Antibody-coated viruses that enter the cytoplasm are cleared by a system that employs a novel class of Fc receptor called TRIM21 (tripartite motif-containing 21) that is expressed by a variety of immune and nonimmune cell types. TRIM21 is a cytosolic IgG receptor that has a higher affinity for IgG than any other Fc receptor, and it also has E3 ligase activity. When a virus that has bound IgG enters the cytoplasm, TRIM21 attaches to the antibody and uses its E3 ligase activity to ubiquitinate viral proteins. This leads to proteasomal degradation of virions in the cytosol before translation of virally encoded genes can occur.
10-22 Fc receptors on phagocytes are activated by antibodies bound to the surface of pathogens and enable the phagocytes to ingest and destroy pathogens.
The most important Fc-bearing cells in humoral immune responses are the phagocytic cells of the monocytic and myelocytic lineages, particularly macrophages and neutrophils. Many bacteria are directly recognized, ingested, and destroyed by phagocytes, and these bacteria are not pathogenic in normal individuals. However, some bacterial pathogens have polysaccharide capsules, a large structure that lies outside the bacterial cell membrane and resists direct engulfment by phagocytes. Such pathogens become susceptible to phagocytosis only when they are coated with antibodies and complement that engage the Fcγ or Fcα receptors and the complement receptor CR1 on phagocytic cells, triggering bacterial uptake (Fig. 10.39). The stimulation
Macrophage membranes fuse, creating a membrane-enclosed vesicle, the phagosome Lysosomes fuse with these vesicles, delivering enzymes that degrade the bacterium When C3b binds to CR1 and antibody binds to Fc receptor, bacteria are phagocytosed Bacterium is coated with complement and IgG antibody FcreceptorsC3bbacteriummacrophagelysosomeCR1
Fig. 10.39 Fc and complement receptors on phagocytes trigger the uptake and degradation of antibody-coated bacteria. Many bacteria resist phagocytosis by macrophages and neutrophils. Antibodies bound to these bacteria, however, enable the bacteria to be ingested and degraded through the interaction of the multiple Fc domains arrayed on the bacterial surface with Fc receptors on the phagocyte surface. Antibody coating also induces activation of the complement system and the binding of complement components to the bacterial surface. These can interact with complement receptors (for example, CR1) on the phagocyte. Fc receptors and complement receptors synergize in inducing phagocytosis. Bacteria coated with IgG antibody and complement are therefore more readily ingested than those coated with IgG alone. Binding of Fc and complement receptors signals the phagocyte to increase the rate of phagocytosis, to fuse lysosomes with phagosomes, and to increase its bactericidal activity.