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The course of lethal cryptococcosis in mice was modified by immunization with the same strain or different strains of Cryptococcus neoformans. Protection was associated with a definite decrease in tissue fungus multiplication over the initial 7 days of infection. Such immunity was species-specific and did not protect against heterologous challenge with Staphylococcus aureus, Klebsiella pneumoniae, or Mycobacterium tuberculosis. Similar modification of lethal cryptococcosis was produced by intraperitoneal inoculation of 100 to 200 µg. of Salmonella endotoxin 7 days prior to challenge. In non-specifically (endotoxin) immunized mice there was only a minimal reduction in tissue cryptococcus census during the 1st week of infection. When small numbers of virulent cryptococci were injected intravenously into normal mice, tissue populations rose markedly in all organs studies during the first 7 days. A progressive fall in tissue fungus census was then observed in most mice during the next 6 months. The increase in resistance to cryptococcal challenge following specific immunization, the non-specific protection conferred by injection of bacterial endotoxin and the ability to control and eventually reduce infections with small inocula may well be dependent in each case on the development of specific antibody.
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