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Chapter 4 : Fc Receptors and Phagocytosis
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
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Phagocytosis is a specialized endocytic response of eukaryotic cells to particulate stimuli, such as microbial pathogens. This response is utilized by myeloid cells of the immune system to aid in host defenses. FcγRI is expressed at especially high levels in freshly harvested mouse dendritic cells from spleen, lymph node, and skin. FcγRIIA mediates phagocytosis of IgG-coated particles by human neutrophils and mononuclear phagocytes. FcαRI associates noncovalently with a γ-subunit homodimer common to other Fc receptors. FcγRn, a neonatal Fc receptor complexed to β2- microglobulin, is a receptor on intestinal epithelial cells that mediates the transfer of maternal Ig from milk to the bloodstream of newborns. Co-ligation of FcγRIIb with the antigen receptor in B cells (BCR) leads to decreased cellular activation. Several tyrosine phosphatases have been identified that modulate ITAM-mediated responses. These include the membrane-bound tyrosine phosphatase CD45 and SHP-1/ SHP-2. The signaling requirements for endocytosis of monomeric Ig and immune complexes and phagocytosis are distinct. ITAM phosphorylation is accompanied by actin polymerization. The enzymatic steps leading to cytoskeletal assembly during phagocytosis are a matter of debate. Formins comprise a family of actin binding proteins that have the interesting property of weakly capping the barbed ends of actin filaments. Cytosolic transients may be involved in other aspects of phagocytic function, such as chemotactic peptide enhancement of FcR-mediated phagocytosis in neutrophils, arachidonic acid production, phagosome-lysosome fusion, and lysosome-enhanced phagocytosis.
Domain structures of human FcγRs expressed in phagocytic cells. Ligand binding subunits are labeled. In dark gray are γ-subunit homodimers with white bars representing the two tyrosine residues that are contained within the consensus sequence of ITAMs. In FcγRIIb1 and FcγRIIb2 are the cytosolic domains (light gray), which contain one conserved tyrosine residue (black bar) within the consensus ITIM. FcγRIIIb is a GPI-linked protein expressed in neutrophils and activated eosinophils, but not in monocytes, macrophages, or dendritic cells.