The lipid A immunity system Induction of heterophile antibodies by enterobacterial lipopolysaccharides and their lipid A componentMice were immunized either with lipopolysaccharides (LPS) or with the respective lipid A components. After four days an increase in the number of direct plaque-forming cells with complement-dependent antibody against sheep red cells was seen. Cross-reactions were observed with red cells of cattle, goats, horses and rabbits. All LPS investigated, of Shigella, Escherichia coli, and S and R form Salmonella, as well as the lipid A component evoked this immune response. We therefore conclude that all enterobacterial LPS induce an antibody which cross-reacts with SRC and that the lipid A component is responsible for this reaction. Evidence is presented that these effects, such as toxicity, fever, pyrogen tolerance, leucopenia/leucocytosis, nonspecific immunity, and tumor inhibition are mediated by lipid A-induced antibodies. Materials and methods BacteriaThe Salmonella cholerae suis strains were kindly supplied by H. Momenteau and L. LeMinor, International Salmonella Centre, Institut Pasteur, Paris, the Escherichia coli strains by F. Grskov, Statens Seruminstitut, Copenhagen, Shigella sonnei (phase 11) by M. Mulczyk, Institut Immunologii i Terapii, D&wiadczalnej, Breslau, Poland. R and S form Salmonella were provided by 0. Luderitz, Max-Planck-Institut fur Immunbiologie, Freiburg and by R. Rohde, Nationale Salmonella-Zentrale, Hygiene-Institut, Hamburg, respectively. The bacteria were kept at 4 O C on peptone agar. 2.2. Preparation of antigens Abbreviations: SRC: Sheep red blood cell(s) PFC: Direct antibody plaque-forming cell(s) LPS: Lipopolysaccharide(s) PBS: Phosphate buffered saline MBB: Modified barbital buffer i.p.: intraperitoneal 2.2.1. Lipopolysaccharides Bacterja were grown in 100 liter steel containers for 30 h at 37 C, slightly aerated, with either modified Fraser's medium [20], or in synthetic medium: 0.1 M Tris, pH 7.4; 0.0005 M KH2P04; 0.002 M sodium citrate, pH 6; 0.02 M NH4C1; 0.001 M MgS04; 1 x M FeCI3; 1 x M W.-R. Rank, R. DiPauli and U. Flie-Rank Eur.