Biologic Markers in Immunotoxicology

Publisher: National Academies Press
ISBN: 9780309043892
eISBN Pdf: 9780309595049
Place of publication: United States
Year of digital publication: 1992
Month: January
Pages: 225
Language: English

Caption

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.

Biologic Markers in Immunotoxicology
Copyright
Preface
Contents
List of Abbreviations
Summary
- HYPERSENSITIVITY
- AUTOIMMUNITY
- IMMUNE SUPPRESSION
- BIOASSAYS OF IMMUNOTOXICITY
- CLINICAL APPLICATION OF EXISTING IMMUNOTOXICOLOGIC BIOLOGIC MARKERS
- ROLE OF BIOLOGIC MARKERS OF IMMUNOTOXICITY IN EPIDEMIOLOGY
- INDOOR AIR POLLUTION AND MULTIPLE CHEMICAL SENSITIVITY
1 Introduction
- BIOLOGIC MARKERS
  - Markers of Exposure
  - Markers of Effect
  - Markers of Susceptibility
- 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
  - IgE-Mediated Hypersensitivity
  - Complement-Mediated and Immune-Complex-Mediated Injury
  - T-Cell Reactions
- EFFECTS OF XENOBIOTICS ON THE IMMUNE SYSTEM
3 Biologic Markers For Immune-Mediated Disease
- DEFINITION OF THE PROBLEM
- EXPOSURE THROUGH INHALATION (PULMONARY HYPERSENSITIVITY)
  - Occupational Asthma and Rhinitis
  - Hypersensitivity Pneumonitis
- EXPOSURE THROUGH INGESTION
- DERMAL EXPOSURE
  - Contact Dermatitis
  - Photocontact Dermatitis
  - Contact Urticaria
- NONSPECIFIC IMMUNE ENHANCEMENT
- BIOLOGIC MARKERS OF HYPERSENSITIVITY
  - History and Clinical Signs
  - Skin Tests
  - Serum IgE Concentration
  - In Vitro Assays for Specific Antibody
  - In Vitro Assays for Cellular Immunity
  - Provocation Challenges
  - Bronchoalveolar Lavage
- ANIMAL MODELS FOR DETECTING CHEMICALLY MEDIATED HYPERSENSITIVITY
  - Techniques Used in Animal Studies to Determine the Potential of Chemicals to Cause Hypersensitivity
  - IgE-and IgG-Mediated Immediate Reactions
  - Cytotoxic Reactions
  - Antigen-Antibody Complexes
  - Contact Hypersensitivity
- SUMMARY
- RECOMMENDATIONS FOR FUTURE RESEARCH
  - IgE Sensitivity
    - Immunologically Mediated Adverse Reactions
    - Local Versus Systemic Immunity
    - Sensitizers
    - Individual Differences in Sensitivity
    - Development of Self-Antigens
    - Effects of Exposure Conditions
    - Epidemiology
  - IGE AND CELLULAR IMMUNITY
    - Cellular and Antibody Immunity
    - Individual Variability
    - Local Versus Systemic Immunity
    - Organic Versus Chemical Hypersensitivity
    - Effects of Exposure
    - Particle Composition
    - Chemical Haptens
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
  - Antinuclear Antibodies
  - Specific Tissue Autoantibodies
  - Histopathologic Examination
  - Immune Complexes
  - Complement
- SUMMARY AND RECOMMENDATIONS
5 The Capacity of Toxic Agents to Compromise the Immune System (Biologic Markers of Immunosuppression)
- CONSEQUENCES OF IMMUNOSUPPRESSION
- ENVIRONMENTAL CONTAMINANTS
  - Human Studies
  - Experimental Studies
  - Aromatic Hydrocarbons
  - Benzene
  - Metals
  - Complex Mixtures
  - Miscellaneous
- INHALATION AND IMMUNOSUPPRESSION
- SKIN AND IMMUNOSUPPRESSION
- MYELOTOXICITY AND IMMUNOSUPPRESSION
- DIFFICULTIES IN ESTABLISHING HUMAN RISK
- FACTORS THAT AFFECT SUSCEPTIBILITY
  - Age and External Factors
  - Metabolic Differences
  - Species Differences
- IMPORTANCE OF MECHANISTIC STUDIES
- SUMMARY
- RECOMMENDATIONS
6 Animal Models for Use in Detecting Immunotoxic Potential And Determining Mechanisms of Action
- ANIMAL IMMUNOTOXICITY BIOASSAYS
  - Pathologic Evaluation
  - Humoral Immunity
  - Cellular Immunity
  - Nonspecific Immunity
  - Bone Marrow
  - Host Resistance
  - Mechanistic Studies
- ASSAYS OF PULMONARY IMMUNOCOMPETENCE
- ASSAYS REQUIRING ADDITIONAL DEVELOPMENT
- USE OF IMMUNOTOXICITY BIOASSAYS
  - Considerations in the Design of Immunotoxicity Testing
  - Immunotoxicity as a Basis for Risk Assessment
- SUMMARY
- RECOMMENDATIONS
7 Human Immune-System Biologic Markers of Immunotoxicity
- TESTS FOR ASSESSING IMMUNITY
- TESTS OF THE HUMORAL IMMUNE SYSTEM
  - Immunoglobulin Concentration
  - Antibody Formation
  - B Cells
- CELLULAR IMMUNE SYSTEM
  - Skin Testing
  - In Vitro Stimulation of Lymphocytes
- OTHER TESTS
- OPPORTUNITIES FOR DEVELOPMENT OF BIOLOGIC MARKERS THAT ASSESS THE EFFECT OF IMMUNOTOXICANTS
  - Primary Humoral Immune Responses
  - Activation Antigens on Lymphocyte Surfaces and in Serum
  - Synthesis and Secretion of Lymphokines After Lymphocyte Activation
  - Proliferative Responses to Super-Antigens
  - Self-HLA-Restricted Cell-Mediated Cytotoxicity
- 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
  - Background
  - Study Design
  - Results
  - Strengths
  - Limitations
  - Background
  - Study Design
  - Results
  - Strengths
  - Limitations
  - Background
  - Study Design
  - Results
  - Strengths
  - Limitations
  - Background
  - Study Design
  - Results
  - Strengths
  - Limitations
- 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
  - Provocative Challenge
  - Skin Tests
- ANTIBODIES TO FORMALDEHYDE-HUMAN SERUM ALBUMIN ADDUCTS
  - Avoidance Regimens
  - T-cell Helper-to-Suppressor Ratios
- CONCLUSIONS
- RECOMMENDATIONS
10 Summary and Recommendations
- CHEMICAL-INDUCED IMMUNOSUPPRESSION IN HUMANS
  - Conclusions
  - Recommendations
- ROLE OF ENVIRONMENTAL CHEMICAL EXPOSURE IN HYPERSENSITIVITY AND AUTOIMMUNE DISEASES
  - Conclusions
  - Recommendations
- ANIMAL AND IN VITRO MODELS
  - Conclusions
  - Recommendations
- MARKERS OF SKIN AND MUCOSAL RESPONSES
  - Conclusions
  - Recommendations
- EDUCATION AND TRAINING
  - Conclusions
  - Recommendations
- ENVIRONMENTAL EXPOSURES AND SENSITIVITY SYNDROMES
  - Conclusions
  - Recommendations
REFERENCES
Glossary
BIOGRAPHIES
INDEX

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