bluuebunny/crossref_metadata_2025 huggingface dataset:
An animal model of enhanced disease development following respiratory viral infection in children with chronic lung diseases
Authors: Cheon In Su , Son Youngmin , Sun Jie
Published: January 2023

Infants born prematurely often develop chronic lung diseases including bronchopulmonary dysplasia (BPD). BPD is associated with greatly increased host susceptibility and severe disease development following respiratory viral infection. To this end, we have recently established a neonatal hyperoxia model respiratory viral infection in hosts with lung prematurity and BPD. Using this model, we observed that mice exposed with neonatal hyperoxia (80% oxygen, BPD hosts) developed enhanced diseases following influenza virus or respiratory syncytial virus (RSV) infection compared to those of influenza or RSV-infected control mice. We showed that neonatal hyperoxia leaded to modestly enhanced viral replication in the respiratory tract. Using nanostring immune gene profiling and multiplex cytokine analysis, we found that neonatal hyperoxia markedly enhanced immune-associated gene expression and the production of a number of proinflammatory cytokines and chemokines in the airway compared to those of control mice. Neonatal hyperoxia also increased the accumulation of multiple inflammatory innate cell types that were shown to be pathogenic during respiratory viral infections. Importantly, antiviral T, B cells and NK cells were similar in the lungs between infected neonatal hyperoxia-exposed and control mice, which are consistent with the similar viral clearance kinetics in those mice. Thus, we have successfully established a clinically-relevant mouse model of respiratory viral infection in BPD hosts. We expect to further uncover novel insights on the viral pathogenesis and host disease devlopment in this novel model of respiratory viral infection in hosts with chronic lung diseases.
CD4+ T cell memory restoration upon antiretroviral initiation in people living with HIV
Authors: Sponaugle Alexis Thieme , Clutton Genevieve , Iannone Marie , Eron Joseph , Goonetilleke Nilu
Published: January 2023

HIV infection causes a rapid loss of CD4+ T cells that is attributed to both direct cytotoxicity of infected CD4+ T cells and bystander loss due to high immune activation. In addition to the absolute decrease of CD4+ T cells, a significant decrease in both frequency and number of long-lived memory CD4+ T cells is observed in untreated HIV infection. Antiretroviral therapies (ART) now reliably achieve viral control (<50 copies/ml) and significantly restore CD4+ T cell levels in people living with HIV (PLWH) within months of treatment initiation. Similarly, ART restores CD4 T cell memory formation as evidenced by an increase in frequency and number of long-lived memory CD4+ T cells and vaccine-induced immunity. However, to date studies have provided limited data on when and how quickly CD4+ T cell memory is restored upon ART initiation particularly in the days to weeks following ART. A greater understanding of CD4+ T cell memory formation following ART initiation may inform the formation of the HIV latent reservoir, the majority of which is harbored in long-lived memory CD4+ T cells. The goal of this study is to characterize in detail CD4 + T cell memory restoration following ART initiation. To do this, we have obtained samples from PLWH during untreated infection, 2, 48 and 96 weeks post ART initiation and used the mass cytometry Maxpar Direct Immune Profiling Assay (Fluidigm) to phenotype these samples. Data to date show that CD4+ T cell memory restoration occurs very rapidly, within 2 weeks of ART initiation.
Maturation State of HIV Infected CD4 T Cells Impacts the Inducible Response of the Latent Viral Reservoir
Authors: Spina Celsa A , Mukim Amey , Deshmukh Savitha , Beliakova-Bethell Nadejda
Published: January 2023

A structured microenvironment is necessary for proper immune cell function. While it is rarely possible to use ex vivo experimental models of human tissue (e.g. tonsil), culture of multiple immune cell types together in close contact may benefit cell survival and function. To study HIV latency in primary CD4 T cells, we use an in vitro model, which produces an infected cell hierarchy closely resembling that found in vivo: HIV frequency in effector memory (TEM) > central memory (TCM) > naïve (TN) cells.

To enable mechanistic investigations, we developed a method to track CD4 cell phenotype origins following long-term culture and T cell receptor (TCR) stimulation. TN, TCM and TEM subsets were isolated by sorting and stained with live-cell tracking dyes: carboxyfluorescein (CFSE), Yellow and Violet dye, respectively. The tagged subsets were pooled with unstained CD4 cells to help preserve a healthy microenvironment. This mixture was co-cultured with autologous productively infected, TCR-activated cells to facilitate cell-to-cell HIV transmission and establishment of latency. After 3 days, dye-labeled cells were removed by sorting and rested an additional 3 days to complete provirus integration. Latent HIV reactivation by TCR stimulation was measured with HIV RNA expression by PrimeFlow analysis. Residual dye staining provided inference of initial subset origin on a single cell basis. Using this design improved viability and survival for all maturation subsets, compared to isolating subsets prior to stimulation. Results showed that HIV provirus in TN cells was the most responsive to TCR activation.

In addition, our study highlights a novel approach that can easily be adapted to other rare cell subsets in biologically relevant settings.
CD3 and CD8 coreceptor down-modulation are inversely associated with CD8 T cell functional avidity in humans
Authors: Clutton Genevieve Tyndale , Kallon Sallay , Weideman Ann , Xu Yinyan , Warren Joanna , Council Olivia , Alzhanov Damir , Thaxton Hannah , Hudgens Michael , Kuruc Joann , Goonetilleke Nilu
Published: January 2023

This study investigated the function of memory CD8 T cells in HIV-infected people durably suppressed on antiretroviral therapy (HIV+ cART). We assessed bulk and virus-specific memory CD8 T cells in HIV+ cART and HIV-seronegative individuals (HIV−) by flow cytometry. We observed a population of CD3+ CD8dim CD14− CD16− (CD8dim) T cells that was expanded as a percentage of total CD8 T cells in both HIV− and CMV-seropositive individuals. Bulk memory CD8dim T cells expressed significantly higher CD69 and less MHC Class I and CD127 ex vivo than CD8bright T cells, suggesting recent activation. CD8dim T cells expressed less GLUT1 and PGC-1α and took up less glucose (2-NBDG) and lipid (Bodipy) than CD8bright T cells, indicating relatively lower metabolic activity. Multimer reactivity was used to examine CMV-, EBV- and HIV-specific CD8 T cells ex vivo. Virus-specific populations were consistently CD8high. However, after peptide stimulation, antigen-specific CD8 T cells down-regulated CD3 and CD8. CMV-specific CD8 T cells down-regulated CD3 and CD8 more than HIV-specific cells. CD3 and CD8 downregulation were strongly correlated with the functional avidity of the response. A strong correlation between GLUT1 down-regulation and CD8 down-regulation was also observed, suggesting an association between CD8 expression and metabolic activity. These results suggest that the expanded CD8dim population in HIV+ cART individuals, who are >90% CMV-seropositive, may be driven by ongoing activation of high-avidity CMV-specific CD8 T cells. They also suggest that different virus-specific CD8 T cell populations differentially downregulate components of the TCR complex and metabolism after antigen stimulation, possibly to avoid excessive activation.
Memory CD8 T cell responses are impaired during Zika virus infection in mice
Authors: Valentine Kristen M , Alves Rúbens , Wang Ying-Ting , Shresta Sujan
Published: January 2023

Nearly half the world’s population is at risk for infection by Zika virus (ZIKV), the causative agent of congenital Zika syndrome in infants and Guillain-Barre syndrome in adults. ZIKV vaccination strategies are currently focused on neutralizing antibody (Ab) generation, yet recent evidence suggests that Abs may contribute to pathogenesis under certain conditions. In contrast, increasing evidence supports a key role for T cells in protecting against ZIKV. We have begun to evaluate the generation of memory T cell responses to ZIKV infection in unmanipulated immunocompetent mice. Four-week-old wild-type C57BL/6 mice were infected with ZIKV for 30 days, followed by challenge with ZIKV and evaluation of memory CD4 and CD8 T cell responses at day 3 after secondary ZIKV infection. As expected, total numbers of CD4 and CD8 T cells expanded during secondary ZIKV challenge when compared to primary ZIKV responses at 7 days post-infection. However, only antigen-experienced CD4 T cells (CD11a+CD49d+) and not antigen-experienced CD8 T cells (CD11a+CD8lo) were similarly expanded in secondary infection. These CD8 T cell responses were comprised of short-lived effector cells and not memory precursors, indicating that CD8 T cells memory responses are impaired after primary ZIKV infection. These data suggest potential mechanisms of immune-evasion by ZIKV, and ongoing studies are focused on defining the mechanisms by which ZIKV inhibits the generation of memory CD8 T cell responses. Our findings should offer new strategies for developing ZIKV vaccines that enhance protective T cell responses and avoid pathogenic Ab responses.
Diverse CD8 T cell responses to infection revealed by the collaborative cross
Authors: Martin Matthew D , Sompallae Ramakrishna , Winborn Christina , Harty John T , Badovinac Vladimir P
Published: January 2023

Enhanced host protection against re-infection requires generation of memory T cells of sufficient quantity and functional quality. Unlike well-studied inbred mice, T cell responses of diverse size and quality are generated following infection of humans and outbred mice. Thus, additional models are needed that more accurately reflect variation in immune outcomes in genetically diverse populations and to uncover underlying genetic causes. The Collaborative Cross (CC), a large recombinant inbred panel of mice, is an ideal model in this pursuit due to the high degree of genetic variation present and because it allows for assessment of genetic factors underlying unique phenotypes. The objectives of this study were to determine if the CC models diversity of immune outcomes seen in the human population, and if it could be used to identify genetic factors contributing to the generation of qualitatively and quantitatively distinct memory CD8 T cells. To this end, we analyzed the T cell response following acute LCMV Armstrong infection in 47 strains of CC mice. We found variability in resting immune cell composition and adaptive immune responses generated among CC strains in response to infection and reveal quantitative trait loci and candidate genes responsible for generation of CD62L+ memory CD8 T cells. Our results support the use of the CC to model diversity in immune responses observed in genetically diverse organisms and to uncover regulatory networks and host genetic factors underlying diverse immune outcomes following infection. This study and future studies utilizing the CC have the potential to improve translational efforts for the generation of protective immune responses against cancer and infections of global importance.
NK cells provide DC-mediated ‘help’ in cellular immunity to HIV
Authors: Anderko Renee R. , Rinaldo Charles R. , Mailliard Robbie B.
Published: January 2023

Natural killer (NK) cells are uniquely positioned to positively impact antiviral immunity to HIV-1 due to the pleiotropic nature of their effector functions, including the ability to respond directly to infected cells and to translate environmental cues into functional ‘help’ for other immune cells. In particular, their interplay with dendritic cells (DCs) is powerful in shaping the quality and character of the adaptive immune response. In this study, we explored the ‘helper’ function of NK cells in response to both innate and adaptive stimuli in chronic HIV-1 infection. Freshly isolated NK cells from virally suppressed HIV-1 seropositive individuals were co-cultured for 48h with autologous monocyte-derived immature DCs in the presence or absence of innate stimuli or opsonized target cells. Responding NK cells were assessed for their ability to produce DC-modulating cytokines; DCs harvested from the co-cultures were analyzed for their expression of maturation-associated surface markers, as well as their subsequent ability to produce IL-12p70 and to drive type 1 immunity. DC-derived co-stimulatory factors efficiently activated the ‘helper’ function of NK cells as evidenced by their robust production of IFNγ. Opsonizing antibodies also synergized with IFNα to promote NK ‘helper’ cell activity. Furthermore, interactions between NK cells and DCs induced the development of mature DCs with a heightened ability to produce IL-12p70 and to drive the development of Th1 and cytotoxic T cell responses. Our data demonstrate the capacity of NK cells to enhance DC-mediated immune responses to HIV-1 and, thus, highlight the potential for harnessing the reciprocal crosstalk between NK cells and DCs in the design of novel anti-HIV-1 therapies.
A Statistical Study of the Relative Goodness of Fit of the Two Proposed Theories of Human Blood Group Inheritance
Authors: Strandskov H. H.
Published: January 2023

The two genetic theories that have been proposed as an explanation of the inheritance of human blood groups, are outlined. Frequencies expected on the basis of the two proposed theories are calculated for 67 large populations. Pearson's x2 test is applied to the observed and calculated frequencies. Of the 67 populations tested more than 70 per cent are in good agreement with the theory of triple allelomorphs; less than 3 per cent agree as well with the two-factor hypothesis. Of the 49 populations that agree with the one or the other proposed theory 48 or 97 per cent agree better with the theory of triple allelomorphs. The conclusion is reached that the theory of triple allelomorphs explains better the inheritance of human blood groups than does the two-factor hypothesis of von Dungern and Hirzfeld whether or not the latter is complicated by linkage.
Parenteral Denaturization of Foreign Proteins
Authors: Sox Harold C. , Azevedo J. L. , Manwaring W. H.
Published: January 2023

In earlier papers of this series (1, 2) it was shown that intravenously injected horse proteins are apparently retained very nearly quantitatively in the normal canine circulation for about six days, but that by the end of this period of time they are so completely denatured as to be without demonstrable anaphylactic antigenicity for dogs. They still retain, however, part of their original antigenicity for guinea pigs (3).

These observations led us to the tentative conclusion that some at least of the intravenously injected horse proteins are presumably converted into proteins of quasi-canine specificity, conceivably into proteins intermediary in specificity between those of their animal of origin and their new host.

The present paper gives additional evidence in support of this postulate, together with an outline of the subsequent history of these hypothetical quasi-caninized horse protein.

Technic. On account of repeated distemper-like infections during the winter months, winter dogs are ill-suited for quantitative serological work.
Antibodies Against Vaccinia Virus Demonstrable in Vitro
Authors: Thompson Richard , Hazen Elizabeth Lee , Buchbinder Leon
Published: January 2023

Sera from rabbits hyperimmunized by intravenous and intraperitoneal injections of vaccinial virus tissues (brain, testicle and skin) caused fixation of alexin in the presence of a suitable dilution of vaccinial brain or skin suspension but not in the presence of non-vaccinial tissue suspensions.

The evidence indicates that this fixation is a process specific for vaccinial virus tissue, regardless of the tissue in which the virus is propagated and that it is not due to the immune reactions of concomitant bacteria.
Studies on the Viscosity of Sensitized Erythrocyte Suspensions
Authors: Went Stephen , Lissak Coloman
Published: January 2023

According to the present state of our knowledge, the alterations produced by agglutinins on bacteria and other cells may occur in quite different ways. It is possible (1) that the agglutinin reduces or neutralizes the electric charge of the cells; (2) that the agglutinin alters the cells by decomposing the protective membranes by which they are held in suspension, or by dehydrating the cellproteins, so that they behave like unprotected inorganic suspensions and are readily precipitated by salts and other electrolytes; (3) that the agglutinin increases the force of attraction between the cells (this force is supposedly exerted by the surface tension of the cells and is termed by Northrop and DeKruif as “cohesive force”). This is in short the present state of the problem we are dealing with as it was developed by a great number of investigators, among them Bechhold (1), Bordet (2), Field and Teague (3), Mansfield (4), Tulloch (5), etc., and particularly by Northrop and DeKruif (6).
Antigenic Analysis of Variants of B. Paradysenteriae and the Serological Relation of One Variant to B. Morgani
Authors: Mackenzie G. M. , Batt Louise N.
Published: January 2023

In a preceding paper (1) the results of a study of the antigenic relationships of five cultures of B. paradysenteriae (Eberthella paradysenteriae) and 4 cultures of B. Morgani (Salmonella Morgani) were described. These cultures were obtained from the stools of ten children involved in a small outbreak of summer diarrhea. The evidence presented in our preceding paper indicated only slight antigenic kinship between the two groups. The overlapping was confined to the group components of the antigenic complex. The present paper describes the results of a study of the antigenic relationships of 2 stable variants which were produced by growing a single cell culture of B. paradysenteriae in homologous immune rabbit serum. Inasmuch as the 5 cultures of B. paradysenteriae isolated during the epidemic of summer diarrhea were found to be serologically identical, only one culture from this group was used in the experimental production of variants.
Attempts to Produce General or Local Hypersensitivity to Vaccinia Virus in Guinea Pigs Actively or Passively Immunized
Authors: Buchbinder Leon
Published: January 2023

The literature relating to the production of specific antibodies in the various virus diseases has been unusually contradictory. However, the trend of current research would seem to indicate that the various antibodies which may be demonstrated as the result of simple infection or hyperimmunization with bacterial antigens can be duplicated with most viruses. Regardless of the cumulative evidence presented in recent years, it cannot be denied that there are obstacles which undoubtedly hinder the demonstration of serological reactivity with antivirus serums in a manner unknown with antibacterial immune serums. The intracellular habitat of viruses has probably been one of the reasons for the lack of similarity and uniformity in the results since in almost all immunological tests these causative agents have not yet been satisfactorily divorced from the animal or plant tissues in which they are propagated.
Studies on Antibodies
Authors: Falk K. George , McGuire Grace , Rosenstein Carolyn
Published: January 2023

Antimeningococcus serums were dried by the method previously used with antipneumococcus serums. Solutions of the dried materials made up a short time after the drying gave practically the same antibody content by agglutination tests as the original materials. As with the dried antipneumococcus serums, the agglutinating titers of solutions of dried antimeningococcus serums kept at room temperatures for longer periods of time were greatly diminished. The possible relation of agglutination results to clinical efficacy was discussed. The change in solubility of dried preparations on standing for longer periods of time and the significance of insolubility and inactivation of antibody preparations in this connection were considered briefly.
Comparison of Different Diphtheria Antitoxin Sera with Regard to Their Rate of Flocculation
Authors: Siebenmann Charles
Published: January 2023

The sera of 15 diphtheria horses (toxin) were studied with regard to their rate of flocculation (Kf). Six of these 15 sera showed an irregular but distinct increase of the Kf values during hyperimmunization of the horse. Three horses, whose sera showed the most marked increase in Kf, were among the ones which developed unmistakable pathological blood changes.

Observations were made on the rate of flocculation of sera obtained from 3 horses hyperimmunized with concentrated toxoid.
A Hypothetical Mechanism of Antibody Formation
Authors: Mudd Stuart
Published: January 2023

Although the mechanism of antibody formation has naturally been a principal problem of immunology from its beginning, it remains still unsolved. Even a tentative hypothesis, giving a rational chemical picture of how antibody formation may occur should at least serve to focus though t and suggest experiment upon this problem. It would seem that the specific correspondence of antigen and antibody can best be explained by some sort of directing mechanism in antibody synthesis. A hypothesis involving such a mechanism ishere proposed and certain of its implications are pointed out.

“By definition an antigen is any substance which, introduced into the tissues orcirculating fluids of an animal, causes the appearance in these fluids, sooner or later, of substances which react specifically with the antigenic substance; i.e., specific antibodies” (1). The essential fact to be explained is that every or nearly every known sort of soluble protein which contains its full quota of amino acids is antigenic, i.e., gives rise on injection to antibodies which possess specific elective combining affinity with itself.
A Quantitative Study of the Precipitin Reaction with Special Reference to Crystalline Egg Albumin and Its Antibody
Authors: Culbertson James T.
Published: January 2023

Numerous methods have been described for the determination of the amount of the precipitable antibody contained in an antiserum. For much of the experimental work, the determination of the presence or the absence of this antibody is the end sought, but frequently accurate quantitative values must be obtained to justify the conclusions drawn from the work. The two methods which were developed earliest and which at present are in widest use to measure the precipitin content of an antiserum are known as the antigen dilution method and the antiserum dilution method. Methods of greater accuracy based on the determination of dry weights and measured volumes of the precipitates have been devised. These methods have proved slow and tedious in manipulation and have not been generally used. Recently chemical analysis for the nitrogen content of the precipitate and of the precipitinogen has been employed.
A Quantitative Aspect of the Hypothetical Incorporation of Injected Antigen in Resulting Antibody
Authors: Hooker Sanford B. , Boyd William C.
Published: January 2023

From the quantitative interrelations of an immune serum prepared by the injection of an arsenic-containing diazo-protein, and as test-antigen, a heterologous arsenic-containing diazo-protein, we calculate conservatively that the Buchnerian hypothesis which claims antibody to be a conjugate of injected antigen and body-globulin, demands the presence of at least 2.5 and more probably 2500 times as much arsenic in the immune serum as could possibly be there according to the testimony of direct quantitative chemical test.

The number of chemically defined groups (haptens) entering the molecule during preparation of a synthetic diazo-protein is determined and shown to agree with the theoretical.

The proportion of protein-combined haptens necessary for visible specific precipitation is approximated for one antigen-antibody system.

A suggestion is given as to the number of specific combining groups (anti-haptens) in one molecule of the antibody in question.
Studies in Tobacco Hypersensitivity
Authors: Sulzberger Marion B. , Scholder B. , Feit Emanuel
Published: January 2023

During the past few years one of us has been patch-testing various types of skin conditions with a 10 per cent solution of nicotine salicylate and tobacco extract. At the Post Graduate Skin Clinic, a group of 43 cases has been tested, to date, including such conditions as dermatitis venenata, occupational dermatitis, etc. In this group there were many positive patch tests to other substances, but, it was astonishing to note, no really definite reactions to the relatively toxic nicotine solution. Two cases had a slight and ephemeral erythema at the test site. In spite of this apparent rarity of eczematous nicotine sensitizations, we have noted three strongly positive eczematous reactions to tests with tobacco extracts which were relatively nicotine free.

It is of interest to note that the only one of the patients with positive eczematous tobacco tests who could also be patch-tested to nicotine was absolutely negative to the alkaloid; and, furthermore, the patients with eczematous hypersensitivity to tobacco reacted only to some tobaccos and not to others.
Studies on Cultures and Broth Filtrates of Staphylococci. I
Authors: Burky Earl L.
Published: January 2023

Summary and Conclusions

Certain strains of staphylococci produce a filtrable substance lethal for rabbits that is not the result of bacterial autolysis or the decomposition of the protein constituents of the media. The lethal factor is produced in cultures independently of the production of hemolysins. Less of hemolytic activity is associated with an increase in toxicity. The hemolysin is unstable while the lethal factor maintains its toxicity for periods as long as one year without refrigeration.

A discussion of the association of source of strains, lethal factor production and types of lesions produced by staphylococci is included. The nature of the toxin and its similarity to tuberculin is also discussed.

It is suggested that the toxin-producing properties of unknown strains of staphylococci can be foretold by the degree of initial acidity and end alkalinity attained in broth cultures.
H and O Agglutination in Typhoid Fever, Other Febrile Diseases, and in Vaccination
Authors: Dulaney Anna Dean , Wikle Walter T.
Published: January 2023

The qualitative receptor analysis of Weil and Felix (1), and Felix (2) for the serodiagnosis of typhoid fever has received little attention in this country. Since the incidence of typhoid fever in this especial locality offers unusual opportunities for such a study, the qualitative receptor analysis has been applied to a series of patients in the Memphis General Hospital who were suffering from typhoid fever and other febrile diseases, and to healthy vaccinated individuals. In all, 243 serums were studied and the results of these tests are presented in the tables which follow.

Felix (2) claims to be able to differentiate the agglutination reaction produced by infection from the one which follows the administration of typhoid vaccine on the basis of the type of macroscopic clumping obtained. The motile bacilli of the typhoid-paratyphoid group possess the double receptor apparatus originally described for the proteus bacilli, which indicates two important antigenic components, the H and O.
The Use of Rabbits in Standardization of Antisera Against Streptococcus Hemolyticus from Scarlet Fever and Erysipelas
Authors: Kolchin Betty S. , Vladimir Frances B. , Shapiro Rebecca , Feig Irena
Published: January 2023

Facts have been presented corroborating Frazer's and Plummer's observations on the use of rabbits for titration of antitoxic sera of hemolytic streptococcus. This titration is done on the basis of the same principle which is applied to titration of antiscarlatinal sera on children. Full-grown white rabbits with thick skin and preferably heavier than 2400 to 2500 grams were used for titrations of sera with at least the same success as the chinchilla rabbits. The variation in the degree of rabbit skin susceptibility as expressed in the number of skin test doses evoking a reaction not less than 10 by 10 mm. is similar to the same variation on human and goat skins. The incidence of rabbits giving a positive reaction to 1 to 5 S.T.D. (human) of a sterile toxin is about 40 to 60 per cent. A skin reaction produced by an intradermal injection on the ventral side of the ear as described by Veldee, is utilized by us as a preliminary test for selection of susceptible rabbits. The test dose most suitable in neutralization tests for serum titrations was found by us to be the same as in tests on humans. Test doses greater than 5 S.T.D. can also be used in groups of rabbits in which reactions to 1 and 5 S.T.D. in a preliminary ear test were found to be below the adopted Standard. Serum values obtained in titrations against different doses of the same toxin are about the same.
So-Called “Serum Sickness” in Rabbits Following the Intravenous Injection of Various Foreign Serums
Authors: Khorazo Devorah
Published: January 2023

Evidence of so-called “serum sickness” occurred in 10 out of 36 rabbits following a single intravenous injection of normal horse serum. The positive reactions were obtained in the winter. During the summer a series of 12 animals gave entirely negative results. Attempts to produce similar reaction in rabbits with other foreign serums, such as normal human, sheep, guinea pig and dog serum were unsuccessful, irrespective of the time of the year the experiments were performed. There were no differences in precipitin production or antigen elimination in rabbits which developed local serum reactions when compared with those which failed to show any symptoms at all. Various observations suggest that the occurrence of serum sickness in man may be due to a peculiarity of horse serum. Since most of the human reactions follow the administration of therapeutic horse serum it would be interesting to learn whether serum sickness occurs in human beings after the injection of foreign serums other than that of the horse. The observations of Kraus suggest that serum sickness in man can be largely avoided by the use of cattle immune serums. We intend to endeavor to parallel these results in rabbits using the serums of immune animals of some of the species employed in the production of therapeutic antiserums.
Complement-Fixation with S and R Antigens and the Sera of 100 Cases of Tuberculosis
Authors: Rice Christine E. , Orr J. H. , Reed G. B.
Published: January 2023

An examination of sera from some 100 cases of active, pulmonary tuberculosis by routine quantitative methods of complement-fixation has shown no consistent correlation between the clinical history and the antibody titre of the serum.

It has been noted, however, that all tuberculous sera do not react equally well with carefully tested antigens prepared from S and R cultures of human tubercle bacilli. These two antigens are about equally efficient in detecting the complement-fixing anti-bodies in sera from cases of the chronic type, but the S antigen fixes specifically, in the presence of serum from the majority of acute cases, twice as much or more complement than is fixed by the R antigen. Serum from cases of the intermediate type usually fall between these extremes.

From the small number of cases studied, it would appear that the relative reactivity of sera with S and R antigens is more closely correlated with the activity of the tuberculous processes than is the actual concentration of complement fixing substances. Whether the S to R antibody index will prove to be valuable in prognosis as is suggested by these results, cannot however be determined without periodic determinations and correlation with a study of clinical progress. A study of this sort is now well advanced.
On the Specificity of Brominated and Iodinated Proteins
Authors: Finkelstein Morris H.
Published: January 2023

In the course of their well known studies on chemically altered proteins, Obermayer and Pick (1) were able to demonstrate that iodination or nitration produced compounds which were antigenically distinct from the original protein and from each other.

These experiments are generally accepted as a proof that the introduction of substituents into the aromatic nuclei of the proteins causes the appearance of a new specificity depending entirely on the nature of the substituent.

This view is not fully supported by the experimental facts and later work would tend to stress the significance of the place of substitution, the number of entering groups, and structural alterations other than substitution. Thus Landsteiner and Prasek (2) obtained cross-reactions between nitro-proteins and diazoproteins and Wormall (3) was able to confirm these results and to demonstrate a close immunological relationship between iodinated and brominated proteins, and by means of the inhibition reaction even some relationship to chlorinated compounds.
Studies on Tissue Reactions in Immunity
Authors: Kahn Reuben L.
Published: January 2023

In a previous article from this laboratory (1), it was pointed out that a rabbit, sensitized to some protein, will show the presence of of both skin sensitivity and serum precipitins for some weeks after it enters the sensitized state; that with time, the serum precipitins disappear from the circulation, while the capacity of the animals to give a skin sensitivity response remains. In this article data will be presented which demonstrate the relation between skin sensitivity and serum precipitins on a more quantitative basis.

Experimental. Preliminary experiments have shown that the greater the quantity of protein used in the sensitization of a rabbit, within certain limits, the more extensive is the production of serum precipitins by the animal. On the basis of this observation, a series of rabbits was sensitized with small amounts of protein, with a view to limiting the production of serum precipitins. It was recognized that the skin sensitivity response would also be limited.
The Volume of Precipitate in Precipitin Reactions
Authors: Jones F. S. , Little Ralph B.
Published: January 2023

A procedure has been described whereby the quantity of precipitate resulting from the action of precipitin and antigen can be measured. At one point in titrations, as usually practiced, the greatest quantity of precipitate is formed and this we have called the zone of maximum precipitation. With this as a basis we have been able to show that the quantity of precipitate will vary proportionately with change in quantity of either antigen or immune serum. A linear type of reaction has been demonstrated. In addition similar linear relationships have been shown in the determinations of antigen and antibody in the supernatant after precipitation has taken place. In cow serum and its precipitin we have not been able to show that in a given series either antigen or antibody is completely utilized. Where a single antigen, such as egg albumin, was employed with its precipitin, there occurred within a narrow zone complete binding of both antigen and antibody, while in either direction one or the other was still present in active form.
The Comparative Value of Tuberculoprotein (MA 100) and Old Tuberculin, with Especial Reference to Sensitization
Authors: Aronson Joseph D. , Nicholas Rae V.
Published: January 2023

A study was undertaken to ascertain the value of tests with tuberculoprotein (MA 100) by comparing the number and the character of the reactions to comparable quantities of this substance and Old Tuberculin, and by determining whether human beings could be sensitized to the tuberculoprotein.

From their studies Funk and Huntoon (1) and Mariette and Fenger (2) concluded that with tuberculoprotein (MA 100) a somewhat higher percentage of positive reactions can be obtained than with Old Tuberculin, that the amount of tuberculoprotein (M100) employed was sufficient to detect the majority of cases of manifest tuberculosis, and that no untoward effects result from its use in this quantity.

These conclusions however were based chiefly upon injections of 0.01 mgm. of Old Tuberculin and 0.0005 mgm. of tuberculoprotein (MA 100), amounts so small that positive reactions are to be expected only in those who are more sensitive to the action of tuberculin.
Meningococcus Toxin and Antitoxin
Authors: Ferry Newell S.
Published: January 2023

Antimeningococcic serum, when injected intraperitoneally into monkeys, following intraspinal inoculation with live meningococci, in doses comparable to those previously used with experimental meningococcus antitoxin, did not prevent death from meningitis.

Meningococcus toxin, when injected intracisternally into monkeys, produced symptoms similar to those found in meningococcus cerebrospinal meningitis following experimental inoculation with the live meningococcus intraspinally.

Meningococcus antitoxin, when mixed with meningococcus toxin and injected intracisternally, had a very appreciable neutralizing effect on the toxin.

Monkeys which had recovered from previous intracisternal injections of meningococcus toxin, either neutralized or unneutralized with meningococcus antitoxin, were protected against a fatal dose of live meningococcus culture.
On Absorption of Phage by Bacilli
Authors: Levine Philip , Frisch Arthur W. , Cohen E. V.
Published: January 2023

In previous publications a specific reaction of phage with crude carbohydrate containing bacterial extracts was demonstrated (1). Obviously the question arose as to the relationship of the specificity of the reaction with bacterial extracts as compared with the bacterial bodies themselves. Although numerous publications on absorption experiments of phage and bacteria are available, systematic investigations analogous to those on absorption of antibodies by bacteria are still lacking largely on account of technical difficulties incidental to absorption experiments, namely prolonged centrifugations or numerous filtrations required to obtain fluids for testing the residual phage.

These difficulties were circumvented in the experiments here reported by making the tests in a manner similar to that employed in the demonstration of a reaction between phage and extracts of bacteria, i.e., by adding the test organism to the previously (non-centrifuged) incubated mixture of phage and constant amounts of heat-killed bacteria (one hour at °C.) of the several Salmonella species.
The Transmission of Diphtheria Antitoxin from Hen to Egg
Authors: Jukes T. H. , Fraser D. T. , Orr M. D.
Published: January 2023

Subcutaneous injection of laying hens with diphtheria toxoid resulted in the appearance of a low but definite antitoxin potency in the serum. Simultaneously, diphtheria antitoxin appeared in the eggs, and was found to be associated with the second protein, livetin, of the yolk. There was some indication of a parallel relationship between the concentration of antitoxin in the blood serum and its concentration in the livetin fraction of the yolk.
On the Use of Immune Serum at Various Intervals after the Inoculation of Yellow Fever Virus into Rhesus Monkeys
Authors: Davis Nelson C.
Published: January 2023

Summary and Conclusions

Immune serum from recovered animals, when injected at 24 to 48 hours following inoculation with yellow fever virus, was capable of preventing fever or ameliorating the disease in a significant proportion of experimental monkeys. After forty-eight hours the effect was less definite. In no instance did the serum prevent death when administration was delayed until the temperature of the monkey had reached 104°F.
The Inheritance of Diphtheria Immunity in Ducks
Authors: Fraser D. T. , Jukes T. H. , Branion H. D. , Halpern K. C.
Published: January 2023

Injection of ducks with diphtheria toxoid resulted in the appearance of antitoxin in their blood serum. The amount of antitoxin present showed wide individual variations. The immunity was found to protect against injections of diphtheria toxin. The serum antitoxin decreased rapidly after injections were discontinued. The decrease coincided with the time when the birds began to lay eggs. The eggs were found to contain antitoxin in the livetin fraction of the egg yolk. The concentration of antitoxin in the yolk was found to vary with the concentration in the serum. The amounts of the proteins vitellin and livetin in unit volume of egg yolk were found to vary independently of each other, and independently of the individual which laid the eggs. No relation was found between yolk livetin concentration and yolk antitoxin concentration. Ducklings newly hatched from eggs laid by immunized birds were found to contain antitoxin in their blood serum. None could be found in the serum of three weeks' old ducklings from the same mothers.
The Relation of Serum Protein Fractions to Serum Sickness in Rabbits
Authors: Jones Lloyd , Fleisher Moyer S.
Published: January 2023

We have shown in previous studies that in order to cause the appearance of serum sickness in rabbits a minimal quantity of whole serum measured in cubic centimeters must be injected into the animals; 5 to 7 cc. of serum pro kilogram was found to be adequate to cause the appearance of serum sickness in 25 to 80 per cent of the animals (1). Furthermore, it was demonstrated that two additional factors influence the occurrence of serum sickness, namely, the reactive capacity of the individual animal injected and the ability of the particular serum or batch of serum to produce serum sickness (2). With the idea of analyzing further this latter factor, it seemed advisable to determine the possible rôle of the various serum protein fractions in causing serum sickness.

In most of the experiments here reported, we have used the pooled serum from a single group of 8 horses.
Concerning Vaccination of Monkeys Against Acute Anterior Poliomyelitis
Authors: Kolmer John A. , Rule Anna M.
Published: January 2023

A chloroform-treated vaccine of monkey poliomyelitic spinal cord in a total dosage of 1 cc. by subcutaneous and intracutaneous injection failed to immunize 2 monkeys against intracerebral inoculations of virus. A sodium ricinoleated vaccine appeared to produce slight immunity in 1 monkey by subcutaneous injection while intracutaneous injections immunized 2 additional animals in a more convincing manner. An untreated vaccine by intracutaneous injection successfully immunized 1 animal but failed to protect 2 animals when administered by stomach tube. A heated vaccine failed to immunize 5 monkeys when administered subcutaneously, intracutaneously and by stomach tube.
A Comparison of the Sensitizing and the Therapeutic Effect of Rabbit and Horse Antipneumococcus Type I Serums in Albino Mice
Authors: Mehlman Julia , Seegal Beatrice Carrier
Published: January 2023

In studies on passive anaphylaxis in the guinea pig Avery and Tillett (1) have reported that while rabbit antipneumococcus serum readily confers passive sensitivity on this animal such that the intravenous injection of the pneumococcus specific carbohydrate results in anaphylactic death, horse antipneumococcus serum injected into guinea pigs fails to produce this passive sensitization. In a further study of passive sensitization in the guinea pig we have shown that rabbit antipneumococcus serum sensitized this animal so that general anaphylaxis, uterine sensitivity, and skin hypersensitivity followed the appropriate injection of the specific pneumococcus carbohydrate. However, horse antipneumococcus serum conferred sensitivity to the skin only, both general anaphylaxis and uterine contraction being absent (2). The marked differences observed in the ability of rabbit and horse antipneumococcus type I serums to passively sensitize the guinea pig led us to study the immunological reactions of these two serums in the white mouse.
A Comparison of the Agglutinogens in Rabbits with Those in Man
Authors: Boyd William C. , Feldman David
Published: January 2023

Some of the properties of the two agglutinogens in rabbits are compared with those of the human A, B, M, and N. The rabbit agglutinogens determine 4 groups, like A and B in man, and are inherited similarly: their frequency is quite different. As in the case of M and N, they are not accompanied by normal isoagglutinins, and they do not seem to occur outside of the erythrocytes or to be extractable from the erythrocytes with alcohol. They differ from A and B, of the human factors, in being destroyed by boiling, and perhaps also from M and N.
Formaldehyde and Serum Proteins
Authors: Horsfall, Frank L.
Published: January 2023

The changes resulting in proteins, and various protein derivatives, when mixed with formaldehyde solutions have interested many investigators. The problem has been approached from both the chemical and the immunological viewpoints. Although much has been added to our knowledge of these reactions, there still remain many unsettled questions. The exact site in the protein molecule to which formaldehyde attaches itself, the extent of the resulting change, and the immunological characteristics of such modified proteins are not yet completely clear.

Benedicenti (1), Schiff (2), and Schwarz (3) found the aldehyde radicle to unite with the free amino groups of the protein molecule. Pick (4) confirmed these observations but believed also that significant structural alterations occurred in the protein molecule after the union with formaldehyde. Kossel and Gawrilow (5) held that only lysine containing proteins united with the aldehyde, and later Kossel and Edelbacher (6) included those which contained histidine.
Development of Precipitins for Protein, Lipoid and Carbohydrate Fractions of S and R Forms of Tubercle Bacilli
Authors: Rice Christine E.
Published: January 2023

Complement-fixation had shown that there were antigenic differences between the S and R forms of the tubercle bacillus, the precipitation tests recorded in this paper indicate small differences in the protein and carbohydrate substances in S and R organisms, although both chemical groups have common fractions. Lipoid fractions show no type specificity.

During the process of immunization with killed S tubercle bacilli, there is a relative increase in precipitins for proteins and carbohydrates from S organisms over that of precipitins for R proteins and carbohydrates. R antisera on the other hand increased in relative reactivity with R protein.

S antisera reacted relatively more strongly with purified globulin and polysaccharide preparations made from virulent cultures of human tubercle bacilli than did R antisera. The latter gave a relatively stronger reaction with purified albumin.
Quantitative Measurements of the Absorption of Agglutinins by Bacteria
Authors: Olitzki Leo
Published: January 2023

Introduction. Eisenberg and Volk (1902) were the first investigators to study the absorption of agglutinins by homologous bacteria quantitatively. They showed that if an agglutinating serum in varying dilutions was treated with a constant number of homologous bacteria, the amount of agglutinin absorbed by the bacteria was not constant. In a concentrated serum the total agglutinin absorbed was greater than in the same serum diluted; on the other hand, the relative amount absorbed was less from the concentrated than from the diluted serum. Dreyer, Douglas and Walker (1909) found that when an agglutinating serum in different concentration was treated with constant numbers of bacteria, the quantity of agglutinin-units absorbed not only increased to a limit value but when this point was passed, might even decrease to zero when the concentration of the serum was further increased. Hitherto these experiments have been accepted as fundamental in discussions of the union between agglutinins and bacteria.