Porth's Essentials of Pathophysiology, 4e

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Innate and Adaptive Immunity

C h a p t e r 1 5

Epithelial Barriers Our outer body surfaces are protected by epithelia, which provide physical and chemical barriers between the internal environment and the pathogens of the external world. Epithelia include the epidermis of the skin and linings of the respiratory, gastrointestinal, and urogenital tracts. The intact skin is a formidable physi- cal barrier because of its closely packed cells, multiple layers, continuous shedding of cells, and presence of the protective protein keratin. In addition to its barrier function, the skin has chemicals that create a salty and acidic environment, and antibacterial proteins, such as the enzyme lysozyme, that inhibit the colonization of microorganisms and aid in their destruction. The mucous membrane linings of the gastrointesti- nal, respiratory, and urogenital tracts are protected by sheets of tightly packed epithelial cells that block the entry of microbes and destroy them by secreting anti- microbial enzymes, proteins, and peptides. Specialized cells in these linings secrete a viscous material called mucus. Mucus traps and washes away microorganisms, especially with the help of additional secretions such as saliva. Also in the lower respiratory tract, hairlike structures called cilia protrude through the epithelial cells. The synchronous action of the cilia moves many microbes trapped in the mucus toward the throat. The physiologic responses of coughing and sneezing further aid in their removal from the body. Once microbes are trapped, various chemical defenses come into play. These include lysozyme, a hydrolytic enzyme capable of cleaving the walls of bacterial cells; complement, which binds and aggregates bacteria to increase their susceptibility to phagocytosis or disrupt their lipid membrane; and members of the collectin fam- ily of surfactant proteins (e.g., surfactants [SP]-A and SP-D) in the respiratory tract (see Chapter 21). The best-defined function of the surfactants is their ability to opsonize pathogens, including bacteria and viruses, and to facilitate phagocytosis by innate immune cells such as macrophages. In the stomach and intestines, death of microbes results from the action of digestive enzymes, acidic conditions, and secretions of defensins, small cat- ionic peptides that rapidly kill many types of bacteria by disrupting their membrane. Cells of Innate Immunity Some pathogens can penetrate the epithelial barriers of the host and cause infection, particularly when the barrier has been breached as in wounds, burns, or loss of the body’s internal epithelia. The subsequent innate immune response to the penetration of these invaders is initiated by several types of immune cells with receptors for recognition of general groups of microbes. The key cells of innate immunity include phagocytic leukocytes and NK cells. Several types of phagocytic leukocytes recognize and kill infectious agents during an innate immune response. The early-responding phagocytic cell is the neutrophil , followed shortly by the more efficient,

Innate Immunity The innate immune system consists of the epithelial bar- riers; phagocytic neutrophils, macrophages, dendritic cells, NK cells; and several plasma proteins, including those of the complement system. These mechanisms are present in the body before an encounter with an infec- tious agent and are rapidly activated by microbes before the development of adaptive immunity. The innate immune system also interacts with and directs adaptive immune responses. With the ever-expanding wealth of information on immune system function, it is becoming clear that the innate immune system not only protects against microbial agents, but may also play a role in the patho- genesis of disease. Among the functions of the innate immune system is induction of a complex cascade of events known as the inflammatory response (discussed in Chapter 3). Recent evidence suggests that low-grade inflammation and activation of the innate immune sys- tem play a key role in the pathogenesis of a number of disorders, such as atherosclerosis and coronary artery disease, bronchial asthma, type 2 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. that react to a unique antigen, can distinguish self from nonself, and develop immunologic memory, allowing a prompt and heightened response on subsequent encounters with the same antigen. ■■ The cellular components of innate and adaptive immunity include the phagocytic cells that are of myeloid lineage and the lymphocytes that are of lymphoid lineage.The phagocytic granulocytes, macrophages, and dendritic cells, along with the natural killer (NK) cells, participate in innate immune responses, and the B andT lymphocytes participate in adaptive immune responses. ■■ The tissues of the immune system consist of the generative or central lymphoid organs in which B andT lymphocytes originate and mature and the peripheral lymphoid organs in which adaptive immune responses to microbes is initiated. ■■ Cytokines are soluble proteins secreted by cells of both the innate and adaptive immune systems that mediate many of the functions of these cells. Some cytokines mediate inflammation or interfere with viral replication. Chemokines are cytokines that stimulate the migration and activation of immune and inflammatory cells. Colony-stimulating factors are cytokines that stimulate the growth and differentiation of bone marrow progenitors of immune cells.