Conversion of Immunological Paralysis to Immunity by Endotoxin

Abstract

INJECTION of animals with relatively large amounts of an antigen results in their failure to mount an immune response. It has been suggested that if endotoxin be given after such a dose of antigen, immunity rather than unresponsiveness will result¹. Claman² reported briefly that when mice injected with unaggregated bovine γ-globulin (BGG), an antigen which normally causes unresponsiveness, were given endotoxin they formed antibodies to the BGG. Immunological paralysis induced by pneumococcal polysaccharides is a classical example of immunological unresponsiveness, yet little if anything is known of its mechanism. In an attempt to explore possible mechanisms, 0.4 mg of the endotoxin of Salmonella typhosa 0901 (Difco) was injected intraperitoneally into 10-week-old CAF₁ mice before, or at various times after, 25, 75 or 200 µg of the soluble specific substance of type III Diplococcus pneumoniae (SIII). At various times, usually commencing 7 days after the injection of the antigen, the mice were bled and their sera, absorbed against natural antibodies to sheep cells, titrated by a haemagglutination test using the filtrate of a type III D. pneumoniae culture coated to sheep erythrocytes as antigen³. Approximately 5 weeks after the injection of the antigen the mice were challenged with one hundred lethal doses of type III D. pneumoniae.