564 



Ontogeny of Immunological Properties 



extent only in a particular tissue. The work 

 on the development of the blood cell antigens 

 also points to a difference in the time at which 

 various genes may come into action in the 

 same tissue. This work does not rule out 

 the possibility that the differences involve 

 primarily rates of activity in different tissues 

 and concomitant differences in distribution 

 of the antigens in various parts of the cell. 



DEVELOPMENT OF NATURAL ANTIBODIES 

 AND OF COMPLEMENT 



While in humans the A and B agglutino- 

 gens are demonstrable in the early fetus, the 

 corresponding isoagglutinins are usually not 

 found in the serum until some time after 

 birth (see Wiener, '43). In fact it has been 

 shown that when agglutinins are present 

 in the serum of the newborn infant these 

 are derived from the mother by transfer 

 through the placenta. The maternal agglu- 

 tinins disappear during the first two weeks 

 of postnatal life while new ones character- 

 istic of the infant begin to appear in the 

 serum. 



In ruminants transfer of antibodies does 

 not occur across the placenta, which is of 

 the syndesmochorial type with four or five 

 layers of cells separating fetal and maternal 

 bloods instead of the two layers of the hemo- 

 chorial type of placenta of primates. How- 

 ever, as is well known since the experiments 

 of Orcutt and Howe ('22), antibodies (both 

 immune and natural) are acquired from the 

 mother by newborn ruminants as a result 

 of ingestion of the colostrum. In the recent 

 experiments of Yeas ('49) the normal anti- 

 R antibody could not be detected in the 

 serum of a lamb at birth but was present 

 after ingestion of the colostrum and per- 

 sisted for a variable period of several weeks. 

 The earliest time of appearance of the lamb's 

 own anti-R was found to be 15 weeks. The 

 transfer of proteins by ingestion of the colo- 

 strum has been stvidied in calves by Hansen 

 and Phillips ('47), who find that gamma- 

 globulin is absorbed only during the first 

 day after birth when the gut wall is appar- 

 ently permeable to large molecules. 



While it has been generally believed that, 

 where transfer of antibodies from mother 

 to fetus occurs, the route is through the 

 placenta, it has been shown recently by 

 Brambell et al. ('49) that this is not neces- 

 sarily the case. These workers demonstrated 

 in rabbits the presence of maternally derived 

 antibodies in the yolk-sac cavity of embryos 

 at a stage prior to establishment of the 



embryonic circulation. They have also 

 shown, by ligaturing the yolk-sac stalk of 

 24-day embryos, that the maternal anti- 

 bodies do not pass through the placenta, but 

 rather by way of the uterine lumen and yolk 

 sac into the fetal circulation. To what extent 

 these results with rabbits may apply to other 

 mammals remains to be determined, but it 

 seems unlikely that the situation would be 

 the same in species with a very rudimentary 

 yolk sac. 



In chickens a naturally occurring hemo- 

 lysin for sheep erythrocytes is not found un- 

 til about 5 days after hatching (Pickering 

 and Gladstone, '25). Apparently this anti- 

 body is not transferred from the hen to the 

 egg, although other antibodies produced as 

 a result of immunization of the adult hen 

 can evidently accumulate in the egg. For 

 example, such transfer has been shown for 

 diphtheria and tetanus antitoxins (Jukes et 

 al., '34; Fraser et al., '34; Ramon, '28) and 

 for antibodies against Newcastle disease vi- 

 rus (Brandly et al., '46). 



Complement (alexin) is apparently formed 

 rather early in mammals. It has been re- 

 ported (Soiling, '37) to be present in low 

 titer in the serum of the 14-week human 

 fetus and to reach full strength at 28 weeks. 

 In chickens, according to one investigation 

 (Sherman, '19), it is present in 17- to 21-day 

 embryos, while according to another (Polk 

 et al., '38) it is not detected until two days 

 after hatching. 



DEVELOPMENT OF ANTIBODY-FORMING 

 CAPACITY 



It is generally assumed that the ability 

 to form antibodies is lacking or poorly de- 

 veloped in the embryo, the fetus and the 

 newborn (see, for example, Needham, '42; 

 Beveridge and Burnet, '46; Topley and Wil- 

 son, '46). Experiments concerning this have 

 been performed with mammals and birds. 

 In mammals the fetus is not readily avail- 

 able for such studies. The problem is also 

 complicated by placental transmission of 

 antibodies and by uncertainties as to whether 

 or not antigens that are introduced into the 

 mother will reach the fetus. However, ex- 

 periments have been performed on newborn 

 mammals and at various ages after birth. 

 Thus, Freund ('30) injected rabbits with 

 sheep red cells, typhoid bacilli, horse serum 

 and egg white and found that those of one 

 to 20 days of age produced either no anti- 

 bodies or only very small amounts of anti- 

 bodies against these antigens. With increas- 



