The immunology of tuberculosis.

Abstract

1 uberculosis is one of the oldest and most widespread of the life-threatening infectious still affecting human and animal populations throughout the world (1, 2). Despite the ready availability of an effective vaccine and the existence of assorted chemotherapeutic agents, pulmonary tuberculosis continues to pose a major health problem, especially for many third world countries (3). Even in the United States, almost 30,000 new cases of pulmonary tuberculosis were reported in 1980, with 3,000 deaths directly ascribable to this disease (4). The continued persistence of a disease that only 20 years ago seemed to be nearly eradicated is highly disturbing, especially because many of the newly diagnosed cases are found in populations especially subject to infection by drug-resistant strains of tubercle bacilli (5). Only when the present incidence of this disease is compared with that observed 100 years ago, when Koch (6) first published his classic paper on the diagnosis and etiology of tuberculosis, can the enormous advances of recent decades be seen in perspective. Koch's landmark paper was, in the view of one of his contemporaries, certainly one of the most important medical papers ever written and a model of logic in the application of the new experimental method to the study of diseases (7). Koch's paper went far beyond the mere description of yet another human pathogen, however. For one thing, it established a set of criteria (the so-called Koch postulates) that must be satisified before a causal relationship can be established between a suspected microbial pathogen and a given disease (8). From a more parochial viewpoint, this paper also served as an important catalyst for Dr. E. L. Trudeau, leading him into tuberculosis research. Trudeau, who had tuberculosis for most of his life, had just established the Adirondack Cottage Sanatarium in Saranac Lake. At the time Koch's paper first appeared in Germany, very little was known in this country about the origin or the bacteriologic diagnosis of tuberculosis. Trudeau obtained an English translation of the paper and quickly succeeded in repeating Koch's experiments, using his own clinical materials for the purpose (7). These studies marked the beginning of a long series of experimental and clinical investigations into this disease by Trudeau and his colleagues (9-11). One of their most important early findings was the demonstration that environmental factors play an important role in determining the spread of this infectious pathogen within an isolated rabbit colony (12). Trudeau was not able to confirm all of Koch's claims, however. Koch had reported that repeated injections of an extract of the tubercle bacillus (Old Tuberculin) possessed significant therapeutic value for humans (13). Repeated attempts to confirm this in tuberculous patients at the Trudeau Sanatarium were almost entirely unsuccessful (14, 15). Despite this early controversy, there is no question that Koch's papers had a lasting influence on tuberculosis research that extended far beyond anything to be expected from a description of yet another human pathogen. It still stands as a classic example of the use of an experimental approach to the study of human infectious diseases. In a review of this nature, it is impossible to do justice to all of the areas of immunology that have been influenced by tuberculosis research. No attempt will be made to cover the voluminous literature dealing with various cell components of the mycobacteria, including the structure and biological activity of tuberculin or the unique mycobacterial lipids. These have been discussed elsewhere (16-20). For the same reason, the biological activity of various antituberculosis vaccines (both live and inactivated) will be considered mostly from the point of view of the cellular response to the tuberculous challenge and the interrelationship between the resulting delayed-type hypersensitivity and cell-mediated immunity. The tubercle bacillus can serve as a potent immunologic adjuvanting or immunosuppressive agent, depending on the experimental conditions. As a result, the tuberculous host offers an ideal opportunity to study the cellular interactions responsible for the modulation of the host defenses against a variety of human pathogens. The results of these studies extend far beyond the initial goal of achieving a better understanding of the mediators of the antituberculous immune response in both man and experimental animals.