Spector W G, Marianayagam Y, Ridley M J
J Pathol. 1982 Jan;136(1):41-57. doi: 10.1002/path.1711360105.
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.
用卡介苗对大鼠进行原发性皮下感染会导致局部反应呈现三个阶段。首先会出现一个短暂的单纯性肉芽肿，这与高水平的细胞介导免疫（CMI）相对应。接着是坏死和局部分枝杆菌增殖的爆发阶段，这与低水平的CMI和高水平的循环抗卡介苗抗体相对应。最后，随着细菌数量减少和CMI恢复，病变通过上皮样细胞肉芽肿得以消退。在原发性感染的不同阶段开始再次感染卡介苗时，会产生截然不同的病变。在第一个短暂阶段再次感染会导致自愈性上皮样肉芽肿。在漫长的第二个阶段再次感染会产生一个明显的坏死性、充满杆菌的病变。在第三个阶段再次感染只会产生一个残留的、短暂的肉芽肿。有人提出，结核病变的演变取决于CMI、细菌负荷和循环抗体之间的相互作用。在高抗体滴度存在的情况下，大量抗原负荷会导致坏死和细菌增殖，而细菌数量减少加上抗体和高CMI则会导致致密的肉芽肿和愈合。第一种情况可能类似于抗原过剩时的免疫复合物疾病，第二种情况类似于抗体过剩时的复合物。文中还将再次感染实验与人类接种卡介苗后的自然感染进行了类比。据推测，人类接种卡介苗后可能会有一个阶段，其中抗体相对于CMI较高。如果由于高流行率，此时更有可能发生大剂量杆菌的自然感染，那么这些结果可能有助于解释卡介苗预防在印度及类似国家失败的原因，而在英国却取得成功。
