Established Lesion (2-3 weeks)
If the T Cell is unable to effectively deal with the infection and it becomes chronic, a more robust immune response may be required. There is, however, a persistence of the manifestations of acute inflammation. The inflammatory infiltrate in the Established Lesion occupies a greater area within the connective tissue, with more destruction of collagen matrix. Again, the junctional epithelium will attempt to occupy the space and wall-off the infection by migrating laterally and apically, resulting in early pocket formation. Another significant change from earlier stages of disease is the predominance of Ig producing Plasma Cells within the inflammatory infiltrate. Thus, an increase in extravascular immunoglobulins (antibodies) can now be detected within the connective tissue and junctional epithelium. These changes may be linked to one or more immune system events.
It is logical that B Cells have migrated to the site of infection in the Established Lesion. Some are memory B cells that have antigen-specific Immunoglobulins (Ig) expressed on their surface membrane. Macrophage-activated T helper-2 Cells (Th2), with receptors for the same specific antigen, will link to the B Cell and activate it. The process of activation results in proliferation and differentiation into Ig producing Plasma Cells. Immunoglobulins will subsequently be available to opsonize and neutralize the antigens. Cytokines Il-3, Il-4, Il-5, Il-6, Il-10 and granulocyte-monocyte colony stimulating factors (GM-CSF), released by the T Cell, are important signaling molecules for proliferation and differentiation of B Cells.
Other B Cells that express IgM antigen receptors may be activated independently of T Cell help. These B Cells respond to T-independent antigens, many of which are large bacterial carbohydrates that cross-link the IgM antibodies. In a similar manner, macrophages may also present multiples of the same antigen to B Cells for cross-linking of IgM.