Specificity of the Anamnestic Response Produced byListeria monocytogenesorMycobacterium tuberculosisto Challenge WithListeria monocytogenes

Abstract

When mice immunized with Listeria monocytogenes were given a second injection of listeria, they showed an anamnestic immune response to intravenous challenge with listeria, as measured by enumeration of the viable infecting organisms in the spleens of the infected animals. This response was independent of the effects of the challenge dose. When mice immunized with living or heat-killed attenuated mycobacterial cells were boosted with living H37Ra, there was also an accelerated response to listeria challenge. The response was greater in the mice given the primary immunization with living cells than in those immunized with heat-killed cells. The response to listeria challenge in mice immunized and boosted with mycobacteria was of less magnitude than that in the mice immunized and boosted with listeria. Growth of listeria in the mice immunized and boosted with mycobacteria was retarded only during the first 2 days of the infection, whereas the infecting listeria in mice immunized and boosted with listeria were permanently inactivated. Mice immunized with mycobacterial ribosomal fraction and restimulated with living mycobacterial cells showed no accelerated response to listeria challenge. It is evident from these results that resistance to these organisms is specifically evoked, but that once evoked it is not completely nonspecific in action. Also, the resistance produced by the mycobacterial ribosomal fraction to challenge with mycobacteria is completely specific in action. Therefore, it has been shown that there are two mechanisms involved in acquired immunity to facultative, intracellular parasites. One is nonspecific and mediated by activated macrophages. The other is specific and mediated by a mechanism as yet unknown.

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

“…This was covered by exhaustive experiments in which mice injected intraperitoneally or intravenously with the same YOUMANS AND YOUMANS small number of viable cells were sacrificed at weekly intervals; the spleens, livers, lungs, and kidneys were homogenized, and samples of appropriate dilutions were plated on suitable media. In all cases, the number of viable cells that could be detected in this way rapidly decreased and had disappeared by 4 weeks.…”

“…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).…”

Shared Antigens Between Heterologous Bacterial Species

“…The possibility that resistance to many bacterial infections may be partly due to immune mechanisms, whether cellular or humoral, that have been stimulated by unrelated bacteria would appear to merit consideration. In addition, the concept that resistance to many infections is sometimes due entirely to nonspecific, nonimmunological mechanisms (7,16,30) should be reevaluated.…”

In Vitro Induction of Nonspecific Resistance in Macrophages by Specifically Sensitized Lymphocytes

“…Nonspecific cellular resistance appears to diminish with the disappearance of the antigenic stimulus from the host but can be rapidly recalled by reintroduction of the specific antigen (12). The Toxoplasma rnodel used in our studies should afford an ideal situation since, unlike the Listeria or Mycobacterium model in which resistance either results in the complete elimination of the organism from the tissues (5,14) or effectively sequesters it and renders it antigenically ineffective (6), a host infected with Toxoplasma remains infected for life, and there is ample evidence for continued antigenic stimulation throughout the life of the host (16,(20)(21)(22). Delayed hypersensitivity is acquired in guinea pigs within 1 week after Toxoplasma infection as measured by in vivo and in vitro techniques (10).…”