Fig. 10.42 Antibody-coated target cells can be killed by cells encounter cells coated with IgG antibody, they rapidly kill the NK cells in antibody-dependent cell-mediated cytotoxicity target cell. ADCC is only one way in which NK cells can contribute to (ADCC). NK cells (see Chapter 3) are large granular non-T, non-B host defense. lymphoid cells that have FcγRIII (CD16) on their surface. When these infection by viruses, and represents another mechanism by which antibodies can direct an antigen-specific attack by an effector cell that itself lacks specificity for antigen.
10-24 Mast cells and basophils bind IgE antibody via the high-affinity Fcε receptor.
When pathogens cross epithelial barriers and establish a local focus of infection, the host must mobilize its defenses and direct them to the site of pathogen growth. One way in which this is achieved is to activate the cells known as mast cells. Mast cells are large cells containing distinctive cytoplasmic granules that contain a mixture of chemical mediators, including histamine, that act rapidly to make local blood vessels more permeable. Mast cells have a distinctive appearance after staining with the dye toluidine blue that makes them readily identifiable in tissues (see Fig. 1.8). They are found in particularly high concentrations in vascularized connective tissues just beneath epithelial surfaces, including the submucosal tissues of the gastrointestinal and respiratory tracts and the dermis of the skin.
Mast cells have Fc receptors specific for IgE (FcεRI) and IgG (FcγRIII), and can be activated to release their granules and to secrete lipid inflammatory mediators and cytokines via antibody bound to these receptors. Most Fc receptors bind stably to the Fc regions of antibodies only when the antibodies have themselves bound antigen, and cross-linking of multiple Fc receptors is needed for strong binding. In contrast, FcεRI binds IgE antibody monomers with a very high affinity—approximately 1010 M–1. Thus, even at the low levels of circulating IgE present in normal individuals, a substantial portion of the total IgE is bound to the FcεRI on mast cells in tissues and on circulating basophils.
Although mast cells are usually stably associated with bound IgE, this on its own does not activate them, nor will the binding of monomeric antigen to the IgE. Mast-cell activation occurs only when the bound IgE is cross-linked by multivalent antigens. This signal activates the mast cell to release the contents of its granules, which occurs in seconds (Fig. 10.43), to synthesize and release lipid mediators such as prostaglandin D2 and leukotriene C4, and to secrete cytokines such as TNF-α, thereby initiating a local inflammatory response. Degranulation also releases stored histamine, which increases local blood flow and vascular permeability; this quickly leads to an accumulation
Resting mast cell has granules that contain histamine and other infammatory mediators Multivalent antigen cross-links bound IgE antibody, causing release of granule contents Fc˜RI IgE antibody Resting mast cell Activated mast cell
Fig. 10.43 IgE antibody cross-linking on mast-cell surfaces leads to a rapid release of inflammatory mediators.