Are environmental pollutants threatening the human immune system? Researchers are rapidly approaching definitive answers to this question, with the aid of biologic markers--sophisticated assessment tools that could revolutionize detection and prevention of certain diseases.

This volume, third in a series on biologic markers, focuses on the human immune system and its response to environmental toxicants. The authoring committee provides direction for continuing development of biologic markers, with strategies for applying markers to immunotoxicology in humans and recommended outlines for clinical and field studies.

This comprehensive, up-to-date volume will be invaluable to specialists in toxicology and immunology and to biologists and investigators involved in the development of biologic markers.

Contents

• Subcommittee on Immunotoxicology
• Committee on Biologic Markers
• Board on Environmental Studies and Toxicology
• Commission on Life Sciences
• Preface
• List of Abbreviations
• Summary
• 1. Introduction
  • Biologic Markers
  • Validity Of Biologic Markers
  • Uncertainty And Risk
  • Ethical And Practical Issues
  • Structure Of The Report
• 2. The Structure and Function Of the Immune System And Mechanisms of Immunotoxicity
  • Development And Function Of The Immune System
  • Mechanisms Of Chemically Induced Immune Disease
  • Effects Of Xenobiotics On The Immune System
• 3. Biologic Markers For Immune-Mediated Disease
  • Definition Of The Problem
  • Exposure Through Inhalation (Pulmonary Hypersensitivity)
  • Exposure Through Ingestion
  • Dermal Exposure
  • Nonspecific Immune Enhancement
  • Biologic Markers Of Hypersensitivity
  • Animal Models For Detecting Chemically Mediated Hypersensitivity
  • Summary
  • Recommendations For Future Research
  • IgE and Cellular Immunity
• 4. Autoimmune Diseases
  • Definition Of The Problem
  • Incidence Of Autoimmune Diseases
  • Susceptibility Versus Exposure
  • Xenobiotic-Induced Autoimmunity
  • Mechanisms
  • Animal Models
  • Biologic Markers
  • Major Histocompatibility Complex
  • Immunoglobulin Allotypes
  • Other Genetic Markers
  • Rate Of Acetylation
  • Summary And Recommendations
• 5. The Capacity of Toxic Agents to Compromise the Immune System (Biologic Markers of Immunosuppression)
  • Consequences Of Immunosuppression
  • Environmental Contaminants
  • Inhalation And Immunosuppression
  • Skin And Immunosuppression
  • Myelotoxicity And Immunosuppression
  • Difficulties In Establishing Human Risk
  • Factors That Affect Susceptibility
  • Importance Of Mechanistic Studies
  • Summary
  • Recommendations
• 6. Animal Models for Use in Detecting Immunotoxic Potential And Determining Mechanisms of Action
  • Animal Immunotoxicity Bioassays
  • Assays Of Pulmonary Immunocompetence
  • Assays Requiring Additional Development
  • Use Of Immunotoxicity Bioassays
  • Summary
  • Recommendations
• 7. Human Immune-System Biologic Markers of Immunotoxicity
  • Tests For Assessing Immunity
  • Tests Of The Humoral Immune System
  • Cellular Immune System
  • Other Tests
  • Opportunities For Development Of Biologic Markers That Assess The Effect Of Immunotoxicants
  • Proposed Testing Regimen
  • Summary
  • Recommendations
• 8. Application of Biologic Markers Of Immunotoxicity in Epidemiology
  • Epidemiology
  • Contribution Of Biologic Markers To Epidemiology
  • Variability In Reference Populations
  • Sensitivity, Specificity, And Predictive Value
  • Authentication Of The Event Status
  • Study Design
  • Reference Populations
  • Case Studies
  • Recommendations
• 9. Use of Biologic Markers In Controversial Areas Of Environmental Health
  • Evidence Of Exposure To Organic Chemicals
  • Health Effects of Indoor Air Contaminants
  • Case Definitions Of Multiple-Chemical-Sensitivity Syndrome
  • Immune-System Dysfunction In MCS Patients
  • Biologic Markers Of Sensitivity To Chemicals
  • Antibodies To Formaldehyde-Human Serum Albumin Adducts
  • Conclusions
  • Recommendations
• 10. Summary and Recommendations
  • Chemical-Induced Immunosuppression In Humans
  • Role Of Environmental Chemical Exposure In Hypersensitivity And Autoimmune Diseases
  • Animal And In Vitro Models
  • Markers Of Skin And Mucosal Responses
  • Education And Training
  • Environmental Exposures And Sensitivity Syndromes
• References
• Glossary
• Biographies

The project was supported by the Environmental Protection Agency; the National Institute of Environmental Health Sciences; and the Comprehensive Environmental Response, Compensation, and Liability Act Trust Fund through cooperative agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, Department of Health and Human Services.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competencies and with regard for appropriate balance.

This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.

The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Frank Press is president of the National Academy of Sciences.

The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Robert M. White is president of the National Academy of Engineering.

The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth Shine is president of the Institute of Medicine.

The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Frank Press and Dr. Robert M. White are chairman and vice chairman, respectively, of the National Research Council.