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Immune hypersensitivity mechanisms play a part in many disorders of occupational medicine. A basic appreciation of the components and physiology of normal immunity are central to the understanding of the pathophysiology of hypersensitivity diseases of the immune system.
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OVERVIEW OF THE IMMUNE RESPONSE
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The function of the immune system is to protect the host from invasion by foreign antigens by distinguishing “self” from “nonself” antigens. Such a system is necessary for survival in all living animals. A normal immune response relies on the careful coordination of a complex network of specialized cells, organs, and biological factors necessary for the recognition of pathogens and subsequent elimination of foreign antigens. An abnormal, exaggerated immune response can cause hypersensitivity to foreign antigens, with resultant tissue injury and the expression of a variety of clinical syndromes, which are often seen in the practice of occupational medicine.
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Innate & Adaptive Immunity
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Living organisms have two levels of response against external invasion: (1) a nonspecific, innate system of natural immunity and (2) an adaptive system, which is acquired and relies on immunologic memory (Figure 17–1). Innate immunity is present from birth, does not require previous antigenic exposure, and is nonspecific in its activity. The skin and mucosal barriers serve as the first line of defense of the innate immune system. Soluble factors, such as proteolytic enzymes, chemoattractants, acute-phase proteins, cytokines and leukocytes, including phagocytes and natural killer cells, provide additional layers of protection. Toll-like receptors (TLR), found on macrophages, mast cells, and immature dendritic cells, recognize conserved patterns found in microbial proteins, DNA, RNA, and lipopolysaccharide (LPS), initiating inflammatory responses prior to adaptive response. Through a series of proteolytic activations, the serum and membrane components of the complement cascade amplify and regulate microbial killing and inflammatory responses. Despite the lack of specificity, innate immunity is largely responsible for protection against a vast array of environmental microorganisms and foreign substances.
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Higher organisms have evolved the adaptive immune system, which is triggered by encounters with foreign agents that have evaded or penetrated the innate immune defenses. The adaptive immune system has specificity for individual foreign antigens and immunologic memory, which allows for an intensified response upon subsequent encounter with the same or closely related agent. Primary adaptive immune responses require clonal expansion, leading to a delayed response to new exposures. Secondary immune responses are more rapid, larger, and more efficient. Stimulation of the adaptive immune system triggers a complex sequence of events initiating the activation of lymphocytes, the production of antigen-specific antibodies (humoral immunity), and effector cells (cellular or cell-mediated immunity), and ultimately, the elimination of the inciting substance. Although adaptive immunity is antigen specific, the repertoire of responses is tremendously diverse, with an estimated 109 antigenic specificities.
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