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partially in the bone marrow and partially in the lymph tissue, but after formation they are transported in the blood to different parts of the body where they are to be used.

The development of the human immune system begins late in the fetal period, is functioning at birth, and reaches maximum capacity near the time of puberty. In human adults the majority of circulating lymphocytes are T cells and the remainder are B cells and NK (natural killer) cells (a lymphocyte that can nonspecifically destroy certain virally infected or tumor cells). The production of B cells and T cells continues, albeit at a reduced rate, throughout life (Twomey, 1982).

The normal function of the immune system involves a complex sequence of cellular and biochemical events. After exposure to an antigen (a molecule that stimulates a specific immune response), there is phagocytosis (ingestion) of the antigen by macrophages during which the antigen undergoes intracellular breakdown by enzymatic hydrolysis. After hydrolysis, the fragments of the antigen move to the surface of the macrophage for reaction with specific T lymphocytes called helper-inducer T cells. Activation of these T lymphocytes occurs only if the interacting lymphocytes have specific receptors that bind to a complex of antigen fragments and a special protein derived from the major histocompatibility complex (Twomey, 1982).

The generation of antibody-producing plasma cells (B cells) and cytotoxic cells (T cells) requires the presence of biochemical factors (lymphokines and cytokines) secreted by T cells and macrophages. Clonal expansion increases the number of these specifically reactive T and B cells, so that subsequent exposure to the same antigen leads to a rapid specific immune response. As an immune response occurs, a decrease of the T cells is likely, and negative feedback into earlier phases prevents excessive reaction. Thus, the specific antibody reacts with the offending antigen to cause neutralization or inactivation while effecter T cells inactivate or destroy cellular targets. When these mechanisms are functioning properly, the immune system recognizes and eliminates foreign agents quickly and efficiently. Opportunities for dysfunction can occur at any point along the pathway of cellular and biochemical processes, resulting in a variety of immunological effects from hypersensitivity to immunodeficiency, as illustrated in Figure 10-1.

For example, exposure to immunotoxicants can cause immunosuppression, resulting in altered host resistance. The outcome of immune suppression is influenced by the dose and mechanism of action of the immunotoxicants, along with concomitant exposure to other agents such as bacteria, viruses, parasites, or chemicals at levels that might normally be innocuous. In its suppressed condition, the immune system does not respond adequately to hazardous agents. Adverse consequences are those of severe disseminated infectious diseases caused by



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