Immunological unresponsiveness in rabbits produced by neonatal injection of defined antigens

Abstract

Previous studies on the ontogeny of the specific immune response shortly after birth in several species (1-10) have indicated that newborn Chicks, guinea pigs, rabbits, and human beings form little or no detectable antibody in response to antigenic stimulation, but develop this ability between 2 and 4 weeks of age. In several known situations, however, such antigenic stimulation is not lost upon the newborn animal but results in a highly specific hiatus in his immunological capacity which persists after maturity. The studies establishing this last concept are reviewed exhaustively by Billingham, Brent, and Medawar (11) particularly in reference to "acquired tolerance" to homografts. In respect to less complex antigens, the investigations of Hanan and Oyama (12), Dixon andMaurer (I3), and Cinader and Dubert (14) have indicated that multiple injections of heterologous plasma proteins during the neonatal period result in prolonged and specific inability to respond immunologically to the injected protein.This investigation has been concerned with the mechanisms which govern the early development of specific immunity in mammals and particularly the unresponsive state resulting from neonatal exposure to antigen, The present paper describes the production of a prolonged state of immunological unresponsiveness in rabbits by a single injection of defined protein antigens at birth, and defines the amount of antigen required, the duration of the unresponsive state, the degradation of antigen in unresponsive animals, and also describes a number of attempts to produce an analogous state with a variety of bacterial antigens. A preliminary report of these studies has appeared else-*

Quantitative and qualitative approaches to GOD: the first 10 years of the clonal selection theory

“…‘[This idea] diverges from Burnet's proposal that the ‘randomisation’ of antibody‐forming cells is confined to perinatal life, thereby generating a set of then stable clones corresponding to the antibody‐forming potentiality of the animal,’ he wrote. Burnet did not appear to adopt this critical insight, which was capable of explaining why experimentally induced neonatal tolerance to a nonproliferating, 27 , 28 , 29 or surgically removed 30 antigen only lasted a few weeks, while that to proliferating antigens was life long 31 . One can only speculate as to the reasons for Burnet's failure in this regard, but it must have been obvious to him that a Nobel Prize was in the wind and that it would be for his work on neonatal tolerance.…”

Spinal cord regeneration in rats made immunologically unresponsive to CNS antigens.

“…In each experiment we attempted to create tolerance with a single injection of spinal cord emulsion on the first day of life. Multiple injections of antigen begun during the neonatal period are more effective than a single injection (Paterson, 1958;Smith and Bridges, 1958;Eitzman and Smith, 1959;Weigle, 1973). Therefore, in this experiment we treated animals on the first day of life and weekly with intraperitoneal injections of 75 mg isogeneic emulsified spinal cord in an effort to achieve a greater degree of immunological unresponsiveness than we have achieved in earlier experiments.…”

The Elimination of Mouse and Bovine Globulins From the Circulation of Newborn and Adult Mice

“…A STATE of acquired immunological tolerance to several different serum protein antigens can be induced by injection of the antigen into animals when they are in utero or newborn. This tolerant state appears to last as long as the antigen can be demonstrated in the animal, or as long as the antigen can be inferred to persist by extrapolation from estimations of the rate of elimination of the antigen in the animal [Smith and Bridges, 1958;Terres and Hughes, 1959;Hirata, Garvey and Campbell, 1960;Dresser, 1961]. This relationship between the persistence of antigen and the duration of tolerance may also apply to cellular and particulate antigens: for instance, the relationship has been demonstrated in chickens by Mitchison [1959] who used homologous erythrocyte antigens and by Friedman and Gaby [1960] who used Shigella antigens.…”