Mast cells are large cells found in connective tissue and can be distinguished by their secretory granules, which contain many inflammatory mediators. They bind stably to monomeric IgE antibodies through the very high-affinity receptor FcεRI. Antigen cross-linking of the bound IgE antibody molecules triggers rapid degranulation, releasing inflammatory mediators into the surrounding tissue. These mediators trigger local inflammation, which recruits cells and proteins required for host defense to sites of infection. These cells are also triggered during allergic reactions when allergens bind to IgE on mast cells. Photographs courtesy of A.M. Dvorak.
of fluid and blood proteins, including antibodies, in the surrounding tissue. Shortly afterward there is an influx of blood-borne cells such as neutrophils and, later, monocytes, eosinophils, and effector lymphocytes. This influx can last from a few minutes to a few hours and produces an inflammatory response at the site of infection. Thus, mast cells are part of the front-line host defenses against pathogens that enter the body across epithelial barriers. They are also of medical importance because of their involvement in IgE-mediated allergic responses, which are discussed in Chapter 14. In allergic responses, mast cells are activated in the way described above by exposure to normally innocuous antigens (allergens), such as pollen, to which the individual has previously mounted a sensitizing immune response that produces allergen-specific IgE.
10-25 IgE-mediated activation of accessory cells has an important role in resistance to parasite infection.
Mast cells are thought to serve at least three important functions in host defense. First, their location near body surfaces allows them to recruit both pathogen-specific elements, such as antigen-specific lymphocytes, and nonspecific effector elements, such as neutrophils, macrophages, basophils, and eosinophils, to sites where infectious agents are most likely to enter the internal milieu. Second, the inflammation they cause increases the flow of lymph from sites of antigen deposition to the regional lymph nodes, where naive lymphocytes are first activated. Third, the ability of mast-cell products to trigger muscular contraction can contribute to the physical expulsion of pathogens from the lungs or the gut. Mast cells respond rapidly to the binding of antigen to surface-bound IgE antibodies, and their activation leads to the initiation of an inflammatory response and the recruitment and activation of basophils and eosinophils, which contribute further to the inflammatory response (see Chapter 14). There is increasing evidence that such IgE-mediated responses are crucial to defense against parasite infestation.
A role for mast cells in the clearance of parasites is suggested by the accumulation of mast cells in the intestine, known as mastocytosis, that accompanies helminth infection, and by observations in W/WV mutant mice, which have a profound mast-cell deficiency caused by a mutation in the gene c-kit. These mutant mice show impaired clearance of the intestinal nematodes Trichinella spiralis and Strongyloides species. Clearance of Strongyloides is even more impaired in W/WV mice that lack IL-3 and so also fail to produce basophils. Thus, both mast cells and basophils seem to contribute to defense against these helminth parasites.