Experimental granulomas induced by mycobacterial immune complexes in rats.
After BCG were complexed with homologous anti-BCG serum IgM was found to be firmly bound to the organisms. Preparations were made at antigen/antibody equivalence and at two-fold and four-fold antibody excess. They were injected subcutaneously into rats. At equivalence the mixtures provoked rapidly developing necrotic destructive lesions containing many bacilli. Injection of mixtures at antibody excess caused the rapid formation of epithelioid cell granulomas without necrosis and containing few bacilli. Compared with the injection of BCG alone, injection of comparable numbers of IgM-complexed bacilli at equivalence led to more rapid necrosis but also more rapid resolution of the granulomas which followed, Delayed-type skin reactions to PPD took longer to develop after injection of complexed BCG, usually as long as 4 weeks. The delay varied directly with the degree of antibody excess. This failure to detect cell mediated immunity was reflected in the histology of the draining lymph nodes which differed strikingly from that seen after injection of BCG alone. In animals injected with bacilli in excess antibody, epithelioid cell granulomas formed and viable bacilli were apparently eliminated before skin reactions to PPD developed. It is concluded that circulating immunoglobulin, perhaps IgM in particular, is likely to play a significant role in the pathogenesis of tuberculosis and similar diseases and that the relative ratio of antigen to antibody within the lesions may be crucial in influencing the balance between tissue destruction and healing.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D007075:Immunoglobulin M / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000648:ultrastructure; D008854:Microscopy, Electron; D009164:Mycobacterium Infections / Q000276:immunology; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000276:immunology; D012871:Skin Diseases / Q000276:immunology* / Q000473:pathology
D000936:Antigen-Antibody Complex; D001500:BCG Vaccine; D007075:Immunoglobulin M