Other evidence points to the importance of IgE antibodies and eosinophils in the defense against parasites. Infection with certain types of multicellular parasites, particularly helminths, is strongly associated with the production of IgE antibodies and the presence of abnormally large numbers of eosinophils (eosinophilia) in blood and tissues. Furthermore, experiments in mice show that depletion of eosinophils by polyclonal anti-eosinophil antisera increases the severity of infection with the parasitic helminth Schistosoma mansoni. Eosinophils seem to be directly responsible for helminth destruction; examination of infected tissues shows degranulated eosinophils adhering to helminths, and experiments in vitro have shown that eosinophils can kill S. mansoni in the presence of anti-schistosome IgG or IgA antibodies (see Fig. 10.41).
The role of IgE, mast cells, basophils, and eosinophils can also be seen in resistance to the feeding of blood-sucking ixodid ticks. Skin at the site of a tick bite has degranulated mast cells and an accumulation of degranulated basophils and eosinophils, an indicator of recent activation. Subsequent resistance to feeding by these ticks develops after the first exposure, suggesting a specific immunological mechanism. Mice deficient in mast cells show no such acquired resistance to ticks, and in guinea pigs the depletion of either basophils or eosinophils by specific polyclonal antibodies also reduces resistance to tick feeding. Finally, experiments in mice showed that resistance to ticks is mediated by specific IgE antibody. Thus, many clinical studies and experiments support a role for this system of IgE bound to the high-affinity FcεRI in host resistance to pathogens that enter across epithelia or exoparasites such as ticks that breach it.
Summary.
Antibody-coated pathogens are recognized by effector cells through Fc receptors that bind to an array of constant regions (Fc portions) provided by the pathogen-bound antibodies. Binding activates the cell and triggers destruction of the pathogen, through either phagocytosis, granule release, or both. Fc receptors comprise a family of proteins, each of which recognizes immunoglobulins of particular isotypes. Fc receptors on macrophages and neutrophils recognize the constant regions of IgG or IgA antibodies bound to a pathogen and trigger the engulfment and destruction of such bacteria. Binding to the Fc receptor also induces the production of microbicidal agents in the intracellular vesicles of the phagocyte. Eosinophils are important in the elimination of parasites too large to be engulfed; they bear Fc receptors specific for the constant region of IgG, as well as receptors for IgE; aggregation of these receptors triggers the release of toxic substances onto the surface of the parasite. NK cells, tissue mast cells, and blood basophils also release their granule contents when their Fc receptors are engaged. The high-affinity receptor for IgE is expressed constitutively by mast cells and basophils. It differs from other Fc receptors in that it can bind free monomeric antibody, thus enabling an immediate response to pathogens at their site of first entry into the tissues. When IgE bound to the surface of a mast cell is aggregated by binding to antigen, it triggers the release of histamine and many other mediators that increase the blood flow to sites of infection; it thereby recruits antibodies and effector cells to these sites. Mast cells are found principally below epithelial surfaces of the skin and beneath the basement membrane of the digestive and respiratory tracts. Their activation by innocuous substances is responsible for many of the symptoms of acute allergic reactions, as will be described in Chapter 14.
Summary to Chapter 10.