DISCUSSION 211 



ation had matured to a degree at which they could respond to H-3 

 antigens. 



Michie: How does it measure up to this point, that the difference 

 between the immunizing and tolerance-inducing dose doesn't seem 

 to change markedly with age ? The difference between the tolerance- 

 inducing dose for a strong (H-2) antigen and a weak one is just about 

 the same in adults as it is in the newborn, that is of the order of 10 or 

 100 times. And if you compare the Y antigen with an H-2 difference, I 

 think you get a factor of the order of at least 100 for equivalent 

 tolerance-inducing dose. But that factor is the same in newborns as it is 

 in adults. 



Medawar: Yes, I see the point. 



Mitchison: Dr. Simonsen, in the second part of your exposition I 

 understood you to interpret the Factor of Immunization as being a 

 measure of the extent of the multiplication of the population of cells. 

 Might it not equally be that this represented a heightened reactivity on 

 the part of cells that did not multiply — that each individual cell be- 

 comes relatively more potent as a consequence of immunization? 

 And so discussions of clonal selection in that context might be 

 irrelevant. 



You mentioned quantitative immunochemistry and I am trying to 

 translate the data which you have given here into the form in which 

 they would appear if one were doing a classical immunization experi- 

 ment. If I have understood you correctly one could translate them 

 into three propositions, which I think are very well established already, 

 namely: (i) that over at least a proportion of the dose-response range 

 the amount of antibody made is proportional to the amount of antigen 

 put in ; (2) that if you compare different antigens, they elicit different 

 quantities of antibody during the primary response, and that those 

 antigens which give a powerful initial stimulus tend to cause a less 

 marked secondary response (contrast the bacterial flagellar proteins 

 with heterologous plasma proteins: the former are more powerful 

 initial immunogens and give less of a secondary response than the 

 soluble proteins) ; (3) that rabbits tend to make antibodies up to some 

 sort of ceihng. Most serologists would say that 2 or 3 mg./ml. is a 

 good response, and this is the sort of thing you would aim to get 

 eventually, whatever antigen you are using to immunize with. Those 



