The passive transfer of delayed hypersensitivity in the guinea-pig. II. The ability of passively transferred antibody to cause local inflammation and retention of antigen and the role of these phenomena in the passive transfer of delayed hypersensitivity.

It is known that serum increases the passive transfer of delayed hypersensitivity to certain antigens, such as bovine γ-globulin, in the guinea-pig. This synergic effect of serum in the passive transfer of delayed hypersensitivity to bovine γ-globulin was partly, but not completely, produced by serum to haemocyanin when a mixture of bovine γ-globulin and haemocyanin was used for skin testing. It was concluded that part of the synergic action of serum was due to a local inflammatory reaction. The ability of serum to cause local retention of antigen in the skin was studied using antigens labelled with radioactive iodine. Immune serum favoured the local retention of antigen. The passive transfer of antiserum to bovine γ-globulin, egg albumin and haemocyanin specifically increased the retention of antigen two- to twelve-fold. This ability of serum to cause the local retention of antigen at the site of intradermal injection was present in serum taken 3 weeks after immunization with bovine γ-globulin in Freund's complete adjuvant but absent in serum taken at 1 week. Antiserum also altered the distribution of antigen at the skin site. Autoradiography showed that it increased the area over which an appreciable concentration of antigen occurred. Active immunization with bovine γ-globulin had a slight effect on the total amount of antigen retained in the skin after intradermal injection. It had a greater effect on the distribution of antigen. In control guinea-pigs 87 per cent of the total amount of bovine γ-globulin retained at 20 hours was found within a radius of 6.5 mm of the centre of injection. In contrast in guinea-pigs immunized with bovine γ-globulin in Freund's complete adjuvant 43 per cent was found beyond this radius. A similar change in the distribution of human serum albumin was seen in guinea-pigs immunized with bovine γ-globulin when the albumin was mixed with bovine γ-globulin. This indicated that factors other than the formation of immune precipitates were sometimes responsible for the local retention of antigen. The total amount of purified protein derivative of tuberculin (PPD) retained and its distribution in the skin was uninfluenced by immunization. It was concluded that the synergic effect of immune serum on the passive transfer of delayed hypersensitivity was due in part to some aspect of the inflammation caused by antibody antigen reaction and in part to the local retention of antigen caused by antibody.