The mechanism of breakdown of immune tolerance to a protein antigen in rabbits.

Rabbits made tolerant to human serum albumin (HSA) were hyperimmunized with either HSA or bovine serum albumin (BSA) incorporated in Freund's complete adjuvant. Eventually, anti-HSA antibodies could be demonstrated which represented most likely a boosted response to minor determinants to which the animals had not been made tolerant. This response was suppressed by a series of intravenous antigen injections and the animals relapsed into a state of unresponsiveness. Renewal of hyperimmunization with BSA in adjuvant did not terminate tolerance a second time, while identical treatment with suphanilated HSA did induce an anti-HSA response again. The theoretical aspects of tolerance breakdown are discussed in the light of these findings.