Section IX 

 ONTOGENY OF IMMUNOLOGICAL PROPERTIES* 



ALBERT TYLER 



ANTIGENS IN DEVELOPMENT 



SOME GENERAL REMARKS 



The various tissues and fluids of an adult 

 organism contain a large assemblage of anti- 

 gens. Of these the serum proteins and red 

 blood corpuscles of mammals have been most 

 extensively studied immunologically, but a 

 large number of investigations have also 

 been performed with soluble and insoluble 

 constituents of various tissue cells. As a gen- 

 eral statement one may say that the diverse 

 antigens exhibit properties of species-specific- 

 ity and tissue-specificity to various degrees. 

 Certain serum or tissue-proteins show a high 

 degree of species-specificity in that the anti- 

 sera that are prepared against these materials 

 of one species of animal fail to react or give 

 weaker reactions with similar preparations 

 from other species, depending somewhat on 

 the degree of phylogenetic relationship. 

 Certain antigens termed Forssman or hetero- 

 genetic antigens, however, are widely and 

 irregularly distributed in various tissues and 

 species of animals. Similarly, immunization 

 with extracts of one kind of tissue yields 

 antisera that react to various degrees with 

 corresponding preparations from other tissues 

 of the same animal. Where extensive cross- 

 reactions occur specific components of the 

 tissue may nevertheless be demonstrated by 

 absorption of the antiserum with the prepara- 

 tion from the heterologous tissue. This pro- 

 cedure removes the antibodies for such anti- 

 gens as may be common to various tissues. 



It is often supposed that if the chemically 

 different proteins of the different tissues were 

 prepared in pure form no cross-reactions 

 would be obtained. This has, however, not 

 as yet been established experimentally. The 

 difficulties here are due to the ability of 



* A presentation of the fundamentals of immunol- 

 ogy is beyond the scope of this chapter. The unin- 

 formed reader should, therefore, consult a recent 

 text such as Boyd's ('47) or Kabat and Mayer's 

 ('48). 



relatively small amounts of antigen to give 

 rise to considerable amounts of antibody, and 

 to the uncertainties involved in specifying 

 the degree of purity of various proteins and 

 other antigenic substances. As an illustration 

 of this, some recent work by Cohn, Wetter 

 and Deutsch ('49) on the proteins of chicken 

 egg-white may be cited. They studied the 

 precipitation of ovalbumin and conalbumin 

 by antibodies produced in rabbits and horses. 

 The ovalbumin was recrystallized six times 

 and found to be of homogeneous molecular 

 size upon sedimentation-velocity and diffu- 

 sion tests. However, it showed two main 

 components upon electrophoresis. The conal- 

 bumin preparation was ultracentrifugally 

 and electrophoretically homogeneous. The 

 electrophoretic patterns (Fig. 205) showed 

 neither conalbumin in the ovalbumin prepa- 

 ration nor the reverse. Nevertheless, the 

 antisera prepared against ovalbumin reacted 

 also with conalbumin. On the other hand, 

 the two ovalbumin components detected 

 electrophoretically were indistinguishable 

 immunologically. From quantitative studies 

 of the various reactions of these preparations 

 these workers conclude that there are anti- 

 genically active impurities in these prepara- 

 tions that are not revealed by the various 

 physicochemical tests. 



It is, of course, well known that there are 

 no absolute criteria of purity even for simple 

 chemical substances and that crystallizability 

 does not necessarily mean molecular homo- 

 geneity. For protein preparations modern 

 methods of determining homogeneity, in 

 regard to different properties, include elec- 

 trophoresis, sedimentation, diffusion and sol- 

 ubility, and each has certain limits of sen- 

 sitivity. Experiments of the type cited above 

 tend to show that immunological methods 

 may be more sensitive for the detection of 

 impurities in protein preparations. However, 

 there is some uncertainty that impurities are 

 really being detected by these methods. It 

 would be necessary to show in the first place 



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