bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Influencing Determination of Antigenic Relationships between Western Equine Encephalomyelitis Virus Strains
Authors: Saturno A. , Henderson J. R.
Published: January 2023

A number of variables influenced measurements of antigenic relationships between Western equine encephalomyelitis (WEE) strains. These were: a) the infectious or noninfectious nature of the immunizing antigen, b) the purity of the antigen, c) the type of animal used for immune serum source and d) the type of serologic test employed for measuring antigenic similarities or differences between virus strains.

Such variations in immune responses have been interpreted as due in part to the selection by various hosts, during multiplication of the virus, of different antigenic subpopulations of WEE and in part to the measurement of different properties of the viruses by different serologic tests.
The Serologic Specificity of Interferon
Authors: Paucker Kurt
Published: January 2023

An improved method for the titration of antibodies against interferon has been described. The assay permits the use of 10 to 15 times less interferon for neutralization by antibody than conventional monolayer techniques. Neutralizing titers of anti-interferon sera are enhanced by a corresponding factor. Reading of the test is based on color change of the phenol red indicator in the medium, which can be recorded visually or in a photoelectric colorimeter. The assay has been used with L, HeLa and chick embryo fibroblast cells.

Antibodies against L cell interferon developed in guinea pigs only after a prolonged course of immunization. Similar results were obtained in rabbits injected with L interferon and in guinea pigs immunized with chick interferon. HeLa interferon of low potency failed to elicit antibodies.

Neutralization tests with anti-interferon sera disclosed that a) L interferon differs antigenically from the producer cell, b) L, chick and HeLa interferons posses different antigenic compositions and c) minor cross-protection of heterologous cells may be due to components in the preparations other than interferon.
Antigenic Variations in Herpes Simplex Virus Isolants from Successive Recurrences of Herpes Labialis
Authors: Ashe Warren K. , Scherp Henry W.
Published: January 2023

Thirteen strains of herpes simplex virus (HSV) were isolated from recurrences of herpes labialis in four persons. Antigenic variations among these strains were defined by comparing the kinetics of their neutralization by rabbit antisera against a range of strains. Successive isolants from the same person frequently varied antigenically, but not in a regular manner. Variations could not be correlated with sequence or temporal proximity of recurrences, or with labial sites of lesions. The data substantiated a previously proposed classification of the majority of HSV strains into four serogroups, and indicated existence of two additional serogroups. Neutralization kinetic analysis of the reactions of eight strains from two of the subjects with five samples of their own sera likewise showed that successive isolants from the same individual are not necessarily identical. Relative rates of neutralization indicated that antibody specific for the HSV isolant associated with a given recurrence of herpes labialis is demonstrable in the subject's serum within 18 to 30 hr after the lesion appears. The respective serologic relationships, however, did not correlate with those established by rabbit antisera, and varied with different serum samples from the same person.
On the Mechanism of Adjuvant Action of Nonspecific Stimulators of Antibody Formation
Authors: Uchitel I. Ya. , Khasman E. L.
Published: January 2023

During recent years, the majority of investigators has been inclined to think that the adjuvant action of different substances is the result of their influence on the cells producing antibodies. However, there is no unity of opinion either on the nature of the changes occurring in the cells, or on their importance for antibody formation.

Opinions have been voiced that adjuvants stimulate the cells to absorb the antigen, with or without subsequent phagocytosis; or that they facilitate the liberation of antibodies or, finally, that they augment the total cellular capacity to produce antibodies (1, 2).

Some investigators attach great importance to the cellular hyperplasia sometimes observed after the administration of adjuvants (3, 4), although after the introduction of endotoxin cellular alterations may be absent (5).
Intracellular Distribution and Degradation of Bacteriophage in Mammalian Tissues
Authors: Uhr Jonathan W. , Weissmann Gerald
Published: January 2023

Following i.v. injection into guinea pigs or rabbits, bacteriophages T2 and φX 174 become associated with the large granule fraction of organs with an active reticuloendothelial system. One hour after injection, it was possible to release plaque-forming bacteriophage from the large granule fraction of guinea pig liver by lysing the granules in vitro with lysolecithin, an agent which disrupts membranous organelles. Forty-eight hours after injection of bacteriophage, the absolute number of plaque-forming units within large granules of liver had decreased, but these fractions were more immunogenic than after 1 hr, suggesting that metabolism preceded immunogenicity. Treatment of guinea pigs with excess vitamin A, an agent known to disrupt lysosomes of these large granule fractions, prolonged the 19 S antibody response to bacteriophage φX. Since the duration of the 19 S antibody response is antigen dependent, these findings support the hypothesis that the sequestration and proper degradation of antigens within lysosomes (or phagolysosomes) are necessary steps in the sequence of events leading to antibody formation.
Topography of Synthesis of S and V Antigens of Sendai Virus
Authors: Zhdanov V. M. , Azadova N. B. , Uryvayev L. V.
Published: January 2023

S antigen of Sendai virus is synthesized in the nucleoli of infected cells and is then transported to the cytoplasm. V antigen of Sendai virus is synthesized in the perinuclear zone of the cytoplasm and moves to the periphery of the cell where S and V components are assembled and mature virus particles are formed. Treatment with proflavine does not affect the synthesis of either antigen but prevents the transportation of S antigen from nucleoli to the cytoplasm.
Association of the Lysosomes of the Reticuloendothelial System with Mouse Anaphylaxis
Authors: Treadwell Perry E.
Published: January 2023

Following anaphylactic reactions induced with mouse antibody-antigen complexes in mice there appears a significant increase in acid phosphatase activity in the plasma and a decrease in three representative lysosomal enzymes of the liver. Intravenous injection of this enzyme fraction causes typical anaphylactic signs without desensitizing to further anaphylactic shock. The results are consistent with the hypothesis that lysosomes of the reticuloendothelial system are involved in anaphylactic shock in the mouse.
Serologic Studies of Primary Epidemic Typhus and Recrudescent Typhus (Brill-Zinsser Disease)
Authors: Murray Edward S. , O'Connor Jane M. , Gaon Jakob A.
Published: January 2023

Summary and Conclusions

The major Rickettsia prowazeki antibody present in sera obtained from primary epidemic typhus patients between 11 and 58 days after onset of illness is 19 S. This is illustrated by the facts that a) the R. prowazeki agglutination titers of such sera are markedly reduced by contact with the sulfhydryl compound 2-mercaptoethanol and b) when such sera are subjected to electrophoresis and then diffused against a sonic vibrated R. prowazeki antigen, they form typical 19 S γ-globulin precipitin lines. The major R. prowazeki antibody present in sera obtained from Brill-Zinsser disease patients between 8 and 24 days following onset of illness is 7 S. This is illustrated by the facts that a) the R. prowazeki agglutination titers of such sera are unaffected by the sulfhydryl compound 2-mercaptoethanol and b) when such sera are subjected to electrophoresis in agar and then diffused against the supernatant of a sonic vibrated R. prowazeki antigen, they form typical 7 S γ-globulin precipitin lines. Various relationships of 19 S and 7 S antibodies to typhus immune responses are discussed.
Relationship between Blood Clearance and Viruria after Intravenous Injection of Mice and Rats with Bacteriophage and Polioviruses
Authors: Schultz Irwin , Neva Franklin A.
Published: January 2023

The relationship between viremia and viruria occurring within 2 hr after intravenous injection with T2 bacteriophage and polioviruses was studied in mice and rats. Poliovirus was cleared from the blood at a slower rate than phage. Blood specimens obtained at 2 hr contained approximately 104 less phage particles but only 101.8 to 102.6 TCID50 less poliovirus than inoculated. Viruria could not be demonstrated if less than 109 phage particles or 105 TCID50 of poliovirus were injected. With larger doses of virus, the incidence of viruria increased and the amount of virus in the urine tended to increase. A gradient of at least 105:1 was observed between blood and urine concentrations of poliovirus and phage. This type of viruria occurring within 2 hr after intravenous injection of large doses of virus was designated “immediate viruria.” Despite bilateral ureteral interruption in mice and rats, poliovirus viruria was demonstrated in amounts comparable to those found in sham-operated or intact animals.
The Heat-Labile Serum Factor Associated with Intracellular Killing of Staphylococcus Aureus
Authors: Li Isabel W. , Mudd Stuart
Published: January 2023

The presence of fresh serum has been shown to be required for rapid phagocytosis and intracellular killing of virulent staphylococci by human blood leukocytes (1, 2). When human serum is subjected to heating, it no longer promotes killing but still causes demonstrable phagocytosis, though slower in rate and reduced in amount. The phagocytosis-promoting ability of human serum is apparently dependent upon the presence of antibody against the staphylococcal surface antigen or antigens and is removed by adsorption with ribitol teichoic acid isolated from the staphylococcal cell wall (3). The present report deals with the results of our study on the heat-labile serum factor responsible for rapid phagocytosis and intracellular killing of staphylococci.

MATERIALS AND METHODS. Human serum and leukocytes. Fresh samples of adult human blood were obtained from healthy subjects by venipuncture. Leukocytes were prepared by dextran sedimentation and were washed and resuspended in Hanks' solution.
Mouse β1C-Globulin: Production of Antiserum and Characterization in the Complement Reaction
Authors: Mardiney M. R. , Müller-Eberhard H. J.
Published: January 2023

Highly specific antibody to mouse β1C-globulin has been produced in rabbits by injecting incomplete Freund's adjuvant containing mouse complement adsorbed onto zymosan. The production of this antisera enabled analysis of the interaction of mouse β1C-globulin with EAC′1,4,2a cells, antigen-antibody precipitates and zymosan. The data revealed that the immediate reaction product upon interaction of β1C-globulin in these in vitro immune systems was a rapidly migrating β-α2-globulin, called β1C-globulin, and that this product was then transferred into an inactive, more slowly migrating component, β1D-globulin.

Ultracentrifugal analysis showed β1C-globulin to have an s-rate of 9.5 S, β1D-globulin to have an s-rate of 6.5 S and β1G-globulin to have an intermediate s-rate. A close similarity is shown to exist between human β1C-, β1G- and β1A-globulin and their mouse homologues.
Interaction of Rheumatoid Factors with Aggregated Subunits of Human γ-Globulin
Authors: Hirose Shun-Ichi , Osler Abraham G.
Published: January 2023

Studies on the reactivity of human γ-globulin for the human rheumatoid factors suggest that the specificity of this reaction derives in part from the aggregated state of the γ-globulin and its component H chains. Native γ-globulin exhibits little, if any, reactivity in hemagglutination or gel diffusion experiments. Aggregated L chain preparations are likewise inactive. In contrast, heat-aggregated γ-globulin and turbid H polypeptide chains, as well as heat-aggregated F and S fragments, react with human rheumatoid factors. The inference has been drawn that the antigenic activity of human γ-globulin, or its subunits, for the rheumatoid factors is intimately associated with a change in the secondary or tertiary structure of these molecules which occurs on aggregation.
Studies on Adenovirus-12
Authors: Smith Kendall O.
Published: January 2023

Suspended KB cells can adsorb the majority of adenovirus particles in a suspension within 20 min. No detectable quantity of virus particles disappears within 1 hr after inoculation. Particles are still physically recognizable at 2 hr, but most have lost their infectivity. New virus appears at about 19 hr after inoculation and is formed at a uniform rate until about 54 hr. Ultimately, about 6700 particles and 67 50% tissue culture infectious doses (TCID50) are produced per infected KB cell. The formation of complement-fixing (CF) antigen roughly parallels the production of virus particles and infectious virus units. Over 98% of the countable virus particles and all of the measurable CF antigen remain intracellular throughout the growth cycle.

Density gradients are sensitive indicators of new virus formation, viral bands being clearly visible early in the growth cycle. Particles from gradients having a density of 1.34 or higher are highly infectious (1 particle in 5 to 8 is infectious), whereas those having densities of less than 1.29 are practically noninfectious (only 1 particle in 500 to 1000 is infectious).

Assembled or partially assembled virus particles account for no more than about 6% of the complement-fixing activity of crude, infected cell lysates. The remainder of the activity is in the form of very small, low density viral subunits. Purified virus having a density of 1.33 to 1.34 is not potent as CF antigen, more than 5 × 109 particles/ml being required for reaction. Ragged, partially assembled particles are somewhat more reactive, about 3 × 109 particles/ml being required to give a positive CF test. Artificially disrupted particles, showing a large number of capsomeres and a few short strands, are 4 to 8 times more potent as CF antigen than are intact particles.

Electron microscopic examination of crude, infected cell lysates shows huge quantities of unassembled viral components. It is calculated that less than one half of the CF antigenic viral materials synthesized is finally assembled into physically recognizable virus particles. Only about 1% of these particles are completed sufficiently to be infectious. Therefore, the efficiency of assembling viral elements into infectious virus particles within the KB cell is probably less than 5 parts in 1000.
Studies of Herpes Simplex Virus by the Gel Diffusion Technique
Authors: Tokumaru Tadasu
Published: January 2023

Using gel diffusion technique, four precipitating antigens were found in preparations of herpes simplex virus. These antigens differed in their particle size, rate of diffusion in agar, density, chromatographic behavior, electrophoretic mobility and susceptibility to the destructive effects of various physical and chemical agents. All of these antigens elicited neutralizing antibodies when injected in laboratory animals.
Studies on Mouse Antibodies
Authors: Adler Frank L.
Published: January 2023

Summary and Conclusions

Mice injected once with ovalbumin or ferritin in Freund's adjuvant responded by producing 19 S and 7 S antibodies. Although 19 S antibody production continued for several months, the relative proportions of 7 S to 19 S changed from 5 to 1 at 2 weeks after immunization to 150 to 1 after 11 weeks. Sera that contained mainly 7 S antibody lost, upon reduction and alkylation, much of their aggregative efficiency and some of their precipitable antibody. The antibody in such reduced sera has been shown to combine promptly with antigen to form soluble complexes. That the effect of the reducing agent on aggregative properties was upon the antibody proper has been shown by experiments in which possible effects upon combining complement were shown to be irrelevant. It has also been shown that original activity was restored to treated serum by oxidation.

Reduced antisera against ferritin failed to agglutinate tanned cells coated with ferritin unless the concentration of ferritin used in coating of the cells was increased 10-fold above that needed to sensitize cells to agglutination by control sera. Complement fixation by reduced 7 S antibody has been shown to be diminished, especially when it was studied in dilute systems and at 37°C.
Antigenic Analysis of Virulent and Attenuated Type I Polioviruses by Quantitative Complement Fixation
Authors: Gerber Paul , Birch Suzette M.
Published: January 2023

The antigenic character of a neurovirulent Type I poliovirus and its attenuated mutant were analyzed by means of a quantitative complement fixation (CF) test. This technique yielded highly reproducible results and clearly distinguished the two virus strains in reciprocal cross-reactions.

In contrast to the results obtained by the quantitative CF test no significant difference was found in the neutralization rate between anti-Mahoney serum and the two viruses.
Immunochemical Properties of Human γA Isohemagglutinin
Authors: Ishizaka Kimishige , Ishizaka Teruko , Lee Evelyn H. , Fudenberg Hugh
Published: January 2023

Isohemagglutinins were detected in pure γA-globulin (IgA), γM-globulin (IgM) and γG-globulin (IgG) fractions of sera from normal and immunized human subjects. The anti-A isoagglutinin in the immune sera was associated with both polymer and monomer forms of IgA. On a weight basis, the polymer form IgA antibody and IgM antibody had comparable hemagglutinating activities. The hemagglutinating activity of the monomer form IgA antibody was lower than that of the polymer form antibody, but higher than that of IgG antibody. The hemagglutinating activity of both polymer and monomer forms of IgA isoagglutinins was markedly diminished by reduction and alkylation.

In contrast to the IgG and IgM isoagglutinins, the IgA isoagglutinins did not hemolyze homologous red cells with either guinea pig or human C′. The IgA isoagglutinin did not sensitize guinea pig skin for passive cutaneous anaphylaxis.
Local Cellular Antibodies
Authors: Thonard John C. , Dalbow Milton H.
Published: January 2023

The gingival tissues of conventionally reared rats and guinea pigs were challenged antigenically with whole sheep erythrocytes. Upon sacrifice, cell suspensions of spleens and gingivae were prepared and assayed for antibody production according to the plaque technique of Jerne. Antibody-forming cells were found in approximately 50% of the inoculated gingivae. Circulating hemolysins were found in the sera of all rats and over 80% of the guinea pig sera. It is concluded that antibody production, associated with indigenous cells, can take place in suitably stimulated oral mucosa; the origin of these immunologically competent cells remains a matter for conjecture.
Detection of Two Antibodies in Single Plasma Cells by the Paired Fluorescence Technique
Authors: Hiramoto R. N. , Hamlin M.
Published: January 2023

The concept that a single antibody-forming cell may have the capacity to synthesize more than one antibody simultaneously was tested. This problem was approached by using a single antigen on which two determinant groups could be detected. Guinea pigs were hyperimmunized with a column-purified human γ-globulin preparation. Animals showing antibodies that reacted with a single band to the whole antigen but with two bands to the papain-digested antigen by immunoelectrophoresis were sacrificed and the spleen sections studied to see if any single cell was responding with two antibodies to both fragments of the whole antigen. A multiple antibody response in individual cells was detected using the sensitive indirect paired fluorescence technique.

From a total of 482 antibody-containing cells counted, 30% had antibodies directed toward the CP-I fragment and 24% to the CP-II fragment. It appeared that about 45% of the cells contained antibodies directed to both the CP-I and CP-II fragments. The gradation of colors caused by the combination of tetramethylrhodamine and fluorescein conjugates in the multiple antibody-producing cells and the selective quenching studies of fluorescence at pH 4.0 indicate that different cells contained different amounts of one type of antibody over the other.
Subtypes of Bence-Jones Proteins
Authors: Nachman Ralph L. , Engle Ralph L. , Stein Stefan
Published: January 2023

Antigenic differences among Bence-Jones proteins within each major type have been demonstrated. This heterogeneity appears to be independent of the Inv (a) type. At least two subtypes were demonstrated among the proteins in the panels of Type K and Type L proteins studied.
Modification of Runt Disease by Treatment of the Donor with Lyophilized Tissues
Authors: Schlesinger Michael , Goitein Ruth
Published: January 2023

The effect of pretreatment of C57BL mice with lyophilized tissues of RIII or Swiss mice on the capacity of their spleen cells to induce runt disease in newborn recipients of these strains was studied. Pretreatment with a transplantable RIII tumor (MMCIA) did not affect the induction of runt disease in RIII mice by large doses of C57BL spleen cells, but increased the incidence of the disease induced by small doses of cells. The mean survival time of mice injected with small doses of cells from either normal or pretreated C57BL donors was longer than that of mice receiving large doses of cells. Spleen cells from pretreated donors had a lower capacity than cells from normal donors to induce runt disease in 2- to 3-day-old RIII recipients. Pretreatment of C57BL donors with Swiss mouse tissues specifically decreased their capacity to induce runt disease in newborn Swiss mice. Surviving Swiss mice did not tolerate C57BL skin grafts and no C57BL antigens could be demonstrated in their spleens.
Immunochemical Study of Antigenic Specificity in Delayed Hypersensitivity
Authors: Leskowitz S. , Jones V. E.
Published: January 2023

Hapten-specific delayed hypersensitivity of guinea pigs was suppressed by a variety of hapten-amino acid and hapten-protein conjugates. Suppression was short-lived when the conjugate carried one, two or three arsanilate groups but lasted longer than 11 days when larger carrier molecules with more arsanilate groups were injected. These results were interpreted as meaning that larger conjugates reacted with and used up the supply of reactive moiety in delayed sensitivity, while smaller conjugates were only inhibitory by virtue of reversible binding with the same entity.
The Immunoglobulin Sequence
Authors: Sahiar Khurshed , Schwartz Robert S.
Published: January 2023

The local administration of bovine γ-globulin (BγG) to rabbits evoked a characteristic sequence of immunoglobulin synthesis: γM antibodies followed by γG antibodies. This progression of the immune response was disrupted by 6-mercaptopurine (6-MP), and rabbits so treated produced low titers of γG antibodies but normal amounts of γM antibodies. The period of γM synthesis was abnormally prolonged in 6-MP-treated rabbits. Passively infused, specific, reactive γG anti-BγG antibodies arrested the formation of γM anti-BγG antibodies in normal and 6-MP-treated rabbits. A second dose of antigen given to 6-MP-treated rabbits resulted in the rapid appearance of γG antibodies and the cessation of γM antibody synthesis. Splenectomized rabbits given a local injection of BγG had enhanced levels of γG antibodies. Splenectomy abolished the disruptive effects of 6-MP on the immunoglobulin sequence. The results of these experiments indicate: a) the process of γG antibody synthesis is more susceptible to the anti-metabolic action of 6-MP than that of γM formation; b) γG antibody exerts a negative feedback effect on the formation of γM antibody; c) antigen may play a direct and intimate role in the actual synthesis of γG antibodies; and d) under certain conditions, the spleen may inhibit the production of γG antibodies.
An Albumin and γ-Globulin Characteristic of Bovine Cerebrospinal Fluid
Authors: MacPherson Catherine F. C. , Saffran Murray
Published: January 2023

Immunoelectrophoretic experiments using a rabbit antiserum to bovine CSF to develop the patterns have shown that a characteristic albumin and a γ-globulin exist in bovine CSF. Both proteins can also be demonstrated in saline extracts of calf brain. This finding suggests that certain as yet unknown neurosecretory cells of the brain are the source of these proteins.

The bovine γc-globulin is analogous to the γc-globulin of human CSF in that it exists in two molecular forms with different electrophoretic mobilities but the same immunologic specificities.

From visual inspection of the immunoelectrophoretic patterns of CSF from immature and mature animals, it would appear that the CSF of the young animal contains more γc-globulin and less γG-globulin than the CSF of the adult.
Adenovirus-Antibody Agglutination Reactions
Authors: Smith Kendall O. , Trousdale Melvin , Gehle Warren
Published: January 2023

Adenovirus particles agglutinate in the presence of optimal proportions of type-specific antisera. Reactions can be visualized either by electron microscopy or, if virus concentrations are sufficiently high, in test tubes with the unaided eye. Virus-antibody complexes are characteristically leaf-like, and are usually composed of only one layer of particles. The width of the fringe (probably antibody molecules) surrounding particles after reaction with antiserum averaged 33 mµ. Agglutination cross-reactions occur between adenovirus types 12 and 18, but other adenoviruses tested (types 1, 2, 3 and 7) agglutinate only with their own antiserum.
Mast Cells and Local Resistance to Russell's Viper Venom
Authors: Higginbotham R. D.
Published: January 2023

It was observed that the subcutaneous injection of Russell's Viper venom initiated an explosive release of heparin-containing granules from local tissue mast cells and that the shed granules were subsequently ingested by fibroblasts and various other cell types involved in the connective tissue response to venom injury. Investigations of the significance of these cellular events indicated that heparin can form acid-base complexes with noxious factors of the venom in vitro and inhibit both local and systemic injury by this venom in mice. Inasmuch as this antivenom effect of heparin is only one aspect of a more general antitoxic activity of this mucopolysaccharide, it is suggested that the degranulation of mast cells may serve an important function in local resistance to injury by various cationic substances.
Accelerated Graft Rejection in the Offspring of Immunized Mothers
Authors: Stastny Peter
Published: January 2023

Infant rats born of mothers sensitized prior to and during pregnancy displayed a) a state of delayed hypersensitivity as manifested by skin reactions to tuberculin in 26% of animals born of mothers immunized with tubercle bacilli and b) a state of homograft immunity manifested by accelerated rejection of donor homografts in infants born of homografted mothers.

Participation of maternal cells in the rejection of homografts in infants was excluded in an experiment in which highly tolerant mothers were used. Accelerated rejection was observed in infants of these mothers after the latter had been injected with trypsinized skin cells. The most likely basis for the accelerated graft rejection appeared to be a process of active immunization resulting from passage of antigen across the placenta.
Changes in Mouse Serum Proteins during Acute and Chronic Infection with an Intracellular Parasite (Toxoplasma Gondii)
Authors: Remington Jack S. , Hackman Robert
Published: January 2023

Electrophoretic and immunoelectrophoretic patterns of mouse serum proteins are markedly altered during the course of the acute and chronic stages of infection with virulent and relatively avirulent strains of Toxoplasma gondii. In mice infected with the virulent RH strain, there was a remarkable increase in α- and β-globulins and decrease in albumin. Immunoelectrophoretic patterns of serum and peritoneal fluid of these animals revealed a marked increase in haptoglobin, conversion of β1C to β1D, disappearance of two major β-globulin precipitin arcs, and an increase in mobility of albumin. Similar but less marked changes were noted in some of the groups of animals infected with less virulent strains. In mice infected with strains M7741 and H44 a state of “chronic” hypergammaglobulinemia developed. Challenge of chronically infected mice with the original avirulent strain or with the RH strain resulted in very high levels of γ-globulins in the absence, in most animals, of significant rises in serologic test titers. Adsorption of such sera with proliferative organisms resulted in disappearance or marked decrease in antibodies but had no demonstrable effect on γ-globulin levels.

These findings are discussed in relation to the chronic infection in animals and humans, and an hypothesis is posed suggesting the existence of a form of the parasite other than the cyst to account for persistent antibody formation, hypergamma-globulinemia and parasitemia.
Enhancement of Immune Responses in Mice by a Booster Injection of Coccidioides Spherules
Authors: Kong Yi-Chi M. , Savage D. C. , Levine H. B.
Published: January 2023

Induced immunity to Coccidioides immitis in mice challenged intranasally was enhanced greatly by the injection of a booster dose of 20 to 200 µg of killed spherules; fungal multiplication was suppressed up to 5 million-fold and 60 to 75% of boosted mice harbored no organisms in their lungs at 10 to 90 days postchallenge with arthrospore doses as high as 100 LD50. Enhancement of immunity was most pronounced when the booster injection was given at >2 months postvaccination and 6 to 7 days before challenge and was not induced by injecting another fungus, Cryptococcus neoformans.

Low numbers of C. immitis in the lungs of boosted mice reflected marked clearance activity during the first 3 days postchallenge. In contrast, clearance activity during this period was less in nonboosted mice and was observed only in those vaccinated <2 months before challenge. Additionally, enhanced clearance in the lungs of boosted mice was paralleled by an early rise in numbers of inflammatory cells obtained by tracheobronchial wash; total cell numbers reached a maximum 2 to 3 days earlier in boosted than in nonboosted mice.

Despite the demonstration of precipitins, attempts to transfer immunity passively with serum were unsuccessful. However, less fungal multiplication occurred after challenge in nonvaccinated recipients of live splenic cells from boosted mice than in recipients of live cells from normal mice or killed cells from boosted mice. The role of cells or serum in immunity was difficult to assess in passive transfer studies, because injection of normal splenic cells, their carrier fluid, or normal serum into intranasally infected mice often potentiated their infection.
Problems Encountered in Double Diffusion Analysis in Agar of Hapten Specific Immune Systems
Authors: Paul William E. , Benacerraf Baruj
Published: January 2023

Complement-independent precipitin lines in double diffusion analysis of anti-hapten sera and hapten protein conjugates may show spurs within a single haptenic system. This phenomenon is observed when anti-DNP antibodies are analyzed with DNP conjugates with different numbers of haptenic groups. A spur is observed when the line formed by the highly conjugated antigen joins the line of the lesser conjugated antigen. This phenomenon is explained by the formation of soluble antigen-antibody complexes between antibody and DNP-BSA of relatively low degree of conjugation which are precipitated by DNP-BSA of high degree of conjugation. A similar finding is observed with the cross-reacting haptenic system—pentaCIB-DNP. An anti-pentaCIB serum causes the formation of a precipitin line with highly conjugated DNP-BSA which spurs over that formed with pentaCIB-BSA conjugated to a lesser degree. In anti-hapten systems spur formation of complement independent precipitin lines is not entirely predictable upon the basis of antigenic relationship.
Antigenicity of Polypeptides (Poly-α-Amino Acids)
Authors: Maurer Paul H.
Published: January 2023

It has been shown that immediate and delayed sensitivities to the synthetic polymers Glu36Lys24Ala40 and Glu36Lys24Ala35Tyr5 can persist in humans for years in the absence of detectable precipitable antibody. Of the new polymers not previously tested in man, the polymer Glu60Ala30Tyr10 composed of L-amino acids and the three polymers of Glu42Lys28Ala30, in which one of the amino acids was of D and two were of the L configuration, were not immunogenic in man following five intramuscular injections in a period of 10 days, whereas Glu42Lys28Ala30 and Glu36Lys24Ala35Tyr5, made of L-amino acids, were very effective immunogens. The specificity of the response was shown by the lack of in vivo or in vitro corss-reactions of the polymers with D-amino acids with the individuals sensitive to the Glu42Lys28Ala30 or Glu36Lys24Ala35Tyr5 made solely of L-amino acids.
Influence of Corticosteroid Therapy on Serum Complement, Agglutinins, Free-Boundary Electrophoresis, Total Protein and Blood Counts in Dogs with Staphylococcal Bacteremia
Authors: Baltch Aldona L. , Lepper Mark H. , Lolans Valentina T.
Published: January 2023

Corticosteroid administration in experimental staphylococcal bacteremia in dogs: Helped to maintain a bacteremic state.Caused a most severe clinical illness, debilitation and weight loss, sometimes terminating in death.Caused the most prominent drop in hematocrit and rise in white blood cell count.Altered serum complement levels by causing them to decrease and/or prevented the occurrence of an expected increase seen in dogs receiving no corticosteroids.Had no influence on the development of Staphylococcus aureus agglutinins.Caused a less prominent total protein increase and a more rapid return to normal than those observed in dogs receiving no corticosteroids.Caused a prominent drop of serum albumin and increase in α3-globulin with these changes returning back to normal more rapidly than in experimental animals receiving no corticosteroids.
Studies on the Mechanisms of Hypersensitivity Phenomena
Authors: Lichtenstein Lawrence M. , Osler Abraham G.
Published: January 2023

The serum from allergic individuals inhibits the antigenically induced release of histamine from sensitive human leukocytes. This is in contrast to the effect of normal serum, which enhances histamine release. On the basis of this observation, an in vitro method for the study of the reaction between ragweed antigen and the anti-ragweed activity contained in allergic sera has been presented. Over a wide range of antigen concentrations, an allergic serum binds a constant percentage rather than a constant quantity of the added antigen. This outcome is demonstrated to be predictable from the mass action law under the limiting condition of extreme antibody excess. Kinetic and multiplicity studies of the reaction are compatible with this formulation.

Determinations of the antigen-neutralizing capacity of allergic sera provide an index of those immunoglobulins in allergic serum which possess anti-anaphylactic properties. The results of these determinations differ only slightly when performed on the cells of the different allergic donors. In agreement with this observation is the demonstration that the concentration of cell-bound antibody is considerably less than that of serum antibody and does not compete with the latter for antigen.

Antigen-neutralizing activity has been demonstrated in every allergic serum tested, irrespective of previous desensitization therapy. The level of this activity in a group of untreated individuals and its increase as a result of immunization has been presented.
Role of Interferon during Viremia
Authors: Baron Samuel , Buckler Charles E. , Friedman Robert M. , McCloskey Richard V.
Published: January 2023

Circulating interferon was shown to protect mice against intracerebral challenge with encephalomyocarditis or vesicular stomatitis viruses, against intraperitoneal challenge with Germiston virus and intradermal infection with vaccinia virus. The possibility that circulating interferon provides similar protection during natural infection, is considered.
The Allergic Response to Stinging Insects: Biochemical and Immunologic Studies on Bee Venom and Other Bee Body Preparations
Authors: Shulman Sidney , Bigelsen Fred , Lang Raymond , Arbesman Carl
Published: January 2023

Bee venom obtained by a method of electric shock contains a purer antigenic fraction than is found in extracts of dissected venom sacs, for the venom sac extract contains larger quantities of body antigen than is found in venom itself.

Bee venoms from the United States, Mexico, England and Germany, seem to be antigenically identical.

Bee venom contains only one prominent antigenic component, and this component is specific for venom. It could not be found in the body.

Bee venom obtained by stinging contains body antigens in trace amounts that could be found only by hyperimmunizing rabbits and allowing the antisera to react with body extracts.

The trace body components found in bee venom may originate in the excreta or other debris deposited on the nylon cloth by bees during the act of stinging.
The Stability of Neutralization of Poliovirus by Native Antibody and Enzymatically Derived Fragments
Authors: Keller Robert
Published: January 2023

The neutralization of poliovirus infectivity by enzymatically derived rabbit antibody fragments has been examined. Although univalent fragments prevented the adsorption of virus on cells and inhibited the infectious capacity of cell-adsorbed virus as efficiently as native γ-globulin, the pepsin-digested (5 S) bivalent fragments and pepsin-digested reduced (3.5 S) univalent fragments were progressively less stable in the maintenance of virus neutralization.

Evidence has been presented that antibody fragments are able to abolish the infectivity of large concentrations of poliovirus prior to dilution. On the other hand, the development of neutralized virus-antibody complexes stable to dilution at neutral pH was considerably slower with univalent antibody fragments than with intact γ-globulin. Moreover, mature neutralized complexes of antibody fragments and virus were more readily reactivated at moderately acidic pH than those with intact γ-globulin. On this basis, it is proposed that the difference in the virus neutralizing activities between native antibody and antibody fragments is due to the reduced capacity of antibody fragments to develop stable unions with virus. These findings are presented as evidence that virus neutralization is not only a function of the antigen-binding sites of the antibody but is dependent on the entire structure of the γ-globulin molecule.
The Immunologic Competence of Mouse Thymus Cells Measured by the Graft vs. Host Spleen Assay
Authors: Sosin Henry , Hilgard Henry , Martinez Carlos
Published: January 2023

The thymus gland has been shown to be directly involved with the development of peripheral lymphatic system. The mechanisms of this relationship are not understood; however, many investigators believe that thymic cells are directly “seeded” to peripheral lymphatic tissues. The present investigations test the immunologic competence of the murine thymus cell itself. Thymus cell suspensions from newborn and adult mice were assayed for immunocompetence by the spleen assay method and compared with the competence of spleen cells from mice of similar ages. Thymus cells from both new born and adult animals were found to be competent, whereas spleen cells from newborn animals showed no immunologic reactivity. A-strain adult spleen cells were found to be approximately ten times as reactive as A-strain thymus cells.
Vaccination against Human Leprosy Bacillus Infections of Mice: Protection by BCG Given during the Incubation Period
Authors: Shepard Charles C.
Published: January 2023

The experimental infection of mice with Mycobacterium leprae and the natural infection of humans have uniquely long incubation periods. To see whether vaccination given during the incubation period of the experimental infection would provide protection, groups of mice were given one or two injections of BCG vaccine at intervals before or after they were challenged with M. leprae. The amount of protection was assessed by microscopic counts of M. leprae in the tissues 7 and 10 months after challenge, at a time when the leprosy infection had developed in the controls. It was found that vaccine given 1 or 2 months before challenge afforded the amount of protection observed previously with this schedule. Vaccines given just after challenge provided no protection. Vaccines given progressively later during the incubation period (closer to the logarithmic phase of growth of M. leprae) caused increasing protection, up to the same level as that provided by vaccine given 1 or 2 months before challenge. These changes in the amount of protection according to the schedule of the vaccine suggest that the vaccines exert their effect on M. leprae shortly after challenge or during its logarithmic phase, and that vaccine protection in the mouse usually deteriorates in a few months. Evidence from the literature on vaccination against M. tuberculosis indicates that protection afforded to man would last very much longer, so that BCG vaccine given early or late in the incubation period of leprosy in humans would be expected to provide protection.
Heterogeneity of Immune Anti-A Antibody in Relation to Forssman Antigen
Authors: Yokoyama Mitsuo , Fudenberg H. H.
Published: January 2023

Guinea pig antigen, sheep red cells (type R), human group A1 red cells and soluble specific blood group substance A contain a similar A-like antigenic determinant. The A-like antigen of certain pig red cells (API) reacts with “immune” but not with “naturally occurring” anti-A antibody in human serum. Pig Ap red cells also absorb anti-sheep red cell hemolysin from human sera containing “immune” anti-A antibody, but not from those containing “naturally occurring” anti-A; furthermore, such cells do not absorb the anti-sheep red cell hemolysin present in immune rabbit serum. These results suggest that immune group O sera may contain an antibody specific against both A antigen and Forssman antigen.
Hemagglutination-Inhibiting Antibody Responses in Human Infections with Group B Coxsackieviruses
Authors: Schmidt Nathalie J. , Lennette Edwin H. , Dennis Juanita
Published: January 2023

Hemagglutination-inhibiting (HI) antibody responses for coxsackievirus types B1, B3 and B5 were compared with neutralizing antibody responses with respect to sensitivity, specificity and diagnostic value in patients with and without coxsackievirus infections. Most sera possessed nonspecific inhibitors for hemagglutinins of these viral types, but treatment of sera with filtrates from a psychrophylic Pseudomonas sp. was found to be highly effective for removing such inhibitors; this treatment appeared to have little or no detrimental effect on specific antibody. HI tests on treated sera were comparable to neutralization tests in diagnostic value, with 46% of patients with isolations of coxsackievirus types B1, B3 and B5 showing significant rises in homotypic antibody titers by both tests. Heterotypic antibody rises seen in HI tests on treated sera corresponded with those observed in neutralization tests. HI antibody was rarely observed in treated sera in the absence of neutralizing antibody for the corresponding viral type.
A Hemagglutination Test and a Specific Depolymerase for Studying Immunologic Paralysis in Mice
Authors: Brooke Marcus S.
Published: January 2023

The specificity of a hemagglutination test for detecting antibodies against the polysaccharide of type III Diplococcus pneumoniae (SIII) and the ability of a specific depolymerase to clear the SIII from the blood of mice are described. Mice injected with relatively large quantities of SIII are specifically prevented from responding to further immunogenic doses of that antigen.

The response of different strains of mice injected with varying quantities of SIII is compared on the basis of the hemagglutination and challenge tests.
Pathogenesis of Experimental Cholera: Biologic Activities of Purified Procholeragen A
Authors: Finkelstein Richard A. , Atthasampunna Pongsom , Chulasamaya Monthree , Charunmethee Pichai
Published: January 2023

Procholeragen A, a choleragenic moiety elaborated by Vibrio cholerae 569 B Inaba, has been concentrated and partially purified by gel filtration with Sephadex G-200. Purified Procholeragen A, which is essentially free of cholera endotoxin but still not pure, gives a single zone of precipitation with rabbit anti-choleragen antibody adsorbed with live vibrios and causes experimental cholera when amounts as little as 6.0-µg are administered, with Procholeragen B, per os in infant rabbits. When inoculated intradermally in adult rabbits in 0.1 to 0.2-µg amounts, it causes a delayed but sustained local erythematous edematous induration which fixes intravenous Evans blue dye. Procholeragen B, which was formerly considered to be essential for the activity of Procholeragen A, simply serves to protect the latter against destruction under acid conditions in the stomach and can be replaced by a variety of buffers. Procholeragen A causes experimental cholera when inoculated, by itself, into the small bowel of infant rabbits. On the basis of the experimental observations, it is suggested, as an operational concept, that an increase of villus capillary permeability, as a consequence of the direct action of a Procholeragen A-like factor elaborated by cholera vibrios in the small intestines, is a major factor in the pathogenesis of cholera.
Further Studies on Acquired Resistance to Murine Cryptococcosis: Enhancing Effect of Bordetella Pertussis
Authors: Abrahams Irving
Published: January 2023

The adjuvant effects of Bordetella pertussis and Freund's adjuvant were compared in mice vaccinated with killed cryptococcus cells. B. pertussis greatly enhanced the immune response, causing the survival rate to increase from the 65 to 70% observed in mice immunized with cryptococcus cells alone to 95 to 100% in animals treated with both cryptococcus and pertussis vaccines. In contrast, Freund's complete adjuvant actually decreased the response to cryptococcus vaccine.

Tests for antibodies in pooled sera collected at intervals following immunization with cryptococcus plus pertussis vaccine or with cryptococcus cells alone were uniformly negative. Actively immunized mice with no demonstrable humoral antibodies inhibited fungal cell multiplication in their tissues more successfully than passively immunized mice with measureable amounts of serum agglutinins. These findings suggest that the protective mechanism in mice actively immunized by these procedures exists primarily at the cellular level.