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Cells of the immune system include several types of leukocytes (white blood cells) (Table 19.1), which are derived from bone marrow. T lymphocytes, a subset of immune
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Disclaimer: This chapter has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily re ects the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. A Textbook of Modern Toxicology, Third Edition, edited by Ernest Hodgson ISBN 0-471-26508-X Copyright 2004 John Wiley & Sons, Inc.
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IMMUNOTOXICITY
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Figure 19.1 Potential consequences of immunotoxicity. Table 19.1 Leukocytes Granulocytes (polymorphonuclear leukocytes) Neutrophils Eosinophils Basophils/mast cellsa Monocytes Lymphocytes Monocytes/macrophagesa Natural killer cells
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Found in blood/more activated form found in tissues.
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cells, undergo differentiation and maturation in the thymus. Leukocytes circulate throughout the body in blood and lymph and populate other lymphoid tissues including the spleen, lymph nodes (scattered throughout the body), tonsils, and adenoids, as well as aggregates of lymphoid tissue in the lung, gut, and skin, which are referred to as bronchus-, gut- and skin-associated lymphoid tissue (BALT, GALT, and SALT). Also immune cells can be recruited to almost any tissue in the body where there is injury or infection. Accumulation of leukocytes in tissues in response to injury is known as in ammation. Cytokines (e.g., interleukins, interferons, and chemokines), soluble mediators produced by immune cells as well as cells outside the immune system, control the maturation, differentiation, and mobilization of immune cells. Immune responses are divided into innate responses directed nonspeci cally against foreign substances, and acquired responses directed against speci c antigens. There is considerable interaction between these two types of immunity. Innate immunity provides a rapid, although usually incomplete, antimicrobial defense. Granulocytes, natural killer cells, and macrophages are important mediators of innate immunity. Granulocytes have the capacity to phagocytize (engulf) infectious agents or other types of particles and to destroy or remove them from the tissue. They release a variety of soluble mediators that can kill invading organisms, increase vascular permeability, and recruit more leukocytes to the tissue. Natural killer cells are large granular lymphocytes that nonspeci cally kill tumor and virus-infected cells. Macrophages are also phagocytic, can release chemotactic and cytotoxic cytokines, and, when activated, can kill tumor or virus-infected cells. Mediators released from
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all of these cells during the acute in ammatory response in uence the development of acquired immune responses. Acquired immunity speci cally recognizes foreign substances (called antigens) and selectively eliminates them. On re-encountering the same antigen there is an enhanced response providing protection against reinfection. Vaccination against infectious agents is based on this principle. T lymphocytes and B lymphocytes (T cells and B cells) are the major players in acquired immunity (Figure 19.2). In both cases there are millions of different clones, groups of immune cells that have speci c receptors for a particular antigen. When a cell encounters that speci c antigen, clonal expansion occurs; that is, B and T cells with that particular speci city divide and differentiate and are thus activated to respond to the current crisis (e.g., infection). Memory cells develop that represent an enlarged clone of long-lived cells that are committed to respond rapidly, by clonal expansion, upon re-exposure to the same antigen. B cells recognize native or denatured forms of proteins or carbohydrates in soluble, particulate, or cell-bound form. Activated B cells differentiate into plasma cells and produce antibodies, soluble proteins known as immunoglobulins (Ig), that circulate freely and react speci cally with the invoking antigen. There are several classes (called isotypes) of Ig molecules IgM, IgG, IgA, IgE, and IgD. IgM is the predominant antibody in the primary immune response (following initial exposure to an antigen). IgG usually appears later, following a primary infection, but is the predominant antibody
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