Defense against Infections
The first line of defense against most potential pathogens is the skin and mucous membranes. In addition to anatomic barriers, certain protective biochemical agents are produced at mucosal sites. These include simple chemicals such as acids and bases, and macromolecular proteins, including lysozyme, lactoferrin, secretory IgA antibodies, and interferons.
The genesis of secretory IgA antibodies is as follows. Under the influence of IL-5, IL-6, and IL-10, B cells bearing surface IgM in Peyer's patches and in the submucosa of the tracheo-bronchial tree switch to IgA-bearing cells. When the surface antibodies of these altered cells combine with a specific antigen, the cells are stimulated to migrate through afferent lymphatics to the regional lymph nodes and then through efferent lymphatic channels into the vascular circulation. They then home to submucosal sites in the upper small intestine, or to the respiratory system, where they differentiate into plasma cells that secrete large amounts of specific dimeric IgA antibodies and are transported across epithelial cells to the lumen by secretory component, as previously described. The resultant secretory IgA is particularly well suited to mucosal sites since it is more resistant than other types of immunoglobulins to the digestive processes of the alimentary tract. These antibodies protect by complexing adherence structures and toxins from microbial pathogens.
The genesis of secretory IgA antibodies is as follows. Under the influence of IL-5, IL-6, and IL-10, B cells bearing surface IgM in Peyer's patches and in the submucosa of the tracheo-bronchial tree switch to IgA-bearing cells. When the surface antibodies of these altered cells combine with a specific antigen, the cells are stimulated to migrate through afferent lymphatics to the regional lymph nodes and then through efferent lymphatic channels into the vascular circulation. They then home to submucosal sites in the upper small intestine, or to the respiratory system, where they differentiate into plasma cells that secrete large amounts of specific dimeric IgA antibodies and are transported across epithelial cells to the lumen by secretory component, as previously described. The resultant secretory IgA is particularly well suited to mucosal sites since it is more resistant than other types of immunoglobulins to the digestive processes of the alimentary tract. These antibodies protect by complexing adherence structures and toxins from microbial pathogens.
The second line of defense consists of local factors and leukocytes that are activated or recruited to the site of microbial invasion. These local elements of defense include the coagulation system, the fibrinolytic system, kallikrein, the complement system, resident macrophages, and elicited inflammatory cells.
If the pathogen is able to overcome the first two lines of defense, systemic acquired responses are marshalled to prevent further invasion and damage. This third line of defense includes intracellular killing by circulating phagocytes, stimulation of monokine production, interleukin production by T cells, production of circulating antibodies by plasma cells in regional lymph nodes and the spleen, intravascular activation of the complement system, and phagocytosis of opsonized pathogens by cells of the RES. Cytotoxic mechanisms directed against ingested microbes or infected cells play a major role in defense.
Unless the microbial inoculum is overwhelming, unusually virulent, or the host defenses are compromised, the infection should be contained and finally obliterated via a combination of local and systemic responses. At the same time local fibroblasts and epithelial cells proliferate, the tissue becomes more vascularized, and debris is removed by local tissue phagocytes. The inflammatory reaction abates and the tissue heals.
Unless the microbial inoculum is overwhelming, unusually virulent, or the host defenses are compromised, the infection should be contained and finally obliterated via a combination of local and systemic responses. At the same time local fibroblasts and epithelial cells proliferate, the tissue becomes more vascularized, and debris is removed by local tissue phagocytes. The inflammatory reaction abates and the tissue heals.