New Insights into the Immunopathology of Tuberculosis

Abstract

Tuberculosis is characterised by fever, weight loss and necrosis in both lesions and tuberculin skin test sites (Koch phenomenon), although the antigens of Mycobacterium tuberculosis are not directly toxic to the tissues. The tissue damage appears to be due to several interacting factors. First, M. tuberculosis induces an immunoregulatory disorder of which a raised percentage of agalactosyl IgG is a marker. This is seen also in rheumatoid arthritis and Crohn’s disease and is associated with tissue-damaging inflammation. Subsequently, several properties of M. tuberculosis exacerbate this disorder by triggering cytokine release, and rendering tissues sensitive to the toxicity of tumor necrosis factor (TNF). Moreover, M. tuberculosis, but not bacillus Calmette-Guérin or several Mycobacterium avium strains, produces a factor which increases the toxicity of TNF for individual cells. Thus, M. tuberculosis may distort the normal protective role of TNF so that this cytokine becomes toxic to the host. The immunoregulatory disorder associated with agalactosyl IgG appears to be susceptible to immunotherapy, so novel types of treatment for the immunopathological component of tuberculosis are being explored.

Distinct ability to accumulate eosinophils during the inflammatory cellular response to M. Bovis BCG in the mouse pleural cavity

“…There was a rapid clearance of bacilli by resident macrophages in vivo. This probably corresponds to the milieu in natural infection, considering the low number of infecting bacilli and the cellular similarity of the pleura to the alveoli [18].…”

Pancytopenia with Hypocellular Bone Marrow due to Miliary Tuberculosis: An Unusual Presentation

“…Haematopoietic stem cells can be affected by the same pathogenetic mechanism. Thus, M. tuberculosis may dis tort the normal protective role of TNF so that this cyto kine becomes toxic to the host [13,14]. Although pancyto penia in MTB is a rare event, as mycobacterial infections show a trend to increase nowadays, we should remember Fountain [15], who wrote in 1954: 'In the presence of pan cytopenia, together with pyrexia and weight loss, tuber culosis should always be considered.…”

IgG glycosylation in autoimmune-prone strains of mice

“…Some of tbe diseases in which strikingly raised GO is found, such as leprosy and tuberculosis, are known to be caused by mycobacteria [3,27]. Others such as Crohn's disease [28] and sareoidosis [29] are associated with the presenee in the lesions of mycobacteriiil genomie material in at least a percentage of cases [S{)].…”