Guinea pigs sensitized with either hen, duck, or goose egg albumin showed delayed hypersensitivity followed by Arthus reactions to the homologous antigen, but tended to have much weaker delayed responses and slower antibody formation to heterologous antigens. Guinea pigs with delayed hypersensitivity to one of the avian antigens had a slower antibody response to a secondary injection of heterologous antigen than to one of the homologous antigen.
Sensitization with a protein conjugated with a hapten such as picryl chloride (Pi) or dinitrofluorobenzene (DFB) resulted in delayed hypersensitivity to the homologous conjugate, the homologous protein, and the homologous protein with a heterologous hapten. Circulating antibody and Arthus reactions occurred subsequently to the homologous conjugate, as well as to the homologous hapten attached to a heterologous protein. Delayed hypersensitivity thus seemed associated with the protein moiety, and Arthus responses with the hapten.
Anamnestic responses followed injection of an antigen causing delayed hypersensitivity, but not of a hapten not causing delayed reactions. Thus, animals sensitized initially with Pi·HEA, DFB·HEA, or HEA produced antibodies sooner after a secondary injection of Pi·HEA than did unsensitized animals. No anamnestic response resulted when animals sensitized to Pi·BGG were injected with Pi·HEA.
Thus, delayed hypersensitivity is indicated to be a preliminary and immature step in the immune process, with specificity directed against broad, more general features of the protein antigen. This intermediate step is followed by production of circulating antibody to any antigen having a similar basic structure, with the specificity of the antibody also directed against smaller immunologically active sites on the antigen molecule.