virus (HIV), can have specific and nonspecific effects on the immune system.

Many tests have been developed to assess immunity (Bentwich et al., 1982, 1988; Rosen et al., 1986). A systemic approach to the evaluation of immunocompetence, which is based on simple screening procedures followed by appropriate specialized tests of immune function, usually permits the definition of the immune defect. Such an approach should include evaluation of the humoral immune system (B-cell system), of the cellular immune system (T-cell system), and of nonspecific resistance (polymor-phonuclear leukocytes, natural killer cells, immune complement). It should be emphasized that although some exogenous agents can alter several elements of the human immune system, others have a primary effect only on a single element. For example, low doses of cyclosporin A selectively affect T cells by acting on lymphokine (interleukin-2) production. Conversely, anticonvulsive drugs, such as phenytoin, act primarily on the humoral immune system, leading to selective deficiency of IgA.

Many of the screening tests were developed to define the position of the defect in the events of cellular maturation and regulatory cellular interaction that lead to profound hereditary immunodeficient states. These tests are not sensitive enough to detect modest immunodeficiency caused by toxic agents. It should be emphasized that normal individuals show a wide range of responses in the tests discussed below. Thus, when studying one person, it should not be concluded that a modest variation from the normal range for an immunologic test is caused by a putative toxic agent. There are numerous testing methods and variations for many immunologic factors and these are constantly evolving. Many of the standard tests are discussed by Reese and Betts (1991) and Aloisi (1988).

The evaluation of the human humoral immune system involves the measurement of serum concentrations of immunoglobulins, the assessment of antibody formation after immunization, the measurement of "natural antibodies," and the enumeration of circulating B cells.

There are five major classes of immunoglobulin: IgM, IgG, IgA, IgD, and IgE. There are two subclasses of IgA: 1 and 2; and four subclasses of IgG: 1-4. Several methods are available for measuring serum immunoglobulin concentration, including single-radial diffusion, double diffusion in agar gel, immunoelectrodiffusion, radiommunoassay, enzyme-linked immunosorbent assay (ELISA), and automated laser nephelometry. Electrophoresis is not satisfactory for the quantitation of immunoglobulins, but it is useful in the detection of monoclonal immunoglobulins (M-components). The single-radial-diffusion assay is widely used. Gel diffusion methods are very sensitive to differences in diffusion constants and thus to differences in molecular size. It is not possible to measure the concentration of immunoglobulin in body fluids unless the molecules measured in the fluid are the same size as those in the standards. Thus, reliable measurements cannot be made of such proteins as low-molecular-weight IgM in abnormal plasma or IgA in external secretions—where it appears as a dimer rather than as the monomer present in the standard sera—unless special standard preparations that contain immunoglobulins of the same size are used. Furthermore, the use of goat or sheep antisera can give spuriously high estimates for serum IgA in patients with selective IgA deficiency because many of

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)