Endotoxins and Exotoxins

Exotoxins are noxious proteins secreted by many bacteria. These toxins are often heat-labile and thus can be heat-inactivated for use as vaccines to prevent toxigenic immunity to bacteria disease. Many bacteria produce more than one protein exotoxin, making vaccine development more difficult.

Endotoxins are somatic lipopolysaccharide-protein complexes. These complex antigens are located in the outer membrane of all gram-negative bacteria. Toxicologic activity is associated with the lipid A component of the endotoxin, whereas the serologic determinants are polysaccharides.

Antibody directed against specific polysaccharides can be protective both by enhancing phagocytosis directly and by fixing complement for lysis. Unfortunately, from an immune standpoint, antigenic differences in the polysaccharide components of endotoxins exist among strains of bacteria. Thus, in general, infection with one strain does not generate protective immunity to reinfection with a different strain of the same species. IgM and IgG antibodies directed against the lipid A component of lipopolysaccharide have different capacities to neutralize the infectivity of gram-negative bacteria.

It appears that IgM is a more potent neutralizing antibody than IgG. This is particularly true for cross-reacting antibody directed against core polysaccharide or lipid A determinants of gram-negative bacteria.

Passive administration of human or murine IgM directed against core determinants of endotoxin has been attempted for treatment of gram-negative sepsis. These attempts have not been efficacious except in selected subgroups of patients.