Studies on the Mechanism of the Immunological Paralysis Induced in Mice by Pneumococcal Polysaccharides

Abstract

Immunological paralysis has been defined as that condition produced in the host by an antigen given in such amount that a subsequent immunizing dose fails to stimulate active immunity. With the preparations of polysaccharide used in C₃H mice the amounts included: For type I 500 μg or more, and for types II and III 50 μg or more. In white mice, one-tenth of these doses was sufficient to “paralyze” the defense. In both strains of mice, smaller amounts immunized the animal. The type-specific immunological paralysis persisted for at least 15 months following a single injection with type I or III polysaccharide and for 18 months with type II polysaccharide. For all three types studied, the reaction was essentially type-specific. Immunological paralysis was produced by 500 μg of type I polysaccharide by intraperitoneal, intravenous, or intradermal administration; but by the oral route the largest does given, 5.0 mg, immunized the mouse. For types II and III the 50 μg dose “paralyzed” the defense whether introduced intraperitoneally, intravenously, or intradermally; orally 5.0 mg immunized against type II, but not against type III infection. By subcutaneous route the “paralyzing” dose of 50 μg was the same for all three types. Repeated daily doses of smaller amounts “paralyzed” the defense when the total reached the above doses. With type I, this “paralysis” was not found in all mice; but with types II and III all mice so injected were unable to respond to a subsequent immunizing dose. Mice which had been previously immunized required four times as much antigenic polysaccharide to produce immunological paralysis as was required by normal mice. “Paralyzed” mice were found to be hypersusceptible to pneumococcus infection and required two to four times as much antibody to give passive protection as normal animals. The only successful means found for counteracting the “paralysis” in mice was the use of whole-cell vaccine, and this was applicable only to type I but not to types II and III.