Normal guinea pigs fed chemical haptens develop a specific state of unresponsiveness, inhibiting subsequent development of dermal sensitization with the same hapten and modifying profoundly the synthesis of anaphylactic antibody in response to hapten conjugated to guinea pig proteins.

The degree of unresponsiveness has been tested by exposing hapten-fed animals to intense haptenic stimulation. Animals of groups that were demonstrably unresponsive to picryl chloride could be made to form hapten-specific antibody by injecting picrylated bovine gamma globulin. Specific anaphylactic-type antibodies, presumably 7S γ1, were synthesized, and in animals given PBGG adsorbed to alumina there arose a measurable concentration of precipitating antibody, presumably 7S γ2, perhaps slightly earlier than in similarly treated control animals.

Attempts to impose contact-type reactivity on such unresponsive animals met with limited success. Injection of picrylated guinea pig erythrocyte stromata in a complete Freund's adjuvant, with subsequent applications of picryl chloride to the dermis, led to definite contact sensitivity to 0.3 per cent picryl chloride, whereas parallel treatment of normal control animals induced sensitivity to 0.006 or 0.002 per cent. By this double method of stimulation, hapten-fed animals did not advance in sensitivity by reason of the secondary dermal applications of the simple chemical, whereas control animals developed increasingly higher sensitivity by these contacts in what appeared to be a stepwise manner.

Picryl chloride-fed guinea pigs injected intradermally with picryl chloride either after or before forming picryl-specific circulating antibody still remained unable to develop picryl-specific contact hypersensitivity.

Control animals synthesizing picryl-specific antibody subsequently responded to intradermal injection of picryl chloride with contact-type sensitivity.

Interpretations of these results are discussed and the view is presented that delayed-type hypersensitivity and circulating antibodies of the varieties measured here are formed independently of each other.

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