PRINCIPLES OF TOXICOLOGY - Biology East Borneo

196 IMMUNOTOXICITY: TOXIC EFFECTS ON THE IMMUNE SYSTEMtemporal variations in most tests are common. In order to demonstrate that an abnormality exists, it isusually advisable to repeat the test one or more times to insure that a consistent result is obtained.Some of the laboratory tests available provide information relevant to assessing humoral immunity,others are useful in evaluating cellular immunity, and some can provide insight regarding both.Described below are examples of assays commonly used in the evaluation of individuals exposed tochemicals in the environment or workplace.Immunoglobulin Concentrations The concentrations in serum of each immunoglobulin can bedetermined with the exception of IgD, which exists primarily on cell surfaces. Single-radial diffusionis commonly employed for most immunoglobulins, although enzyme linked immunosorbent assay(ELISA) or radioimmunoassay (RIA) is often needed to measure the low concentrations of IgEtypically present. Diminished immunoglobulin concentrations, either in total or of specific classes,may suggest immunodeficiency, but is not sufficient to establish a diagnosis. Conversely, immunoglobulinswithin normal limits do not necessarily indicate immunocompetence. There may be defectsin subtypes of immunoglobulins not quantified by the assay, and patients with normal or high valuesmay nonetheless exhibit increased susceptibility to disease. Immunoglobulin values may be profoundlyinfluenced by viral or bacterial infections and the presence of some drugs.T- and B-Cell Concentrations Immunotyping of T- and B-cell subsets by ethidium bromide andcytofluorometry techniques is used by many laboratories for screening studies of chemical-relatedinjury. Concentrations of B cells, either in absolute terms or as a percentage of peripheral bloodlymphocytes, can be expressed, and the distribution of B cells expressing different immunoglobulintypes (IgM, IgG, IgA) can be measured. Some studies have sought to evaluate a potential immunosuppressiveeffect through measurement of the ratio of T H to T S lymphocytes in peripheral blood, usingthe CD4 + marker to indicate T H cells and the CD8 + marker for T S cells. As discussed above, thesemarkers are not specific for T H and T S cells, however, and interpretation of a decreased CD4 + to CD8 +ratio as a loss of T help relative to T suppression is an oversimplification. A significant reduction inCD4 + cells is associated with several immunodeficient states (e.g., in patients with AIDS, undergoingradiotherapy, or chemotherapy), implying that diminished CD4 + is indicative of impaired antibodyproduction. This assumption is not infallible, however, because there are also circumstances in whichCD4 + cells may be reduced without loss of antibody production. Significant changes in absolute orrelative concentrations of lymphocyte subsets may be suggestive of immunotoxic effects fromchemical exposure, but are not, by themselves, reliable indicators of compromised function.Cutaneous Anergy Anergy is a generalized clinical condition of non-responsiveness to ubiquitousskin test antigens that is frequently observed in patients who are immunosuppressed. Cutaneous anergymay suggest functional impairment or abnormalities of the cellular immune system. The mostcost-effective method for evaluation of cutaneous anergy is the use of a battery of attenuated,premeasured and well-standardized ubiquitous antigens that are available from commercial sources.The assessment of a person who is thought to be immunologically suppressed due to exposure to anenvironmental chemical can be attained within 48 h through the use of these antigens. The intradermalskin test antigens frequently used to measure cellular delayed hypersensitivity are: tetanus toxoid,diphtheria toxoid, Streptococcus (group C), old tuberculin (PPD), Candida albicans, Trichophytonmentagrophytes, and Proteus mirabilis. Measurement of specific IgG antibodies to diphtheria andtetanus toxoids in serum at 2 weeks following booster immunization is also useful in assessing theability to form antibodies to protein antigens.In Vitro Tests Functional capabilities of lymphocytes can be evaluated by taking a blood sample andperforming a variety of tests in vitro. In general, these tests involve isolating lymphocytes from a bloodsample, placing them in culture, and exposing them to a stimulatory agent. The ability of the cells toproliferate in response to the stimulus and, in the case of B cells, to synthesize immunoglobulins, canbe measured. For example, treatment of peripheral blood lymphocytes with pokeweed mitogen (PWM)