bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional cytotoxic T cells exhibit tissue-specific phenotypic differences during chronic Friend virus infection
Authors: Myers Lara , Tal Michal Caspi , Messer Ronald J , Carmody Aaron B. , Weissman Irving L , Hasenkrug Kim J
Published: January 2023

Friend virus (FV) is a murine retroviral complex that establishes chronic infection characterized by the induction of CD4+Foxp3+ Tregs and prolonged exposure to antigenic stimulation. This leads to a state of diminished CD8+ T cell function, termed “exhaustion”, in the spleens of FV-infected mice. We report that during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of signal regulatory protein alpha (SIRPα), whose expression had previously been reported on neurons, myeloid and hematopoietic stem cells but not T cells. This subset of SIRPα+ CD8+ T cells has high expression of multiple inhibitory receptors including PD-1, Tim3 and Fas, while maintaining high expression of activation/stimulatory molecules including ICOS and CD43. In addition, SIRPα+CD8+ T cells exhibit enhanced proliferation and maintain cytolytic capability, despite the conditions of exhaustion existing within the spleens of chronically infected mice. Furthermore, target cells that express the ligand for SIRPα, CD47, are more susceptible to CD8+ T cell-killing in vivo. We now demonstrate that SIRPα expression on CD8+ T cells is tissue specific, occurring in the spleen but not liver. This is interesting as we have previously reported that the liver has a 10-fold reduction of chronic FV levels, which correlates with reduced Treg-mediated suppression and increased CD8+ T cell function. Furthermore, the SIRPα− CD8+ T cells from the liver of chronically infected mice appear equivalently cytolytic to SIRPα+ CD8+ T cells from the spleen. Therefore, SIRPα expression identifies functional cytotoxic T cells in the spleen but not the liver during chronic exhaustion, highlighting tissue-specific differences of viral control.
Th1 guided evolution of protective de novo Th17 response in severe influenza
Authors: Dutta Avijit , Hung Chen-Yiu , Hsieh Yu-Chia , Chang Chia-Shiang , Chen Ting-An , Huang Yu-Lin , Lin Yung-Chang , Chen Tse-Ching , Lin Chun-Yen , Huang Ching-Tai
Published: January 2023

The 6.5 CD4+ T cell receptor (TCR) transgenic mice have a monotonous CD4+ TCR which responds to the hemagglutinin (HA) antigen of PR8 influenza virus. Naive 6.5 CD4+ T cells adoptively transferred into wild type mice were activated by PR8 influenza virus with Th1 response. With PR8 influenza virus infection, all CD4+ T cells in 6.5 mice were activated and they were predominantly Th1 in phenotype at the early phase of infection and Th17 at the late phase. Th1 effector responses made infected mice sick and even succumb to death. The 6.5 mice were sicker at the early phase but recovered with better survival at last. IL-17KO 6.5 mice cannot display Th17 responses and lost the survival benefit as well. IL-17 supplement at the late phase of infection enhanced survival of wild type mice with PR8 influenza virus infection. With consecutive two adoptive transfers of naive 6.5 CD4+ T cells, 6.5 CD4+ T cells of the first transfer evolved into Th1 cells but 6.5 CD4+ T cells of the second transfer demonstrated a de novoTh17 response. Thymectomy or aging in 6.5 mice limited the thymic output of naive 6.5 CD4+ T cells and diminished the Th17 response. Viral neuraminidase activated TGF-β in the Th1 6.5 CD4+ T cells at the early phase. T-bet dominance was altered with excessive ROR-γt activation in the following responding 6.5 CD4+ T cells. They have substantial IL-17 with restrained IFN-γ production. We demonstrated a Th1 guided evolution of protective Th17 response in severe influenza.
The influence of TIGIT on natural killer cell activity against HIV
Authors: Holder Kayla , Grant Michael
Published: January 2023

During chronic human immunodeficiency virus (HIV) infection, inhibitory molecules are upregulated and contribute to effector cell dysfunction and exhaustion. People living with (PLWH) HIV are at a greater risk for age-related morbidities, an issue magnified by human cytomegalovirus (HCMV) co-infection. As HCMV modifies NK cell phenotype and function, we considered the role of upregulated inhibitory molecules in this context and their potential to affect NK cell-based strategies to eliminate HIV-infection.

To evaluate impacts of HCMV-driven NK cell adaptation in HIV infection, PLWH were distinguished by HCMV status or by high (>20%) versus low (<6%) percentages of adapted NK cells. Adapted NK cells did not display a classical exhausted phenotype as there was low LAG-3, PD-1 (<1%), and TIM-3 (<10%) expression. In contrast, TIGIT was present on a large fraction of NK and CD8pos T cells and levels were associated with HCMV status. Since CD4pos T cells latently infected with HIV upregulate CD155, a ligand for TIGIT, we investigated TIGIT modulation of NK cell functions. Blocking TIGIT/CD155 interactions increased NK cell cytotoxicity and correlated with the extent of NK cell adaptation to HCMV. Engaging TIGIT reduced levels of antibody-dependent cell-mediated cytotoxicity (ADCC) against pseudo HIV-infected (vPE16) P815 cells with the extent of reduction again reflecting NK cell adaptation to HCMV. Measuring HIV-specific ADCC against HIV-infected CEM.NKR CCR5pos cells transduced with CD155 will allow assessment of the role of TIGIT inhibition in a genuine HIV infection model. Blocking TIGIT may be an appropriate strategy to invigorate antibody-dependent NK cell activity against HIV reservoirs in cure or treatment strategies.
CD8 regulatory T cells during Zika virus infection
Authors: Zanluqui Nagela Ghabdan , de Oliveira Lilian Gomes , Polonio Carolina Manganeli , de Oliveira Marilia Garcia , de Souza Angelo Yan , Peron Jean Pierre Schatzmann
Published: January 2023

Introduction

Flavivirus infections are cause of great concern worldwide due to recurrent epidemics and high mortality rates, being a major public health problem. The relevance to study Zika virus infection was highlighted after the discovery that ZIKV infection during pregnancy could cause microcephaly, besides others abnormalities. Knowing that ZIKV, like other flaviviruses, can modulate host innate and adaptive immune response, we aim to understand the role of CD8+ regulatory T cells in the control of viral replication in an experimental infection.

Methods

C57BL/6 Foxp3GFP and C57BL/6 CD8−/− mice were infected with 106 PFU of ZIKV (Brazilian strain), followed by viral quantification, gene expression, and flow cytometry analysis.

Results

Infection of CD8 knockout mice presented viral load with an oscillatory profile compared to WT mice, and analysis of CD8 T cells populations in WT mice showed that CD8Foxp3 cells are induced on the first day post infection and it pool of cells are maintained during infection, as could be noted on day 30 post infection. These cells are related to increase of viral replication as shown in cell transfer experiment. However, naïve CD8Foxp3 cells are responsible to increase virus replication, while CD8Foxp3 cells from infected mice seems to be not capable to respond to antigen.

Conclusion

This finding leads us to believe that there is an attempt by the pathogen to modulate the adaptive immune response, in order to facilitate its replication and permanence in the host. In short, our work seeks to elucidate the immunobiology of the ZIKV infection and to correlate this with the susceptibility to the Congenital Syndrome caused by Zika virus.
DEC-205+ DCs within the CNS critically modulate CD8+ T cell-mediated immunity against WNV encephalitis
Authors: Khatri Hemisha R , Santana Anthony , Durrant Douglas M.
Published: January 2023

West Nile Virus (WNV) is the leading cause of mosquito-borne neuroinvasive disease in the United States. Upon entry into the central nervous system (CNS, WNV infects neurons causing neuronal injury and inflammation potentially resulting in long-term sequelae and death. In order to restrict viral replication and pathogenesis within the CNS, infiltrating virus-specific CD8+ T cells are dependent on dendritic cell (DC) mediated reactivation. While previous reports have shown that DCs rapidly accumulate within the CNS during infection, the subset necessary to induce T-cell mediated protection against WNV has not been clarified. Previously, DEC-205+ DCs were detected within the CNS during WNV infection. DEC-205, an endocytic receptor expressed on a subset of DCs, promotes cross-presentation and induction of anti-viral immunity. However, the specific role of DEC-205+ DCs in establishing immunity against WNV encephalitis is not known. We hypothesize that DEC-205+ DCs restrict WNV pathogenesis by activating anti-viral T cell immunity in the CNS. We show that DEC-205−/− mice have increased clinical disease and mortality compared to wild-type (WT) controls. The enhanced susceptibility of the DEC-205−/− mice arose from increased viral burden, however, this was associated with increased neuronal chemokine expression and numbers of infiltrating T cells and inflammatory myeloid cells. These results suggest that DEC-205+ DCs promote protective immune responses to CNS viral infection that limits immunopathology. These findings will uncover the mechanism by which DEC-205+ DCs modulate protective immune responses within the CNS in order to restrict a neurotropic viral infection.
Investigating pathogen-driven evolution of the human Natural Killer (NK) receptor, NKR-P1A/CD161
Authors: Aguilar Oscar A , Tabata Takako , Chen Peter , Pereira Lenore , Carlyle James R , Lanier Lewis L
Published: January 2023

Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via NK cell receptors (NKRs). They serve an important role in controlling viruses and have been described as being particularly important in managing herpesvirus infections. Among the various NKRs, inhibitory NKR-P1 receptors have recently being shown to be targeted by virally-encoded proteins of cytomegalovirus (CMV), a member of the beta-herpesvirus family. In rodents, the NKR-P1B receptor interacts with Clec2d/Clr-b, an inhibitory ligand abundantly expressed on healthy cells. Clr-b is downregulated during stress and serves to alert NK cells of pathogenesis. Interestingly, both rat and mouse CMVs encode viral ligands (RCTL and m12 respectively) that directly engage the NKR-P1B receptor and serve as decoys to subvert NK recognition. In humans, the homologous receptor is NKR-P1A/CD161 and binds CLEC2D/LLT-1. Given the findings in rodents, we are investigating if human CMV (HCMV) similarly employs a mechanism to escape NK detection through NKR-P1A/CD161. Using cell reporters capable of detecting receptor-ligand interactions and various HCMV strains, we are undergoing a systematic approach address this hypothesis.
A Quantitative Aspect of the Hypothetical Incorporation of Injected Antigen in Resulting Antibody
Authors: Hooker Sanford B. , Boyd William C.
Published: January 2023

From quantitative data relative to the weight of injected antigen and to the potency of resulting antibody it is conservatively estimated that one molecule of active antigenic substance gives rise to an amount of agglutinin capable of flocking 600 bacteria. This result is difficult to reconcile with the hypothesis that antibody is a conjugate of antigen and body globulin. The surface relationship (implicated in the mechanics of agglutination) between one globulin molecule and 600 bacteria is 1:25,000,000. Even with the assumption of multiple monospecific determinants in a single molecule of antigen the above discrepancy is extreme. A theory of antibody formation involving catalysis would seem more promising.
Heredity of the Agglutinogens M and N of Landsteiner and Levine
Authors: Wiener Alexander S.
Published: January 2023

Summary and Conclusions

The theory that the inheritance of the agglutinogens M and N of Landsteiner and Levine depends upon a single pair of allelomorphic genes may be tested by determining the frequencies of the three types in various populations. The frequencies of the genes is determined by the formulae: and where m and n are the frequencies of the genes M and N respectively, and it is then determined how closely the relation m + n = 1 holds. The size of the deviation, D = 1 — + depends upon (1) size of the sample examined, (2) whether or not the population is a homogeneous one, (3) whether or not the sample is a random one and (4) whether or not there are errors in technique. The probable error of D is equal to , where N equals the number of individuals in the sample examined.

It would be desirable to determine the distribution of the agglutinogens M and N in as many homogeneous populations as possible (just as was done for the Landsteiner blood groups), and determine the size of D and compare it with its probable error for each case. When a sufficient number of populations have been studied in this manner, we shall really be able to determine whether or not statistical data favor the theory of a single pair of allelomorphic genes.
Chemical and Immunological Studies of the Pneumococcus
Authors: Wadsworth Augustus , Brown Rachel
Published: January 2023

Until the ether-soluble material in the pneumococcus cell can be obtained in quantities sufficient for complete chemical and immunological analyses, it is difficult to determine the significance of its various antigenic activities or its relationship to other substances concerned in the immune reaction. Since these ether extracts appeared to be free from protein, glycerol, sterol, and carbohydrate, it is important to note the fixation of complement in the presence of antipneumococcus sera of all types and the lack of definite specificity in this activity. In vivo no immunity was demonstrated against pneumococcus infection in mice inoculated with the ether extractive, and suspensions of dried pneumococci extracted with ether immunized mice to the same extent as suspensions of unextracted cells. It was not possible to demonstrate agglutinative, precipitative, or complement-fixing activities in the sera of inoculated rabbits, although mice were protected against pneumococcus infection by such sera.
Complement Binding Properties of Brucella Abortus of Bovine and Porcine Origin
Authors: Walton S. T.
Published: January 2023

Summary and Conclusions

As is shown in figure 7 the greatest variation in the complementbinding ability of anti-porcine and anti-bovine sera as measured by a number of porcine and bovine antigens was 0.002 cc. This difference occurred after the antibody content of the blood had declined considerably. At the peak of antibody production, and for a period of about twelve days before and a like period after the zenith was reached, there was a difference of only 0.0005 to 0.0008 cc.

There was a difference in the rate of production of anti-bacterial antibodies, and also a difference in the height of production as induced by the different strains of organisms, but in each case both the rate and height of production of antibodies in a given animal for both types of antigen was practically the same.

The amount of agglutinating antibodies present in a given sample of antiserum, whether it was anti-porcine or anti-bovine, was apparently as great for one type of antigen as for the other. When there was a variation of antibody content in a sample it was not constant for either type of antigen, but showed a difference for different strains of both types. In the absorption of agglutinins no antigen took appreciably more antibodies out of a serum for itself than it did for the other antigens, and the small variation in the absorbing power was not constant for either type of antigen.

It appears from this investigation that complement fixation as a means of detecting B. abortus antibody is on a par with the more widely used method of agglutination. No particular advantage can be claimed for it over agglutination, but, as is the case with any serologic test when the laboratory report conflicts with the clinical evidence, or when clinical signs are wanting as is often the case in dealing with these organisms, an additional test, detecting a different type of antibody, might often be advisable as a confirmatory measure.
Serum Sickness in Rabbits
Authors: Hagebusch O. E. , Robben F. J. , Fleisher Moyer S. , Jones Lloyd
Published: January 2023

In a previous paper there have been described the manifestations of serum sickness in rabbits (1) which occur subsequent to a first and single injection of a large amount of horse serum. The reaction is characterized by the presence of a more or less confluent erythema which may be morbilliform or scarlatinal involving especially the lower third of the ears but often extending over the lower three-quarters of the ears. Frequently there is associated with this a more or less marked edema again especially evident in the lower third of the ears. Such reactions were noted in 69 per cent of 103 animals. The reactions of serum sickness as seen on the ears in rabbits differ distinctly from reactions noted in normal animals both as to character and location. It appears that these manifestations can be considered as essentially analogous to the phenomenon of serum sickness in man.
Immunization of Chimpanzees with Human Blood
Authors: Landsteiner K. , Levine Philip
Published: January 2023

With the aim to produce antibodies which possibly would differentiate red cells of various human individuals, chimpanzees were injected with human blood. Whereas in this respect the results were not striking enough to warrant a detailed investigation, it may be worth while to put on record observations which have been made in the course of these experiments.

Three chimpanzees, belonging to blood group A, were injected intramuscularly with washed human blood at intervals of seven to nine days, the animals receiving the following amounts in terms of whole blood: Chimpanzee 1 : 5, 5, 25, 25, 25 cc.; chimpanzee 2 : 10, 20, 15 cc.; chimpanzee 3: 10 cc. Titration of the sera are given in table 1.

Tested in suitable dilutions, the chimpanzee immune sera differentiated sharply human and chimpanzee blood (table 2) with the exception of a particular sample to be mentioned (serum of chimpanzee 2).
The Purification and Concentration of Diphtheria Toxoid by Means of Electrodialysis
Authors: Reiner L.
Published: January 2023

It has been pointed out by Wm. H. Park (1) that the active immunization of humans with diphtheria toxoid has many advantages above the immunization with toxin-antitoxin mixture. Its only disadvantage is that it produces more or less severe local reactions in adults or older children. It was of interest to find out whether or not these reactions could be diminished by purification of the toxoid.

Glenny and Walpole (2) were the first to show that after it had been dialyzed diphtheria toxin was precipitated at pH 4 while most of the nitrogen containing substance of the crude toxin was dialyzed out or remained in solution. These results have been confirmed, among others by Watson and Wallace (3), Watson and Langstaff (4), Sédaillan and Gaumont (5), Sédaillan, Leulier and Clavel (6), Kulikoff and Smirnoff (7), and Schmidt and Kjaer (8). Furthermore, it has been stated that similar results could be obtained by simply acidifying the crude toxin and that toxoid behaved in this respect like the toxin.
Agglutination Reactions in Rheumatoid Arthritis
Authors: Dawson Martin H. , Olmstead Miriam , Boots Ralph H.
Published: January 2023

The studies presented in the foregoing paper are reviewed at this time as matters of observation only. A discussion of the interpretation and possible significance of the results will be found in the following communication.

It has been shown that, in the majority of cases, the sera of patients with rheumatoid arthritis possess the property of agglutinating strains of Streptococcus hemolyticus (at 55°C.) to an extraordinarily high titer. No correlation was observed between the source of the strains and their agglutinability in the sera examined. Strains of Streptococcus hemolyticus obtained from cases of scarlet fever, erysipelas and rheumatic fever were agglutinated to as high a titer as were the “typical strains” of Cecil, Nicholls and Stainsby. Agglutination tests with a wide variety of other Gram-positive cocci revealed that these organisms were either not agglutinated at all or were agglutinated to a very low titer. An exception to this generalization is made in the case of R pneumococci which were agglutinated to almost as high a titer as were strains of Streptococcus hemolyticus. With the exception of certain instances, which are referred to in some detail, control sera did not agglutinate strains of Streptococcus hemolyticus in a titer which was comparable with that observed in rheumatoid arthritis.
A Comparison of the Toxicity of Various Meningococcus Preparations
Authors: Riley C. V. , Wilson M. A.
Published: January 2023

Various preparations of meningococci were tested by the Shwartzman method. Those containing the products of cell disintegration were found to be much more toxic than the simple filtrate of culture washings, the most toxic of all being a defatted coccus antigen made by extracting the cells with alcohol and ether, and grinding them in a mortar. The reactions obtained with this toxic defatted coccus could be neutralized with homologous immune rabbit serum, but only consistently when the serum was used undiluted and inoculated intravenously in equal volume with the diluted suspension.

The antimeningococcus therapeutic horse serum in 1:10 dilution neutralized the toxic effects of all four of the preparations in Shwartzman's skin sensitivity tests.

In the mouse protection tests Murray's endotoxin, unfiltered, was more toxic than the other preparations.

High dilutions of the antimeningococcus horse serum protected mice against Shwartzman's toxin filtrate, Murray's endotoxin filtrate and the cellular suspension. High dilutions of the serum did not protect against Murray's endotoxin, unfiltered, nor against the defatted coccus.

No conclusions have been drawn from these experiments, but the tests indicate that the same toxic substance is present in all of the preparations. The nature of the toxic substance has not been demonstrated by our tests.
Meningococcus Antitoxin
Authors: Ferry Newell S.
Published: January 2023

The preparation of bouillon filtrates of the meningococcus exhibiting properties characteristic of a soluble toxin and the employment of these filtrates for the production of an antitoxin was recently described by Ferry, Norton and Steele (1). It was found that filtrates from young cultures of the four recognized Gordon types of the meningococcus contain extracellular toxins specific to the four types, as well as a toxin common to all types, that individual animals injected with the toxins of the four types develop, respectively, antitoxins specific to the homologous toxins as well as antitoxins which will neutralize the heterologous toxins, and that an animal injected with toxins of all four types develops a polyvalent antitoxin containing immune bodies specific to the four individual toxins.

The present experiments were carried out to further test the protective properties of this experimental antitoxin by using it prophylactically and therapeutically in guinea pigs inoculated intraperitoneally with fatal doses of the meningococcus.
Active Immunization of White Mice by a Non-Polysaccharide and Probably Non-Protein Derivative of the Pneumococcus
Authors: Felton Lloyd D.
Published: January 2023

Summary and Conclusions

The inferences which may be drawn from this study are: White mice may be immunized with a fraction of pneumococcus which is soluble in copper acetate in the presence of saturated sodium chloride and may be extracted with alcohol from the dried copper-free filtrate. This antigen gives a negative Molisch reaction and is probably free from protein. Also no precipitation occurs with antipneumococcus horse serum.The soluble carbohydrate of Avery and Heidelberger in proper dosage prevents the immunizing effect of this antigen.The immunizing antigen has been extracted by the copper method from samples of both type I and type II polysaccharide.Demonstrable immunity is developed in seventy-two hours after intraperitoneal injection, and in a shorter time following intravenous injection.Immunity after a single injection of antigen remains maximum for at least three weeks.The immunity conferred on white mice from a single injection is type specific.
Phenomenon of Local Skin Reactivity to Pneumococcus
Authors: Shwartzman Gregory
Published: January 2023

In this paper there is described the phenomenon of local skin reactivity to pneumococcus. The phenomenon is elicited by skin preparation with B. typhosus “agar washings” filtrate and intravenous injection either of active pneumococcus filtrate, or a mixture of inactive pneumococcus filtrate with antipneumococcus immune serum.

The methods for preparation of pneumococcus reacting factors are described in the text.

The observations reported suggest new considerations in immunopathology and therapy of pneumococcus infections.
A Specific Reaction of Convalescent Serum on the Streptococcus Isolated in Studies of Poliomyelitis
Authors: Rosenow Edward C.
Published: January 2023

A specific reaction of convalescent poliomyelitis serum on the streptococcus isolated in studies of poliomyelitis is reported.

By studying the effect of convalescent serum on the streptococcus having characteristic cataphoretic velocity as isolated in cases of poliomyelitis, a marked and specific slowing or chargereducing effect has been discovered. This action of the serum increases during recovery from poliomyelitis, and is at its maximum during the fourth week after onset of the acute attack, after which there is gradual diminution, but it remains readily demonstrable even twenty years after recovery. The reaction is specific in that the serum of persons and monkeys who have recovered from typical attacks, affects both the strains from cases in human beings and in monkeys in that streptococci and other bacteria from sources other than poliomyelitis are not affected, and in that the reacting antibodies can be removed by absorption only with the streptococcus from poliomyelitis. The results indicate that the streptococcus isolated by us so consistently in poliomyelitis is not a contamination or an agonal or post-mortem invader.
Studies of Scarlet Fever
Authors: Hooker Sanford B.
Published: January 2023

We have reported briefly (27) that some strains of scarlatinal streptococci produce qualitatively different and specifically neutralizable erythrogenic active substances which we regard as toxins. Before describing their properties, frequency of occurrence, and relation to scarlet fever it is deemed desirable to consider some of the theoretical obstacles that have been interposed in the way of accepting these substances as “true” toxins. Such is the purpose of this paper.

Some students (5, 8, 12, 23, 25, 31, 38, 43) of scarlet fever interpret its mechanism in terms of allergic rather than toxin-antitoxin reactions. They look upon the active substance in scarlatinal streptococcus filtrates as a new type of pathogenic agent—an “allergin” or “toxallergin”—and seem persuaded that the allergic hypothesis more plausibly explains the many puzzling observations that have been recorded during the recent productive years of study of this disease.

Our ability to control a disease improves pari passu with our understanding of its mechanism.
The Antigenic Property of Gelatin-Diazo-Arsanilic Acid
Authors: Hooker Sanford B. , Boyd William C. , Alley Otis E. , Derow Matthew A.
Published: January 2023

A serum obtained after injections of gelatin-diazo-arsanilic acid precipitated and fixed alexin in the presence of other proteins coupled with arsanilic acid, and its reactivity was specifically inhibited by phenol-diazo-arsanilic acid and by the gelatin compound itself. The latter did not react visibly with the antiserum.

The results indicate that antigenicity may be conferred upon gelatin by coupling it with an unsaturated cyclic compound; they do not show that the non-antigenicity of gelatin is due solely to its deficiency in aromatic amino-acids; the possibility that other prosthetic groups may be similarly effective has not been excluded.

On the basis of certain quantitative relationships observed, the suggestion is offered that some diazo-proteins may produce two or more specifically different anti-haptens.
Adsorption of Diphtheria Toxoid by Cellulose Derivatives and Iron Hydroxide Gel
Authors: Reiner L.
Published: January 2023

Adsorption of diphtheria toxoid by cellulose derivatives (cellulose nitrate, cellulose acetate, and iron hydroxide gel) was studied quantitatively. Cellulose nitrate adsorbs the toxoid far better than cellulose acetate. Slightly acid reaction and low temperature were found favorable for the adsorption. Toxoid can be obtained in a purified form by elution of the adsorbate from cellulose nitrate or iron hydroxide gel at slightly alkaline pH (7.6 to 7.8). The substance, associated with diphtheria toxoid, which causes non-specific reactions in adults and older children, behaved in respect to its adsorbability similarly to the toxoid. It was not adsorbed at slightly alkaline reactions and was partially adsorbed at pH about 5. This indicates that these substances are closely associated or are similar in their physical properties.
Serum Sickness in Rabbits
Authors: Fleisher Moyer S. , Jones Lloyd
Published: January 2023

In a previous article (1) we have stated that in animals which received into the subscapular tissue a second injection of a large amount of serum, there occurred on the ears, either or both erythema or edema which in relation to the time of the second injection could be compared with immediate and accelerated serum sickness in man. We wish to report here in greater detail regarding these reactions.

It may be well to recall as a basis for comparison that the reactions which we speak of as serum sickness in rabbits are manifested on the ears. The rather generalized distribution of the erythema involving most markedly the basal half or two-thirds and leaving unaffected a more or less triangular area at the tip is quite distinctive; the erythema may be morbilliform or scarlatinal in part or in whole. The edema, usually basal, may be more or less marked or more or less extensive.
Studies in Tobacco Hypersensitivity
Authors: Sulzberger Marion B. , Feit Emanuel
Published: January 2023

In previous publications (1, 2 and 5), attention has been called to the fact that patients suffering from thromboangiitis obliterans have a skin hypersensitiveness to tobacco and, in some cases, to other allergens (frequently inhalants (1, 5). This is demonstrable by the fact that these patients react with immediate wheal reactions to the intradermal injection of the allergens in question.2

In the following, we report the results of passive transference experiments with the sera of 22 unselected consecutive cases of thromboangiitis obliterans; as well as with the sera of 3 patients suffering from other conditions, who also had a marked immediate wheal reaction to intradermal skin tests with tobacco.

The technic which we have employed in our passive transference experiments is one which has been used by one of us (S.) in many hundreds of experiments, during the last eight years.
The Effect of Normal and Immune Staphylococcus Rabbit Serums on the Action of Staphylococcus Bacteriophage
Authors: Burky Earl L.
Published: January 2023

d'Herelle (1) has stated that body fluids and tissues have no inhibitory effect on the action of the bacteriophage. Applebaum and MacNeal (2), seeking for an effective therapeutic agent against staphylococci, have found that the action of bacteriophage is inhibited by animal serums and purulent exudates. It is the purpose of this report to confirm the findings of Applebaum and MacNeal and to show, in addition, that the serums of rabbits, immune to staphylococcus toxin, do not have an inhibitory effect on the action of the bacteriophage on certain strains of staphylococci.

As reported elsewhere (3), three strains of staphylococci isolated from ocular sources have been studied in detail. These three strains seem typical of types of staphylococci isolated from a variety of human lesions. Strain Ha, from a chronic indurated blepharitis produced a broth filtrate that kills rabbits when injected intravenously in doses of 0.1 to 1.0 cc. per kilogram of body weight.
Immunization Phenomena in Rabbits Vaccinated with Heat-Killed Tubercle Bacilli
Authors: Hughes Joseph
Published: January 2023

The serum of rabbits vaccinated by repeated injections of heat-killed tubercle bacilli shows progressive increase in its ability to promote phagocytosis of living tubercle bacilli by polymorphonuclear and mononuclear cells.

The close parallel between bacteriotropic action of the serum upon polymorphonuclear leucocytes and upon mononuclear leucocytes indicates that the same antibody is concerned in the phagocytosis of tubercle bacilli by the two types of cell.

The earliest manifestation of bacteriotropic action precedes the onset of sensitization indicated by cutaneous reaction to injection of dead tubercle bacilli.

Infection with living tubercle bacilli has caused earlier appearance of bacteriotrophic substance than repeated injections of the dead organism but the titer attained is no higher.
A Specific Precipitation Test for the Standardization of Type I Antipneumococcus Serum
Authors: Brown Rachel
Published: January 2023

Summary and Conclusions

Forty-six type I antipneumococcus sera were tested for precipitative activity with a solution of the type I cellular carbohydrate. The results obtained agreed in 91.3 per cent of the cases with the results obtained by mouse protection tests. Eight concentrated antipneumococcus sera were similarly tested and found to agree in seven instances. The results indicate that the precipitation test described provides a titration which appears to be a reliable index of the development of the protective activity in the course of immunization; in the preliminary evaluation of the serum it can thus replace the more complicated protection test which, at present, however, should still be used in the final standardization.
Local Organ Hypersensitiveness
Authors: Seegal Beatrice Carrier , Seegal David , Khorazo Devorah
Published: January 2023

The injection of small amounts of a foreign protein into the anterior chamber of the rabbit's eye produces an altered reaction capacity in this organ. After an appropriate incubation period the intravenous injection of the same antigen results in a transitory inflammatory response in the prepared eye. This was first demonstrated by Kummel (1), Fuchs and Meller (2), Von Szily (3) and by Riehm (4). Seegal and Seegal (5) studied the phenomenon, using a number of different antigens and established certain facts from which they inferred that the inflammatory eye response was the result of an antigen antibody reaction. The three main reasons for such a conclusion were: (a) an incubation period of at least five days is necessary before the reaction in the eye can be demonstrated. (b) The reaction is highly specific since only the protein injected into the eye will produce the local response on subsequent intravenous injection.
Species Specificity of Fibrinogens
Authors: Kenton Harold B.
Published: January 2023

Introduction. The selectivity with which antibodies react with the particular proteins used in their production affords a biological method of differentiating proteins which is far more delicate than that of direct chemical analysis.

Applications of this method, in one form or another, have been made by various workers in an attempt to determine whether the blood protein, fibrinogen, is an identical protein in all animal species or is in each particular instance a protein peculiar to that species.

The conclusions reached by the several investigators are contradictory and the purpose of this paper is to present experiments which offer more extensive proof that fibrinogens are species specific, as are other blood proteins.

In 1912 Bauer and Engel (1) reported that beef and swine fibrinogens exhibited individual and species specificity when tested by the method of complement fixation. They also used the precipitin reaction but found that specificity was not so definitely demonstrable by this method.
The Survival of Neurotropic Yellow Fever Virus in Testicular Tissues
Authors: Lloyd Wray , Mahaffy Alexander F.
Published: January 2023

Neurotropic yellow fever virus of the French strain and of mouse origin has been transferred through nine passages in the testicular tissues of albino mice. Virus isolated from the sixth and seventh passages respectively in the testes of mice has been demonstrated to give a specific immunological reaction as yellow fever virus in passive immunity tests. Testicular virus of mouse origin when injected subcutaneously into a Macacus rhesus monkey resulted in the immunization of the animal, with the development of only a retarded and mild febrile reaction.
Pneumococcus Leucocidin
Authors: Oram Florence
Published: January 2023

Summary and Conclusions

A toxin has been produced from active growing cultures of pneumococcus which destroys leucocytes as demonstrated by the Neisser and Wechsberg method. This leucocidin has been demonstrated in aerobic and anaerobic cultures, from growths of both virulent and avirulent strains and from types I, II and III.

It is believed that a peroxide which is formed in the aerobic cultures modifies the potency of the toxins through oxidation. The peroxide appears earlier and is of greater concentration in cultures of the virulent strains; this may account for the avirulent cultures apparently containing toxins of as great a potency as the virulent strains, although they may actually be weaker.

The leucocidin is readily oxidized; it loses strength in a few days under vaseline seal at 5°C; it is not injured at 70°C. for one hour. Evaporation in vacuum at 5°C. does not deteriorate it; and the toxicity may be enhanced three to four times by the addition of laked red blood cells.

The soluble specific substance of pneumococcus type I was found to be destructive for leucocytes: 0.5 mgm. to 15,000,000 leucocytes, but this polysaccharide is not identical with the leucocidin.

Rabbit clasmatocytes are more resistant to the pneumococcus leucocidin than are rabbit polymorphonuclears, and leucocytes of the naturally resistant dog are less affected than the leucocytes of the rabbit. Organ tissues, as exemplified by liver and adrenal, are destroyed by this pneumococcus toxin, the adrenal being less resistant than the liver.

Hemotoxin was produced from an avirulent strain of pneumococcus type III in cultures from four hours to three weeks old. As it was present only in cultures of twenty-two hours and older when virulent strains were employed, it would seem that the peroxide hindered its production in young growths. Apparently the same conditions in the cultures govern the production and preservation of the hemotoxin and leucocidin, for where the most potent leucocidin was produced the best hemotoxin was found. But the leucocidin is separable from the hemotoxin by its greater thermostability and its appearance in cultures where no hemotoxin can be demonstrated.

The leucocidin filtrates are not toxic for mice in 2 cc. amounts injected intraperitoneally, and repeated doses give very slight protection. Ten cubic centimeters of the filtrates injected intrapleurally into rabbits does not produce any toxic symptoms and an avirulent strain of pneumococcus injected simultaneously does not become virulent. Sterile supernatant fluids of pleural exudates of rabbits with empyema while in themselves not toxic, upon repeated doses intravenously, produce an antileucocidin.

Normal rabbit serum does not neutralize the pneumococcus leucocidin, but the majority of human sera tested possessed a neutralizing property.
The Rôle of Leucocytes in Immunity to Herpes
Authors: Jamuni Abhaya , Holden Margaret
Published: January 2023

Discussion and Summary

It is suggested by these experiments that leucocytes have a definite tropinizing function in destroying herpes virus in the presence of immune serum. Both normal and immune cells aided in the inactivation of the virus in the presence of immune serum when the latter alone was present in an amount insufficient to neutralize the virus. At times results almost equally good were obtained with immune cells in the presence of normal serum, which suggests that leucocytes, or possibly tissue cells, may be even more important than the serum antibodies in active herpes immunity.

The evidence presented in the third experiment might indicate, under the conditions of our test, that mononuclear cells are more efficacious than polymorphonuclear cells in the disposal of herpes virus.

We suspect that the enhancing action is due to phagocytosis of the opsonized virus although this statement cannot be verified, lacking demonstration of whatever morphological unit constitutes the virus. These experiments at least indicate that immune or normal phagocytic cells bring about a greater virucidal effect than can be obtained with immune serum alone.
Failure to Find Individual Blood Differences in Guinea Pigs or in Mice
Authors: Boyd William C. , Walker Elisabeth W.
Published: January 2023

Since the discovery of the human blood groups, there have been many attempts to find similar groups in laboratory and domestic animals. The genetic study of such groups would be most interesting. Such studies are evidently now being completed on the rabbit in Castle's laboratory (1). MacDowell and Hubbard (7) failed to find isoagglutinins in mice. Hektoen (2), Lawson (5), and Weszeczky (9) all failed to find isoagglutinins in guinea pigs. However, the discovery of factors such as M and N in human blood, and the recent work of Landsteiner and Miller (4), Landsteiner and Levine (3), and Todd (8) on chickens, and of Levine and Landsteiner (6) on rabbits, suggested the possibility that isoagglutinogens not accompanied by corresponding agglutinins might be found.

Blood was taken from 8 guinea pigs, not completely alike genetically, as judged by coat and eye color.
Sensitization of Bacteria with Normal and Immune Human Serum
Authors: Mudd Stuart
Published: January 2023

Sensitization by serum renders various dissimilar bacteria similar with respect to their surface properties. This convergence of surface properties is carried further by homologous immune than by heterologous or normal sera, and the homologous immune sera are effective in higher dilutions.
The Sensitization of Guinea Pigs to Poison Ivy
Authors: Simon Frank A. , Simon Margaret G. , Rackemann Francis M. , Dienes Louis
Published: January 2023

It is common knowledge that certain individuals are more susceptible than others to the effects of poison ivy and such other plants as primrose and sumac. Great individual variations in the capacity to develop sensitiveness exist and there is considerable evidence to show that previous contact, its degree and its duration, is the important factor in making one person more sensitive than another.

The introduction of the patch test has been an important contribution. In 1896, J. Jadassohn (1) studied a patient sensitive to mercury and observed that a piece of “gray plaster” 5 cm. square applied to the upper arm gave rise to a violent local reaction which appeared under the plaster in twenty-four hours and then spread rapidly over the whole body. In 1920, Markley (2) had a patient whose pet guinea pig caused a dermatitis of her breast and forearm.
The Immunological Characteristics of the Poliocidal Substance in Human Serum
Authors: Jungeblut Claus W.
Published: January 2023

The property of serum to inactivate the virus of poliomyelitis in vitro, as is generally known, was first discovered with the blood of monkeys and man after recovery from the experimental or spontaneous disease. It is only comparatively recent that similar neutralizing substances have been found, seemingly in the same or even greater quantities, in the serum of a majority of normal adults who give no clinical history of previous attacks of infantile paralysis.

The question as to the nature and origin of this virucidal function of the normal human serum has continued to engage the attention of investigators during the last few years. It is obvious that neutralizing substances which make their appearance in the serum after immunization with the virus or following recovery from the disease, should be regarded as typical antibodies in the classical sense of the word. This, however, does not necessarily prove that similar substances in the normal serum must have originated by contact with the specific antigen.
A Study of Pneumococcus Carriers
Authors: Bliss Eleanor A. , McClaskey William D. , Long Perrin H.
Published: January 2023

The purpose of this study was to determine whether, in Baltimore, the constant carrying of pneumococci in the throat was associated with frequent infections of the upper respiratory tract. Throat cultures were taken from a group of 20 young adults approximately once a week over a period of two academic years. One thousand and sixteen throat cultures were obtained; 34.5 per cent were positive for pneumococci.

It seemed, after the first year's study, that individuals could be divided into three groups with respect to the carrying of pneumococci, namely, chronic carriers, intermittent carriers and noncarriers. However, at the end of the second year's study it became apparent that, those individuals who had been classed as intermittent carriers were, in reality, chronic carriers, for, although few positive cultures were obtained from them, and those irregularly, the same type of pneumococcus recurred in their cultures. It was found, during the two years, that there was little difference in the frequency and duration of upper respiratory tract infections between the chronic carriers and the noncarriers.

While the same type of pneumococcus tends to recur in the throat cultures from a chronic carrier, it is frequently possible to demonstrate the simultaneous carrying of two or three types of pneumococci in these individuals, if the proper procedures are used. This demonstration is added evidence in favor of the theory of the stability of pneumococcus types in the human being.
The Mechanism of Antibody Formation After Extirpation of the Antigen-Depot
Authors: Cannon Paul R. , Burt Kenneth L.
Published: January 2023

Several investigators (1, 2, 3) have questioned the assumption that antigen must reach the tissues usually considered as the principal sources of antibody in order that formation of antibody may occur. Their doubts are based on experiments in which antigen was injected into the skin of the ear in rabbits, and, at varying intervals of time, usually from a few seconds to an hour or more, the antigen-depot was extirpated by amputation of the ear at the base. The abundant formation of antibody in animals so treated suggested to these observers that dissemination of antigen may be unnecessary for the formation of antibody. Reitler, in particular, concluded that antibody formation is a reflex-like process of non-nervous origin in which contact of the antigen with the antibody-forming tissues is not essential. Such an opinion obviously differs radically from the conventional ideas concerning antibody production and should be accepted only if accompanied by irrefutable proof.