THE '"TWO-STAGE" AND THE "LATTICE" HYPOTHESES 



209 



A 



CA) 



CAi) 



(Bi) 



that are more readily explained by the assumption of multivalent antibody as 

 well as of multivalent antigen. According to this view, first outlined by Marrack 

 (1934), the specific precipitate consists of antigen particles linked to one another 

 by antibody to form a continuous mass in which antigen and antibody alternate 

 (Fig. 33C). The initial combination and subsequent precipitation as a " lattice " 

 of antigen and antibody, result from binding of the particles at their specific 

 combining sites. This is the " lattice " hypothesis, and it will be seen that its 

 validity depends on the demon- 

 stration of multivalent antibody. 



Let us see how far the two 

 hypotheses fit the observed facts. 

 The constant-antibody optimum is 

 defined in terms of the velocity of 

 precipitation, which will be deter- 

 mined by differences in concentra- 

 tion, composition and flocculability 

 of the antigen-antibody compound 

 (see Miles 1933). 



Given a constant amount of 

 antibody, the speed of flocculation 

 will increase with increasing con- 

 centration of antigen, since, in the 

 standard volume used in the titra- 

 tion, there is a greater concentration 

 of antigen particles to act as centres 

 of aggregation, and the speed in- 

 creases until the equivalence zone 

 is reached. The falling off in the 

 speed of precipitation that occurs 

 if the amount of antigen added is 

 greater than the optimal amount is 

 attributed to a reduced precipita- 

 bility of the compound formed in 

 the presence of excess antigen. 



According to Bordet's two-stage 

 hypothesis, the optimal mixture 

 contains enough antibody to sensi- 

 tize fully a maximum number of 

 antigen particles ; in the antigen - 

 excess zone, the available antibody 

 for each antigen particle is insuf- 

 ficient to sensitize it fully, and with a great excess of antigen, there is no sensitiza- 

 tion at all. We shall consider the nature of this sensitization in detail in the 

 section on agglutination. Briefly, the hydrophobe nature of the antigen-antibody 

 complex is thought to be due to the distortion of the antibody molecule as a result 

 of its combination with the antigenic surface, with a consequent partial denatura- 

 tion, and the simultaneous occlusion of hydrophile groups on the surface of the 

 antigen. In the region of antigen excess, then, though there may be maximum 

 distortion of the Uttle antibody that combines with the antigenic particle, sufficient 



CD) 



(C) 

 (E) 



•J) 



(F) 



i) 



^-Ant/gen (^-Antibody 

 ((~ "Distorted "Antibody 



Fig. 33. — Schematic representation of various 

 antigen-antibody compounds, according to the 

 lattice (A to V) and the two-stage (D to F) 

 hypotheses. 



