Specificity of Acquired Resistance Produced by Immunization with Mycobacterial Cells and Mycobacterial Fractions

Abstract

Mice were immunized intraperitoneally with 5.0 mg of living and 5.0 mg of heat-killed H37Ra cells of the attenuated strain Mycobacterium tuberculosis and challenged intraperitoneally with Listeria monocytogenes and Klebsiella pneumoniae. The period of protection provided by the living and heat-killed H37Ra cells against both heterologous infections was the same. When mice were immunized intraperitoneally with graded doses of living and heat-killed H37Ra and challenged intraperitoneally with listeria or klebsiella, the lowest immunizing dose providing protection against both klebsiella and listeria challenge was the same for living and heat-killed cells. Living and heat-killed cells also immunized equally effectively when the routes of immunization and challenge were different. Mice also were immunized intraperitoneally with mycobacterial ribosomal fraction, mycobacterial cell walls, and several nonspecific agents (Escherichia coli endotoxin, mineral oil emulsion, and Freund's incomplete adjuvant). The mice were challenged intraperitoneally with listeria or klebsiella at varying times after immunization. The mycobacterial components and all the nonspecific agents provided transitory protection lasting no longer than 4 days after immunization. Only the mycobacterial cell walls and the endotoxin provided protection against listeria challenge. It was concluded that the protection provided by the mycobacterial ribosomal fraction is specific for tuberculosis infection, since this fraction provided no protection against listeria infection and only transitory protection against klebsiella. It was also concluded that the mycobacterial component providing protection against heterologous infections is heat stable and probably is found in the cell wall.

Role of interferon in mice in protection against influenza A virus by bacterial ribosomes together with membranal glycoproteins of Klebsiella pneumoniae as adjuvant

“…Content, and G. Nis, Arzeim. Forsch., in press) against homologous infections; others have emphasized the uniquely specific protective power of these preparations (1,6,27,40). However, these preparations may also have a nonspecific immunostimulant effect, as we have shown previously (12,20,39).…”

Immunizing Capacity of Viable and Killed Attenuated Mycobacterial Cells Against Experimental Tuberculous Infection

“…Finally, the marked superiority of living mycobacterial cells over killed cells for immunization against tuberculous infection is not noted when mice are challenged with Listeria monocytogenes and Klebsiella pneumoniae (2,3,4). In fact, living and heat-killed mycobacterial cells perform equally well in inducing protection against these heterologous organisms, and the magnitude of the immune response is equivalent only to that noted with the killed cells when challenge is with M. tuberculosis.…”

“…In fact, there is no agreement that acquired immunity in tuberculosis is specific, since some believe that it operates equally well against other facultative intracellular parasites (10). This point of view, however, is not supported by the work of Coppel and Youmans (2,3,4).…”

“…On the other hand, it is clear that certain attenuated or avirulent mycobacterial strains, such as the H37Ra mutant, do not multiply in vivo (in fact, they are rapidly destroyed), yet these strains produce as great an immune response in experimental animals as the supposedly viable and multiplying BCG strains (9,13,17,30). As for the second given above, evidence has now accumulated which clearly shows that there are at least two immunizing moieties in the mycobacterial cell, one of which is heat stable and located predominantly in the cell wall, which induces a low-grade immune response to tuberculous infection and which is responsible for the nonspecific immunity noted to other intracellular parasites (2,31). The second immunogen is quite labile and is found in the ribosomal fraction when viable broken mycobacterial cells are fractionated by differential centrifugation under the proper conditions (24)(25)(26)(27).…”

Cellular Immunity to Listeria monocytogenes Induced by Sensitization and Challenge with Bovine Gamma Globulin

“…Unchallenged but sensitized animals and FCA-treated controls which received a "challenge" dose of BGG show a significant, but lesser resistance to Listeria infection, but there is no detectable difference between these two control groups. This effect may be due population by the mycobacterial constituents of the adjuvant (1,3).…”