Immunopathology of Rheumatoid Synovium

The character of the immunologically stimulated chronic inflammatory infiltrate is to a considerable extent determined by nonspecific factors governing mononuclear cell traffic. The volume, composition, and distribution of this traffic is strongly dependent on an initial adhesive interaction between circulating mononuclear cells and the EC of the postcapillary venules (PCV) of the involved tissues. The emigration of lymphocytes from the PCV is preceded by binding of the lymphocytes to the endothelial lining cell. This binding is enhanced by lymphokines (IFN-γ, TNF-β, IL-4) and monokines (IL-1, TNF-α), secreted by perivascular inflammatory cells and acting on the EC. This enhancement may permit an initial, immunologically generated small focus of mononuclear cells to amplify itself to a larger infiltrate. Two general mechanisms appear to be operative in chronic inflammation: (1) a specific mechanism in which an antigen stimulates an immune response with an initial secretion of cytokines, and (2) a nonspecific mechanism in which the cytokines released mediate a largely nonspecific infiltration of chronic inflammatory cells. The specific mechanism may determine the site of the inflammatory response and the nature of the antibodies which may be locally synthesized. The nonspecific mechanism creates the conventional pattern of chronic inflammation observed in variable sites in a number of diseases.