be given to their use in immunotoxicity investigations.

Models need to be developed for closer extrapolation to humans by using severe combined immunodeficiency and transgenic and congenic mouse and human cell lines.

The relationship between indicators of immune status in peripheral blood and lymph nodes (spleen) should be established. Because the business end of the immune system is in the immune system's organs and the available marker medium in humans is blood, the relationship of these components should be well defined with agents that are known to alter the immune system.

The mechanisms by which classes of chemicals produce immune alterations should be determined. Mechanisms classified according to chemical family will assist the regulatory establishment in making decisions related to risk assessment. Knowledge of the mechanism of immune-system injury will enhance extrapolation to humans and give a rational basis to remediation.

There should be investigation of the role of immunocompetent cells in metabolizing chemicals to reactive agents that are either immunosuppressive or that are recognized as nonself and elicit a hypersensitivity reaction.

In vitro immunologic assays that can be used for rapid detection of potential immunosuppressive agents need to be developed to determine cellular and subcellular sites of action.

There needs to be investigation of the relationships between specific chemically induced immunosuppression and quantitative and qualitative changes in host resistance to microorganisms, parasites, and neoplastic diseases.

In host-resistance assays, research should be directed to measure more sensitive end points than mortality. Some suggested approaches include measurement of the generation of an immune factor that is known to eliminate a pathogen after exposure. For example, measurement of viral-induced natural-killer-cell function might be more sensitive and relevant to human disease than is death of a rodent.

Front Matter (R1-R18)

Summary (1-8)

1 Introduction (9-22)

2 The Structure and Function of the Immune System and Mechanisms of Immunotoxicology (23-32)

3 Biologic Markers for Immune-Mediated Disease (33-52)

4 Autoimmune Diseases (53-62)

5 The Capacity of Toxic Agents to Compromise the Immune System (Biologic Markers of Immunosuppression) (63-82)

6 Animal Models for Use in Detecting Immunotoxic Potential and Determining Mechanisms of Action (83-98)

7 Human Immune-System Biologic Markers of Immunotoxicity (99-112)

8 Application of Biologic Markers of Immunotoxicity in Epidemiology (113-126)

9 Use of Biologic Markers in Controversial Areas of Environmental Health (127-140)

10 Summary and Recommendations (141-148)

References (149-182)

Glossary (183-192)

Biographies (193-198)

Index (199-206)