Three forms of delayed skin-test response evoked by mycobacteria

Abstract

KOCH¹ first reported that when guinea-pigs which had been infected 4–6 weeks previously with tuberculosis were challenged intracutaneously (i.e.) with a small number of virulent organisms, there was induration and necrosis within 48 h, and localisation of the challenge dose. This phenomenon (classical tuberculin-type hypersensitivity) has often been regarded as a direct correlate of protective immunity. But, the same challenge dose was not localised if injected intramuscularly (i.m.). This raised the possibility that ‘protection’ from the i.e. challenge was a trivial consequence of necrosis and sloughing of the infected skin. The controversy was highlighted by Wilson² who noted that pre-immunised guinea pigs showing an exquisite degree of hypersensitivity at the time of a small i.m. challenge with virulent Mycobacterium tuberculosis died more than 40 d before unimmunised controls, whereas weakly hypersensitive animals showed protection. We describe here a form of delayed foot-pad response which is evoked by all the non-pathogenic mycobacteria studied, but differs from the Koch-type response in timing and suppressor cell activity. It is not seen following injection of pathogens, and it is suggested that failure to evoke this response may account for their pathogenicity.