Immunization of guinea pigs with denatured autologous gamma globulin results in the development of delayed hypersensitivity to some form of gamma globulin. When the autologous gamma globulin is subjected to denaturation with alkaline treatment as employed in this study, guinea pigs regularly develop reactivity to the immunizing material and occasionally to some form of heterologous gamma globulin. With other forms of denaturation, such as produced by urea, ultrasound, or heat, guinea pigs rarely develop sensitivity to the immunizing material but frequently exhibit delayed reactivity to native or denatured heterologous gamma globulin. Reactivity against native autologous gamma globulin does not occur. Guinea pigs immunized with undenatured autologous gamma globulin fail to develop reactivity to any form of gamma globulin.
Rabbits immunized with denatured autologous gamma globulin develop circulating antibodies against some form of gamma globulin. Rabbits immunized with alkaline denatured autologous gamma globulin develop antibodies against the preparation used for immunization and against heterologous gamma globulin; rabbits immunized with autologous gamma globulin subjected to freeze-thaw or heat denaturation develop antibodies against heterologous globulin, but antibodies against the immunizing material can only rarely be demonstrated.