The role of antibody in primary and reinfection BCG granulomas of rat skin.
Primary subcutaneous infection of rats with BCG leads to a three stage local reaction. There is first a short-lived simple granuloma corresponding with high levels of cell mediated immunity (CMI). This is followed by an explosive phase of necrosis and local Mycobacterial multiplication corresponding with low levels of CMI and high levels of circulating anti-BCG antibody. Finally the lesion resolves via an epithelioid cell granuloma as bacteria fall in number and CMI returns. Reinfection with BCG produces quite different lesions when initiated at different stages of the primary infection. Reinfection during the short first stage causes a self-healing epithelioid granuloma. Reinfection during the long second stage produces a florid necrotic, bacilli-laden lesion. Reinfection during the third stage produces only a vestigial, transient granuloma. It is suggested that the evolution of tuberculous lesions depends on the interplay of CMI, bacillary load and circulating antibody. A large antigenic load in the presence of high antibody titres causes necrosis and bacillary multiplication, whereas reduced bacterial numbers plus antibody and high CMI lead to compact granulomas and healing. The first situation may be analogous to immune complex disease in antigen excess and the second to complexes in antibody excess. An analogy is drawn between the reinfection experiments and natural infection after BCG vaccination in humans. It is postulated that BCG vaccination in man may be followed by a phase in which antibody is high relative to CMI. If because of high prevalence rates, natural infection with large doses of bacilli was more likely to occur at this time, the results might help to explain the failure of BCG prophylaxis in India and comparable countries, as opposed to its success in the UK.
D000818:Animals; D000906:Antibodies / Q000032:analysis*; D001500:BCG Vaccine / Q000276:immunology*; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000276:immunology; D009164:Mycobacterium Infections / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000276:immunology* / Q000473:pathology
D000906:Antibodies; D001500:BCG Vaccine