bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial neuraminidase C reverts neuraminidase A and B mediated suppression of anti-influenza immunity and aggravates the disease in influenza with pneumococcal superinfection
Authors: Huang William , Hsieh Yu-Chia , Hung Chen-Yiu , Chen Yi-Yin , Chen Tse-Ching , Chang Chia-Shiang , Huang Yu-Lin , Chen Ting-An , Lin Yung-Chang , Lin Chun-Yen , Huang Ching-Tai , Dutta Avijit
Published: January 2023

Bacterial superinfection aggravates the disease of influenza virus infection. Streptococcus pneumoniae is a frequently encountered bacterial pathogen. Superinfection with neuraminidase (Nan) C deficient wild type pneumococcus, which expresses NanA and NanB only, suppressed antigen-specific anti-influenza immunity, with impaired viral clearance. There was augmented TGF-β activation in the lung-infiltrating influenza hemagglutinin (HA)-specific CD4+ T cells. Mice suffered from exacerbated disease and died with higher virus loads in the lung. We modified this wild type strain with NanC insertion. This modified strain expresses all neuraminidases A, B and C. Superinfection with this NanC inserted pneumococcus reverted the immune-suppressive effect of the wild type pneumococcus with NanA and NanB only. There were augmented inflammatory cytokines IFN-γ and TNF-α production and suppressed TGF-β activation in the lung-infiltrating influenza HA-specific CD4+ T cells. The pro-inflammatory response enhanced viral clearance. Even the virus eradication is enhanced, the mice actually suffered from even more severe disease. Our results demonstrated the important role of NanC-mediated inflammation in the disease of severe influenza with pneumococcal superinfection.
Anti-Influenza D immunity contributes to improved survival after secondary bacterial infection in mice
Authors: Rynda-Apple Agnieszka , Huber Victor C. , Shepardson Kelly , Nelson Raegan , Hatton Alexis Alexandria
Published: January 2023

Clinical evidence suggest that the newly emerging Influenza D viruses (IDV) co-circulate in humans with influenza A viruses (IAV). However, how IDV contributes to human disease is currently not known. Because IAV is known to create a suppressive environment permissive to development of life threatening secondary bacterial infection (SBI), it is important to understand whether IDV affects the host immune response to IAV and to SBIs. Using a combination of in vivo and ex vivo approaches we evaluated host immune responses to both primary pulmonary IDV infection and subsequent SBI with Staphylococcus aureus in mice. Consistent with lack of disease symptoms in humans, we found that IDV infection did not induce clinical signs of disease in WT mice, evidenced by no weight loss or morbidity/mortality. Contrary to IAV that is known to increase susceptibility to SBI at least partially by inhibiting type I interferon (IFN) signaling, we found that IDV infection appeared to protect mice from the typical clinical features of SBI, as demonstrated by improved weight loss, survival (100% vs 60%), and recovery when compared to S. aureus-infection alone. Consistent with our previous report of IFN-beta reducing SBI susceptibility, we found that IDV induced production of IFN-b. We also found that IDV infection resulted in increased weight loss and morbidity in mice deficient in type I IFN receptor subunit 2 (Ifnar2−/−), but not in Ifnar1−/− mice suggesting a role for IFN-b signaling through Ifnar2 in IDV anti-viral immunity. Thus, our results demonstrate for the first time that IDV infection does not increase the susceptibility to SBI with S. aureus in mice, with evidence that anti-IDV immune responses might protect the host from these potentially deadly SBIs.
Aging T cell Immunity to Conserved Viral Epitopes
Authors: Malone Michael J , Jiang Ning
Published: January 2023

Although seasonal vaccination is widely accessible, its efficacy is inconsistent. Older individuals, in particular, tend to have difficulty mounting adequate immunity to infection. A possible reason for this struggle may be due to high mutagenesis in influenza hemagglutinin (HA), the major component of vaccines. Since older individuals possess diminished immune repertoire diversity compared to younger individuals, large sweeps in the viral proteome can be devastating. Unlike the antibody response, which primarily targets mutagenic surface proteins like HA; however, the T cell response can target more conserved regions of the viral proteome. Vaccines designed to stimulate T cells may thus provide greater protection in older individuals. To better understand the T cell repertoire in relation to the conserved regions of the viral proteome, we have predicted highly conserved viral T cell epitopes from various influenza strains and used our next-generation sequencing based method, TetTCR-seq HD, to pair T cell receptor (TCR) sequence, antigen specificity, transcriptome, and surface protein expression at the single cell level. In addition to novel antigen discovery, our high dimensional data have revealed the presence of immunity toward highly conserved influenza epitopes in older and younger individuals. Additionally, although age appears to decrease TCR repertoire and antigenic diversity, other factors such as immunodominance toward other viral epitopes, such as human cytomegalovirus, interestingly have a greater impact on the influenza-specific repertoire and phenotype. Our data ultimately indicate that healthy individuals harbor a reservoir of influenza-specific T cells that may be targetable by vaccines.
The T-box transcription factors T-bet and Eomes repress protective Th17 CD4 T cell responses against Influenza A Virus
Authors: Dhume Kunal , Finn Caroline , Singh Ayushi , Tejero Joanne , Devarajan Priyadharshini , Swain Susan L , McKinstry Karl Kai
Published: January 2023

Promoting strong CD4 cell immunity is an attractive strategy to generate a universal Influenza A Virus (IAV) vaccine. Though most CD4 cell responses against IAV are classified as Th1, Th17 and cytotoxic CD4 cells (ThCTL) may also contribute to viral clearance. Interestingly, we find the transcription factor T-bet (Tbx21), the ‘master regulator’ of Th1 differentiation, to be dispensable for protective CD4 responses against IAV. Surprisingly, Tbx21−/− cells develop Th17 characteristics but retain Th1 functionality, highlighted by strong IFN-γ production. While the transcription factor Eomesodermin (Eomes) can compensate for loss of T-bet to promote antiviral CD8 responses, its roles in CD4 cells is still unclear. Here we analyze Eomes−/−, Tbx21−/− and Tbx21−/−Eomes−/− CD4 cell responses against IAV using an adoptive transfer model to determine the extent to which Eomes regulates antiviral CD4 functions. Eomes−/− cells mirrored the prototypical Th1 responses of WT CD4 cells. Strikingly, Tbx21−/−Eomes−/− cells exhibited near complete loss of both Th1 responses and ThCTL function. In contrast, Tbx21−/− Eomes−/− developed stronger Th17 attributes than Tbx21−/− cells. We assessed protection provided by transfer of in vitro Th17-primed WT, Eomes−/−, Tbx21−/− and Tbx21−/−Eomes−/− cells to unprimed WT mice infected with lethal IAV. While WT and Eomes−/− effectors gained Th1 characteristics in vivo, Tbx21−/−Eomes−/− cells strengthened their Th17 phenotype. Remarkably, all of the Th17 effectors were equally protective. Our observations reinforce the concept that Th17 cells can provide strong protection against IAV, independently of Th1 and ThCTL responses, and suggest Th17 cells use unique pathways to do so.
CD8+ T cell cross-reactivity during heterologous flavivirus infection results in cross-reactive immunodomination and enhanced cytolytic capacity at the expense of virus-specific responses
Authors: Hassert Mariah , Brien James D. , Pinto Amelia K.
Published: January 2023

Flaviviruses constitute a genus of closely related arthropod-borne viruses including Zika virus, the four serotypes of dengue virus, and yellow fever virus, which circulate in the same geographic regions. These viruses share a substantial degree of genetic similarity and consequently, antigenic overlap has been reported by evaluating T cell and antibody responses in humans, non-human primates, and mice. However, it has not been determined how existing immunity to a heterologous flavivirus impacts functional immune responses to virus-specific and cross-reactive epitopes. We hypothesize that cross-reactive T cells from prior flavivirus exposures will expand robustly during a heterologous challenge and that these cells primed during a heterologous infection will be functionally different from cells of the same specificity primed during a homologous infection. Using various mouse models of flavivirus infection, we have identified a pan-flavivirus reactive CD8+ T cell epitope. We show in a heterologous infection model in which dengue virus exposure precedes Zika virus infection, T cell responses to the cross-reactive epitope dominate at the expense of the Zika-specific T cell responses. These cross-reactive T cells display enhanced killing capacity, in addition to other functional changes. The culmination of these features drive altered protective capacity when compared to homologously primed T cells in our mouse model of Zika infection. Our findings provide a mechanistic understanding of cross-reactive T cell control during heterologous infection and have important implications for vaccine design, as these results define the functional consequences of priming a cross-reactive T cell response for a pan-flavivirus vaccine.
A Study of the Relationship of Surface Phenomena to the Reaction of Toxin and Antitoxin, with Toxin Produced in an Infusion-Free Peptone Medium
Authors: Berthelsen Knud C.
Published: January 2023

Summary and Conclusions

It has been demonstrated that the toxin-antitoxin flocculation first takes place at the liquid-air surface, where the surface energy is at a minimum.

Tests of toxin made during its production in infusion-free peptone medium and particularly after purification by ultrafiltration, showed that the shorter the flocculation-reaction time the higher the surface tension, measured in dynes.

The results of tests made with an antitoxic serum in which the protein particles had been denatured by heat, showed that there exists a parallelism between the flocculation-reaction time and the surface tension in dynes.

These experiments indicate that changes in the colloidal state of the toxin-antitoxin interfaces probably result in changes in the reaction time.
Loss of Immune Substances from the Body
Authors: Neill James M. , Gaspari Emidio L. , Mosley Robert A. , Sugg John Y.
Published: January 2023

The paper dealt with diphtheria antitoxin in human sweat. Significant amounts were found in the sweat of three men possessing large amounts in their blood (two with “natural” immunity and one previously injected with toxoid); none was found in the sweats of people with no or only small amounts of antitoxin in their blood.

The data are compared with the previous data on saliva and urine on the basis of the following questions: comparative frequency of people with detectable antitoxin in the secretion, comparative ratios to serum antitoxin, daily output, and significance of sweat as a channel of loss of immune substances.
Parenteral Denaturization of Foreign Proteins
Authors: Boone T. H.
Published: January 2023

In a previous paper (1) it was shown that horse proteins injected intravenously into normal dogs are so completely denatured by the end of four days that they no longer call forth a recognizable anaphylactic reaction on massive blood transfusion into horse-protein-hypersensitive recipients. To throw light on the physiologic mechanism of this process, we have tested the effect of starvation on denaturization rate.

Technic. For from three to ten days before horse serum injection, selected transfusion donors were deprived of all food, though given an abundant supply of water, and remained without food during the subsequent denaturization test. Two cubic centimeters of horse serum per kilogram of body weight were injected intravenously into these donors. At varying intervals after this injection massive blood transfusions were made into partially exsanguinated horse-protein-hypersensitive recipients by the technic outlined in our initial paper, the severity of the resulting anaphylactic shock being judged from kymograph records.
A Rapid and Simplified Method for Conducting the Agglutinin Absorption Test of Hemolytic Streptococci
Authors: Spicer Sophie , Rachstein Rose
Published: January 2023

Streptococci as a group, in their relation to human infection, occupy a position of first rank among the pathogenic bacteria. These organisms are widely distributed in nature, are the cause of many disease entities, include many saprophytic as well as parasitic varieties and are very often found on mucous membranes of healthy carriers. It is of paramount importance, from an epidemiological as well as a clinical point of view, to classify these organisms in order to differentiate the pathogenic from the non-pathogenic varieties and to determine the relationship between a certain strain of streptococcus and a particular disease process. The application of such classification to diagnostic, therapeutic and prophylactic measures is then possible.

Many attempts have been made to classify the streptococci, but there is still much confusion concerning their classification.
The Skin As an Immunological Organ
Authors: Tuft Louis
Published: January 2023

Summary and Conclusions

During the course of some experiments in serum sickness, it was observed that the skin seemed to possess an unusual capacity for sensitization to horse serum, this sensitization being accompanied by the production of anaphylactic antibodies, and these experiments suggesting the possibility that the skin may act as an important immunological organ. Numerous clinical observations bear out the close relationship existing between the skin and processes of immunity in infectious and allergic diseases. These have been further substantiated by many experimental contributions reported in the past few years in the foreign literature, which appear to indicate not only that the skin may have the power to form antibodies, but that such antibodies may be specific and that the ability to form such antibodies resides specifically in the skin. Our own experiments do not bear out this latter view, at least for antibacterial antibodies, for from a comparison of the antibody response after intradermal, subcutaneous, intramuscular and intravenous injection of mixed typhoid vaccine, both in the human and in the lower animals, it would appear that though it is possible that the skin participates actively in antibody production, it does not carry out this function exclusively in respect to other tissues or organs. The marked antibody response particularly after local injection can be best explained upon the basis of a local tissue stimulation of the cells of the reticulo-endothelial system, these cells being particularly abundant in the skin. That the active antibody response after intradermal injection may be due in part to a slower abosrption of the antigen is entirely possible, although this process may in turn allow for local fixation of a greater amount of antigen and thus greater local stimulation of antibody.

The conception of the skin as an important immunological organ explains in part the satisfactory results of those nonspecific mechanical therapeutic measures employing the skin surface for stimulation, and suggests the possibility of utilizing the skin, therapeutically, for measures of specific active immunization in infectious and allergic diseases. It also substantiates the rationale of the various measures of cutano-therapy advised by the French and Germans, and our own satisfactory experience with typhoid vaccine used intradermally is further evidence of the efficacy of such methods. These could well be extended to other bacteria, particularly such skin-affecting organisms as the pyogenic cocci, with good results.
A Study of the Antigenic Activity of Preparations Made from Various Strains of Treponema Pallidum
Authors: Rice Christine E.
Published: January 2023

Distilled water, salt solution, and methyl alcohol are satisfactory solvents of the antigenic substances from all strains of Treponema pallidum studied. Extracts of certain strains of ethyl alcohol were of low antigenic activity.

Although more marked fixation occurred in the presence of homologous antiserum, there was considerable cross fixation between strains which would suggest that, although the strains vary, they do not differ essentially in antigenic activity.

Alcoholic extracts of Kroó and Klopstock strains react in the presence of syphilitic serum, more strongly than similar extracts of the Zinsser and Noguchi strains but always to a much less degree than do routine nonspecific organ extracts. Aqueous or saline extracts show little activity in such systems.

From the fact that the relationship between the amount of complement fixed by the alcoholic spirochete extracts and by the routine antigens remained fairly constant, it is assumed that the reaction in both cases is dependent upon the lipoidal character of the preparations.
Phenomenon of Local Skin Reactivity to Meningococcus: Production of Neutralizing Antibodies in Horses
Authors: Shwartzman Gregory
Published: January 2023

Titrations of neutralizing antibodies of antimeningococcus horse sera with the aid of the auxiliary antibody disclosed wide fluctuations in their concentration during the immunization. A description is given of a simple and economical method of immunization which shows high titer of neutralizing antibodies for the phenomenon of local skin reactivity.

Incidental observations reported are those on full antigenicity of meningococcus toxic filtrates, and also on the fact that the neutralizing antibodies may fluctuate in their concentration, while the agglutination and precipitation titers remain stationary.

The author wishes to express his gratitude to Mr. Arno Koovits for his capable technical assistance.
Typhoid Agglutinins in Man Following Vaccine Injection
Authors: Lamson R. W. , Kessel John F.
Published: January 2023

The injection of typhoid vaccine produces, according to the most popular belief, an appreciable increase in the agglutinins in the blood of the vaccinated person. Some are of the opinion that the titer may be raised to a level comparable with that produced in the experimental animal. The literature on the subject lends some support to these views.

By the use of the microscopic or hanging drop technique high titers have been reported by a few workers. Twenty-one young adults (students) were studied by Moon (1). He designated as a positive reaction the highest dilution at which definite clumping of the suspension could be detected under the microscope. Most of his subjects received but two injections of vaccine. The sera were collected at two, twelve and twenty-four months after the last injection. The highest titers were obtained on the first specimen. In one the titer was 1–16, in three 1–64, in five 1–96, in six 1–128, in five 1–192 and in the remaining one 1–256.
Factors Influencing the Antigenic Power of Toxin-Antitoxin Mixture
Authors: Githens Thomas S.
Published: January 2023

The ability of mixtures of diphtheria toxin and antitoxin to bring about, when injected subcutaneously, active immunity to poisoning by diphtheria toxin as well as power to resist diphtheritic infection, is now firmly established by the published studies of numerous workers in this country and abroad. It is recognized that certain mixtures have a greater antigenic power than others, but the factors which give rise to these differences in activity are not well understood.

We have had the opportunity to study the influence of several factors on the relative efficiency of such mixtures, having devoted attention especially to differences between mixtures containing greater or less excess of toxin; the influence on antigenic value of the character of the toxin entering into the mixture; and the effectiveness of one large dose as compared to that of several small doses.
Natural Agglutinins and Their Relationship to the Somatic and Flagellar Antigens of Bacteria
Authors: Gibson H. J.
Published: January 2023

Normal serum from various mammalian animals contains agglutinins which react with the “H” and “O” antigenic constituents of many bacteria. Flagellar suspensions have been used to demonstrate H-agglutinins. Agglutinin-absorption experiments show that the specificity of natural agglutinins (as described in a previous communication) depends chiefly on the “H” type. The “O” type agglutinins appear to possess affinities for antigenic constituents which are more widely shared by different organisms. It was not found possible to demonstrate the antigenic relationship among members of the Salmonella and B. proteus X groups so precisely with normal sera as with immune sera. the thermolability of the O-agglutinins was found to be greater than that of the “H” type in the normal serum of a number of animal species. Both showed greater lability than the corresponding immune agglutinins. “Rough” and “smooth” variants of the same bacterial strain showed antigenic differences in their reactions with normal sera.
Carroll G. Bull
Authors: Pritchett Ida W.
Published: January 2023

During the years of my association with Dr. Bull in the laboratory, I seldom heard him talk about his boyhood or his efforts to get an education. Only occasionally would he describe some small incident of his early life. Since his death I have discovered, in accumulating the material for this account of him, just how stirring and courageous was his fight to attain his end against difficulties that would have discouraged a less hardy soul. It is the same moving story of endurance with which histories of our pioneers are filled.

Carroll Gideon Bull was born June 22, 1884, in Sevier County, Tennessee. He was the son of Nancy Emma and William Gernade Bull, the fourth child in a family of eleven, of whom nine lived to reach maturity. His parents came of English and Pennsylvania Dutch stock, but his family had lived in Tennessee for a hundred years.
Variations in the Encephalitogenic Power of Vaccinia Virus
Authors: Thompson Richard , Buchbinder Leon
Published: January 2023

The presence or absence of the encephalitogenic property in various strains of vaccinia virus cannot be ascribed to heterogenetic origin since derivants of the same parent strain differ in this respect. Variations in the character of the skin lesions produced by neurotropic and dermotropic viruses are apparently associated with the presence or absence of the ability to produce encephalitis. The encephalitogenic strains are not obviously contaminated with herpes virus since recovery from neurovaccinial infection affords as little immunity to herpes virus as does recovery from dermovaccinial infection. The power of neurotropic strains to produce encephalitis is not referable to contamination with the virus of poliomyelitis since the latter virus does not cause a non-encephalitogenic vaccinia strain to become encephalitogenic for rabbits. Evidence is presented which indicates that the neurotropic vaccinia strains are not contaminated by some unknown virus capable of producing encephalitis alone or when aided by a vaccinial infection. The encephalitis producing power of certain vaccinia strains is probably a property of the vaccinia virus itself. It is suggested that the presence or absence of this property may be due to a process similar to the process of dissociation in bacterial cultures.
Studies of Diseases of the Lymphoid and Myeloid Tissues
Authors: Parker. Frederic , Jackson, Henry , Hugh Greene Fitz , Spies Tom D.
Published: January 2023

Tuberculin tests using both human and avian tuberculin were carried out on patients with Hodgkin's disease, malignant lymphoma, leukemia, pernicious anemia and malignancy. Similar tests were done on tuberculous and normal individuals. Fewer positive reactions were obtained in the patients with the diseases of the lymphoid and myeloid tissues and with malignant disease as compared with the normals and the tuberculous patients. More positive reactions to avian tuberculin than to human were found except in the normal group.
Anaphylaxis to Diphtheria Toxin
Authors: Sugg John Y. , Richardson Lurline V. , Neill James M.
Published: January 2023

The offspring of antitoxic immune guinea pigs gave anaphylaxis when injected intravenously with toxin-containing material thirty to sixty days after their birth. Sufficient controls were made on the possibility of participation of non-toxin antigens and of non-antitoxin antibodies to justify the conclusion that the anaphylaxis was due to reaction between the toxin antigen and the placentally transmitted antitoxin.

The advantage of the use of carefully selected offspring was demonstrated by the high degree of completeness of non-reactivity to non-toxin diphtheria antigens that was exhibited by the offspring of individual mothers whose serum contained none or only small amounts of diphtheria antibodies other than antitoxin.

Apart from the question of toxin anaphylaxis the present demonstration of anaphylaxis to diphtheria material on the part of the offspring of immune guinea pigs is of interest as an example of placental transmission of hypersensitiveness to an antigen of bacterial origin.
Natural Resistance to Disease in the Chicken
Authors: Lambert W. V.
Published: January 2023

This report presents the results of five generations of selection for resistance to a standard infection with the fowl typhoid bacterium in the chicken. A marked increase in the resistance of the selected population has resulted, the observed mortalities in the selected stocks, from the first to fifth generations, being 39.8, 29.3, 15.4, 15.0 and 9.4 per cent. In the unselected (control) populations tested concurrently the respective mortalities were 89.6, 93.2, 86.2, 86.4 and 85.0 per cent. A combined total of 3355 chicks, 1999 in the selected and 1356 in the control stock, was used in these studies.

Reciprocal crosses of selected (resistant) with unselected birds demonstrated that the male, as well as the female, transmits resistance to the offspring; and that a passive transfer of immunity was not a great, if existent, factor in the enhanced resistance of the selected progeny.
Natural Resistance to Disease in the Chicken
Authors: Lambert W. V.
Published: January 2023

A total of 1568 chicks from five breeds and strains of the fowl, and of one group consisting of hybrids between two of the breeds, were injected in the same way with a standard dosage of virulent fowl typhoid bacteria. The percentage mortalities observed for the various breeds were: White Plymouth Rock, 79.7; White Leghorn, 87.7; White Leghorn II, 86.3; White Wyandotte, 93.4; Rhode Island Red, 94.4; and for hybrids between the White Leghorn and Rhode Island Red, 86.4 A number of these differences are greater than would be expected from random sampling. Differences in the rate of mortality also were observed for the different breeds.

Significant differences in resistance were not observed between the chicks from separate colony matings, one male with several females, in one strain of the White Leghorn breed.
Notes on the Antigenic Activity of Hemolytic Streptococci from Different Types of Infection
Authors: Wheeler Mary W.
Published: January 2023

In this study of the antigenic activities of hemolytic streptococci from different infections, the potency and valency of antitoxic goat sera produced with 8 strains were compared with that of a serum produced with a standard strain. One slightly toxic strain apparently had little antigenic activity. Six strains producing potent toxins neutralized by the standard serum varied markedly in their antigenic activities. One produced a serum which in all instances reacted similarly to the standard serum. None of the other 5 strains produced a serum of such broad valency. Two of the sera neutralized the toxins of 4 of the strains used for serum production; two had slight or definite activity with only one toxin other than the homologous; the fifth was apparently active with the homologous toxin only. A serum produced by the use of the toxins of 2 of these 5 strains was more broadly valent than the monovalent serum of either strain but not so broadly valent as the serum produced with the standard strain. The eighth strain, the toxin of which was not neutralized by the standard serum, produced a serum active against the homologous and one of the heterologous toxins used for serum production, but inactive against the standard toxin. No other serum neutralized the toxin of this strain. Neutralization tests of these different sera with a large number of different toxins gave similar results.
Meningococcus Antitoxin
Authors: Ferry Newell S.
Published: January 2023

Encouraged by results of experiments reported previously on guinea pigs (1) with experimental meningococcus antitoxin (2), the work was extended to include the monkey.

The writer found, as did Flexner (3) many years previously, that acute and fatal cerebrospinal meningitis can be produced in the monkey by intraspinal inoculations with virulent meningococci and that results are fairly consistent in susceptible animals when the cultures are recently isolated and the animals are about of the same weight and age.

It was found by the writer, however, that the susceptibility of this animal toward the meningococcus varied considerably, depending not only upon age and weight but also upon individual natural resistance. The findings of Flexner were also corroborated to the effect that any infection in the monkey with this organism, by way of the spinal canal, which results fatally, has a very acute onset and is of short duration, and, that if the first inoculation does not produce typical symptoms, the second or third, made shortly afterwards, will probably do so.
Are Antiviruses Specific?
Authors: Besredka A.
Published: January 2023

“… I believe there can no longer be any doubt that the effect produced (by antivirus) is a non specific one.”—Frederick P. Gay, Jour. Amer. Med. Assoc., October 24, 1931, p. 1196.

This question, which many bacteriologists have asked is of unquestionable importance, considered either from a theoretical or a practical standpoint. If it could be shown that antiviruses are not specific, and, that their effect was identical with that of ordinary broth, then it would be identified with proteinotherapy. The basis of local immunity would not be shaken, but the scope of its action would be largely limited, for we would then be compelled to give up the application of dressings of wounds with bacterial filtrates and the instillation and irrigation of infected tissues, which have become increasingly common in general practice.

As soon as our researches on the specific immunizing effect of antiviruses appeared, we were not spared critics.
Further Studies in Serum Sickness
Authors: Tuft Louis , Rule Anna M.
Published: January 2023

In previous studies upon the antibody response in serum sickness Tuft and Ramsdell (1) were able to corroborate the findings of others in demonstrating that after the injection of immune sera circulating antibodies of various types appear. Also, that the appearance of such antibodies could not be correlated in any way with the phenomena of serum sickness. In addition to precipitins and anaphylactic antibodies, they showed for the first time the presence of transferable human skin-sensitizing antibodies according to the technic first described by Prausnitz-Küstner and also the transferred guinea pig skin reaction of Ramsdell, the latter being among the first reactions to appear and the last to disappear.
Studies on Cultures and Broth Filtrates of Staphylococci III
Authors: Burky Earl L.
Published: January 2023

Rabbits four months old and younger are not susceptible to the lethal action of staphylococcus toxin. This lack of general systemic reactivity is paralleled by non-reactivity of the skin.

These results compare with the results obtained in humans and it is suggested that a study of this naturally occurring allergic-like phenomenon may throw some light on the problem of bacterial allergy in general.
The Power of Normal Human Sera to Inactivate the Virus of Poliomyelitis in its Relation to Blood Grouping and to Exposure
Authors: Jungeblut Claus W.
Published: January 2023

Summary and Conclusions

A series of 30 normal adult human sera collected from metropolitan individuals and consisting of 10 O, 10 A and 10 B sera, were tested for neutralizing power against poliomyelitis virus. The following incidence of neutralization was obtained with the different blood groups: group O = 60 per cent, group A = 30 per cent and group B = 80 per cent. These percentages agree closely with the corresponding figures previously reported for 26 convalescent sera. The titer of three lots of pooled neutralizing O, A and B sera was determined by quantitative titration. The highest dilution capable of completely inactivating the virus was with the O sera 1:20 and with the A sera 1:5 while the B sera neutralized up to a 1:60 dilution. Similar discrepancies in virucidal titer were obtained with Wassermann samples pooled according to blood group. Three adult Eskimo sera and twelve adult Chinese sera were tested for virucidal property. All sera neutralized the virus of poliomyelitis, excepting one Chinese serum of blood group A. In view of the wide quantitative and qualitative variations in neutralizing power among normal adult human sera, depending as it seems in a large measure on the blood group of the individual, the virucidal test must be considered basically unsound as a means to determine previous exposure to the virus in epidemiological studies.
The Immunologic Specificity of Brain Tissue
Authors: Lewis Julian H.
Published: January 2023

Suspensions of foreign brain tissue are strongly antigenic when injected into rabbits. A suspension of rabbit brain is not antigenic for the rabbit. Alcoholic extracts of all brains, including those of rabbit brain, are antigenic for the rabbit when activated with a foreign protein. Brain antisera produced with a suspension of brain tissue and those produced with an activated alcoholic extract of brain are indistinguishable as to their content of antibodies that react with organs. Brain antisera do not react with suspensions or alcoholic extracts of liver, kidney, heart, spleen and lungs of homologous or of all heterologous species tested. Neither do they react with blood serum. Brain antisera react strongly with both the suspension and alcoholic extract of the brains of a group of animals representing mammals, birds, and cold-blooded types. The brains of all animals tested are indistinguishable by complement fixation reactions with an antibrain serum. Brain antisera react strongly with either the suspension or alcoholic extract of the testes of homologous and of all heterologous species tested. There is no qualitative difference between the reaction of a suspension and an alcoholic extract of brain, or between a suspension and an alcoholic extract of testes with an anti-brain serum. The spinal cord and all anatomical parts of the brain react similarly with an antibrain serum. Lecithin (Merck's egg) does not react with an antibrain serum. Cholesterol (commercial) gives marked reactions.
Comparison of the Combining, Antigenic, and Toxic Properties of Chemically Altered Diphtheria Toxoid and Toxin
Authors: Reiner L.
Published: January 2023

Azodyes were prepared from crude and from purified diphtheria toxoid by coupling them with the diazonium salt of arsanilic acid. The dyes obtained were purified by dialysis and precipitation with acid at about pH 4 and pH 3. The dyes had practically lost their immunizing power but retained their combining power as measured by the Ramon test. The specific toxic and the non-specific reaction-causing properties of the dye were approximately the same as those of the original toxoid or toxin. Micro arsenic and nitrogen determinations were made on the toxoid dye. High values were obtained for the ratio of arsenic to nitrogen, hence a high content of cyclic amino acids in the toxoid or else a decomposition during the dye formation is assumed.
The Participation of Cutaneous Epithelium in Immunity Response
Authors: Dienes L.
Published: January 2023

In allergic (contact) dermatitis and certain cases of drug idiosyncrasy, the epithelium of the skin is probably sensitized. The hypersensitiveness of the epithelium develops by contact with the injurious agent in the same manner as the usual forms of hypersensitiveness.

The tuberculin type of skin reactions present many characteristics that suggest the direct participation of the cutaneous epithelium in the reaction. The characteristic necrosis in the reactions is often limited to the epithelium and a thin layer of connective tissue below it. The epithelium is involved early before the macroscopic reaction is strong. The epithelium is often infiltrated with polymorphonuclear leucocytes even in slight tuberculin reactions. The occurrence of necrosis is in no direct connection with the size of the reaction or with the general sensitiveness.
Inheritance As a Factor in Resistance to an Infectious Disease
Authors: Irwin M. R.
Published: January 2023

A specific dose of a strain of S. enteritidis injected intraperitoneally into members of an inbred strain of rats over a four-year period produced a mortality of 93.5 per cent.

The slight discrepancy from the reaction of an ideal control stock could not be explained on the basis of seasonal effects, environmental changes, or by any measurable physical differences in the animals.
Inheritance As a Factor in Resistance to an Infectious Disease
Authors: Irwin M. R.
Published: January 2023

Summary and Conclusions

Selection within a random-mated stock of rats has been effective in isolating lines which continually produced an appreciable increase in the number of individuals resistant to a specific dose of a strain of S. enteritidis over the number that were found in the non-selected parental population.

Considerable variation was noted among the survivors in their ability to transmit resistance to their offspring.

The hybrid progeny from matings between survivors and members of a susceptible inbred race showed a greater resemblance in mortality to that of their resistant parents than to that of the susceptible parental strain. Offspring from matings of hybrid survivors to members of the susceptible strain, and inter se, gave further evidence that hereditary factors were in large part responsible for the resistance displayed in the selected stocks.

The genetic factors operative in the experiments were seemingly multiple, presumably cumulative in effect, and some were at least partially dominant over those making for susceptibility.
On the Usefulness of Blood-Grouping in Medicolegal Cases Involving Blood Relationship
Authors: Wiener Alexander S.
Published: January 2023

The chances of proving non-paternity, when the type of the falsely accused man is known, were calculated. In New York City the average chances of proving non-paternity by means of all four agglutinogens, A, B, M, and N are approximately one in three. A man of type A++ has less than one chance in ten to prove his innocence, and a man of type B++ has only one chance in seven. Men of the remaining ten types, however, have chances ranging from one in four (O++) up to two in three (AB−+).

The chances of detecting interchange of infants in hospitals by means of the agglutinogens A, B, and M and N are seven in ten.
Individuality of the Red Blood Cells of Inbred Strains of Fowls
Authors: Kozelka A. W.
Published: January 2023

In conformity with the results of Landsteiner and Miller (1924) the experiments here reported do not disclose any racial differences in the factors concerned with hemagglutination; the same factors are apparently found in the various breeds but differently assorted in the various individuals.

There is evidence that the number of factors underlying the reaction with a hetero-agglutinating serum is rather small; the individual variation might well be accounted for by a variable assortment of a small number of factors.

Inbred strains show a relatively high degree of homogeneity in their agglutinogens as compared with unrelated birds. This undoubtedly is due to the Mendelian transmission of the factors that are responsible for the formation of specific agglutinogens.
The Lipoidal Content of Antipneumococcic Horse Serum
Authors: Felton Lloyd D. , Kauffmann Gladys
Published: January 2023

The relationship of lipoids to immune reactions may be considered from a dual standpoint, first their possible antigenicity, and second their presence and possible function in immune sera. Only the latter of these is within the scope of this report; for the present study was undertaken to ascertain whether or not lipoid content is increased in serum of horses after they have been immunized against pneumococci. Earlier work of such a nature has been limited. In 1908 Takaki (1) reported the average weight of alcohol-chloroform extracts of various antitoxic sera (tetanus, diphtheria, and others) as 0.58 gram per 100 cc. serum as contrasted with 0.41 gram per 100 cc. of normal serum. His figures thus show a significant increase of lipoidal material in certain antitoxic sera. Koldaev (2) in 1921, however, found no difference in the amount of cholesterol in the serum of normal horses or of horses immunized against tetanus, diphtheria, or typhoid bacilli.
Proof of the Presence of Agglutinogen “A” in All the Erythrocytes of Type AB
Authors: Boyd William C. , Derow Matthew A.
Published: January 2023

The production of a group-specific hemolysin and an experiment indicating that the factor “A” occurs in each erythrocyte of a type AB blood, are described. There is no reason to doubt that the same is true of the “B” factor.
The Blood Grouping of Macacus Rhesus
Authors: Buchbinder Leon
Published: January 2023

Summary and Conclusions

The species Macacus rhesus cannot be divided into blood groups. In this respect the species behaves like pure-bred human races (Eskimos, North American Indians, etc.). Macacus rhesus erythrocytes have no antigen identical with or closely related to either of the two human isoagglutinogens (A or B). Rhesus serums, however, contain a hemagglutinin which is indistinguishable from the α isoagglutinin possessed by certain human serums. The anti-A agglutinin titer of rhesus serums can be raised by immunization of the animal with human red cells of group A. This enhancement of titer apparently is due to stimulation by the specific A isoantigen, since red cells of groups O or B have no such effect. The injection of human cells of group B, on the other hand, did not cause the formation of anti-B agglutinins de novo. The erythrocytes and organs (kidney) of Macacus rhesus and man possess an antigen in common. This antigen resembles the human isoantigens since it is alcohol soluble and heat stable. Rhesus monkeys inoculated with human red cells of groups O, A or B produce agglutinins for all human cells, regardless of their blood group. The antigen which causes this serological response is apparently species specific. It is not alcohol soluble. The species Macacus rhesus belongs to the so-called Forssman negative or rabbit group, since heterophile antigen is absent in its erythrocytes or organs, while a normal heterophile lysin or Forssman antibody is present in its serum.
The Existence of Antigenic Determinants of Diverse Specificity in a Single Protein
Authors: Hooker Sanford B. , Boyd William C.
Published: January 2023

The results of a quantitative study of the inhibition reaction, using dyes of different degrees of resemblance to the haptens concerned, are not incompatible with the conception that the injection of a single “complete” protein coupled with diazotized arsanilic acid leads to the production of two different antihaptens, one corresponding more closely to the tyrosin-diazo-arsanilic acid group, the other to the histidin-diazo-arsanilic acid group. In the case of the “deficient” protein, gelatin, the coupled protein seems to give rise to only one of these antihaptens.
Merthiolate As a Preservative for Biological Products
Authors: Morgan L. C. , Jamieson W. A. , Powell H. M.
Published: January 2023

Introduction. Previous to the fall of 1931 this laboratory produced diphtheria toxoid by formolizing diphtheria toxin having the usual range in potency values. The minimum values of such toxin was that set forth by the National Institute of Health, namely, of an L + value of 0.2 cc. and an m.l.d. value of 0.0025 cc., and maximum values were in the range of 25 to 50 per cent greater than these.

Following detoxification the toxoid was subjected to safety and antigenic tests in the usual manner. In addition to testing the toxoid undiluted, various dilutions were prepared with saline and subjected to antigenic and safety tests. It was noted that in some cases dilutions of 50 per cent or even 33⅓ per cent toxoid in saline possessed satisfactory antigenic qualities, namely, immunization of 8 out of 10 guinea pigs in six weeks against 5 m.l.d. of diphtheria toxin, the latter test being based on observation for ten days.
A Test for the Therapeutic Value of Antipneumococcus Serum
Authors: Goodner Kenneth
Published: January 2023

Although it is now generally recognized that certain antibacterial sera may have therapeutic value when employed under proper conditions, it has been found very difficult to devise methods to detect the relative therapeutic value of various samples of any of these apparently effective sera. For instance, the experience of a number of clinicians now indicates that the employment of large amounts of antipneumococcus serum type I is useful in the treatment of cases of lobar pneumonia due to infection with the homologous microörganism. It is not likely, however, that equal amounts of serum derived from different horses and prepared in different ways will all have the same efficiency in the treatment of patients suffering from pneumonia.
Studies on Trachoma
Authors: Weiss Charles
Published: January 2023

Summary and Conclusions

The rhesus monkey was shown to be rendered relatively susceptible to infection with fresh tissue derived from human trachoma, by previous preparation of the conjunctiva by irritation with powdered Portland cement. Clinically and histologically, these lesions resemble those induced in other varieties of monkeys and can be transmitted in series from rhesus to rhesus. The New World monkey, Cebus capucinus, was also found to be susceptible to infection with human material. No evidence of a filterable virus was found in tissues removed from monkeys whose conjunctivae had developed lesions in reponse to inoculation with human trachomatous material. No evidence of an inclusion producing virus was found, upon serial passage of human trachomatous material from brain to brain or from testis to brain of mice or rabbits.
A Precipitin Reaction in Yellow Fever
Authors: Hughes T. P.
Published: January 2023

Sera taken from monkeys recently recovered from severe yellow fever infections possess a precipitin capable of reacting with a precipitinogen which occurs in the blood of monkeys during the period of acute illness. This precipitinogen is not the virus of yellow fever, but appears to be associated with a protein of the albumin fraction. Its concentration reflects the severity of illness. It disappears with recovery, after stimulating the formation of a precipitating antibody. This resulting precipitin is entirely independent of the protective antibody resulting from an infection.

A similar precipitin occurs in the serum of humans recently recovered from a severe yellow fever infection. This precipitin reacts with the precipitinogen occurring in the blood of monkeys during the acute phase of illness.
Studies on Tissue Reactions in Immunity
Authors: Kahn Reuben L.
Published: January 2023

A method that makes possible the quantitative determination of the degree of skin sensitivity in animals is discussed and some quantitative aspects of the phenomenon of sensitization are considered.