IMMUNOLOGICAL TOLERANCE 



qualitative character of the proUferative response will 

 depend greatly on where the stimulated cell lodges. De- 

 pending on the site and the physiological condition of the 

 site, proliferation may give lymphocyte, plasma cell, epi- 

 thelioid cell or, with greater reservations, eosinophil 

 granulocytes. 



It may be useful to consider the situation where tolerance 

 to BSA is induced by a single injection in the new-born 

 rabbit in the Ught of this diagram. At the time of primary 

 inoculation we are concerned with the line nearest the 

 horizontal, and a dose of antigen large enough to produce 

 inhibition of proliferation is given. The contact with anti- 

 genic determinant also prevents any movement of the cell's 

 reactivity from that curve to the next in the family. As soon 

 as antigen has disappeared the cell can resume its inter- 

 rupted maturation and then will respond normally. 



This is a simple and natural explanation of the facts, which 

 include the abihty of the tolerant rabbit to produce antibody 

 against any unrelated antigen. Any non-clonal interpreta- 

 tion immediately encounters some grave difficulties. Any 

 suggestion must take the form that all potential antibody- 

 producing cells have taken up the antigen and are so affected 

 that while the antigen remains they cannot respond. It will 

 probably be assumed that the antigen initiates the first step 

 in producing the necessary template, but then in some way 

 inhibits any further progress without interfering with the 

 organization and functioning of other immunological tem- 

 plates in the same cells. This would demand a series of 

 independent antibody-producing mechanisms in each cell 

 capable of independent stimulation or inhibition, a very 

 difficult situation to imagine. 



Immune paralysis as exemplified by mice inoculated with 

 moderate or large doses of pneumococcal polysaccharide 

 seems to be based on a very effective adsorption of all anti- 

 body produced by polysaccharide held in the macrophages. 

 The deposition of antibody on this material (Dixon, Maurer 



94 



