bluuebunny/crossref_metadata_2025 huggingface dataset:
CD8+ T cell intrinsic MAVS promotes antigen-specific responses and mitochondrial metabolism during West Nile Virus neuroinvasive disease
Authors: Vanderheiden Abigail , Aguilar-Valenzuela Renan , Verkerke Hans , Price Madeline , Boss Jeremy M , Grakoui Arash , Suthar Mehul S
Published: January 2023

West Nile Virus (WNV) is an arbovirus of the Flaviviridae family that causes annual outbreaks of encephalitis across North America. RIG-I like receptor (RLR) signaling through the central adaptor Mitochondrial antiviral signaling protein (MAVS) is essential for promoting immunity against WNV infection. While MAVS has been associated with type I interferon (IFN) induction during virus infection, here we describe a novel, cell-intrinsic role for MAVS in regulating antigen-specific CD8+ T cell responses. MAVS is expressed in CD8+ T cells and remains constant during the differentiation of CD8+ T cells. Generation of an effective CD8+ T cell response against WNV is essential for limiting virus replication in neurons, mitigating pathology in the brain, and protecting against lethal outcome. To understand how MAVS impacts CD8+ T cell responses during WNV infection, we utilized the WNV mouse model and adoptively co-transferred WT and Mavs−/− CD8+ T cells into congenically marked WT mice. We found that compared to WT cells, Mavs−/− antigen-specific CD8+ T cells displayed reduced accumulation of antigen-specific CD8+ T cells, reduced IFN-γ production and reduced formation of memory precursor cells during virus infection. At the peak of brain infection, Mavs−/− antigen-specific CD8+ T cells displayed highly divergent transcriptomes, including altered metabolic profiles, compared to WT CD8+ T cells. Further mechanistic studies found that after TCR stimulation of CD8+ T cells, MAVS promotes oxidative respiration and remodeling of mitochondrial morphology. Our findings identify a novel, non-canonical role for MAVS in the regulation of antigen-specific CD8+ T cell responses and mitochondrial function during neuroinvasive viral infection.
Abundance, diversity and functionality of cytomegalovirus-specific T cells depends on HLA genotype of the donor and hierarchy of the immunodominant epitopes
Authors: Maleeva Alexandra Vladimirovna , Zornikova Ksenia Victorovna , Kiryukhin Dmitry Olegovych , Shakirova Naina Talgatovna , Shmarov Vyacheslav Anatolevich , Efimov Grigory Alexandrovich
Published: January 2023

Cytomegalovirus (CMV)-specific T-cells from healthy donor are used as a treatment of CMV infection in patients receiving immunosuppressive therapy following transplantation. To choose the optimal donor and to select the best isolation method (MHC-tetramer or IFNy secretion assay) CMV-specific T-cells should be characterized by specificity and functionality.

We compared the antigen specificity, diversity and functionality of T-cell responding to CMV pp65 and to three pp65-derived immunodominant epitopes: NLV restricted by HLA-A*02, TPR and RPH restricted by HLA-B*07.

87 healthy donors were divided into 4 groups according to the presence of HLA-A*02 and/or HLA-B*07. CMV-specific response was analyzed by flow cytometry. For 6 donors antigen-specific cells were isolated by MHC-tetramer staining and pp65 IFNγ secretion assay followed by FACS. cDNA libraries of T-cell receptor β-chains were prepared and sequenced by NGS.

We found that pp65-specific T-cell response (IFNy-producing T-cell after stimulation with pp65 CMV) was strongly focused on pp65-derived epitopes NLV, TPR and RPH in fixed hierarchy. NLV-specific clones constituted most pp65-specific cells in presence of HLA-A*02 but not when HLA-B*07 was also present.

NLV-specific fraction consisted of few large clones, TPR− and RPH-specific cells were more diverse. Many MHC-tetramer+ clones were non-functional as they were not detected in IFNy+ fraction after pp65 stimulation.

In summary, HLA-genotype significantly affects magnitude and structure of pp65-specific T-cell response. It should be taken into consideration for choosing a donor of CMV-specific T cells. IFNy secretion assay produces more diverse and more functional cell product.
Stochastic modelling of the T cell repertoire with epitope affinity
Authors: Duque Daniel F Luque , Molina-Paris Carmen , Lythe Grant , Garcia Martin Lopez , Thomas Paul Glyndwr , Gaevert Jessica
Published: January 2023

Mathematical models devised to simulate competition of species for a survival resource can also be used to model the competition of T cell clonotypes for stimulus from self-pMHC complexes. A clonotype is analogous to a species that receives survival stimuli from different self-pMHC with different strengths. Thus, we can describe the T cell repertoire as a set of naive clones that are crossreactive. By studying this model we obtain informative statistics such as the mean time to extinction of a clonotype, which depends on the starting number of cells per clone and the number of self-pMHC that it can recognise. Next, we introduce viral peptides into the model, as survival resources that provide stimuli orders of magnitude stronger to that provided by self-pMHC, simulating the immune response to foreign antigens. With this addition to the model we study the effect of such perturbations on the distribution of clonal sizes. The model will be updated to include naive, effector and memory compartments of T cells, so that changes in the repertoire can be studied over the course of more than one infection. An application of this model is in the study of Influenza A viruses, where research is being done on immune response to a second exposure to a different strain.
Priming by lung-mDCs in the spleen initiates CD8+ T cell responses during influenza infection
Authors: Jenkins Meagan M , Bachus Holly , Botta Davide , Leon-Ruiz Beatriz , Ballesteros-Tato Andre
Published: January 2023

Initiation of CD8+ T cell responses to influenza virus requires the trafficking of activated lung-migratory dendritic cells (mDCs) from the lung into the lung-draining mediastinal LN (mLN) in response to influenza virus infection in the lungs. As such, when mDCs are absent or are unable to migrate into the mLN, T cell responses are severely compromised, and the mortality rate increases in mouse models of influenza infection. Importantly, it is generally considered that mDCs die shortly after reaching the mLN. Thus, the current paradigm suggests that priming of influenza-specific T cell responses by lung-mDC takes place entirely in the mLN. Recent reports have suggested that CD8+ T cell responses may also be initiated in the spleen, although influenza derived antigens to not freely reach the spleen or blood circulation. Together, these data and recent reports highlight a gap in knowledge of basic antigen trafficking. We show here, that a fraction of the lung mDCs egress the mLN, enter the blood circulation, and subsequently traffic to the spleen, where they prime influenza-specific CD8+ T cell responses. Mechanistically, the exit of mDCs from the mLN is controlled by Sphingosine-1-Phosphate Receptors (S1PRs) expressed by lung-mDCs, and when these receptors are blocked, CD8+ T cell activation is conjointly blocked. Collectively, our results demonstrate a novel DC trafficking pathway and support a new paradigm for the initiation of CD8+ T cell responses, where a portion of the total response, including the memory response, is primed in the spleen instead of only the mLN.
Moving in for the kill: natural killer cell immunoregulation requires CXCR3
Authors: Ali Ayad , Moran Michael T , Tuazon Jasmine , Rajaram Sanjeeth , Waggoner Stephen N
Published: January 2023

Natural killer (NK) cells dictate the pathogenic outcomes of infection via both direct killing of virus-infected cells and indirect immunoregulatory killing of antiviral T cells. The latter involves a perforin-dependent mechanism targeting activated CD4 T cells during the first three days of infection. Given that perforin-dependent killing involves cell-cell contact, we speculated that NK cells must re-locate proximal to recently activated T cells within the white pulp (WP) follicles of secondary lymphoid tissue during this critical temporal window of immunoregulatory activity. As expected, virus infection prompted a gradual accumulation of NK cells within T cell rich regions of splenic WP that peaked by the third day of infection. NK cells deficient in the chemokine receptor CXCR3 exhibited impaired localization to the WP and a markedly diminished capacity to suppress antiviral T-cell and germinal center B-cell responses. Our results reveal a critical role for CXCR3 in properly positioning NK cells to prune developing antiviral T cell responses, which potentially explains loss of tolerance and enhanced immune-mediated organ damage in absence of CXCR3. Strategies to curtail localization of NK cells in the WP during immunization may be an effective means to enhance vaccine-elicited immune responses.
CD8+ T cells mediate an NS3-based vaccine protection against Zika virus
Authors: Ngono Annie Elong , Syed Thasneem , Nguyen Anh-Viet , Nava Jose Regla , Susantono Mercylia , Spasova Darina , Aguilar Allison , West Melissa , Sparks Jessica , Gonzalez Andrew , Branche Emilie , DeHart Jason L. , Kamrud Kurt , Aliahmad Parinaz , Wang Nathaniel , Shresta Sujan
Published: January 2023

Zika virus (ZIKV), a member of the flaviviridae family, is associated with severe congenital malformations in infants born to infected mothers, and with neurological disorders, such as Guillain–Barré syndrome, in infected adults. To date, the development of anti-flavivirus vaccines has focused predominantly on the induction of neutralizing antibodies. Paradoxically, a suboptimal antibody response may enhance disease severity upon subsequent flaviviral infection through a phenomenon known as antibody-dependent enhancement. Thus, alternative approaches to ZIKV vaccine design are necessary. Here, we report induction of a protective anti-ZIKV CD8+ T cell response in the HLA-B*0702 Ifnar1−/− transgenic mouse model using an alphavirus-based replicon RNA vaccine expressing ZIKV nonstructural protein NS3, a potent T cell antigen. The NS3 vaccine did not induce an antibody response, but elicited polyfunctional CD8+ T cells that were necessary and sufficient for controlling viral burden and preventing death in lethally infected adult mice. In addition, the NS3 vaccine prevented fetal growth restriction and death in infected pregnant mice. These data identify CD8+ T cells as the major mediators of the ZIKV NS3 vaccine-induced protection and suggest a new strategy to develop safe and effective anti-flavivirus vaccines that avoid inadvertent antibody-dependent enhancement.
Phosphoproteomic landscaping of HIV-1 in vitro identified phosphorylated epitopes capable of eliciting CD8+ cytotoxic T cell (CTL) responses in patient samples ex vivo
Authors: Chowdhury Fatema Z , Maddali Shivaali , Szucs Matthew J , Ahmad Rushdy , Carr Steven A , Lichterfeld Mathias , Yu Xu G
Published: January 2023

Significant progress has been made in recent years in our abilities to simultaneously detect proteome and posttranslational modifications (PTMs), including phosphorylation responsible for regulating protein functions. We have an incomplete understanding of the role of phosphorylation in host-pathogen interaction. The objective of this study was to fine-map phosphorylation of HIV-1 proteins and subsequently study the consequences of these PTMs. Using mass-spectrometry, we identified over 30 unique phosphorylated sites on HIV-1 proteins detected in infected primary CD4+ T cells and in cell-free virus, with the majority being present on the viral proteins Gag, Pol, and Rev proteins. Interestingly, many of these phosphorylated sites were within previously identified optimal CTL epitopes. While CTL responses to phospho-neoepitopes is subject to recent research in cancer immunology, we lack any understanding of how phosphorylation of virus affects antiviral immune responses. We stimulated PBMCs from HIV-1 infected patients ex vivo in the presence of HIV-1 epitopes with or without phosphorylation, followed by assessment of IFN-γ, TNF-α, MIP1β, and CD107a expressions by flowcytometry. Two Gag-derived phospho-epitopes were able to elicit immune responses in CTLs, potentially indicating the genesis and functional responses to such modified epitopes in vivo in HIV-1 infected patients. Moreover, CTL clones of HLA B*5701 background responded with significantly more cytotoxic marker without any effector cytokine expression, suggesting that phospho-epitopes can modulate the quality of CTL responses. Taken together, our studies shed light on a new way of evaluating host-pathogen interaction with potential for vaccine research.
HIV-infected macrophages evade NK cell-mediated killing while driving inflammation
Authors: Clayton Kiera , Stuart Heather , Mylvaganam Geetha , Ocando Alonso Villasmil , Maus Marcela , Walker Bruce D
Published: January 2023

The primary targets for HIV infection are CD4 T cells, however macrophages (MΦ) are also infected and persist despite antiretroviral therapy, suggesting evasion of immune responses. Our previous work shows that while HIV-infected MΦ are recognized by cytolytic CD8 T lymphocytes (CTL), killing is inefficient and causes hypersecretion of CTL cytokines that propagate inflammation, emphasizing the need for rapid killing to limit inflammation. Thus, we hypothesized that NK cells would be able to rapidly kill HIV-infected MΦ while limiting inflammation. To test this hypothesis, innate interactions between NK cells and HIV-infected MΦ or CD4 T cells were assessed via flow cytometry-based recognition/killing assays. To characterize the potential for antibody-dependent cellular cytotoxicity (ADCC), HIV envelope expression on MΦ was characterized by flow cytometry and HIV-specific CAR T cells. Finally, ADCC responses against infected CD4 T cells and MΦ were assessed via flow cytometry. Despite similar levels of recognition of HIV-infected CD4 T cells and MΦ (degranulation and TNF-α production), NK responses to MΦ were significantly skewed towards non-cytolytic, cytokine production (p<0.0001), which was associated with poor elimination (p<0.0001). Surface HIV envelope is equally accessible on both MΦ and CD4 T cells, as determined by CAR T cell recognition. While ADCC enhanced NK cell responses to both cell types, responses to MΦ were significantly lower compared to that of CD4 T cells (p<0.05). Together, these data suggest HIV-infected MΦ employ a unique mechanism to evade cytolytic NK cell recognition while preserving inflammatory cytokine responses, emphasizing the need to develop alternative strategies to eliminate infected MΦ.
On the Mechanism of Toxin-Antitoxin Reactions
Authors: Freund Jules
Published: January 2023

As long as the chemical constitution of antibodies is not established and as long as antibodies are not available in pure state it seems desirable to study the action of substances that have a similar effect upon antigens. Probably of all the antigen-antibody reactions agglutination can be most readily studied by immunologic and physico-chemical methods. There are many substances that cause agglutination of bacteria or red blood cells, but only a few of them imitate the action of antibodies. Bordet has shown that specific agglutinins do not clump bacteria or red blood cells directly but mediate agglutination by sensitizing them to the action of electrolytes. Substances that act like agglutinins without being specific, such as ricin (Stillmark) and collodial stannic acid (Landsteiner and Jâgić) might be called non-specific sensitizers.
The Correlation of the Protective Value with the Titers of Other Antibodies in Type I Antipneumococcus Serum
Authors: Felton Lloyd D.
Published: January 2023

Summary and Conclusions

Thirty-nine freshly drawn polyvalent type I and type II anti-pneumococcus horse sera were studied to find the degree of correlation between the protective titer and various immunological reactions, namely, specific precipitation, agglutination, neutralization, and immune protein precipitable by soluble carbohydrate. It has been found that for type I the correlation coefficient between protection and precipitin titer is 0.93; between protection and agglutination is 0.80; between protection and neutralization is 0.88; and between protection and the amount of protein precipitated with specific carbohydrate is 0.91. From this degree of correlation it appears evident that, at least for type I freshly drawn sera, immunological examination other than the expensive mouse protection test can be utilized to estimate the probable therapeutic activity and to standardize antipneumococcus serum. Reproducible and accurate results in our experience have been possible by the use of the amount of protein in the sera precipitable with the soluble specific carbohydrate.
A Note on Improvement in the Method of Vaccine Production with Rickettsiae of Mexican Typhus Fever
Authors: Zinsser Hans , Castaneda M. Ruiz
Published: January 2023

In previous publications (1, 2, 3) the writers have reported the successful protection of guinea pigs against infection with both Mexican and European typhus virus by intraperitoneal administrations of Rickettsia suspensions killed with 0.2 per cent formalin in salt solution. Since that time, experiments have been carried out with monkeys which cannot, however, be regarded as anything more than encouraging; for although two vaccinated monkeys appeared to be immune to massive injections of European typhus virus, and two control monkeys exhibited characteristic temperature curves, a third control monkey failed to react. The guinea pig experiments, however, have given such definite results that we consider it important to submit our present method of vaccine production for further investigation by others.

In our preceding communications, we failed to mention similarly encouraging active immunization with killed Rickettsiae, reported by Weigl in 1930. We had not seen Weigl's paper, which appeared in the Bulletin de l'Academie Polonaise des Sciences, a periodical not ordinarily available to us.
Studies on the Adsorption of Diphtheria Toxin to and Elution from Magnesium Hydroxide
Authors: Ecker E. E. , Weed L. A.
Published: January 2023

An improvement on the purification of diphtheria toxin by adsorption to colloidal magnesium is reported. Whereas, the original toxic broth contained 37 mgm. of dried materials per gram the purified toxin contained only 0.17 mgm. of total solids per gram. The raw toxin gave 3.4 antigenic units per cubic centimeter. Neither the purified toxin, nor its filtrate or a mixture of the two, although each contained about 32 antigenic units per cubic centimeter, were capable of immunizing rabbits and guinea pigs.

“Le pouvoir antigène intrinsèque” of Ramon (the neutralizing power of the toxin toward antitoxin as determined by the flocculation method) being the true indicator of antigenicity does not hold for a toxin purified by adsorption to colloidal magnesium.
Blood Groups of Indians in Certain Maya Areas of Central America
Authors: Rife Dwight W.
Published: January 2023

One hundred twenty-four full-blooded Indians in the Upper Usumacintla Valley and the Yucatan Peninsula were grouped and all of these with the exception of 2 were found to be group O.
Immunity to Exotoxin of Streptococcus Hemolyticus Developed During Scarlet Fever, and Other Conditions as Shown by Skin Tests
Authors: Nemhauser Gustave
Published: January 2023

A historical note shows that skin tests may be used as an approximate quantitative measure of scarlet fever antitoxin in the blood stream.

Method. We found intradermal injections of 1, 2, and 6 s.t.d. of scarlet fever toxin was a suitable method for testing the degree of immunity to scarlet fever. Somewhat more antitoxin-treated cases of scarlet fever showed immunity in convalescence, as well as a somewhat greater degree of immunity than the untreated cases, after the serum was believed to have disappeared. Only severe cases were given serum. Seven of 13 cases that remained Dick positive in convalescence were classed as mild, 6 severe. Figures comparing immunity, in convalescence, of mild and severe cases of scarlet fever are given (see tables 1 to 4 and charts 1 and 2).

Our patients (mostly suffering from contagious diseases) possessed a greater degree of immunity to scarlet fever than our normal adults (see table 7).

It was shown that carrying diluted toxin about in a pocket for eight hours caused some deterioration (see table 8).

Repeated (at three-day intervals) injections of 1, 2, and 6 s.t.d. of scarlet fever toxin (5 to 9 triple injections) in Dick positive young adults caused most to become negative to 1 and 2 s.t.d., but none became negative to 6 s.t.d. None of 3 Dick positive children became negative to 2 triple injections (see table 9).

Subcutaneous injections of 1, 2, and 6 s.t.d. of scarlet fever toxin, gave varying results from intracutaneous in 4 of 14 cases. Subcutaneous reactions, in addition, seemed to be paler and more diffuse than the intracutaneous.

Our negro patients did not possess a greater degree of antitoxic immunity to scarlet fever than our white patients.

Our measles patients having a negative Dick test showed a greater average degree of immunity to scarlet fever than the average of our groups of infected patients having a negative Dick test (excepting scarlet fever patients).

The per cent of tonsils present in Dick negative individuals, Dick positive individuals, and cases of scarlet fever was compiled, as well as in cases of scarlet fever grouped as to severity. Between the Dick negative individuals, the Dick positive individuals, and the cases of scarlet fever, there was no significant variation in the percentage of tonsils present. The group of scarlet fever cases classed as mildest in severity of 4 groups showed the smallest percentage of tonsils present (see table 10).
Diphtheria Antibodies Transmitted to the Offspring of Immune Guinea Pigs
Authors: Richardson Lurline V.
Published: January 2023

Measurements were made of the diphtheria antibodies, antibacterial and antitoxic, in the sera of the offspring of guinea pigs previously immunized with diphtheria filtrate. The data showed that diphtheria antibodies of the antibacterial sort as well as antitoxin are placentally transmittted. The proportion of found in the sera of the offspring shortly after birth was comparable to that in the sera of their respective mothers.

The sera of a number of families were studied over periods of sixty or more days following the births; the data of these tests showed that the amount of antibodies originally transferred by the mother is the important factor in determining the duration of the passive immunity of the offspring.
Studies in Anaphylaxis in the Rabbit
Authors: Grove Ella F.
Published: January 2023

Histamine does not kill the rabbit by arteriospasm of the pulmonary artery. The pulmonary arterial bed in rabbits killed with BaCl2 resists high pressures of the perfusion fluid in most of the animals. Some rabbits are not killed by the lethal dose of BaCl2 for the majority of rabbits. Rabbits that have received the usual series of sensitizing injections of an antigen and have been found insensitive by test may still die in typical anaphylactoid symptoms upon the injection of BaCl2; therefore the variability in the degree of the anaphylactic reaction in rabbits that have received the same treatment with egg white and horse serum is not due to a corresponding variation in the general reactivity of the pulmonary medial muscle to stimulation. Histamine, epinephrine and BaCl2 may produce a characteristically different effect (contraction, relaxation of normal tone, no change) upon the same unstriated muscular tissue (bronchial) in the same animal. Unstriped muscle from different sites in the same animal may be affected in quite different manner by the same substance. The same substance usually produces the same qualitative effect upon the unstriped muscle of the same organ in guinea pig and rabbit. The action of a substance upon the isolated unstriped muscular tissue in the bath is not always reflected in the physiologic action of the substance upon the same tissue in the living animal.
Studies in Anaphylaxis in the Rabbit
Authors: Grove Ella F.
Published: January 2023

The experiments described in this paper confirm the well established rôle of unstriped muscle in acute anaphylactic shock in the rabbit. They also confirm the view of Simonds and of Wells that the difference in the pathology of acute anaphylaxis in the guinea pig and rabbit are due to differences in the structural relations in the respective shock organs because both bronchial and arterial muscle in the same animal (guinea pig) have been shown capable of specific contraction and therefore both contract during acute anphylactic shock; yet in the one situation the contraction results in closure of the lumen, whereas in the other, it does not.
Studies on Meningococcus
Authors: Malcolm Wilbur G. , White Benjamin
Published: January 2023

By various methods, some of which have been previously described, it is possible to extract from meningococci of the four agglutination groups a substance or substances highly toxic for mice and rabbits. Evidence is presented which seems to prove that the toxin is an endotoxin. A method is described for preparing uniform and stable lots of meningococcus endotoxin, upon which definite m.l.d. determinations can be made. The precipitation and removal of cellular protein by means of acetic acid from sodium hydroxide extracts of meningococci appears to be an important step in the method. This toxin is a tissue poison, has a dilating effect on the blood vessels and produces hemorrhage in the brain. The Shwartzman phenomenon may be reproduced by the endotoxin. Some rabbits may be made tolerant or possibly immune to the local and systemic effects of the toxin. The endotoxin may be neutralized by some lots of specific immune horse and rabbit serum. The study is being continued.
Further Studies on the Meningococcus with Special Reference to the Shwartzman Reaction
Authors: Powell H. M. , Jamieson W. A.
Published: January 2023

In recently reported experiments dealing with the Shwartzman toxic principle of meningococci (1) we have verified the fact that an injury-producing substance may be prepared from these organisms (2). Also we have noted neutralization effects of a moderate degree, and have used the Shwartzman reaction in order to investigate further antimeningococcic sera.

It appears that the exact nature of the Shwartzman meningococcus toxic principle, in common with that from other bacteria, has not yet been fully determined. Shwartzman has presented evidence, including multiple proportion neutralization experiments, indicating that this toxic principle resembles exotoxin. Burnet (3) in an interesting paper has pointed out the similarity of the Shwartzman toxic principle to endotoxin. His research indicates a greater degree of similarity between the Shwartzman toxic principle and endotoxin than with any other known bacterial substance. Burnet inclines to the view that the Shwartzman toxic principle is not of itself antigenic, and that neutralization effects of homologous antiserum may be attributed to bacterial substance usually associated with the toxic principle.
The Relationship of the Tuberculin Proteins of Different Acid-Fast Bacilli to Sensitization As Indicated by Their Reactivity in Sensitized Animals
Authors: Seibert Florence B. , Morley Nelle
Published: January 2023

The great variation in degree of sensitiveness of tuberculous guinea pigs to tuberculin is a factor of considerable importance in the standardization of tuberculin, as well as in many research problems concerning tuberculosis. The cause for such fluctuations is at the present time entirely unknown. During the course of an experimental study of tuberculin extending over a period of eight years it had been noted that the skin sensitiveness of tuberculous guinea pigs was at times of such a low degree as to prevent any quantitative study of the potency of tuberculins by that method. The minimal lethal dose test was therefore resorted to (1). At other times, as at the time of writing, the sensitiveness was so great that the most delicate titration of potency by means of the skin test has been possible.
The Sedimentation Rate of Red Blood Cells of Tuberculous Rabbits Injected with Tuberculin
Authors: Freund Jules , Frank Dee E.
Published: January 2023

Since, on the one hand, the injection of old tuberculin into a tuberculous animal is followed by inflammation in organs containing tuberculous tissue, and, on the other hand, inflammation is associated with an increased sinking velocity of red blood cells in the sedimentation test tube, the injection of old tuberculin might be expected to cause an increase in the sedimentation rate of red blood cells of tuberculous animals. If so, it may be possible to demonstrate hypersensitiveness by measuring the rate of sedimentation of erythrocytes before and after the injection of old tuberculin. To test this possibility we have chosen the rabbit as our experimental animal. This test may prove useful in detecting tuberculous infection in rabbits, since in this animal neither the skin nor the temperature reaction is a dependable indication of hypersensitiveness to tuberculin.

The settling of red blood cells was observed in tubes 40 mm. long with an inner bore 5 mm. in diameter.
The Influence of Pregnancy and of Menstruation on the Power of Normal Human Sera to Inactivate Poliomyelitis Virus
Authors: Jungeblut Claus W. , Engle Earl T.
Published: January 2023

An impression has been gained by clinicians after many years of observations that a number of infectious diseases occur with notable rarity during pregnancy (1). This physiological protection which nature has temporarily provided for the expectant mother extends also into the first few weeks of life of the newborn, only to be followed shortly later by a period of maximum susceptibility to the common infections of childhood. The mechanism of this spontaneous and transitory phase of enhanced resistance is not clear, neither in the mother nor in the baby. The constitutional conditions, however, which are associated with the stated epochs of life, must evidently be of fundamental character since several examples have become known of an increase in the titer of certain normal protective principles in the serum during the period of gestation. We refer here only to the increase in anthrakocidal substances (2) and in dysentery agglutinins (3) in the serum of pregnant women.
Influenzal Meningitis
Authors: Fothergill LeRoy D. , Wright Joyce
Published: January 2023

Influenzal meningitis is rarely seen under two months of age or beyond six years of age. About 80 per cent of the cases occur between the ages of two months and three years. The bactericidal power of whole defibrinated blood in various age groups for a meningitic strain of B. influenzae has been studied. Cord blood and the blood of infants under two months of age has considerable bactericidal power. With rare exceptions the blood of children between the ages of two months and three years has practically no bactericidal power. After three years the bactericidal power gradually rises and appears to be permanent in adult life.
Serum Sickness in Rabbits
Authors: Fleisher Moyer S. , Jones Lloyd
Published: January 2023

In previous articles concerning serum sickness in rabbits we have reported some of the manifestations of this reaction (1) and certain phenomena associated with this reaction such as appearance of antibodies (2), alterations in temperature and white blood cells (3). The results here reported are based upon experiments carried out to determine some of the factors concerned in the occurrence of serum sickness in rabbits. As concerns the appearance of this phenomenon in man there have appeared in the literature statements that serum from various horses differed in their activity in causing serum sickness, that age of the serum might be of moment and that the individual variation of the person injected played a rôle. Very little has been stated regarding the effect of serum from species other than horse in causing this reaction. Our studies were undertaken to throw some light upon these questions in their relation to manifestations in the rabbit.
Experimental Study of an Antipoliomyelitic Serum from Monkeys Artificially Immunized with an Organism Cultivated from Poliomyelitis Nervous Tissue
Authors: Eberson Frederick , Mossman William G.
Published: January 2023

Summary and Conclusions

By means of a series of subcutaneous injections of an organism cultivated from Berkefeld N filtrates of poliomyelitis virus, Macacus rhesus monkeys were apparently immunized against the virus of the disease.

The protection conferred upon the test animals was measured by the neutralizing power of their serums for poliomyelitis virus. In two instances the resistance of monkeys toward intracerebral inoculation of the virus was also tested.

The serums of animals treated with the cultures neutralized completely or in part the poliomyelitis virus in vitro. The outcome of an intracerebral inoculation test in two other instances showed that the monkeys had become resistant to infection by this route.

During the course of immunization with the living cultures 1 animal developed typical poliomyelitis. In an earlier series of experiments 3 monkeys also showed symptoms and signs of typical abortive infection.

The cultures used in the experiments were in the twenty-fourth subplant and represented a dilution of the original virus material that had been cultivated of approximately 2 × 10−38.

The results have been discussed with reference to possible survival of any hypothetical adsorbed virus and with reference to the viability of virus as compared with the cultures at incubator temperature.

The experiments, it is believed, confirmed further the previously reported observations on the possible relationship of this organism to the poliomyelitis virus.
Electric Charge of Antibodies
Authors: Olitzki Leo
Published: January 2023

A number of investigators have studied the nature of electric charge of antibodies, especially of agglutinins. Landsteiner and Pauli (1908) were the first to record from cataphoresis experiments that the haemagglutinin of chicken serum carries a negative charge in neutral and alkaline solution and a positive charge in acid solution. Michaelis and Davidsohn (1912) determined the isoelectric point of various antibodies. They found the isoelectric point of agglutinins for B. typhosus to be between (H·) 1.0 × 10-6 and 5.1 × 10-6 and for precipitins between 3 × 10-6 and 6 × 10-6. From that they concluded that the antibodies are amphoteric and that their isoelectric point is identical with that of the globulins, that is (H·) 4 × 10-6. Recently Vera Schroeder (1930) found that the isoagglutinins are amphoteric proteins with an isoelectric point at pH 4.0.
The Distribution of the Virus of Poliomyelitis in the Cerebrospinal Axis of Monkeys
Authors: Brodie Maurice
Published: January 2023

The lesions of poliomyelitis are found mainly in the central nervous system and take the form of inflammatory changes and nerve cell destruction. The latter is the outstanding pathological feature of the disease, but even in severe cases the reaction to the virus of poliomyelitis has an irregular distribution and varies in intensity throughout the cerebrospinal axis of monkeys. Thus, in the spinal cord, most of the neurones are affected, in the pons and medulla there may be considerable inflammatory exudate but there is decidedly less nerve cell destruction and specific changes are rarely present in the brain.

Whether the virus acts directly or indirectly upon the nerve cells, it appears reasonable to suppose an irregular distribution of the virus in the central nervous system, with greatest concentration in those areas having most nerve destruction.
The Titration of Poliomyelitic Virus Containing Tissue
Authors: Brodie Maurice
Published: January 2023

There is reason to believe that during the serial transmission of a single strain of poliomyelitis virus through monkeys, periodic changes in its infectivity occur (Flexner and Lewis (1), Flexner et al. (2), Flexner and Amoss (3)). It is not surprising, therefore, that the infectivity of the different strains in common use show no agreement. This is revealed in the experiences of various workers. Amoss (4), for example, states that as little as 0.001 cc. of a 5 per cent emulsion can infect monkeys, while Fair-brother (5), infected with 0.003 cc. and Stewart and Rhoads (6) with 0.005 cc. of a 5 per cent emulsion. On the other hand, Shaughnessy, et al. (7) and Rosenow (8) failed to infect monkeys with as much as 1 cc. of a 5 per cent emulsion.

Furthermore, as is shown in an accompanying paper, poliomyelitis virus is not uniformly distributed throughout the brain and cord.
The Preparation of Diphtheria Toxoid by Treatment of the Toxin with 1 Per Cent Formalin and Precipitation with Acetone
Authors: Wadsworth Augustus , Quigley James J. , Sickles Gretchen R.
Published: January 2023

An earlier study having established that (1), as soon as the detoxification of diphtheria toxoid is complete, the formalin can be eliminated by precipitation with acetone without apparent injury to the toxoid, further experiments were undertaken to determine the most suitable concentration of formalin and period of exposure when the preparation was incubated at from 36 to 37°C.

The preparation of diphtheria toxoid by the methods of Glenny (2) and of Ramon (3) involves prolonged incubation at elevated temperatures and with minimal quantities of formalin, from 0.3 to 0.4 per cent, so carefully adjusted that, when detoxification has reached the desired stage, changes affecting the antigenic action will not take place. There are obvious advantages in avoiding this complicated procedure and in adopting one that would eliminate the formalin as soon as the product was satisfactorily detoxified.
Studies on Trachoma
Authors: Weiss Charles
Published: January 2023

Summary and Conclusions

By repeated irritation with an alkaline dust (Portland cement) or by previous infection with a virulent hemoglobinophilic bacillus, the monkey's conjunctiva was at times rendered more vulnerable to infection with Bact. granulosis. The use of the Reynals' factor or the selection of monkeys whose general resistance had been lowered by a tubercular infection, by severe malnutrition, or by the injection of benzol, did not increase the virulence of old strains of Bact. granulosis. This investigation has confirmed the observations of Noguchi; Olitsky, Knutti and Tyler and Thygeson that characteristic lesions of granular conjunctivitis (“monkey trachoma”) may be initiated in rhesus monkeys by inoculating freshly isolated, virulent strains of Bact. granulosis, but more effectively by infected monkey tissue containing Bact. granulosis. The lesions thus induced at times pass spontaneously to the uninoculated eye and are transmissible in series by injection of tissue suspensions. It was not possible to demonstrate the presence of any filtrable virus or auxiliary agent in the conjunctival lesions of monkeys which were used in transmission experiments. It was demonstrated in several monkeys which showed no gross evidence of follicles after inoculation with Noguchi's bacillus, that microscopical evidence of changes indicative of a chronic inflammation may be present. These consist of lymphocytic and plasmocellular infiltration, edema of the conjunctiva with mucoid degeneration of the cylindrical cell epithelium and congestion of the capillaries. Clinical and experimental data are presented which indicate that spontaneous folliculosis of rhesus monkeys is a disease distinct from that which is produced by the inoculation of virulent cultures of Bact. granulosis.
Studies on Tissue Reactions in Immunity
Authors: Kahn Reuben L.
Published: January 2023

It is widely believed that rabbits sensitized to complex proteins, such as horse serum, cannot be desensitized by the intravenous injection of the specific protein. In order to desensitize an animal, it is apparently necessary to cause the disappearance of the precipitins from the circulation. In the case of purified proteins this disappearance of the precipitins appears to be an established fact (1) and is believed to be due to the union in vivo of the injected precipitinogen with the circulating precipitins. A complex protein, however, consists of a number of antigens, and when injected into an animal, presumably calls forth the production of a corresponding number of precipitins. The removal of the precipitins from the circulation would require that all of the precipitinogens and their corresponding precipitins are in correct proportion for complete precipitation, a condition that is not likely to occur, and as long as precipitins remain in the circulation, complete desensitization is believed to be impossible.
Studies on the Antigenic Substances of Clostridium Parabotulinum. II
Authors: Gunnison J. B.
Published: January 2023

In studies on the complement fixation and precipitin reactions (1, 2, 3), it has been shown that extracts prepared by alternate freezing and thawing of suspensions of Clostridium parabotulinum are highly group specific when tested with antiserums produced by the inoculation of intact organisms. It was thought that it would be of interest to test the antigenic properties of such extracts when injected into the animal body.

Extracts were prepared from seven representative strains of Cl. parabotulinum by various methods. Twenty-four hour cultures in glucose veal broth were centrifugalized and washed three times in salt solution. In one series the organisms were suspended in neutral distilled water, in a second in neutral 0.85 per cent salt solution, and in a third in alkaline salt solution (pH 8.0). The suspensions were frozen in a mixture of crushed ice and salt and thawed rapidly by plunging into warm water (70°C.).
A New Heterophile Antigen Common to Avian Erythrocytes and Some Varieties of Genus Pasteurella; Its Significance in the Classification of Birds
Authors: Buchbinder Leon , Rubin William
Published: January 2023

The presence of a new heterophile antigen, in some strains of the haemorrhagic septicaemia group of bacteria and in the erythrocytes of birds, is described. In contrast to the apparent chance appearance of this antigen in members of the Pasteurella group of organisms, it is present in many birds in an orderly fashion. The significance of this heterophile antigen in bird erythrocytes is discussed from the standpoint of species evolution. Additional strains of the haemorrhagic septicaemia organism containing Forssman's heterophile antigen are described.
Studies on Vascularization of the Cornea
Authors: Julianelle L. A. , Harrison R. W. , Morris M. C.
Published: January 2023

Summary and Conclusions

Repeated inoculations of Staphylococcus aureus by corneal scarification and conjunctival instillation, stimulate clouding and vascularization of the cornea of monkeys, (M. rhesus). Similar inoculations of monkeys with Bact. granulsosis apparently do not induce corneal reactivity under conditions favorable for stimulating reactivity to Staphylococcus. Repeated intracorneal injections of crystalline egg albumin also stimulate clouding and vascularization of the cornea. Corneal reactivity of the uninoculated eye as well as heightened skin reactivity does not occur under the conditions stated above. No specific antibodies are detectable in the serum of monkeys inoculated as described in this report. Certain contrasts in corneal vascularity induced under similar conditions in the rabbit and monkey are indicated.
The Existence of Antigenic Determinants of Diverse Specificity in a Single Protein
Authors: Hooker Sanford B. , Boyd William C.
Published: January 2023

Immune sera produced by the injection of 6 times crystallized duck ovalbumin and hen ovalbumin into rabbits were at first rather specific, those produced by the former apparently absolutely so, as was a serum produced by injecting a hen with duck albumin. Rabbit serum from later bleedings reacted equally with both proteins, but from such sera the reactivity to the heterologous antigen could be removed by specific adsorption, leaving that to the homologous antigen practically unchanged. It was found by the method of optimal proportions, that a titration of antibody in such an adsorbed serum indicated that there remained after adsorption with the heterologous antigen as much antibody against the homologous antigen as was there originally. These facts are thought to support the idea that in one molecule of a pure substance there may exist several antigenic determinants of diverse specificity.
The Influence of Nutrition on the Natural Immunity Reactions of the Blood and on Skin Reactions to Bacterial Toxins
Authors: Anderson E. J. M. , Fraser A. H. H.
Published: January 2023

Experiments are described in which the natural immunity reactions of the blood and cutaneous reactions to injected toxins were studied in relation to known variations of the diet. A caloric dietary deficiency was found to decrease both the haemolytic activity of sheep serum towards rabbit erythrocytes and its complementing power, but to increase the agglutinating action with B. abortus (Hog). The reaction to the intradermal toxin tests employed was unaffected. Cod liver oil and calcium had no effect on the natural immunity reactions studied nor on the intradermal toxin tests used.
Inactivation of Poliomyelitis Virus and of Diphtheria Toxin by Various Endocrine Principles
Authors: Jungeblut Claus W. , Meyer Karl , Engle Earl T.
Published: January 2023

Inactivation of poliomyelitis virus in vitro occurred with certain biological products of human and animal origin containing anterior pituitary-like principles and with the cortical and medullary adrenal hormones. It could also be shown that diphtheria toxin is inactivated in vitro by pregnancy urine preparations and by adrenal cortical hormone. The possible nature of this protective principle is discussed in its relation to the recognized endocrine secretions.
The Rôle of the Autonomic Nervous System in the Anaphylactic Smooth Muscle Contraction
Authors: Seastone, C. V. , Rosenblueth Arturo
Published: January 2023

It is generally believed that there is some relationship between the nervous system and anaphylaxis, although opinion on this point is not unanimous. Biedl and Kraus (1) believed that such a relationship does not exist. They based their conclusions on the fact that the low blood pressure in the dog during anaphylactic shock is not raised by the stimulation of the peripheral end of the cut splanchnic nerve, or by the administration of 0.1 to 0.2 mgm. of adrenin, although barium chloride which acts directly on smooth muscle does increase the blood pressure. The fact that adrenin as well acts directly on the smooth muscle was not generally recognized at the time this work was done. Arnold and Leschke (2) conclude that excitation of the parasympathetic fibers is responsible for shock. Pottinger (3) believes vagal stimulation to be a factor, although Scheurer and Strasman have shown that section of the vagi will not prevent shock; they conclude that the nerve endings are responsible if nervous tissue is involved at all.