Ontogeny of Immunological Properties 



567 



the gelatinous coat (which is constituted of 

 fertilizin) of the sea-urchin egg an anti- 

 fertilizin could be extracted from the naked 

 eggs. This antifertilizin, derived from within 

 the egg, was capable of agglutinating intact 

 eggs or of forming a precipitate with the 

 surface coat substance (fertilizin). Thus, 

 from one and the same cell a pair of sub- 

 stances are obtainable that interact in sero- 

 logical manner, and which may be termed 

 complementary substances. Tests with verte- 

 brate blood cells and with bacteria have 

 also yielded such auto-aggkitinins, but meth- 

 ods for obtaining them consistently have 

 not as yet been fully worked out. The diffi- 

 culties here appear to involve interaction 

 and precipitation of the complementary sub- 

 stances in extraction procedures that cause 

 destruction of the cell before surface sub- 

 stance can be sufficiently removed. Also, 

 some may be "univalent" (Tyler, '45, '54) 

 and, thus, not readily detectable by direct 

 testing. There have, however, been a suffi- 

 cient nvimber of reports in the literature 

 (see Tyler, '47, for references) in which 

 auto-antibodies have been evidently ob- 

 tained, so that it seems safe to conclude that 

 the situation is a general one for all kinds 

 of cells. Tests have also been made of the 

 possibility that such auto-antibodies might 

 have protective action against toxins, ven- 

 oms, etc., and evidence for such action has 

 been obtained (Tyler, '46) in the case of a 

 venom. Thus, it has been found that the 

 lethal action on mice of the venom of the 

 Gila monster can be neutralized by serum 

 or by an extract of liver of the same animal. 

 According to the auto-antibody concept 

 the formation of immune antibodies by an 

 animal, in response to the injection of a 

 foreign antigen, is a special case of the gen- 

 eral type of process involved in the synthesis 

 of the macromolecular constituents of cells. 

 The now fairly generally accepted view of 

 the manner of formation of immune antibody 

 is that which was proposed by Breinl and 

 Haurowitz ('30), Alexander ('32), and Mudd 

 ('32) and which has been extended by Paul- 

 ing ('40). This view proposes that foreign 

 antigen becomes incorporated in the site of 

 synthesis of serum globulin so that, as the 

 polypeptide chains of the new globulin that 

 is being formed fold up, the molecules now 

 bear regional surface configurations that are 

 complementary to certain structures on the 

 antigen. The auto-antibody concept in fact 

 may be inferred from this view, if one con- 

 siders the situation in the absence of foreign, 

 introduced, antigen. Under such conditions 



the normal globulin that is formed should 

 bear regional structural configurations that 

 are complementary to chemical structures of 

 the normal site of synthesis. The concept is 

 not, however, restricted to the special case 

 of the formation of serum globulin but ap- 

 plies to any of the macromolecular con- 

 stituents of cells. Since it is the formation of 

 such substances that is involved in the proc- 

 ess of growth, that process, then, may be 

 considered to result from the operation of 

 the same sort of mechanism exemplified in 

 the formation of immune antibodies. Growth 

 also involves an increase in self-dviplicating 

 entities, such as genes, and for the formation 

 of these one may assume structures that are 

 both complementary and identical, as Paul- 

 ing and Delbriick ('40) suggest, or the pro- 

 duction of an intermediate template, as Em- 

 erson ('45) proposes as an alternative. 



RELATION TO SPECIFIC ADHESION OF 

 CELLS 



This general point of view has been ap- 

 plied (Tyler, '47) to two aspects of the prob- 

 lem of differentiation. One is the question 

 of the nature of the forces that are re- 

 sponsible for the specific adhesion or non- 

 adhesion of cells and tissues. The other is 

 the phenomenon of induction. In regard to 

 the former Loeb ('22) had early suggested 

 that specific agglutination is the factor in- 

 volved in binding cells into tissues. That 

 some mechanism analogous to antigen-anti- 

 body interaction is involved is suggested by 

 the specificity of the tissue affinities. Thus 

 species specificity is exhibited, for example, 

 in experiments on the reconstitution of a 

 sponge from cells that have been dissociated 

 from one another by forcing the organism 

 through fine bolting cloth (Wilson, '07, 

 '32; Galtsoff, '29). When the dissociated cells 

 of two species are mixed, coalescence is 

 found to occur only between those of the 

 same species. The degree of cell-type spec- 

 ificity that is exhibited in these experiments 

 is not entirely clear, but the evidence is to 

 the effect that the archeocytes are mainly 

 involved and that other cells, such as collar 

 cells, that are on hand may be incorporated. 

 Experiments by Holtfreter ('43-48) with 

 amphibian embryos offer illustration of the 

 specificity of association of cells within the 

 species. He has shown that isolated cells or 

 clumps of cells from blastulae or early 

 gastrulae will fuse regardless of their pro- 

 spective significance. While the cells of the 

 same germ layer remain fused, separation 



