io84 A CRITIQUE OF THE EHRLICH THEORY 



d) This acquired histamine-like insusceptibility of smooth muscle structures can- 

 not be transferred from an immune dog to a normal dog by even massive immune 

 blood transfusion.' This finding is readily harmonized with the enzyme theory by the 

 assumption that the histamine-like insusceptibihty is due to secondary intracellular 

 antibodies chemically different from the primary humoral antibodies. 



THE ENZYME THEORY AS AN EXPLANATION OF KNOWN SEROLOGICAL FACTS 



With one minor hypothesis as to the difference in the relative stability and dis- 

 sociability of earlier and later conjugates, the enzyme theory of antibody formation 

 will explain and co-ordinate all known properties of specific antibodies. Antitoxins, 

 for example, would be pictured as non-toxic dissociation products of slightly disso- 

 ciable humoral conjugates. During the process of immunization this specific disso- 

 ciation product would be gradually increased in the body as a result of repeated con- 

 jugations of the dissociated toxin with new proteins. This would lead in time to an 

 almost complete suppression of the toxin by the laws of mass action. Toxin added to 

 antitoxic serum would be suppressed by conjugation with the superabundant non- 

 toxic dissociation product. Similar conceptions would apply to agglutinins, precip- 

 itins, opsonins, and bacteriolysins. Heat inactivations, reactivation, and "comple- 

 ment deviation" could be explained under this theory without the necessity of the 

 assumption that the only possible method of action of a lytic serum is by a direct 

 chemical union between "amboceptor" and "complement." 



Unstable or highly dissociable serum conjugates might readily account for the 

 explosive colloidal readjustments of humoral anaphylaxis. Unstable or highly disso- 

 ciable cellular conjugates might lead to the explosive increases in cell permeability in 

 cellular anaphylaxis.^ Later stable, relatively non-dissociable cellular conjugates 

 might account for the partial or complete disappearance of this increased permeabili- 

 ty in immune animals. Passive desensitization of fixed tissues by immune blood trans- 

 fusion^ might be explained as a result of a complete disintegration of the earlier, un- 

 stable, highly dissociable anaphylactic cellular conjugates in the presence of more 

 stable and relatively non-dissociable later immune conjugates. 



THE ENZYME THEORY IN THE INTERPRETATION OF CLINICAL DATA 



The enzyme theory, however, would necessitate a reinterpretation of much of 

 our accumulated experimental and clinical data. For example, specific serum titra- 

 tions, though admittedly accurate measures of the specific primary humoral anti- 

 bodies, could no longer be assumed to be a measure of the specific immunological 

 adaptations of the body as a whole. This might readily account for a puzzling lack of 

 parallelism between serum titre and clinical picture, and between the specific titre of 

 a proposed antiserum and its therapeutic effects. Specific intracellular antibodies 

 chemically different from the humoral antibodies might readily account for the high 

 organ-specificity of certain micro-organisms, so difficult to credit under our present 

 theory. Variations in immunizing power of the same antigen with different methods 

 of Injection might be explained on the same basis. Secondary non-specific humoral 

 antibodies might readily account for non-specific serum reactions. 



^ J. Immunol., 13, sg. 1927. ' Ibid., 8, 232. 1923. i Ibid., 13, $9- 1927. 



