50 IMMUNO-CATALYSIS 



b. The immediate immune response to an antigenic substance when 

 introduced into an individual belonging to a different species. 



A reasonable understanding of the difference in immune response 

 under the above two conditions would necessitate that we become 

 acquainted with in vivo metabolism of protein and other non-protein 

 antigenic substances. It is an established fact that antibody protein is 

 a modified globulin. Immune globulin which has been obtained from 



which the thyroglobulins were derived. Thyroglobulin is a conjugated protein con- 

 taining thyroxine and a protein. Since the thyroxine group, common to the thyro- 

 globuUns of various species, would be expected not to function as a common deter- 

 minant haptenic group, the overlapping precipitin reactions described by Hektoen 

 and Schulhof could be due to the denaturation and thereby loss of the specificity 

 of thjTToglobulins they isolated. Thyroglobulin is known to circulate in normal blood 

 and does not function as an antigen under these circumstances. Its reported antigenic- 

 ity in homologous species might very well be due to its denaturation incurred during 

 its preparation. 



Kato (1924) reported that the serum of rabbits immunized with a heterologous 

 fihrinogen may react with it and also with that of other species, but not with rabbit 

 fibrinogen; and the serum of rabbits immunized with rabbit fibrinogen reacts with 

 other fibrinogens but not with the immunizing rabbit fibrinogen. These findings woiald 

 indicate that the rabbit fibrinogen exercises species specific and non-specific serological 

 activity as well, and that fibrinogens from various species possess a common denomi- 

 nator or, as antigens, they represent mixtures of denatured and native fibrino- 

 gens. Hektoen and Welker (1927) obtained overlapping reactions among the fi- 

 brinogens from chicken, duck, goose, guinea-hen, pigeon and turkey. They studied 

 the fibrinogens of the common mammals and concluded that they have antigenic 

 elements that are more or less common, but that bird fibrinogen does not belong 

 immunologically to this group; however, it is not wholly distinct and different from 

 manrnialian fibrinogen. Fibrinogen is unique among the serum proteins. It is in- 

 soluble in salt-free water but is soluble in dilute salt solutions. It is the most readily 

 precipitable of all the common blood proteins by concentrated salt solutions e.g., 

 half saturation with sodium chloride or 20 per cent ammonium sulfate. It is also 

 unique among the blood proteins in that it is readily converted into insoluble fibrin 

 by the action of thrombin. It is an asymmetrical molecule with dimensions of 

 33x900A. Though the coagulation temperature of fibrinogen is 55°C in neutral 

 solution, the heat coagulation of fibrinogen (and fibrin) during a period of one 

 hour, according to Robbins (1945), did not aEFect the antigenic nucleus. 



In view of these properties, one may wonder whether or not the laboratory prepara- 

 tions of fibrinogen are removed from the native form. In this respect it may be of 

 some interest to reinvestigate the problem with a view to the role of — S— S— or 

 — SH groups in fibrinogen in relation to their possibly masked immunological speci- 

 ficities as has been demonstrated with keratins and ocular lens proteins discussed 

 below, also for the possible reasons that, according to Baumberger's suggestion (1941), 

 -S-S- ^ -SH relationship might play a role in the conversion of fibrinogen into 

 fibrin, and that reducing agents, e.g., cysteine, glutathione, sodium bisulfite (ChargafF, 

 1945) inhibit fibrin formation (see page 282). 



For a long time keratins were considered immunologically indistinguishable. 

 Pillemer, Ecker and Wells (1939), Pillemer, Ecker and Martiensen (1939) showed, 

 however, that species specificity is an individual characteristic of keratins and that 

 the observed specificity is dependent on the redox state of the sulfhydryl groupings 

 in the protein molecule. In a similar study, Ecker and Pillemer (1940), contrary to 



