THE ANTIGENIC STRUCTURE OF THE PNEUMOCOCCI 573 



found that a given serum would protect against the homologous strain of pneumo- 

 coccus, but not against heterologous strains. Dochez, Avery and their colleagues 

 (Dochez and Gillespie 1913, Dochez and Avery 1915, Avery 1915, Avery et al. 

 1917) later studied the antigenic relationships of a large collection of pneumococci, 

 using the methods of direct agglutination and agglutinin absorption. They confined 

 their attention, for the most part, to strains isolated from cases of lobar pneumonia 

 in man, and among these they were able to recognize three well-differentiated types, 

 Types I, II and III, leaving a large heterogeneous group unclassified. Lister (1916) 

 carried out a similar study on strains isolated from cases of pneumonia among 

 the mine- workers in South Africa. He was able to differentiate several antigenic 

 types, which he labelled with letters instead of numbers. These observations have 

 since been confirmed and extended by workers in many parts of the world, the three 

 classical American types being generally accepted as the standard of reference ; 

 and it was not long before we obtained a reasonably adequate picture of the distribu- 

 tion of these three types in cases of lobar pneumonia, in other pneumococcal infec- 

 tionr., in healthy contacts and in the population at large. For many years, however, 

 no serious attempt was made to analyse the unclassified heterologous group, which 

 formed a considerable proportion (25-50 per cent.) of the strains isolated from cases 

 of lobar pneumonia, and the majority of those isolated from the upper respiratory 

 tract of normal persons. It was the custom to refer to such strains as belonging 

 to Group IV, an unfortunate nomenclature that became frankly misleading when the 

 label was changed to " Type IV ", which not infrequently happened. 



Within recent years, Cooper and her colleagues (Cooper, Edwards and Rosenstein 

 1929, Cooper et al. 1932, Cooper and Walter 1935) have made a detailed study of this 

 previously unclassified group. Among strains isolated from lobar and broncho- 

 pneumonia, from various other pneumococcal infections, and from normal persons, 

 they have identified 29 new antigenic types, making 32 in all, including the classical 

 Types I, II and III. Most of these types are, it should be noted, sharply differenti- 

 ated from each other, so that they may be identified by direct agglutination. 

 Since Cooper's study, further types have been described by other workers (see 

 Kauffmann et al. 1940, Walter et al. 1941, Morch 1942). Unfortunately two 

 systems of labelling have been used, the one making use of numbers irrespective 

 of antigenic components shared with other types, the other using letters in addition 

 to numbers to bring out antigenic components possessed by different types in 

 common. Eddy (1944) has described the cross-reactions that may be met with, 

 and has suggested the use of a series of Arabic numbers ranging from 1 to 74 to 

 cover the types known at present. We may be quite sure that there are still 

 new types of pneumococci to be identified, and new labels to be given ; but it seems 

 likely that our present 74 types include most of those that are parasitic in man. 

 Gundel and Schwarz (1932), for instance, report that, of 364 strains of pneumococci, 

 isolated from sick or healthy children or adults, and containing no examples of the 

 classical Types I, II and III, only 3 per cent, were unassignable to one or other 

 of Cooper's new Types IV-XXXII. 



It has long been recognized that the antigenic behaviour of intact pneumococci, in 

 the normal smooth state, is probably determined by the nature of the capsules surrounding 

 the bacterial cells. Neufeld (1902), for instance, noted that the capsules of pneumococci, 

 when acted upon by a specific antiserum, become greatly swollen ; and, within recent years, 

 it has been shown that this phenomenon can be utilized in the identification of pneumococcal 

 types (Neufeld and Etinger-Tulczynska 1931, Etmger-Tulczynska 1932, Armstrong 1932, 

 Logan and Smeall 1932, Sabin 1933, Beckler and MacLeod 1934, Cooper and Walter 1935). 



