454 BIOLOGY OF THE LABORATORY MOUSE 



comparison with nonspecific factors is questioned. Webster and Hodes 

 (328) have recently demonstrated that highly susceptible mice are not 

 immunized to a subsequent test dose by repeated, sublethal doses of mouse 

 typhoid bacilli or St. Louis encephalitis virus given by a natural route. 

 They further emphasize that reinoculation of survivors is not an adequate 

 test of active immunity unless the animals employed are known to be 

 '' ... at least 90 per cent susceptible to the test agent given by a normal 

 portal of entry." An animal surviving the first dose by virtue of nonspecific 

 resistance may withstand a second dose in the same manner without neces- 

 sarily having an active immunity. Moreover, in such diseases as mouse 

 typhoid and ectromelia, vaccination by the methods thus far employed may 

 give some protection but does not confer a solid immunity (306, 205, 289, 92). 

 Nonspecific resistance appears to be a characteristic of the individual, 

 dependent on heredity and probably on other factors as yet unknown, as 

 modified by age and environmental influences. The degree of resistance 

 varies among individuals in a single breed of mice as well as among different 

 breeds (295, 277, 312, 315, 206, 208, 209, 90, 245). Because of this fact it is 

 possible by selective inbreeding to develop stocks with a relatively high 

 resistance or susceptibility to one infectious agent but not necessarily to 

 another (316, 317, 289, 321, 322, 97, 326, 327, 323, 324). A study of hybrid 

 and backcross generations (295, 90, 321, 324) indicates that resistance is 

 dominant, but segregates independently of the sex and color factors. The 

 responsible genetic factors are considered by Hill (97) to be multiple, since 

 litters of long inbred lines may show more variation in reaction than can be 

 ascribed to chance, whereas Webster (323) supports the theory of a single 

 factor type of inheritance with possibly a number of small modifiers, since 

 mortahties in succeeding generations showed no definite progress with selec- 

 tion. Both Hill and Webster have emphasized the need for extreme precau- 

 tions in work of this kind in order to exclude the specific resistance of 

 acquired immunity, either active or passive. 



There are numerous observations, some of which are mentioned in the 

 preceding pages (see also 183), to indicate that resistance varies with age, 

 older animals in general becoming more resistant. Nonspecific anatomical 

 and physiological factors (228) undoubtedly play a role, but there is also 

 evidence that specific factors may be involved, since immature animals are 

 less able than mature ones to respond to an antigenic stimulus by the forma- 

 tion of antibodies (20, 53, 175). 



The above work is important not only because it aids in the selection and 

 use of animals experimentally, but also because it points out many of the 



