The exact mechanisms whereby lead interacts with the immune system remains unclear. However, several effects of lead on the immune system can be explained in the context of activation of the nuclear factor-κB (NF-κB) signal transduction pathway that represents a group of structurally related proteins. NF-κB plays a critical role in triggering and coordinating both innate and adaptive immune responses (Dietert and Piepenbrink 2006). In addition, Fischbein et al. (1993) suggested that lead may exert suppressive effects on lymphocyte functions because of its high affinity for the sulfhydryl groups on T-lymphocyte surface receptors and thus its interference with antigen processing from monocytes to T lymphocytes and consequently with cell-to-cell cooperation. Lead also appears in animal models to affect the immune system indirectly by altering regulation of the endocrine and nervous systems (Mishra 2009).

To provide a better understanding of the studies discussed in this section and to provide perspective on the relevance of such effects on human health, an overview of the immune system is provided below.

Immune System Overview and Early Biologic Effects

The immune system consists of a complex network of cells and soluble mediators that interact in a highly regulated manner to generate an immune response of appropriate magnitude and duration. In animals and humans, immunotoxicity can be manifested in several distinct immunopathologic conditions, including allergic disease, immunodeficiency (immunosuppression), and autoimmunity. On contact with the immune system, chemicals can exert direct toxicity to specific components of the immune system, which can lead either to malfunctioning of the system as a whole or to disruption of regulatory systems that in turn can give rise to immunosuppression or exaggerated responses (manifested possibly as atopy or autoimmunity). In the former case, the immune system responds to the agent as an allergen (of low or high molecular weight), and this results in such disorders as allergic contact dermatitis (Descotes et al. 1995; Luster et al. 2001). In immunodeficiency, the immune system acts as a passive target for the chemical, and the result may be increased incidence or severity of infectious disease or cancer. Autoimmunity, a breakdown in immune tolerance, occurs when the agent directly or indirectly induces an immune response to “self” constituents, such as specific proteins or DNA, that leads to pathologic conditions.

The immune system has three basic components: humoral, cell-mediated, and innate (nonspecific) immune responses. Humoral immunity is primarily associated with B lymphocytes and the production of antibodies, also known as immunoglobulins (Ig). Differentiated B cells produce five Ig isotypes, each with unique structure and function: IgG, IgM, IgD, IgE, and IgA. For example, IgE is associated with allergic type 1 immediate hypersensitivity reactions, and IgA (a secretory antibody) is found in bodily secretions.



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