566 



Ontogeny of Immunological Properties 



can grow well in the presence of serum and 

 mesenchymal tissues of an immunized rabbit 

 (Medawar, '48). However, prolonged treat- 

 ment (Billingham and Sparrow, '54) can pre- 

 vent dissociated Malpighian cells from form- 

 ing epithelium upon grafting, thus indicating 

 a specific, in vitro, antibody effect. In tissue 

 culture it has been shown (Harris, '43) that 

 mouse and rat tissues are quite compatible. 

 Even when mouse tissues are taken from ani- 

 mals previoiisly immunized against tissues of 

 the rat, guinea pig or chicken there is no in- 

 compatibility exhibited in mixed cultures 

 with each of the latter (Grobstein and Young- 

 ner, '49). 



It appears, then, that tissues grown in 

 vitro behave much like embryonic tissues in 

 regard to the absence of incompatibility re- 

 action, and this, it seems, should provide a 

 clue to the analysis of the incompatibility 

 problem on the basis of features common to 

 both. One feature common to both is that 

 they are actively growing. Taking this into 

 consideration it would seem reasonable to 

 suppose that any antibodies that might be 

 produced by the tissues of the host embryo 

 or by one of the tissues in culture, in re- 

 sponse to the presence of the foreign anti- 

 gens, would be incorporated into the growing 

 cells. In this location, intimately bound in 

 or on the cells, the antibodies would not be 

 available for action on the foreign tissue. 

 On this basis it is not a necessary conclusion, 

 from the experiments reported in the first 

 part of this section, that the embryo is in- 

 capable of antibody formation. Those ex- 

 periments do not exclude the possibility that 

 any antibodies that are formed may be 

 simply used as part of the building blocks 

 of the tissue. Later, when growth slows 

 down and material is released from the 

 tissue, such antibodies may be liberated and 

 then initiate the incompatibility reaction. 



However, there are cases in which cells 

 may survive well into the adult life of a 

 genetically different recipient embryo. This 

 is ilkistrated by the persistence in the adult 

 chicken of melanoblasts transplanted between 

 embryos (Willier and Rawles, '40, '44) and 

 by the occurrence of erythrocyte mosaicism 

 in adult dizygotic cattle (Owen, '45) and hu- 

 man twins (Dimsford et al., '53), due most 

 likely to reciprocal transfer of the fetal blood 

 through the common placenta. In addition, 

 experiments by Billingham, Brent and Meda- 

 war ('53) now show that adult animals may 

 be indviced to tolerate foreign skin grafts if 

 they are inocvilated during fetal life with 

 cells from the donor strain. Thus mice of 



CBA strain injected in utero, at the 15th- 16th 

 day, with tissue (isolated cells and clumps 

 from chopped-up adult testis, kidney and 

 spleen) of A strain can tolerate /1-strain skin 

 transplanted in adult life. In chickens trans- 

 fusion of blood between embryos of different 

 strains renders the recipient, at two weeks 

 after hatching, similarly tolerant to skin 

 grafts received from the donor strain. A some- 

 what related investigation (Buxton, '54) has 

 shown that the inoculation of chick embryos 

 with killed Salmonella pullorum results in a 

 marked decrease in the capacity of the 

 hatched chickens to produce antibodies in 

 their sera when challenged again with the 

 bacterial antigen. Billingham et al. ('53) sug- 

 gest that the faikire of the host's immuno- 

 logical response in their experiments may be 

 related to a specific immunological paralysis 

 provoked by high doses of antigen (see Fel- 

 ton, '49). Another possibility is that "type- 

 transformation" (see below) has been in- 

 duced in those host cells responsible for the 

 immune response. These highly interesting 

 experiments will undoubtedly stimulate ex- 

 tensive investigation leading to their inter- 

 pretation, so that one need not speculate fur- 

 ther at this time. 



THE CONCEPT OF NATURAL 

 AUTO-ANTIBODIES 



The results of certain experiments on the 

 interacting substances of eggs and sperm 

 (see Section IV, Chapter 1), along with con- 

 sideration of various findings of others, re- 

 ported in immunological literature, led 

 Tyler ('40-48) to propose a view of cell 

 structure and growth termed an "auto-anti- 

 body" concept. This concept states that each 

 of the various macromolecular substances of 

 which cells are constructed bears the same 

 sort of relationship to another of these sub- 

 stances as do antigen and antibody, and that 

 their mode of origin is analogous to that of 

 antibody formation. This view has been 

 applied to the interpretation of certain as- 

 pects of the problems of differentiation (Ty- 

 ler, '47). A brief accovmt of this is presented 

 here along with some of the background of 

 the concept. 



The experiments with the fertilizins and 

 the antifertilizins that are derived from the 

 surface layer of eggs and of sperm, respec- 

 tively, have shown that these substances 

 interact in a manner analogous to that of 

 antigen with antibody (see Section IV, Chap- 

 ter 1). In the course of this work it was 

 found (Tyler, '40) that upon removal of 



