bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary cholesterol affects the pathogenesis of influenza A virus infection in mice
Authors: Louie Allison Y , Wetzel Lisa , Diaz Katiria Soto , Dray Evan , McKim Daniel , Steelman Andrew J 
Published: January 2023

Abstract
Influenza is one of the most prevalent and devastating infectious diseases in the world. But it is unclear how host factors may function to increase disease susceptibility or severity. Here, we sought to determine the role of dietary cholesterol in modulating the immune response or altering viral activity during influenza A infection. A pilot experiment indicated mice fed a 2% cholesterol diet prior to inoculation with mouse-adapted human influenza A virus (Puerto Rico/8/1934 H1N1; 1 HAU) exhibit greater morbidity compared to controls fed an energy density-matched diet. To confirm these data, 5-week-old C57BL/6 mice were fed either standard rodent diet or matched diet with 2% cholesterol for 5 weeks, then inoculated intranasally with either saline or flu (0.7 HAU). The effect of diet on circulating leukocytes was determined by flow cytometry. Serum cholesterol was measured by ELISA. Viral load and pathology were quantified by RTqPCR and immunohistochemistry. Finally, serum virus-neutralizing antibody levels were evaluated by haemagglutination inhibition. As observed previously, infected cholesterol-fed mice exhibited greater weight loss than diet matched controls. Total plasma cholesterol did not differ between diet groups. Infection increased the percentage of circulating granulocytes and decreased that of B cells at day 4 post-infection (p.i.). In contrast, diet did not affect circulating leukocytes. The amount of viral RNA at day 8 p.i. as well as serum neutralizing antibody levels were not affected by diet. Taken together, these data suggest dietary cholesterol affects the pathogenesis of influenza infection but prompt further study into better understanding the mechanism.
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Summary
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

Abstract
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

Abstract
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

Summary
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

Summary
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

Abstract
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

Abstract
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

Summary
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

Abstract
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.