Immunologic unresponsiveness induced by protein antigens.

1. Repeated large infusions of heterologous plasma proteins can induce a state of specific immunologic unresponsiveness in rabbits. In normal adult rabbits this unresponsiveness in most instances lasts only about as long as the heterologous proteins are detectable in the host (3 to 4 months). In rabbits infused from the time of birth and perhaps x-radiated adult rabbits the induced immunologic unresponsiveness lasted throughout the period of observation (10 to 11 months), long after disappearance of all detectable foreign proteins. 2. This unresponsiveness appears to be specific for the antigens administered in excess and does not prevent antibody responses to even closely related antigens. 3. The unresponsiveness was not transmitted to first generation offspring. 4. The mechanism of the temporary unresponsiveness which occurs in normal adult rabbits may be dependent upon the actual presence of the antigen in the host. However, the unresponsiveness does not result from a simple neutralization of antibody, as it is formed, by the antigen, as has been suggested in the case of pneumococcal polysaccharide induced immunologic paralysis. 5. On the other hand, the mechanism of the lasting immunologic unresponsiveness developing in the "newborn" and perhaps the x-rayed rabbits may depend upon the acceptance of the foreign protein as essentially non-antigenic by the host. A similar situation is seen in the naturally occurring placental transfer of dissimilar red blood cell types between fraternal twins.