last two chapters address some of the biochemical conse­quences of these interactions. Drs. Clayman, Goldstein, and Neilson review the role which immunogenetics, the RES, and the cellular influence on the develop­ment of antigen-recognition and immunoregulation have in renal injury. They consider events associated with responses to antigens of both renal and non­renal origin. Finally, Drs. Mitchell and Wood deal with the extracellular mac­rophage-related events in the immunology of parasitism. They emphasize the role of the macrophage in, or from, parasitized hosts as a regulator of anti­parasite immune responses and as an effector cell of host resistance involving mediator release. They present their studies pertaining to the immunoregulatory role of parasitized macrophages in murine cutaneous leishmaniasis and examine the role of macrophage products in the control of infection with plasmodia and related intraerythrocytic protozoa.

In creating this volume we realized that the subject matter was somewhat

PREFACE xiii

arbitrary and could not be all-inclusive. We are most grateful to all the authors for their enthusiastic response to our request to review current knowledge on the general or specific aspects of the RES and Hypersensitivity.

We owe a very special debt of gratitude to Dr. Peter Abramoff who, more than anyone else, was instrumental in the initial formulation of the concepts and selection of the contributors for this volume. The expert and generous assistance given to us by Mr. Kirk Jensen from Plenum Publishing Corporation and Ms. Charlotte Phillips from the Medical College of Virginia are sincerely appreciated.

S. Michael Phillips Mario R. Escobar

Contents

1. Cellular Regulation in Hematopoiesis

LEON WEISS

1. Introduction 1 2. The Nature of the Hematopoietic System as Exemplified by the Life

Cycle of Macrophages 1 3. Migratory Character of the Hematopoietic System 3 4. Hematopoietic Microenvironments 4 5. Hematopoietic Stem Cells 5 6. Cell Types Associated with Hematopoietic Regulation 7

6.1. Thymic Epithelium 7 6.2. Bone-Lining Cells 9 6.3. Reticular Cells 9 6.4. Macrophages 12 6.5. Antigen-Presenting Cells 12 6.6. T Lymphocytes and Other Blood Cells 13

7. Vasculature in Hematopoietic Regulation 14 8. Regulatory Arrangements in Hematopoiesis: Regulatory Factors 15 9. Conclusion 17 References 17

2. Endothelial Reactions

BURTON ZWEIMAN

1. Introduction 23 2. Structure of Vascular Endothelium 23 3. The Normal Endothelium as a Selective Barrier for Fluids 24 4. Normal Leukocyte-Endothelium Interactions 24 5. In Vitro Studies of Leukocyte-Endothelium Interactions 27 6. A Possible Role for Endothelial Cells in Lymphocyte-Mediated Immune

Responses 28 7. The Vascular Endothelium in Inflammation: General Concepts 29 8. Lymphocyte-Endothelium Interactions in Inflammation 29

xv

xvi CONTENTS

9. Granulocyte-Endothelium Interactions in Inflammation 30 10. Inflammatory Cell-Endothelium Interactions in Human Allergic

Responses 31 11. Conclusion 32 References 33

3. Regional Specialization in Antigen Presentation

J. WAYNE STREILEIN, JOAN STEIN-STREILEIN, and JUDITH HEAD

1. Introduction 37 2. Regional Spheres of Immunologic Influence 39 3. Gastrointestinal Tract 40

3.1. Barrier Properties 40 3.2. Structural Specialization for Antigen Presentation 41 3.3. Antigen-Presenting Cells of GALT 43 3.4. Sites of Antigen Recognition 45 3.5. Specialized Lymphocytes That Traffic through GALT 46 3.6. Local and Systemic Consequences of Antigen Presentation and

Recognition within the Gut 48 3.7. Summary 51

4. Skin 52 4.1. Barrier Properties 52 4.2. Structural Specialization for Antigen Presentation 53 4.3. Unique Antigen-Presenting Cells of the Epidermis 53 4.4. Site of Antigen Recognition 56 4.5. Specialized Lymphocytes That Traffic through the Skin 57 4.6. Epidermotropism of T Lymphocytes 59 4.7. Local and Systemic Consequences of Antigen Presentation and

Recognition within the Skin 62 4.8. Summary 63

5. Lung 64 5.1. The Gas Exchange Parenchyma 64 5.2. The Airways 64 5.3. The Vasculature 65 5.4. Nature of Barriers to Antigen in Presentation 65 5.5. Structural Specializations Allowing Antigens to Gain Access into the

Body 69 5.6. Unique Antigen-Presenting Process 71 5.7. Local and Systemic Consequences of Immune Responses That Are

Initiated by Antigen Presented to (in) the Lung 72 5.8. Summary 74

6. Reproductive Tracts 74 6.1. Barrier Properties and Antigen Presentation 75

CONTENTS xvii

6.2. Sites of Antigen Recognition and Specialized Cell Types 77 6.3. Local and Systemic Immune Consequences 78

7. Summary 79 References 81

4. Structure and Expression of IgE Receptors

ANTHONY KULCZYCKI, JR.

1. Introduction 95 2. Interaction of IgE with High-Affinity FCE Receptors on Mast Cells and

Basophils 95 3. Structure of Mast Cell/Basophil FCE Receptors 96 4. Expression of Mast Cell and Basophil IgE Receptors 97 5. The Role of the IgE Receptor in the Release and/or Production of

Mediators from Mast Cells and Basophils 98 6. FCE Receptors with Lower Affinity and/or Less Specificity for IgE 99 References 100

5. Interaction of Phagocytic Cells with Immune Complexes of Anaphylactic Antibodies

JEAN-PAUL DESSAINT and ANDRE CAPRON

1. Introduction 103 2. Receptors for Anaphylactic Antibodies on Phagocytic Cells 104

2.1. Receptors for IgE on Mononuclear Phagocytes 104 2.2. Receptors for IgE on Eosinophils 107 2.3. Receptors for Anaphylactic IgG 108

3. Function of the Receptors for Anaphylactic Antibodies 108 3.1. Macrophage Activation by IgE 109 3.2. Dimeric IgE as the Minimal Degree of Aggregation for Macrophage

Triggering 110 3.3. IgE Antibody-Dependent Macrophage-Mediated Cytotoxicity 111 3.4. Eosinophil Cytotoxicity by Complexes of Anaphylactic IgG

Antibodies 114 3.5. Eosinophil Activation by IgE 116

4. The Case of Neutrophils 117 5. Summary and Conclusions 118 References 120

xviii CONTENTS

6. Leukocyte Function in Human Allergic Disease

MICHAEL R. SIMON

1. Introduction 125 2. Expression of Histamine Receptors on Human Mononuclear and

Polymorphonuclear Leukocytes 126 3. Histamine Effects on Cell Surface Receptors 127 4. Effects of Histamine, Histamine Agonists, and Antagonists on Cellular

Functions in Vitro and in Vivo 128 4.1. Histamine Suppression of Lymphocyte Function 128 4.2. Histamine Agonist Effects on B-Cell Function 131 4.3. Histamine Antagonist Effects on Lymphocyte Function 133 4.4. In Vivo Effects of H2 Blockade 135 4.5. In Vivo Interaction of Immediate and Delayed

Hypersensitivity 136 4.6. Histamine Effects on Neutrophil and Monocyte Function 136 4.7. Summary 138

5. Effects of Other Mediators of Immediate Hypersensitivity 138 5.1. Neutrophil Chemotactic Factor and Eosinophil Chemotactic Factor

of Anaphylaxis 138 5.2. Platelet-Activating Factor, Serotonin Hydroxyeicosatetraenoic Acid,

and the Leukotrienes 139 6. IgE and the Macrophage 139 7. Immunological Abnormalities Which May Relate to Immediate

Hypersensitivity 141 7.1. Respiratory Allergy 141 7.2. Atopic Dermatitis 144 7.3. Syndrome of Recurrent Severe Bacterial Infections, Atopic

Dermatitis, Hypetimmunoglobulinemia E, and Defective Neutrophil Chemotaxis 150

7.4. Chronic Mucocutaneous Candidiasis 151 7.5 Chronic Dermatophytosis 152 7.6. Allergic Bronchopulmonary Aspergillosis, Coccidioidomycosis; and

Histoplasmosis 154 8. Conclusion 155 References 156

7. Complement-Mediated Injury

MICHEL D. KAzATCHKINE and URS E. NYDEGGER

1. Introduction 173 2. Proteins of the Complement System and Pathways of Complement

Activation 173

2.1. Proteins of the Complement System 173 2.2. The Classical Pathway of Complement Activation 2.3. The Alternative Pathway of Complement Activation 2.4. Interrelations between the Classical and Alternative

Pathways 182 3. Effector Functions of the Complement System 183

3.1. The Terminal C5b-9 Complex 183

176 179

3.2. Biologically Active Peptides Derived from Complement Activation 185

CONTENTS xix

3.3. Interactions between Complement Proteins Bound to Targets of Complement Activation and Specific Cellular Receptors 187

3.4. Complement-Mediated Processing of Immune Complexes 190 References 191

8. Antibody-Mediated Cytotoxicity

JAMES W. }(AZURA

1. Introduction 197 2. Effector Cells 198

2.1. Lymphoid Cells 198 2.2. Monocytes and Macrophages 199 2.3. Granulocytes 200 2.4. Mechanisms of Effector Cell-Mediated Cytotoxicity 200

3. Antibody Classes Active in ADCC 203 3.1. IgG Subclasses 203 3.2. IgM 203 3.3. IgA 204 3.4. IgE 205

4. Future Considerations 205 References 206

9. Inflammatory Lymphokines in Hypersensitivity Reactions

MARION C. COHEN, JANICE K. GUTOWSKI, and STANLEY COHEN

1. Introduction 209 2. Histologic Manifestations of Cellular Immunity 210

211 213

3. General Properties of Effector Lymphokines 4. Lymphokines Affecting Inflammatory Cells 5. Other Migration-Modifying Lymphokines 218 6. Lymphokines Affecting Vascular Permeability 219 7. In Vivo Effects of Lymphokines 220 8. Conclusion 224 References 225

XX CONTENTS

10. Macrophage Procoagulants, Fibrin Deposition, and the Inflammatory Response

RICHARD 1. EDWARDS, VEETA A. EWAN, and FREDERICK R. RICKLES

1. Introduction: The Inflammatory Response 233 2. Fibrin and Inflammation 234 3. Cells, Fibrin, and Inflammation 235 4. Leukocyte Procoagulant Activity, the Generation of Fibrin, and

Inflammation 238 4.1. Cell of Origin of Leukocyte Procoagulant Activity 238 4.2. Characterization of Leukocyte Procoagulants 241

5. Regulation of Monocyte/Macrophage Procoagulant Generation 249 5.1. Activation of Monocyte Procoagulant(s) 249 5.2. Modulation of Monocyte Procoagulant Generation 251

6. The Potential Relationship between Monocyte/Macrophage Procoagulant Generation and Thromboembolic Complications of Disease 254 6.1. Conditions Associated with Enhanced Monocyte Procoagulant

Generation and Thromboembolic Disease 254 6.2. Conditions Associated with Impaired Monocyte Procoagulant

Generation 257 7. Summary 258 References 259

11. Leukotrienes

MICHAEL K. BACH

1. Introduction 267 2. Nomenclature 267 3. Historical 268

3.1. Discovery of SRS-A 268 3.2. Proof of Structure 269

4. Assay 271 5. Structure-Activity Studies 273 6. Receptors 274 7. Cells Producing Leukotrienes and Eliciting Stimuli 276

7.1. Various Tissues, Various Stimuli 276 7.2. Polymorphonuclear Leukocytes 276 7.3. Macrophages and Mononuclear Cells 277 7.4. Mast Cells and Basophils 278 7.5. Eosinophils 278 7.6. Other Cells 279

8. Biosynthesis, Interconversion, and Metabolic Breakdown 279 8.1. Arachidonate Mobilization 279

CONTENTS xxi

8.2. 5-Lipoxygenase 281 8.3. Regulatory Effects of 12-HPETE and of 15-HPETE 281 8.4. LTA4 and LTB4 Synthetases 282 8.5. LTA4: Glutathione S-Transferase 283 8.6. 'Y-Glutamyl Transpeptidase, LTD4 Dipeptidase 283 8.7. w-Oxidation, Peroxidative Inactivation 284

9. Actions of LTB4 285 9.1. Leukocyte Activation 285 9.2. In Vitro Effects 285 9.3. In Vivo Effects 287

10. Actions of Thiol Ether Leukotrienes 10.1. Smooth Muscle Contraction 10.2. Cardiovascular Effects 289

288 288

10.3. Effects on Vascular Permeability 291 10.4. Effects on Cell Activation and Hormone Secretion 10.5. Effects on Mucus Production and Mucus Transport 10.6. Effects on Nerve Cells 293 10.7. Effects on the Immune Response 293

291 292

10.8. Effects on Production, Release, or Action of Leukotrienes, Prostaglandins, and Other Mediators 294

11. Role of Leukotrienes in Disease 295 12. Pharmacologic Intervention 297

12.1. Fatty Acid Analogues 297 12.2. Piriprost (U-60,257) 298 12.3. AA861, Quinones, Hydroquinones, and Flavonoids 299 12.4. FPL 55712 300 12.5. Other End-Organ Antagonists 300

13. Concluding Remarks 301 References 301

12. Cutaneous Basophil Hypersensitivity

STEPHEN J. GALLI and PHILIP W. ASKENASE

1. Introduction 321 2. Techniques for Morphologic Analysis of Delayed-Onset Immunologic

Reactions Containing Basophils 322 3. Origin and Normal Distribution of Basophils and Mast Cells 326 4. Prototypic Reactions of Cell-Mediated Immunity 331

4.1. Historical Perspective 331 4.2. Classic Delayed (Tuberculin-Type) Hypersensitivity 333 4.3. Cutaneous Basophil Hypersensitivity as Originally Described

(Classic CBH) 334 5. Immunology of the Induction and Expression of Delayed Reactions

Containing Basophils 339

xxii CONTENTS

5.1. The Role of T Lymphocytes 339 5.2. The Role of Antibodies 342 5.3. The Regulation of Basophil Recruitment to Delayed Reactions in the

Guinea Pig 346 6. Biologic Function of Basophils in Delayed Reactions 348

6.1. Introduction 348 6.2. Use of Antibasophil Serum 349 6.3. Complex CBH Responses to an Intestinal Nematode 350 6.4. Complex CBH Responses to Infestation with Ixodid Ticks 351 6.5. CBH Responses to Tumors 354 6.6. Summary 355

7. Does CBH Occur in Species Other Than the Guinea Pig? 355 8. Nomenclature of CBH: Summary 356 References 360

13. The Nephritogenic Immune Response and Renal Immunopathogenesis: A Progress Report

MICHAEL D. CLAYMAN, CARL S. GOLDSTEIN, and ERIC G. NEILSON

1. Introduction 371 2. Antigen-Recognition, Immunogenetics, and the Afferent Phase of the

Nephritogenic Immune Response 373 2.1. Basic Considerations 373 2.2. Antigen 376 2.3. Immunogenetics of Renal Disease 390

3. Immune Regulation and the Nephritogenic Immune Response 397 3.1. Immune Regulation and Experimental Renal Disease 398 3.2. Immune Regulation and Human Renal Disease 400

4. Effector Limb Function and the Nephritogenic Immune Response 401 4.1. An Overview of the Humoral Immune Response in Renal

Disease 402 4.2. The Role of T Lymphocytes in the Effector Pathway 404 4.3. Analysis of Macrophage Effector Function 405 4.4. NK cells in Renal Disease 420 4.5. Interferon and Renal Histopathogenesis 420

5. Summary 421 References 421

14. Macrophages in Immunoparasitology

GRAHAM F. MITCHELL and PAUL R. WOOD

l. Introduction 435 2. Macrophages and the Regulation of Immune Responses to Parasite

Antigens 436

CONTENTS xxiii

3. Macrophages and Destruction of Parasites not Within Macrophages 447 3.1. Macrophages in Murine Malaria

and Babesia Infections 449 References 456

Index 473