Principles and Methods of Immunotoxicology

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ISBN: 9780444510938 | 0444510931
Cover: Hardcover
Copyright: 12/13/2004

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Lyon Poison Center, France. First volume of a three-volume set covers the many facets of current immunotoxicology, such as clinical, experimental, mechanistic, and regulatory aspects. Includes the principles and methods of experimental and clinical immunotoxicology and highlights significant historical events. For researchers. Previous edition: c1988.

Preface

vii

Chapter 1 Definition, history, and scope of immunotoxicology

Definition of immunotoxicology

(1)

A short history of immunotoxicology

(6)

First phase: the 'prehistorical' phase

(1)

Second phase: the birth of immunotoxicology

(1)

Third phase: the scope of immunotoxicology widens

(1)

Fourth phase: immunotoxicology comes of age

(1)

Fifth phase: the future of immunotoxicology

(1)

The scope of immunotoxicology

(4)

Immunosuppression

(2)

Immunostimulation

(1)

Hypersensitivity

(1)

Autoimmunity

(1)

References

(6)

Chapter 2 The immune system: a toxicologist's overview

Introduction

(2)

The lymphoid organs

(3)

Central lymphoid organs

(2)

Peripheral lymphoid organs

(1)

Immunocompetent cells

(7)

Lymphocytes

(2)

Phagocytes

(1)

Other immunocompetent cells

(3)

Innate (natural) immunity

(5)

Components of innate immunity

(4)

Recognition of pathogen-specific molecular patterns

(1)

Inflammation

(1)

Adaptive (specific) immunity

(9)

Cell-cell interactions

(1)

Humoral immunity

(2)

Cellular immunity

(6)

External influences on the immune system

(4)

Psychoneuroimmunology

(1)

Interactions between the nervous, endocrine and immune systems

(2)

Age and immunocompetence

(1)

Implications for immunotoxicity evaluation

(1)

Conclusion

(1)

References

(6)

Chapter 3 Health consequences of immunotoxic effects

Introduction

(1)

Immunosuppression

(11)

Impaired resistance against microbial pathogens

(3)

Immunosuppression and malignancies

(4)

Other adverse effects related to immunosuppression

(1)

Immunosuppression vs. immunodepression

(2)

Immunostimulation

(4)

Flu-like reactions

(1)

Increased incidence of autoimmune diseases

(1)

Hypersensitivity reactions to varied allergens

(1)

Inhibition of drug-metabolizing enzymes

(2)

Other complications associated with immunostimulation

(1)

Hypersensitivity

(18)

Epidemiology

(1)

Clinical signs and symptoms

(12)

Diagnosis

(4)

Pseudoallergy

(1)

Autoimmunity

(9)

Incidence of autoimmune diseases and autoimmune reactions

(1)

Systemic autoimmune reactions

(3)

Organ-specific autoimmune reactions

(5)

Isolated autoantibodies

(1)

Conclusion

(1)

References

(30)

Chapter 4 Mechanisms of immunotoxic effects

Introduction

127

(1)

Mechanisms of immunosuppression

128

(3)

Introduction

128

(1)

Nonspecific mechanisms

129

(1)

Antigen-specific mechanisms

130

(1)

Mechanisms of immunostimulation

131

(2)

Introduction

131

(1)

Flu-like reactions and acute cytokine syndromes

131

(1)

Autoimmune diseases and immunostimulation

132

(1)

Inhibition of drug-metabolizing enzymes

132

(1)

Mechanisms of hypersensitivity reactions

133

(16)

Introduction

133

(1)

Immune-mediated hypersensitivity reactions

134

(9)

Pseudoallergic hypersensitivity reactions

143

(2)

Mechanisms of autoimmune reactions

145

(1)

Pathophysiological hypotheses

146

(2)

Predisposing factors

148

(1)

Structure-immunotoxicity relationships

149

(1)

Conclusion

149

(1)

References

149

(14)

Chapter 5 Nonclinical evaluation of unexpected immunosuppression

Introduction

163

(1)

Histopathology

163

(7)

Conventional histology examination

164

(1)

Histology of lymphoid organs

165

(5)

Hematology and clinical chemistry

170

(3)

Blood cell counts

170

(1)

Bone marrow toxicity

171

(1)

Lymphocyte subset analysis

171

(1)

Serum immunoglobulins

172

(1)

Measurement of humoral immunity

173

(4)

General considerations

173

(1)

The PFC assay

174

(2)

ELISA

176

(1)

ELISPOT

177

(1)

Measurement of cellular immunity

177

(5)

In vivo animal models

177

(2)

Lymphocyte proliferation assays

179

(1)

T lymphocyte cytotoxicity assays

180

(1)

Cytokine assays

181

(1)

Measurement of innate immunity

182

(4)

Phagocytosis

182

(2)

Chemotaxis

184

(1)

NK cell activity

184

(2)

Complement

186

(1)

Host resistance models

186

(3)

Experimental infection models

186

(3)

Implanted tumor models

189

(1)

Conclusion

189

(1)

References

189

(16)

Chapter 6 Nonclinical evaluation of unexpected immunostimulation

Introduction

205

(1)

Histopathology

205

(1)

Hematology and clinical chemistry

206

(1)

Immune function assays

206

(1)

Cytokine release assays

207

(1)

Host resistance models

207

(5)

Experimental infection models

208

(1)

Animal models of autoimmune diseases

208

(4)

Conclusion

212

(1)

References

213

(6)

Chapter 7 Nonclinical evaluation of the potential for hypersensitivity

Introduction

219

(1)

Prediction of immune-mediated hypersensitivity

220

(12)

Prediction of IgE-mediated hypersensitivity reactions

220

(4)

Prediction of T lymphocyte-mediated hypersensivity reactions

224

(8)

Pseudoallergy

232

(1)

Conclusion

233

(1)

References

233

(10)

Chapter 8 Nonclinical evaluation of the potential for autoimmunity

Introduction

243

(1)

Systemic autoimmune reactions

243

(7)

Animal models of systemic autoimmune reactions

243

(1)

The popliteal lymph node assay (PLNA)

244

(6)

Organ-specific autoimmune reactions

250

(1)

Conclusion

251

(1)

References

251

(6)

Chapter 9 Regulatory aspects of immunotoxicity evaluation

Introduction

257

(1)

Early immunotoxicity regulations

257

(3)

First EPA guideline on pesticide immunotoxicity

258

(1)

Commission of the European Communities

259

(1)

Japanese drug antigenicity guideline

260

(1)

FDA Red Book II

260

(1)

Recent immunotoxicity guidelines

260

(4)

OECD Guideline 407

261

(1)

Second EPA guideline on pesticide immunotoxicity

261

(1)

ICH guideline on the preclinical safety evaluation of biotechnology-derived pharmaceuticals

262

(1)

EMEA concept paper on immunotoxicity

262

(1)

FDA CDRH immunotoxicity testing guidance

262

(1)

CPMP note for guidance on repeated dose toxicity

263

(1)

FDA guidance on immunotoxicology evaluation of investigational new drugs

264

(1)

Conclusion

264

(2)

References

266

(3)

Chapter 10 Nonclinical strategies of immunotoxicity evaluation and risk assessment

Introduction

269

(1)

Good laboratory practices in immunotoxicology

269

(3)

Impact of animal-related factors on immunity

270

(2)

Standardization of reagents and assays

272

(1)

Strategies for the prediction of immunosuppression

272

(8)

General considerations

273

(4)

Selection of assays

277

(3)

Strategies for the prediction of immunostimulation

280

(1)

Strategies for the prediction of hypersensitivity

280

(1)

Strategies for the prediction of autoimmune reactions

281

(1)

Risk assessment

281

(3)

Definitions and concept

281

(1)

Immunotoxicity risk assessment

282

(2)

Conclusion

284

(1)

References

284

(11)

Chapter 11 Clinical immunotoxicology

Introduction

295

(1)

Objectives of clinical immunotoxicology

295

(3)

Identification of immunotoxicants in human beings

296

(1)

Surveillance of at-risk humans exposed to immunotoxicants

297

(1)

Validation of nonclinical immunotoxicity assays and animal models

297

(1)

Clinical assessment of immunotoxicity

298

(2)

Clinical immunology end-points to assess humoral immunity

298

(1)

Clinical immunology end-points to assess cellular immunity

298

(2)

Clinical immunology end-points to assess nonspecific immunity

300

(1)

Biomarkers of immunotoxicity

300

(2)

Immune end-points adopted by the ATSDR

301

(1)

Recommendations of the US National Research Council

301

(1)

Environmental epidemiology studies

302

(1)

Experimental vs. observational epidemiological methods

302

(1)

Use of epidemiological studies in immunotoxicity assessment

302

(1)

Disease clusters and sentinel diseases

303

(2)

Disease clusters

304

(1)

Sentinel events

304

(1)

Conclusion

305

(1)

References

305

(6)

Chapter 12 Immunotherapy of human poisonings

Introduction

311

(1)

Experimental studies

312

(3)

Medicinal products

312

(1)

Industrial and environmental chemicals

313

(2)

Clinical studies

315

(5)

Immunotherapy of envenomations

315

(1)

Digitalis

316

(1)

Tricyclic antidepressants

317

(1)

Colchicine

318

(1)

Vaccines for the treatment of drug dependence

318

(2)

Mechanism of specific antibodies efficacy

320

(1)

Conclusion

321

(1)

References

321

(6)

Chapter 13 Chemical immunoteratology and developmental immunotoxicology

Introduction

327

(1)

Immunity in newborns

328

(1)

Chemical teratogens and the immune system

329

(2)

Morphological changes in lymphoid organs induced by teratogens

329

(1)

Reproduction toxicity assessment of immunopharmaceuticals

329

(1)

Nonclinical assessment of developmental immunotoxicity

330

(1)

Developmental immunotoxicants

331

(12)

Drugs as developmental immunotoxicants

331

(6)

Chemicals as developmental immunotoxicants

337

(6)

Conclusion

343

(1)

References

344

(11)

Chapter 14 Immunotoxicity and wildlife

Introduction

355

(1)

Immunotoxicity in fish

355

(3)

Fish immune system and diseases

356

(1)

Immunotoxicity studies in fish

356

(1)

Immunotoxicity of chemicals in fish

357

(1)

Immunotoxicology in marine mammals

358

(1)

Seals

358

(1)

Dolphins

358

(1)

Whales

359

(1)

Immunotoxicity in birds

359

(1)

Conclusion

359

(1)

References

359

(4)

Chapter 15 New methods in immunotoxicology

Introduction

363

(1)

Enhanced pathology

363

(2)

Immunohistochemistry

364

(1)

Computerized processing and image analysis

364

(1)

In situ hybridization

365

(1)

In situ polymerase chain reaction

365

(1)

In vitro immunotoxicology

365

(4)

General considerations

366

(1)

In vitro assays for the prediction of unexpected immunosuppression

367

(1)

In vitro assays for the prediction of unexpected immunostimulation

368

(1)

In vitro assays for the prediction of contact hypersensitivity

368

(1)

In silico immunotoxicology

369

(1)

Molecular immunotoxicology

369

(1)

Microarray analysis

369

(1)

New animal models

370

(1)

Immunodeficient mouse models

370

(1)

Genetically modified animals

371

(1)

Computational immunotoxicology

371

(1)

Conclusion

372

(1)

References

372

(7)

Chapter 16 Classification of immunotoxicants

Introduction

379

(1)

Selected criteria

379

(3)

Potential consequences of exposure to immunotoxicants

380

(1)

Reliability and magnitude of available data

381

(1)

Proposed classification

382

(1)

Group 1: unclassifiable xenobiotics

382

(1)

Group 2: possibly immunotoxic xenobiotics

382

(1)

Group 3: probably immunotoxic xenobiotics

382

(1)

Group 4: certainly immunotoxic xenobiotics

382

(1)

Group 5: nonimmunotoxic xenobiotics

382

(1)

Examples

383

(1)

Discussion

383

(2)

References

385

(2)

List of Abbreviations

387

(2)

Index

389

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Principles and Methods of Immunotoxicology

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Principles and Methods of Immunotoxicology

Summary

Author Biography

Table of Contents

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