Experimental epithelioid cell granulomas tubercle formation and immunological competence: An ultrastructural analysis

Abstract

An ultrastructural study of the cells comprising tubercles in experimental mycobacterial granulomas in rats is presented. Tubercle formation was compared in: (1) primary infections due to BCG at 49 days, (2) reinfection with BCG at 7 days, 8 months after primary infection and (3) lesions due to preformed BCG/anti-BCG complexes in antibody excess in unprimed animals at 10 days. The most rapid elimination of antigen with resolution of the lesion in the reinfection lesions, was effected by the early recruitment of cells morphologically characteristic of activated macrophages and immature epithelioid cells. The next best performance was in the immune complex lesion which at its height was maintained by a roughly constant size due to promonocytes, monocytes, macrophages, activated macrophages and immature epithelioid cells accumulated at the site. True epithelioid cells were rare. The slowest rate of healing in the primary 49 day granulomas, was associated with the whole spectrum of mononuclear phagocyte series of cells. All granulomas were surrounded by a cuff of mixed lymphocytes, interdigitating cells and fibroblasts. The rapid resolution of the reinfection lesions appeared as a loosely compacted infiltration of cells which allowed intimate contact of lymphocytes and macrophages. This was distinct from the tightly compared and compartmentalised zones of lymphocytes and macrophages which inhibited contact in the most slowly resolving lesions. An intermediate arrangement was seen in the immune complex granuloma. Another factor which predisposed to rapid resolution was the high vascularity of the central region of the granulomas. In the slow resolving group vascularity was diminished and peripherally situated.

Dynamic Nature of Host-Pathogen Interactions inMycobacterium marinumGranulomas

“…Surprisingly few ultrastructural studies of chronic mycobacterial lesions have been reported. Moreover, many conclusions about the ultrastructure of granulomas have been drawn from examination of tissues of laboratory animals infected with Mycobacterium bovis BCG or killed M. tuberculosis (2,3,38,49). The granulomas produced in these studies were short-lived, as the inciting agents did not persist and the outcome of the host-pathogen interaction was essentially one where the pathogen was cleared, a scenario that is quite different from infections with pathogenic mycobacteria.…”

“…Cells were identified and classified by their morphological resemblance to photographs of electron micrographs and descriptions of cells in various mammalian species (16,33,37,38,42,49). Immunohistochemistry with a rabbit polyclonal serum to M. marinum (45) (gift of D. Brooks and P. L. C. Small) was performed as described previously (50).…”

Angiogenic Activity of Sera from Pulmonary Tuberculosis Patients in Relation to IL-12p40 and TNFα Serum Levels

“…M. tuberculosis antigens are considered an important factor participating in the pathogenesis of Eales’ disease—an idiopathic retinal periphlebitis characterized by capillary nonperfusion and angiogenesis [22]. In one study, an intense angiogenesis was shown ultrastructurally in active pulmonary tuberculosis lesions [23], but the meaning of this phenomenon is not completely understood yet. An important role in the pathogenesis of TB and also in the modulation of angiogenesis is played by some cytokines, especially IL-12 and TNFα [24–26].…”

Purified protein derivative of tuberculin upregulates the expression of vascular endothelial growth factor in T lymphocytes in vitro

“…VEGF is 10 000 times more potent than histamine in enhancing vascular permeability 16 . Intense angiogenesis has been found in the lesions of pulmonary tuberculosis 17 . Therefore, we propose that VEGF may induce hypervascularity and contribute to the recruitment of inflammatory cells to the lesions of pulmonary tuberculosis.…”