[Frontiers in Bioscience 3, c27-33, May 1, 1998]

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Arthur M. Dannenberg, Jr.

Departments of Environmental Health Sciences, Molecular Microbiology and Immunology, and Epidemiology, School of Hygiene and Public Health; and the Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205

Received 3/9/98 Accepted 3/14/98


Vaccines have no effect on whether or not an inhaled tubercle bacillus establishes a microscopic lesion in the host. Vaccines can only prevent the development of microscopic tuberculous lesions once they have been established. These statements are conclusions derived from the following principles.

(a) Pulmonary alveolar macrophages (AM), the first cells of the host to ingest inhaled tubercle bacilli, possess no immunologic specificity. Therefore, vaccines cannot increase the power of AM to destroy tubercle bacilli, after the nonspecific effects of the vaccine have returned to normal levels.

(b) The bacillary unit that reaches the pulmonary alveoli to start a tuberculous lesion contains no more than 1 to 3 bacilli (1). Such a small number of bacilli do not contain high enough levels of antigens to call forth the immune response --- even an immune response enhanced by a vaccine. Therefore, the inhaled bacilli must multiply, thereby increasing the amount of their antigens, before memory lymphocytes, which do possess immunologic specificity, are able to affect the progress of the disease. Such multiplication is within the accumulating macrophages, and a microscopic lesion is thereby established (described more fully below). [Bacillary units containing 4 or more bacilli do not stay in the airstream, but impinge upon the (rather resistant) bronchial walls and do not reach the alveolar spaces.]

TB vaccines prevent clinical tuberculosis by stopping the progression of these early pulmonary lesions while they are still small enough to remain inapparent to the host. Once such lesions are grossly visible, they are well established and often progress into clinical disease. A quantitative measure of a vaccine’s ability to prevent clinical disease is therefore its ability to reduce the number of established grossly visible tubercles in the lungs.