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Chapter 12: Toxic Responses of the Immune System

Barbara L.F. Kaplan; Courtney E.W. Sulentic; Michael P. Holsapple; Norbert E. Kaminski

  • Introduction

  • The Immune System

    • Antigen Recognition

      • Immunity

      • Antigen

      • Antibodies

      • Complement

      • Antigen Processing

    • Innate Immunity

      • Cellular Components: Neutrophils, Macrophages, Dendritic Cells, Natural Killer Cells, NKT Cells, and γδ T Cells

    • Acquired (Adaptive) Immunity

      • Cellular Components: Antigen-Presenting Cells, T Cells, and B Cells

      • Humoral and Cell-Mediated Immunity

    • Inflammation

      • Cellular Components: Macrophages, Neutrophils, and T Cells

    • Immune-Mediated Disease

      • Hypersensitivity

      • Autoimmunity

    • Developmental Immunology

    • Neuroendocrine Immunology

  • Assessment of Immunological Integrity

    • Methods to Assess Immunocompetence

      • General Assessment

      • Functional Assessment

      • Molecular Biology Approaches to Immunotoxicology

      • Mechanistic Approaches to Immunotoxicology

      • Approaches to the Assessment of Human Immunotoxicity

      • Regulatory Approaches to the Assessment of Immunotoxicity

      • Biomarkers in Immunotoxicology

  • Immune Modulation by Xenobiotics

    • Halogenated Aromatic Hydrocarbons

      • Polychlorinated Dibenzodioxins

      • Polychlorinated Dibenzofurans

      • Polychlorinated Biphenyls

      • Polybrominated Biphenyls

      • Polycyclic Aromatic Hydrocarbons

    • Pesticides

      • Organophosphates

      • Organochlorines

      • Organotins

      • Carbamates

      • Atrazine

    • Metals

      • Lead

      • Arsenic

      • Mercury

      • Cadmium

    • Solvents and Related Chemicals

      • Aromatic Hydrocarbons

      • Haloalkanes and Haloalkenes

      • Glycols and Glycol Ethers

      • Nitrosamines

    • Mycotoxins

    • Natural and Synthetic Hormones

      • Estrogens

      • Androgens

      • Glucocorticoids

    • Therapeutic Agents

      • Immunosuppressive Agents

      • AIDS Therapeutics

      • Biologics

      • Anti-inflammatory Agents

    • Drugs of Abuse

      • Cannabinoids

      • Opioids

      • Cocaine

      • Methamphetamine

      • Ethanol

    • Inhaled Substances

      • Oxidant Gases

      • Particles: Asbestos, Silica, and nanoparticles

      • Pulmonary Irritants

    • Ultraviolet Radiation

  • Xenobiotic-Induced Hypersensitivity and Autoimmunity

    • Hypersensitivity

      • Polyisocyanates

      • Acid Anhydrides

      • Metals

      • Therapeutic Agents

      • Latex

      • Food and Genetically Modified Organisms

      • Formaldehyde

    • Autoimmunity

      • Therapeutic Agents

      • Halothane

      • Vinyl Chloride

      • Mercury

      • Silica

      • Hexachlorobenzene

  • New Frontiers and Challenges in Immunotoxicology

Introduction

Immunotoxicology can be most simply defined as the study of adverse effects on the immune system resulting from occupational, inadvertent, or therapeutic exposure to drugs, environmental chemicals, and, in some instances, biological materials. Studies in animals and humans have indicated that the immune system is comprised of potential target organs, and that damage to this system can be associated with morbidity and even mortality. Indeed, in some instances, the immune system can be compromised (decreased lymphoid cellularity, alterations in lymphocyte subpopulations, decreased host resistance, and altered specific immune function responses) in the absence of observed toxicity in other organ systems. These studies coupled with tremendous advances made in immunology and molecular biology have led to a steady and exponential growth in our understanding of immunotoxicology during the past 30 years. Recognition by regulatory agencies that the immune system is an important, as well as sensitive, target organ for chemical- and drug-induced toxicity is another indication of the growth of this subdiscipline of toxicology. With the availability of sensitive, reproducible, and predictive tests, it is now apparent that the inclusion of immunotoxicity testing represents a significant adjunct to routine safety evaluations for therapeutic agents, biological agents, and chemicals now in development.

Understanding the impact of toxic responses on the immune system requires an appreciation of its role, which may be stated succinctly as the preservation of integrity. It is a series of delicately balanced, complex, multicellular, and physiological mechanisms that allow an individual to distinguish foreign material (ie, “nonself”) from “self,” and to neutralize, eliminate, and/or coexist with the foreign matter. Examples of self are all the tissues, organs, and cells of the ...

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