Some particles are too large for a phagocyte to ingest; parasitic worms are one example. In this case the phagocyte attaches to the surface of the antibody-coated parasite via its Fcγ, Fcα, or Fcε receptors, and the contents of the secretory granules or lysosomes of the phagocyte are released by exocytosis. The contents are discharged directly onto the surface of the parasite and damage it. Thus, stimulation of Fcγ and Fcα receptors can trigger either the internalization of external particles by phagocytosis or the externalization of internal vesicles by exocytosis. The principal leukocytes involved in the destruction of bacteria are macrophages and neutrophils, whereas large parasites such as helminths are usually attacked by eosinophils (Fig. 10.41), nonphagocytic cells that can bind antibody-coated parasites via several different Fc receptors, including the low-affinity Fcε receptor for IgE, CD23 (see Fig. 10.38). Cross-linking of these receptors by antibody-coated surfaces activates the eosinophil to release its granule contents, which include proteins toxic to parasites (see Fig. 14.10). Cross-linking by antigen of IgE bound to the high-affinity FcεRI on mast cells and basophils also results in exocytosis of their granule contents, as we describe below.
10-23 Fc receptors activate NK cells to destroy antibody-coated targets.
Virus-infected cells are usually destroyed by T cells that recognize virus-derived peptides bound to cell-surface MHC molecules. Cells infected by some viruses also signal the presence of intracellular infection by expressing on their surface proteins, such as viral envelope proteins, that can be recognized by antibodies originally produced against the virus particle. Host cells with antibodies bound to them can be killed by a specialized non-T, non-B cell of the lymphoid lineage called a natural killer cell (NK cell), which we met in Chapter 3. NK cells are large cells with prominent intracellular granules and make up a small fraction of peripheral blood lymphocytes. Although belonging to the lymphoid lineage, NK cells express a limited repertoire of invariant receptors recognizing a range of ligands that are induced on abnormal cells, such as those infected with viruses; NK cells are considered to be part of innate immunity (see Section 3-25). On recognition of a ligand, the NK cell kills the target cell directly without the need for antibody. Although first discovered for their ability to kill some tumor cells, NK cells play an important role in innate immunity in the early stages of virus infection.
As well as this innate function, NK cells can recognize and destroy antibody-coated target cells in a process called antibody-dependent cell-mediated cytotoxicity (ADCC). This is triggered when antibody bound to the surface of a cell interacts with Fc receptors on the NK cell (Fig. 10.42). NK cells express the receptor FcγRIII (CD16), which recognizes the IgG1 and IgG3 subclasses. The killing mechanism is analogous to that of cytotoxic T cells, involving the release of cytoplasmic granules containing perforin and granzymes (see Section 9-31). ADCC has been shown to have a role in the defense against
Fig. 10.41 Eosinophils attacking a schistosome larva in the presence of serum from an infected patient.
Large parasites, such as worms, cannot be ingested by phagocytes; however, when the worm is coated with antibody, eosinophils can attack it through binding via their Fc receptors for IgG and IgA. Similar attacks on large targets can be mounted by other Fc receptor-bearing cells. These cells release the toxic contents of their granules directly onto the target, a process known as exocytosis. Photograph courtesy of A. Butterworth.