Epithelial cells are cells which line a cavity, or cover a surface and can form a selective barrier to the exchange of molecules between the lumen of an organ and an underlying tissue. In many types of epithelia, the extracytoplasmic leaflet of apposing cells is fused together by tight junctions, which preclude the paracellular diffusion of macromolecules.
The principal mechanism of transport of macromolecules across cells with tight junctions is via vesicular carriers, in a process which is known as transcytosis. Normally, the molecule that is to be transcytosed first binds to a receptor. The receptor-ligand complex then enters the cell by endocytosis to form a vesicle. Transcytotic vesicles are subsequently formed which are delivered to the opposite cell surface where they fuse with the plasma membrane and release their contents into secretions. Transcytosis may occur in either direction, from the apical to basolateral surface or from the basolateral to apical cell surface.
IgA is an immunoglobulin which is found in a wide variety of mucosal secretions, including gastrointestinal and respiratory secretions, and also bile. After formation, secretory IgA (sIgA) is taken up by an overlying epithelial cell, transported across the cell and released into external secretions where the IgA forms the first specific immunologic defence against infections. The receptor that transports the sIgA (and also the IgM) is known as the polymeric immunoglobulin receptor (pIgR). In the normal route of secretion, sIgA interacts with the pIgR on the surface of epithelial cells. The antibody is internalised and transported through the cell within a vesicle to the apical surface. On release from the cell the pIgR is proteolytically cleaved, releasing a polypeptide known as the secretory component (SC) which remains attached to the antibody. The receptor is specific for polymeric immunoglobulins, such as IgA and IgM, but IgG will not interact with the receptor.
Immunoglobulin G (IgG) is a distinct immunoglobulin from IgA and IgM. IgG immunoglobulins have a molecular weight of about 160,000 and constitute over 85% of the immunoglobulins in the sera of most normal and hyperimmune individuals. The molecule consists of two heavy chains having a molecular weight each of about 50,000 and two light chains having a molecular weight each of about 25,000. The proteins of the IgG class may be differentiated into four sub-classes, IgG-1 to IgG-4, each of which has a distinct heavy chain. IgG preparations from human blood products are used in the clinical management of a wide variety of diseases, and is used in particular for patients with immunodeficiency. The IgG preparation is normally delivered intravenously, but also may be delivered intramuscularly or by subcutaneous injection. Whilst IgG preparations are effective in many circumstances, because IgG is not capable of being secreted across mucosal membranes, it is therefore less able to function as part of the first immunologic defence against infection, in, for instance, the gastrointestinal and respiratory tracts.