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The Local Nature of Immunity in Tuberculosis, Illustrated Histochemically in Dermal BCG Lesions^1,2,

From the Department of Radiological Science, School of Hygiene and Public Health, and Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, and the Pathology Division, Fort Detrick, Frederick, Maryland 21701

Abstract

Dermal BCG lesions and the subsequently developing cellular immunity and allergy were evaluated periodically in rabbits with the following procedures: a) measurements of the lesions during growth and regression, b) tuberculin tests, and c) biopsies of the lesions for histology, histochemistry and enumeration of acid fast bacilli. Certain sections were stained for both bacilli and -galactosidase activity.

Macrophages were the most prominent cell type found in the lesions, although other cells especially PMN and lymphocytes were present in varying numbers. Macrophages developed into first immature epithelioid cells and then mature ones under the stimulus of tubercle bacilli and their products. This development was accompanied by a decrease in the number of bacilli present and a marked increase in certain enzymes, namely the lysosomal enzymes: -galactosidase, acid phosphatase and -glucuronidase, and the mitochondrial enzymes: succinic dehydrogenase and cytochrome oxidase.

Thus certain macrophages become highly activated in the local lesion. The association of such activation with an apparent destruction of intracellular bacilli suggests that cellular immunity involves both processes. In addition, the high degree of macrophage activation observed in the lesion suggests that cellular immunity is mainly a local (in contrast to a systemic) phenomenon.

In the BCG lesions, certain granulocytes (either eosinophils or toxic PMN) were found to contain considerably more RNase than the other cells present. In necrotic and liquefied areas RNase and DNase were especially active, and acid phosphatase and -glucuronidase were somewhat active. It therefore seems likely that nucleases and other lysosomal enzymes contribute to cell autolysis and the liquefaction of the caseous focus. The latter process helps perpetuate tuberculosis in mankind.

Footnotes

This investigation was supported at various times by contracts with Fort Detrick, the Defense Atomic Support Agency, the Army Medical Research and Development Command, and the Office of Naval Research (Microbiology Branch); and by Grant No. AI-07263 from the National Institute of Allergy and Infectious Diseases, United States Public Health Service.

² In conducting the research reported herein the investigators adhered to the "Guide for Laboratory Animal Facilities and Care," established by the ad hoc committee of the Institute of Laboratory Animal Resources, National Academy of Sciences-National Research Council.

³ Capt., Medical Corps, U.S. Army Reserve.

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