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SummaryA medium consisting of 1% dextrose beef infusion agar pH 7.8 and type specific antipneumococcus serum is presented. Pneumococci of the homologous type when grown in the depths of the immune serum-agar plate develop well defined annular opacity surrounding each colony. The development of the annular opacities has been found to be strictly type specific.

The intramuscular administration of a single dose of antipneumococcal serum in the treatment of pneumonia in childhood was attempted in an effort to obtain the advantages of serum-therapy without the dangers and technical difficulty inherent in intravenous administration. A very severe reaction with a marked chill and a rise in temperature to 108.6° followed the intravenous administration of serum to a child 7 years of age ill with Type I lobar pneumonia, and although she recovered we did not feel that in a disease which carried such a low mortality we were justified in jeopardizing the patient's chances of recovery. Nemir1 reports 2 deaths which she believes were due to the intravenous administration of the serum. The above experiences with the intravenous route are not uncommon in institutions where a great deal of serum-therapy is used. Without serum-therapy the mortality varies from 4 to 7%. Trask2 reported a mortality of 6% in type specific pneumococcal pneumonias studied at New Haven. Holt and McInt...

Pneumococci are commonly classed among the best examples of bacterial type-specificity. While cross-reactions frequently occur involving types 3 and 8 and less frequently other types, they have usually been considered from the standpoint of the cross-reacting antibodies that sometimes develop during immunization rather than from the standpoint of the antigenic type-multiplicity which causes them.1, 2Several strains of pneumococci that conspicuously violate the prevailing conception of type-specificity have been isolated recently in this laboratory. Neufeld tests with sera of 3 different manufacturers show that each of these strains reacts with at least 3 type-specific sera.Table I summarizes the reactions of 6 such strains. It will be noted that each strain shows somewhat greater capsular swelling with one serum (either type 29 or type 24) than with others. However, reaction is only slightly less with a second, and in some strains with a third, serum.With the exception of the Hoge strain all 6 were isolat...

SummaryThe development of type-specific anti-M precipitins was studied in 2 groups of patients suffering from hemolytic streptococcal infections. Most of the patients in group I, none of whom developed rheumatic fever, showed relatively strong type-specific reactions in their serum by the 4th or 5th week after the onset of infection. The members of group II all developed rheumatic fever; some had similar strong antibodies early; but most rheumatic patients from whom hemolytic streptococci were obtained in significant numbers did not show strong anti-M precipitins until distinctly later than was the rule for the non-rheumatic group.

It has been recently demonstrated that the soluble specific substance of Pneumococcus type I, as originally prepared by Heidelberger, Goebel and Avery, represented a form of the polysaccharide lacking the acetyl group which, when present, conferred upon the substance distinct physico-chemical and immunological properties.1, 2 In the case of the type specific polysaccharide from Pneumococcus type III, purified according to the procedure described by the same authors, certain observations such as those of Ward3 have led us to believe that an analogous alteration in chemical structure may have occurred during the chemical manipulations required for its purification. We have, therefore, attempted to prepare this material by a method which avoids insofar as possible the use of strong acids.Six- to 8-day cultures of Pneumococcus type III in dextrose phosphate broth were concentrated over a boiling water bath to one-tenth of the original volume. The concentrate was precipitated several times with about 1.2 volum...

ConclusionFrom the observations made on the chemical and immunological studies of the polysaccharide, lipoid, and protein fractions obtained from representative serological and cultural types it is justifiable to conclude that the alkalisoluble protein is the cellular constituent responsible for type-specificity in C. diphtheria.

SummaryA simple and inexpensive method for producing antisera with a high degree of neutralizing capacity for poliomyelitis viruses has been described. By repeated intravenous injection of rabbits with small doses of poliomyelitis viruses grown in tissue culture, antisera with a high degree of homo-typic with little or no heterotypic neutralizing capacity have been produced regularly. Such antisera develop also to a lesser degree the capacity to lyse or agglutinate the cells in culture, in the absence of virus. When testing for heterotypic neutralization, this reaction may mask cross neutralization.

In the preceding communications, the intracutaneous vaccination of rabbits with Pneumococcus (S forms) has been shown to give rise chiefly to the formation of the antiprotein rather than the type specific antibodies, and to the development of an increased resistance to infection with organisms of homologous and heterologous types. The present paper describes briefly the development of an altered tissue reaction to Pneumococcus and its protein derivatives in rabbits which have been inoculated repeatedly into the skin with heat killed suspensions of R and S pneumococci.Mackenzie and Woo1 have shown that guinea pigs, injected intracutaneously with an alkaline extract of Pneumococcus, develop an allergic reaction in the skin to the bacterial protein; Zinsser and Grinnell2 have produced allergic sensitization to pneumococcus autolysates in guinea pigs previously injected intradermally or intraperitoneally with the same material. Bull and McKee3 have recently shown that rabbits, after recovery from infection in...

Summary and ConclusionsIntraperitoneal injection of human erythrocytes in pre-natal or neo-natal rats reduces antibody response to subsequent immunizations. No ill-effects were observed in any of the experimental animals surviving the initial injection and there was no difference in growth rate from the uninjected controls. These studies suggest that it is possible to confer type specific tolerance to subsequent immunization of A and D (Rho) antigens of human erythrocytes.

Summary and ConclusionsThe agglutination test, using standardized, type specific, heated and phenolized antigens, prepared from stock culture strains, representative of the prevalent types of meningococci, offers a simple method for the demonstration of agglutinins in the serums of individuals suffering from meningococcic infection. The test may be useful as an additional diagnostic procedure in cases where other laboratory confirmation is lacking.

Dawson and Sia1, 2 described a method for inducing transformation of pneumococcal types by an in vitro technique. In this procedure the transformation of pneumococci from one specific S type into other specific S types was effected through the intermediate stage of the R form. The method consisted in growing small inocula of R forms, derived from S forms of one specific type, in media containing vaccines prepared from cultures of heterologous S types.

Fleming1 has shown that type specific antipneumococcus serum increases the antibacterial action of sulfapyridine in vitro against pneumococci. McIntosh and Whitby2 have shown, moreover, that sulfapyridine does not stimulate phagocytosis or antibody production against pneumococci, but suppresses their growth to a point that biological defense can become effective. Subsequently, we3 showed that a small dose of broadly acting non-type-specific antipneumococcus serum, of itself only partially effective, becomes highly effective when fortified with a single partially effective dose of sulfapyridine. This enhanced effectiveness was demonstrated in rat infections with pneumococci of 6 different types, and simplification of treatment was attained through use of a single broad antiserum.Maclean, Rogers, and Fleming4 have recently shown the importance not alone of passively introduced pneumococcus antibody but also antibody actively incited by pneumococcus vaccine in the combined immuno and chemotherapy of pneumoco...

SummaryUnder the conditions of our experiments the protective value of highly concentrated type specific serum in optimal doses and that of sulfapyridine in optimal doses are approximately equal when the infecting dose of Type III pneumococci is relatively small, resulting in a mortality of 63% in untreated animals. When the infecting dose is sufficiently large to produce an initial mortality of 100%, the mortality after sulfapyridine therapy is significantly less than after serum therapy. Combining serum and sulfapyridine, each in optimal dose, does not reduce mortality below that of sulfapyridine therapy alone in Type III pneumococcic pneumonia, differing in this respect from results previously obtained from similar experiments with Type I pneumococcic pneumonia.

The isolation of chemically different polysaccharides by Heidel-berger and Avery1 from various types of pneumococci places the problem of type-specificity in immunologic reactions on a definite chemical basis. Since the polysaccharide from Type I pneumococcus, called the “Soluble Specific Substance,” was not antigenic, it can only be considered as a hapten of the pneumococcal antigen. Later Wadsworth,2 Enders,3 and others obtained preparations of polysaccharide from pneumococcus Type I, which were antigenic in mice. Therefore they were believed to be different from the soluble specific substance.Recently Avery and Goebel,4 by omitting the alkaline treatment, isolated an acetyl polysaccharide from the autolyzed broth-culture of pneumococcus Type I. Like similar preparations from other laboratories, the acetyl polysaccharide was antigenic in mice. However, the antigenicity was destroyed by treatment with alkali with accompanying loss of acetyl groups. Thus it is probable that Enders and Wadsworth's polysacc...

Polysaccharides derived from gravis, intermediate, and mitis types of C. diphtheriœ were found to be group-specific.1 Recent findings,2 however, indicate that any of these different cultural types may be present in a single serological type. Because of this an attempt was made to extend our previous study to include polysaccharides of different serological types of C. diphtheriœ with the object of determining the existence of type-specific polysaccharides.One organism from each of 5 distinct serological types kindly supplied to us by Sia and Huang2 was employed for the present study. All organisms, with the exception of Park 8 (Type D41) were isolated locally. The various characterizations of these organisms were as follows:All of the cultures were capable of eliciting precipitin antibodies in rabbits from 4 to 5 weeks when administered intravenously as heat-killed vaccines. The cultivation of organisms, the preparation of polysaccharides, and the immunization of rabbits were the same as those described p...

In a previous communication, Robertson and Sia1 found that the sera of animals, such as cat, dog, sheep and pig, that are naturally resistant to pneumococcus infection, contained normal opsonins for the pneumococcus, whereas the sera of susceptible animals did not possess such opsonic power for pneumococci virulent for the species. In the course of that study it soon became evident that the serum from a resistant animal, under proper conditions, could be shown to opsonize pneumococci belonging to any of the various serological groups. The question whether the sera of naturally resisant animals contain a common pneumococco-opsonin for all pneumococci, or separate opsonins for each type of the organism immediately arose. The results of Bull and McKee2 in demonstrating the existence of separate protective substances in normal chicken serum for each type of pneumococcus, together with the author's findings, reported in a previous paper,3 on the specific effect of pneumococcus soluble substance on the growth o...

SummaryThe similarity in elution characteristics of the ERM factor and type-specific CF antigen following fractionation of adeno-virus type 1 and type 2 suspensions by chromatography with DEAE-cellulose; the formation of only a single precipitation line in agar-gel double diffusion tests with purified material containing both activities; and the type-specific serologic reaction of both antigens indicated that the type-specific CF antigen was the carrier of the ERM factor.

The report of Avery and Dubos1 that the specific carbohydrate of pneumococcus type III was split by an enzyme from a soil microorganism appeared to offer a new approach to the study of relationship...

In the preceding communication it was shown that the antibody response elicited in rabbits vaccinated intracutaneously with specific type strains of Pneumococcus is characterized by the presence in the serum of antiprotein antibodies in excess, together with a corresponding decrease or complete absence of type specific antibodies. That this change in the order of specific antibodies is related to the mode of inoculation was shown by the fact that the same strain (Type I Pneumococcus), when injected intravenously, invariably stimulates the formation of the dominant type-specific antibodies.The present paper summarizes the results of a study of the occurrence and nature of the active resistance to infection which develops in rabbits vaccinated intracutaneously with R and S forms of Pneumococcus. Briefly, it may be stated that, following repeated skin inoculation of heat-killed suspensions of type-specific pneumococci or of the R variants, rabbits acquire a considerable degree of active immunity against infe...

Although pneumococci can be typed directly from sputum, it has been recognized that the results are sometimes unsatisfactory. Taplin, Meneely and Hettig1 have outlined an improved method using fresh sputum to obtain the Quellung phenomenon. Essentially, this method consists of breaking up and suspending the sample in saline, centrifuging, and using the sediment for typing. The authors suggested that the water-soluble capsular polysaccharide might well be the interfering substance, which was removed by their technic.In work published elsewhere,2 it has been determined that in undiluted samples of ground lung from pneumonic rats, pneumococci present did not give the Quellung reaction with specific antiserum. The reaction did occur if the material were sufficiently diluted with PSS. Heidelberger3 has shown that excess of antigen prevents visible evidence of antigen-antibody reaction, and has ably discussed the reversibility of the precipitin and agglutinin reactions. Since the above findings indicated that e...

Branham1 has recently emphasized the value of serologic typing of meningococci for epidemiologic studies as well as for more exact etiologic diagnosis. The methods currently employed for this purpose include (a) capsular swelling with hyperimmune rabbit serum and (b) agglutination with monovalent antisera prepared in rabbits or chickens. One of the advantages of using chickens as a source of agglutinating serum is their ability to tolerate doses of meningococci which may be toxic or even lethal for rabbits.2, 3During the past 18 months we have had occasion to prepare such antisera in adult chickens. The course of injections was based on the report of Phair, Smith and Root.2 Doses of 2 to 4 billion living organisms, derived from casein-hydrolysate starch agar cultures4 and suspended in physiological saline, were given intravenously at intervals of approximately one week. After 4 injections the animals were allowed a rest period of 7 to 16 days before being bled; in some instances this bleeding was followed...