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COMPONENTS OF THE IMMUNE SYSTEM

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While simplistic in its view, the effectors of the immune system are generally divided into those components that support innate immunity and those that support acquired immunity. The classification suggests a dichotomous relationship, but there is necessary and frequent cross-talk between the 2 arms. Innate immunity is active from birth, is the first line of defense against most pathogens, and does not require modification for activity. Acquired immunity largely requires activation of B lymphocytes and T lymphocytes and uses a complex process of activation, modification, expansion, and suppression in response to changing stimuli.

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Innate immunity includes physical barriers (skin, mucous membranes), chemical components (hydrolytic enzymes and complement), and several cellular components. For example, polymorphonuclear lymphocytes are phagocytic cells with lysosomes containing enzymes and generally fight infection. Recent data suggest that neutrophil survival is modulated by T-cell responses, thus illustrating 1 area of cross-communication between the innate and acquired immunity systems. Monocytes are heavily granulated cells that migrate from blood to various tissues and differentiate depending on site. They become Kupffer cells in the liver, microglial cells in the central nervous system, and macrophages in the lung, spleen, and peritoneal surface. Collectively, these differentiated cells (histiocytes and macrophages) become part of the reticuloendothelial system with a major function of phagocytosis of invading entities. The role of the macrophage is much more complex, however, because it produces proinflammatory proteins (cytokines and chemokines) that stimulate the growth of specific immune and inflammatory cells and positions them where needed. They mediate inflammatory responses during wound healing and, after consuming pathogens, can present them to the corresponding T-helper cell. This is another example of communication between traditionally defined innate and acquired immunity effectors. This presentation is done in conjunction with attaching to a major histocompatibility complex (MHC) class II molecule to identify the macrophage as self despite the foreign antigens on its surface. Macrophages can also play a counterproductive role in tumor elimination through the production of molecules that promote tumor growth and angiogenesis (eg, vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [FGF]). Because they promote inflammation, they also release compounds such as tumor necrosis factor (TNF), resulting in nuclear factor-ĸB activation, which inhibits apoptosis.

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Natural killer (NK) cells are granular lymphocytes (10%-15% of total blood lymphocytes) that recognize and destroy tissues that have been altered or stressed, typically by viruses or by malignant transformation. They differ from T lymphocytes in that they do not have antigen-specific receptors. Instead, they have inhibiting receptors that can recognize the MHC class I molecules on normal cells preventing activation. MHC-I expression is absent or aberrant on many virus- and tumor-infected cells. In another example of cooperation between innate and acquired immunity, NK cells participate in the process of antibody-dependent cell-mediated cytotoxicity (ADCC). Immunoglobulin (Ig) G antibodies can bind to infected cells. Fc receptors found on NK cells (also are present on macrophages, neutrophils, and eosinophils) bring the ...

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