Ontogeny of Immunological Properties 



565 



ing age the titers of antibody obtained 

 increased. 



A detailed study of antibody production in 

 chickens of various ages from hatching to 

 12 weeks has been made by Wolfe and Dilks 

 ('48). These workers used bovine serum as 

 antigen and obtained very weak, or no, 

 precipitins from the newly hatched chicks. 

 The titers increased up to 5 weeks of age 

 and remained approximately the same to 

 12 weeks (see Table 26). 



That the embryo chick also fails to pro- 

 duce detectable antibodies has been shown 

 by several investigators using a variety of 

 antigens. For example, no antibody response 



showed that such grafts begin to regress at 

 the eighteenth day of incubation, and sim- 

 ilar results have been subsequently obtained 

 by others (see Waterman, '36). It should be 

 noted, however, that this is the time when 

 the chorioallantois itself starts to regress. 



It is also now well known, since the 

 original experiments of Born (1897) and 

 Harrison (1898), that tissue grafting homo- 

 plastically or heteroplastically succeeds read- 

 ily in embryonic stages, whereas it generally 

 fails in the adult. Other chapters of this 

 book deal with the work along this line, and 

 detailed discussion of the greater part of 

 the literature on this subject is presented in 



Table 26. Precipitin Titers (Ring Tests) of Antisera vs. Bovine Serum Pro- 

 duced in Chickens Given Three Alternate-Day Injections Starting 

 at Various Ages and Bled 6 and 9 Days after Last Injection {from 

 Wolfe and Dilks, '48) 



Age in weeks 

 Av. titers as tube* 

 numbers 



1/712345 6 7 8 9 10 11 12 



1.0 3.0 5.5 6.2 7.7 11.1 11.9 11.1 11.6 11.1 11.4 12.1 12.2 



Number of antisera 

 tested 



25 26 29 20 



31 



31 



42 



59 



36 



31 



18 



18 



* Tube 1 is a 123^ fold dilution and succeeding tubes are serial twofold dilutions. 



was obtained with such good antigens as 

 diphtherial and tetanal toxoids (Grasset, 

 '29), B. sporogenes and Vibrio septique 

 (Weinberg and Guelin, '36) and with a 

 bacteriophage and influenza virus (Beveridge 

 and Burnet, '46). There is a report (Gebauer- 

 Fuelnegg, '32) of antibodies being found in 

 the egg white at 14 days of incubation after 

 injecting the embryos with sheep serum four 

 or five times on alternate days starting at 

 the third day of incubation. This result was 

 obtained in only 5 out of 126 eggs used. 



The ability of many viruses and rickettsiae 

 to grow readily on the membranes and 

 tissues of the chick embryo, as first demon- 

 strated by Rous and Murphy ('11) and by 

 Goodpasture and his collaborators ('38-'44), 

 seems to correlate with lack of antibody- 

 forming capacity (see Beveridge and Bnrnet, 

 '46). For example, Brandly et al. ('46) find 

 that neutralizing antibodies against New- 

 castle disease virus are not detected in chick 

 embryos earlier than 15 days of incubation. 

 Similarly the ability of various normal and 

 tumor tissues of the same or of other species 

 to grow on the chorioallantois, as shown 

 initially by Murphy ('13), Willier ('24) and 

 Hoadley ('24) appears to depend upon in- 

 ability of the embryo to form antibody (see 

 Needham, '42; Loeb, '45). Murphy ('14) 



the recent book by Loeb ('45). Here we will 

 consider briefly the question of whether or 

 not antibody formation may be responsible 

 for tissue incompatibility. 



Loeb and Wright ('27) established the 

 genetic basis of tissue incompatibility in 

 their classic demonstration, with inbred lines 

 of guinea pigs, that the reaction was due to 

 the absence in the host of factors present in 

 the grafted tissue. Kozelka ('33) showed, in 

 chickens, that the factors responsible for the 

 incompatibility of homografts are not rep- 

 resented by the agglutinogens of the blood 

 cells. In rabbits, too, the red cell antigens 

 do not appear to be involved (Medawar, 

 '46b). However, in mice incompatible skin 

 homografts stimulate the formation of anti- 

 bodies that react with red cells and leuko- 

 cytes (Amos et al., '54). That an antibody 

 mechanism of some sort is involved in graft- 

 incompatibility is evident from many ex- 

 periments showing immunity to second trans- 

 plants. For example, in experiments of Me- 

 dawar ('46a), inhibitory effects are obtained 

 in rabbit skin that is transplanted to a rabbit 

 that has previously been "immunized" by 

 grafting skin from the same donor or, to a 

 less extent, from another rabbit. Injection of 

 leukocytes also is found to induce this type of 

 immunity to subsequent skin grafting. Skin 



