296 IMMUNOLOGICAL METHODS OF DIAGNOSIS 



while all the bacteria had settled to the bottom. This peculiar 

 behavior, as we now know, is owing to the presence, in the sera in 

 question, of certain antibodies known as agglutinins which are 

 formed as a result of infection (sc., immunization), and are char- 

 acterized by the fact that in suitable dilution they will cause the 

 arrest of motility and agglutination of the corresponding organisms 

 (see also section on Antibodies). Normal serum, it is true, will 

 also do this to a certain extent, but only when used in a fair degree 

 of concentration, and then only imperfectly, while with immune 

 sera the complete reaction may be obtained even though the serum 

 be diluted many times. In this sense the reaction is specific, and 

 may be employed both for the identification of a given organism 

 as also for the recognition of the nature of an immune serum. In 

 the first instance an emulsion of the unknown bacterium is brought 

 together with diluted test sera, corresponding to those organisms 

 which would enter into consideration from a diagnostic stand-point. 

 If, then, the bacterium in question is agglutinated by an antityphoid 

 serum, for example, but not by an anticolon or an antidysentery 

 serum, the inference would be (within certain experimental limita- 

 tions) that we are dealing with the typhoid bacillus. On the other 

 hand the unknown serum, in a certain degree of dilution, is tested 

 against a series of organisms, when a positive result with one of 

 these would indicate the nature of the infection. From both stand- 

 points the agglutination reaction has thus a wide sphere of 

 application. 



Very soon after the discovery of Griiber and Durham, Widal 

 found that the formation of agglutinins in typhoid fever begins 

 quite early in the course of the disease, i. e., at a time when from 

 the usual symptoms the diagnosis cannot as yet be made with 

 certainty, and he thus established a method of diagnosis which in 

 some one of its numerous technical modifications is now used the 

 world over, and is generally known as the Widal reaction. Further 

 studies, then, showed that the formation of agglutinins in other 

 infections likewise begins while the disease is in actual progress, 

 and that the same principle may be successfully utilized for diag- 

 nostic purposes in a number of other maladies besides typhoid 

 fever. This is notably the case in paratyphoid infections, in Malta 

 fever, and in meningococcus infections. In other maladies agglu- 

 tinin formation also takes place, but either does not begin early 



