ANTroODY FORMATION 



by design or accident, to environmental extremes of low tempera- 

 ture or high altitude are accounts of changes in resistance to in- 

 fection and disease. However, little quantitative experimental work 

 on the immune response has been done under controlled environ- 

 mental conditions. Some of our first studies were those utilizing 

 rabbits acclimatized to an environmental temperature of -15° C, 

 or else exposed to an altitude of 12,500 ft. at the Bar croft Laboratory 

 of the White Mountain High Altitude Station in California. 



A first approach to the investigation of the immune response was 

 the study of protein turnover, by passive immunization techniques. 

 In this procedure, homologous gamma globulin containing specific 

 antibody is injected intravenously into recipient animals. The 

 animals are bled periodically, and the concentration of serum anti- 

 body estimated by quantitative micro- precipitin analysis (Lanni, 

 Dillon, and Beard, 1950). The results are plotted semi- logarith- 

 mically as the percentage of the injected dose remaining in the 

 circulation versus time. The slope of the linear portion of the curve 

 (assumed to be steady state loss of antibody) is calculated by the 

 method of least squares, extrapolated back to zero time, and the 

 half-life of the injected antibody calculated from that point. 



The half-life of passively administered homologous antibody for 

 controls, cold- exposed, and high- altitude adapted animals was: 

 4.7 ± 0.2, 3.4 ± 0.2, and 4.5 ± 0.2 days, respectively. The cold ex- 

 posed animals have a significantly increased rate of antibody turn- 

 over, while those at high altitude do not. 



Rabbits exposed to -15° C for 10 weeks and clipped of hair during 

 the latter half of that period were actively immunized by the sub- 

 cutaneous injection of BSA (10 mg per kg body weight) in Freund's 

 adjuvant. Levels of circulating antibody were followed for a period 

 of 52 weeks (Fig. 1). Rabbits maintained at room temperature 

 and treated in the same manner were used as controls. 



The level of circulating antibody in the cold exposed group in- 

 creased at a slower rate than in the control group and approached 

 control levels at approximately 14 weeks. There was then a decline 

 in both groups, but at different rates, throughout the remainder of 

 the experimental period, so that by the end of 52 weeks the level 



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