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The Magnitude of the Immune Response Incited by Killed and Attenuated Mycobacteria

From the Leonard Wood Memorial Laboratory, Department of Bacteriology and Immunology, Harvard Medical School, Boston, Massachusetts

Abstract

Results of the present inquiry indicate that the problem of securing protection against mycobacterial disease cannot be attributed to a failure of available antigens to incite high orders of immune response in the "average" person or animal. The calculated enhancements of resistance after moderately effective immunization of rats against murine leprosy by means of BCG or heat-killed M. lepraemurium were equivalent to x 10⁵ challenge doses. An adjuvant combination of these antigens raised this value to nearly x 10¹¹ challenge doses. On the basis of relative extensions of incubation or survival periods, evidence was presented that equal or superior responses have been observed following the use of BCG to immunize mice against experimental tuberculosis. The degree and persistence of these immune responses were consistent with the known potency of mycobacterial antigens as judged by sensitization, antibody production and adjuvant effects.

These facts have permitted a reinterpretation of the classical observations of small differences between control and immunized groups, of greater differences between individuals within a group than between experimental groups, and of the prolongations of incubation or survival periods without complete protection against mycobacterial disease. It is concluded that basic difficulties concern the exceptionally high activations required to deal effectively with the agents of mycobacterial disease and the problem of maintaining these levels in individuals who are unable to make an "average" response.