C3H/HeNMTV mice were immunised intraperitoneally (i.p.) with lipopolysaccharide (LPS) or detoxified LPS (D-LPS) derived from Salmonella typhimurium strain SR-11. In both cases, effective protection was achieved against a challenge dose of greater than 2 x lo2 LD50 of the same organism given by i.p. injection. However, by comparison with LPS, approximately 6-to 10-fold more of D-LPS by weight was needed to protect mice to an equivalent degree. Histopathological studies showed that the initial lesions in infected mice protected with either LPS or D-LPS were composed of self-limiting abscesses which transformed into granulomas as the animals recovered. It is suggested that D-LPS may be modified to become a highly effective, non-toxic salmonella vaccine.
The fate of virulent
Salmonella typhimurium
within macrophages of guinea pigs was assessed by a suspended cell culture procedure. The present study confirmed that macrophages of normal guinea pigs were capable of inactivating the ingested salmonellae. Macrophages of previously infected guinea pigs were not endowed with any significant increase in their ability to eliminate the ingested pathogen. However, the immune macrophages were observed to clump together tightly when they were exposed to salmonellae. This phenomenon was attributed to the presence of specific cytophilic antibodies on the immune macrophages. When immune macrophages were inactivated with Merthiolate, they agglutinated with both the H and the O antigens of
S. typhimurium
, but not with the O antigens of other species of
Salmonella
nor with the O antigens of
Escherichia coli.
Cytophilic antibodies could be eluted from immune macrophages by incubation in the absence of immune serum. Conversely, cytophilic antibodies could be passively transferred onto normal macrophages by incubation in the presence of immune serum. Furthermore, using immune serum previously adsorbed with the O antigens of
S. typhimurium
, cytophilic antibodies against the H antigens alone could be transferred onto normal macrophages, or those against the O antigens alone could be eluted from immune macrophages. These data suggest that immune macrophages possess specific cytophilic antibodies against both the H and the O antigens of
S. typhimurium.
It is proposed that the presence of cytophilic antibodies on immune macrophages represents an expression of antibacterial cellular immunity by enhanced clumping and phagocytic activities of the macrophages.
A suspended cell culture procedure was described for the cultivation of guinea pig macrophages infected with Salmonella typhimurium. The fate of the intracellular bacteria was assessed by quantitative recovery of viable bacteria with 0.5% solution of sodium desoxycholate. Two strains of S. typhimurium with different degrees of virulence for mice were compared. There was an initial destructoin of intracellular bacteria of both strains; however, the extent of this destruction differed. Approximately 1% of the avirulent bacteria initially phagocytized survived at the end of 4 hr, whereas approximately 8% of the virulent bacteria survived at the end of 3 hr. After this initial killing, the intracellular bacteria began to multiply at a logarithmic rate between 3 and 21 hr after phagocytosis, and then a stationary phase was attained. The rate of this multiplication was comparable for both strains.
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