Extravascular immune complexes in experimental Mycobacterial BCG granulomas

Abstract

Quantitative results of Mycobacterial BCG antigen, immunoglobulin and complement in rat skin lesions during the evolution of the granuloma reveal peak values of these factors at 49 days. The combination of antigen, Ig and complement, present extracellularly and in polymorphs at this time, indicates immune complex formation at an antigen-antibody ratio which may approximate to equivalence. This development coincides with mass lysis of host macrophages, and is followed by a sharp reduction in the antigen load. At 8 mth, surviving bacilli are coated with antibody and complement, and sequestrated in activated macrophages. It is possible that this antibody is non-specific and protective to the bacilli, leading to a second multiplication of organisms. But by 1 yr and 8 mth all the bacilli are dead, and immunoglobulins and complement are at very low levels. Although immune complex deposition and macrophage lysis was not associated with complete elimination of bacilli, it marked a turning point in the infection when the bacterial load was high and cell mediated immunity (CMI) was lacking. CMI may be important, especially at low antigen levels, but the crucial role here appears to have been played by complexed antibody. These experimental findings parallel those in human cutaneous leishmaniasis. They may explain some forms of necrosis in this condition and in tuberculosis.

Granulomas and Hepatitis C

“…Nothing is known about the pathways leading to the development of granulomas in HCV. It has been shown that immune complexes play a role in the development of granulomas 10 and, as immune complex formation is seen in HCV 11;12 , this is a possible pathogenic pathway.…”

Immune Complexes Isolated from Patients with Pulmonary Tuberculosis Modulate the Activation and Function of Normal Granulocytes

“…One of these studies reported the presence of extravascular immune complexes with high bacterial load and low cell-mediated immunity in experimental TB (26). Another study concluded that the antigen/antibody ratio within the lesions might be crucial in modulating the balance between tissue destruction and healing (27).…”