A proposed mechanism for natural immunity to enterobacterial pathogens.

The bactericidal effect of normal mouse serum, generally ascribed to natural “O” antibodies, can be removed by absorption with rough microorganisms. Passive hemagglutination tests disclose the presence of thermolabile, non-agglutinating “R” antibodies in normal mouse serum; titers in germ-free animals are much lower. Horse hyperimmune serum against rough S. typhimurium protects mice against infection with unrelated virulent smooth K. pneumoniae. Provided the Klebsiellae are preincubated in normal mouse serum bactericidal activity can also be demonstrated in vitro. This activity does not require the presence of complement and can be removed either by the same Klebsiella strain or by rough strains of Salmonellae but not by the smooth strain of Salmonellae from which these mutants originate. Although these effects would most easily be accounted for by specific antibodies it is also possible that they are instead attributable to a serum protein capable of charge interaction with rough antigens. In any event these findings, together with previous observations concerning degradation of somatic antigen and phenotypic modification of Klebsiellae recovered from endotoxin-treated mice, have led to the development of a new concept of natural immunity to Enterobacteriaceae. In this hypothesis, enzymatic factors capable of attacking cell wall components unmask R antigenic sites common to many bacterial strains and species. Thereafter the presence of a few types of “R” antibodies or of serum factors reacting with rough antigens have the capability of coping, like masterkeys, with a very wide range of infections due to serologically unrelated organisms.