bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoglobulins of the Rhesus Monkey (Macaca Mulatta)
Authors: Lakin James D. , Patterson Roy , Pruzansky Jacob J.
Published: December 2022

Separation of rhesus monkey IgG and IgM anti-bovine serum albumin (BSA) antibody from other immunoglobulin components of hyperimmune whole serum was accomplished by a combination of ammonium sulfate precipitation, diethylaminoethyl cellulose and Sephadex G 200 chromatography. Neither the IgG nor the IgM antibody preparations sensitized normal rhesus monkey skin for Prausnitz-Küstner type passive cutaneous transfer reactions. However, IgG anti-BSA antibody was shown to sensitize guinea pig skin for passive cutaneous anaphylaxis whereas IgM antibody of equal antigen-binding capacity did not. The relative efficiency of rhesus IgM anti-BSA in tanned red blood cell hemagglutination was found to be more than 23 times greater than that of an equal amount of IgG, as measured by BSA-binding capacity. In contrast, the ability of IgM to participiate in the precipitin reaction with soluble BSA was found to be poor in comparison to that of IgG antibody.
Induction of Tolerance in Immunologically Competent Primates
Authors: Howard Richard J. , Landon John C. , Dougherty Suanne F. , Notkins Abner L. , Mergenhagen Stephan E.
Published: December 2022

Immunologic tolerance has been induced in mice, rats, guinea pigs, rabbits and chickens with protein and polysaccharide antigens (1, 2). In addition, tolerance has been produced in fetal rhesus monkeys with large doses of bovine γ globulin and in newborn humans with blood group antigens (3, 4). However, the induction of immunologic tolerance has not been reported in older primates. We report here the induction of tolerance to human γ globulin (HGG) in immunologically competent monkeys.

Six-month- and one-year-old rhesus monkeys (Macaca mulatta) were bred and maintained at Bionetric Research Laboratories, Inc., Kensington, Maryland. In the first experiment, 6-month-old monkeys weighing 1500 to 2000 g were used. Animals were treated in a manner similar to that used to induce tolerance in adult mice (5, 6). Ten milligrams of HGG/ml (Cohn Fraction II, Hyland Laboratories, Costa Mesa, Calif.) in pyrogen-free saline was centrifuged for 2 hr at 105,000 × G in a Spinco model L-2 ultracentrifuge to remove aggregated proteins.
Studies on the Mechanism of the Suppression of Active Antibody Synthesis by Passively Administered Antibody
Authors: Chang Henry , Schneck Sidney , Brody Neil I. , Deutsch Alice , Siskind Gregory W.
Published: December 2022

F(ab′)2 and Fab′ anti-DNP antibody fragments suppressed anti-DNP antibody formation. The fraction of anti-DNP antibody elutable from a specific precipitate by p-nitrophenyl-ε-aminocaproic acid (p-NP-EACA) suppressed anti-DNP antibody formation but did not alter the percentage of the anti-DNP antibody that could be eluted with p-NP-EACA.

The data are consistent with the concept that passively tranferred antibody causes suppression by binding antigen thus preventing it from stimulating potential antibody-forming cells.
Delayed Hypersensitivity to Purified Streptococcal M Protein in Guinea Pigs and in Man
Authors: Beachey Edwin H. , Alberti Humberto , Stollerman Gene H.
Published: December 2022

Purified M antigen extracted from Group A streptococci was not homogeneous but was distributed among several molecular populations of protein. The type-specificity of delayed hypersensitivity to a selected single population of M protein, which appeared immunochemically pure, was studied. The majority of normal human adults showed delayed skin hypersensitivity to the highly purified fractions of both rare and common M serotypes with equal frequency. Similar delayed skin reactions were elicited often in normal adult guinea pigs. Like human infants, baby guinea pigs were more tolerant to purified M protein, and in these young animals type-specific delayed allergy could be demonstrated soon after immunization with a single dose of purified M protein in Freund's complete adjuvant. Weak cross-reactions between M serotypes were observed in some animals suggesting contaminating antigens of unknown nature.

Both type-specific and cross-reactive delayed hypersensitivity were confirmed by in vitro inhibition of migration of peritoneal macrophages of sensitized guinea pigs. Although some degree of type-specificity of delayed allergy was induced in young guinea pigs, the ubiquitous nature of cross-reacting determinants was apparent. the latter may constitute contaminating antigens or may be common antigenic determinants of the M moiety uncovered during purification.

The possibilities that the guinea pig model of human delayed allergy to M protein may prove useful in evaluating the purity of M protein vaccines and in studying the role of type-specific delayed hypersensitivity in immunity to streptococcal infections were discussed.
Biologic Properties of Rat Antibodies
Authors: Morse Herbert C. , Austen K. Frank , Bloch Kurt J.
Published: December 2022

Two different classes of rat antibodies have been shown to mediate the i.p. antigen-induced release of histamine. The heat-stable antibodies, associated with IgGa, involved in histamine release could be clearly differentiated from heat-labile homocytotropic antibodies. Antibodies associated with IgGa have been previously shown to mediate the antigen-induced release of SRS-A. It was not possible to dissociate the two biologic activities associated with IgGa antibodies by physical means.
Immunosuppression by Leukemia Viruses
Authors: Ceglowski Walter S. , Friedman Herman
Published: December 2022

Infection of adult BALB/c mice with Friend disease virus resulted in a marked alteration of the expected immune response to a second injection of sheep erythrocytes. Whereas normal control mice primed 4 weeks previously with sheep erythrocytes had a vigorous cellular and humoral immune response following a second injection of erythrocytes, mice infected with FDV before the booster injection had a markedly suppressed response. Both high- and low-efficiency hemolysin-forming cells, presumably due to 19 S IgM and 7 S IgG antibody, respectively, were depressed in spleens of infected mice. The appearance of 7 S PFC's was suppressed to the greatest extent.

Infection of mice with virus and antigen at the same time resulted in only a slight to moderate suppression in the number of antibody-forming cells appearing 4 days later, the day of peak response. However, by the 7th to 10th day after immunization and virus infection there was a marked depression in the number of cells forming both 7 S or 19 S plaques. When mice were injected with erythrocytes 1 month after primary immunization, and then infected with virus 2 days later, there was a stimulation in the number of 19 S and 7 S PFC's 2 days later (4th day after secondary immunization). However, by the 7th to 10th day most of the infected mice had fewer 7 S PFC's than did the controls. Splenomegaly was generally evident at this time.

Serum antibody titers in secondarily immunized mice were only slightly affected, if at all, when mice were infected with FDV either simultaneously or after immunization. Infection 3 days before immunization had a slight effect on antibody titers, whereas infection 8 days before immunization generally resulted in a significant depression. Most of the serum antibody was resistant to 2-ME treatment before and after secondary immunization, both in control and infected animals, suggesting that much of the antibody was 7 S IgG.
In vitro Antibody Synthesis by Diffusion Chamber Cultures of Spleen Cells
Authors: Vann Douglas C. , Makinodan T.
Published: December 2022

Techniques for the study of antibody production by primed antigen-stimulated spleen cells in cell-impermeable diffusion chambers have been developed. The chambers were recovered from their host animals and incubated in vitro with radioactive amino acids. Antibody production was measured by determining the amount of radioactivity which would specifically bind to erythrocyte stroma of the type used for immunization.

In addition, the effect of kiloroentgen doses of radiation on antibody production by plateau phase cultures was studied in a system in which primed spleen cells in cell-impermeable diffusion chambers were irradiated 6 days after antigen stimulation. One and three days later the chamber cultures were incubated in vitro in the presence of 14C-labeled amino acids. The incorporation of radioactivity into total extracellular proteins, γG-globulin, and specific antibody was measured. Isotope incorporation in cultures which had received 10,000 r of x-radiation was qualitatively and quantitatively similar to that by unirradiated controls—as judged by a variety of criteria. It has been shown previously that irradiation of diffusion chamber cultures of antigen-stimulated spleen cells with kiloroentgen doses of x-radiation in the plateau phase of their response leads to a purification of mature antibody-producing cells and virtually eliminates cell multiplication. It is shown here that the surviving immunocompetent cells are as efficient as unirradiated cells in synthesizing antibodies. Thus, it appears that heavily irradiated cultures of lymphoid cells should be useful for further biochemical studies of antibody synthesis and regulation.
In vitro Antibody Synthesis by Diffusion Chamber Cultures of Spleen Cells
Authors: Vann Douglas C.
Published: December 2022

The effect of free antibody on antibody production in the secondary immune response has been studied by use of antigen-stimulated primed spleen cells in diffusion chamber cultures. The cultures were exposed to high concentrations of antibody at various times after the cultures were begun, and antibody production was assayed by determining the amounts of in vitro radioactive amino acid incorporation into specific antibody. Chamber cultures implanted from the start in animals hyperimmunized to the test antigen (sheep red blood cells) failed to exhibit any significant antibody production. When the cultures were grown for 7 to 9 days in normal animals and exposed to free antibody either at the time of in vitro incubation or by transfer into hyperimmune animals for 1 or 2 days prior to the in vitro assessment of antibody production, there was no significant depression of antibody production. This was true even if the cultures were exposed to kiloroentgen doses of x-ray at the beginning of the plateau phase of their immune response to eliminate turnover in the antibody-producing cell population. These results suggest that antibody-mediated regulation of antibody production occurs at the level of the antibody-producing cell population, possibly by preventing antigenic determinants from triggering progenitor cells that participate in the immune response, and not through control of the synthetic or secretory activities of antibody-producing cells.
Comparisons of Reaginic Antibodies from Three Species
Authors: Patterson Roy , Roberts Mary , Pruzansky Jacob J.
Published: December 2022

Reaginic antisera from three species were fractionated by gel filtration. The reaginic activity was localized and compared with other major immunoglobulins in each serum. The reaginic antibody appeared distinct from the major immunoglobulins in sera of man, monkey and dog. Heterologous antisera prepared against the reaginic antibody of all species absorbed reaginic activity. These antisera were prepared in a manner such that they had no detectable activity against the major immunoglobulin classes. These results were interpreted as being consistent with demonstrating similarities between reaginic antibodies of the three species. It is provisionally suggested that reaginic antibodies in sera of dogs and monkeys may reside in a γE analogous to human γE.
Quantitative Estimation of Antibodies in Different Immunoglobulin Classes
Authors: Torrigiani Giorgio , Roitt Ivan M.
Published: December 2022

Human thyroglobulin autoantibodies in each major Ig class can be estimated quantitatively by adsorption onto insoluble antigen followed by dissociation with acid and assay by single radial immunodiffusion using appropriate antisera. The antibodies were preponderantly IgG. The results correlated well with values for antigen-binding capacity determined by coprecipitation with specific anti-Ig, of complexes formed with labeled thyroglobulin. The method, which was previously used in a study of antiglobulin factors in sera of patients with rheumatoid arthritis, can be applied to other antigen-antibody systems and to the determination of antibody in immunoglobulin sub-classes.
A Study of Immunologic Tolerance in the Dinitrophenyl Poly-l-Lysine Immune System
Authors: Theis Gail A. , Green Ira , Benacerraf Baruj , Siskind Gregory W.
Published: December 2022

DNP-PLL genetic “non-responder” guinea pigs made tolerant to BSA by a low dose method exhibit a reduced synthesis of anti-DNP antibody upon immunization with DNP-PLL complexed electrostatically to BSA. The anti-DNP antibody synthesized by such animals is of low affinity as compared with that synthesized by normal “non-responder” guinea pigs.
Effect of Serum on Cells Producing Hemolytic Antibodies in Short-Term Experiments in Vitro
Authors: Strander H.
Published: December 2022

Suspended mouse spleen cells forming antibodies against sheep erythrocytes were incubated at 37°C in the presence or absence of serum. The number of plaque-forming cells (PFC) was determined after various times of incubation by the technique of direct localized hemolysis in gel (LHG).

The presence of serum during incubation invariably increased the rate of antibody production while its presence in the LHG assay led to no improvement. The effect was sensitive to temperature, dependent on serum concentration, and independent of the serum source. The combination of crystalline bovine serum albumin and N-Tris (hydroxymethyl) methylglycine was at least as effective as serum.
The Effect of Induced Isohemagglutinin on the Course of Blood-Induced Plasmodium Lophurae Infections in Chickens
Authors: Congdon L. L. , Farmer J. N. , Breitenbach R. P.
Published: December 2022

Experiments were designed to evaluate the importance of induced isohemagglutinin on blood induced Plasmodium lophurae infections. Prior injection with homologous whole blood caused a striking reduction in mean peak parasitemia presumably due to the induced isohemagglutinin. The low level infections which did occur in birds with induced isohemagglutinin appeared to run a normal course. It was suspected that free merozoites in the blood inoculum might be responsible for the low level infections in experimental birds. However, washing the erythrocytes of the inoculum did not reduce the magnitude or course of the low level infections. Prior injection with washed homologus erythrocytes was also strikingly effective in inducing isohemagglutinin and reducing the expected parasitemia. However, a comparison of the effects of prior injection of homologous infected and homologous noninfected whole blood showed that isohemagglutinin is not solely responsible for resistance to homologous superinfection. Apparently specific plasmodial antibody is essential for absolute resistance to homologous superinfection since there is an abrupt termination in the course of challenging infections.
Biologic and Immunologic Characteristics of Cold-Adapted Influenza Virus
Authors: Maassab H. F.
Published: December 2022

Cold variants of influenza virus showed an impaired capacity to reproduce at acid pH (5.7 to 6.3) and elevated temperature (41°C). These features were used as markers to differentiate the cold variant from the original “wild” strain. After eight consecutive passages in mice, the viral strains recovered from the lungs of infected mice could still be identified by these selective markers as the cold variants. They showed no reversion to virulence upon ten consecutive passages in mice and retained their capacity to elicit a good antibody response.

Ferrets responded as did mice to infection with the cold variants; the animals showed no evidence of disease and developed good HI antibody response. In addition, ferrets that possessed circulating antibody showed a heightened antibody response after they were reinoculated intranasally with cold variant virus.
The Effect of Intravenous Antigen on Circulating Monocytes in Animals with Delayed Hypersensitivity
Authors: Yoshida Takeshi , Benacerraf Baruj , McCluskey Robert T. , Vassalli Pierre
Published: December 2022

A study was made of the effect of intravenous antigenic challenge on the levels of circulating leukocytes in delayed sensitive rats and guinea pigs.

A sharp decrease in the level of blood monocytes was observed 6 hr after antigenic challenge. This drop was generally followed after 24 hr by a compensatory increase in the number of these cells in the circulation.

The decrease and subsequent rebound of the level of blood monocytes following antigenic challenge was shown to be a systemic manifestation of delayed hypersensitivity and could not be elicited by the passive administration of antibody followed by antigen.

The increase in blood monocytes observed 24 hr after challenge was found to be the result of the release of new cells from the bone marrow.

No effect of antigenic challenge was detected on the levels of circulating lymphocytes or polymorphonuclear cells.

The relationship between these phenomena and in vivo and in vitro manifestations of delayed hypersensitivity is discussed.
Studies of the Macrophage Inhibition Test
Authors: Ferraresi R. W. , Dedrick Claire T. , Raffel S. , Goihman-Yahr M.
Published: December 2022

The course of development of delayed skin reactivity in vivo and inhibition of peritoneal cell migration in vitro were compared in guinea pigs vaccinated with diphtheria toxoid (Dtd) and human γ globulin (HGG) in complete Freund's adjuvant. A modification of the capillary tube method of migration-inhibition provided a simple and reproducible system that was susceptible of statistically analysis and that allowed the detection of low levels of reactivity.

Delayed skin reactivity appeared earlier and developed more rapidly than migration-inhibition in the first 2 weeks after immunization. Studies with graded doses of Dtd later after sensitization indicated that, once sensitivity was well established, the in vivo and in vitro reactivities followed the same course.

Arthus reactivity in skin test sites did not coincide with maximum delayed skin reactivity or migration-inhibition.
Factors Influencing the Production of Early, Heat Labile, Rabbit Anaphylactic Antibody
Authors: Zvaifler Nathan J. , Robinson Jennifer O.
Published: December 2022

The purpose of this study was to determine if the production of early heat-labile rabbit anaphylactic antibody could be facilitated or impaired by changes in the method of immunization or by manipulations which are known to influence other classes of rabbit antibodies. Our analysis suggests that decreasing the amount of antigen (DNP-BGG) causes anaphylactic antibody to be made by fewer animals and delays its time of appearance. Keeping the protein concentration constant while decreasing the hapten groups resulted in a lesser number of positive animals, but did not delay the appearance of antibody. Changing the route of antigen administration did not affect the anaphylactic antibody in the primary response, but repeated intraperitoneal injection of antigen resulted in the reappearance of an anaphylactic antibody. The possibility is considered that this late anaphylactic antibody is not the same as that in the primary response. Treatment with 6-mercaptopurine had little influence on the production of rabbit anaphylactic antibody, even though there was a simultaneous enhanced and prolonged 19 S antibody response and impaired 7 S antibody synthesis. Anaphylactic antibody was made by rabbits whose spleens had been removed prior to immunization, suggesting that this organ is not essential for its production.
Complement-Fixing Activity of Antibodies Associated with Different Classes of Immunoglobulins
Authors: Ishizaka T. , Ishizaka K.
Published: December 2022

Antibodies belonging to different immunoglobulin classes and subclasses exhibit characteristic immunochemical properties. Among these properties, which serve to differentiate between these immunoglobulin classes, is the ability to fix C′. Using a C′1a-fixing system comprised of human anti-γA isoantibodies and type A red cells, both γG and γM antibodies have been shown to fix C′1a, whereas γA antibody in both monomeric and polymeric forms lacks this ability. It was also found that monospecific aggregates of γG and γM fixed C′, whereas aggregated γA failed to do so. Among the subclasses of γG globulins, evidence has been obtained that γG1, γG2, and γG3 globulins fix C′ and C′1a on aggregation but γG4 globulin does not.

Although antibodies of both the γG and γM type have been shown to fix C′, whether the same mechanisms of fixation exist for both classes has not yet been resolved.
Purification of C′3 Inactivator and its Possible Role in Immunochemical and Immunopathological Reactions
Authors: Torisu M. , Sonozaki H.
Published: December 2022

The C′3 inactivator was reported to be a naturally-occurring serum factor which inactivates C′3 in EAC′1423 as measured by immune hemolysis and immune adherence.

The inactivator was purified from human serum by column chromatography on diethylaminoethyl (DEAE)-cellulose and carboxymethyl (CM)-cellulose followed by Pevikon C-870 zone electrophoresis and Sephadex G-200 superfine gel filtration.

A sample of C′3 inactivator was analyzed by ultracentrifugation. A single peak was observed, which remained symmetrical throughout sedimentation, with an S20,w = 5.2 S. In sucrose density gradient ultracentrifugation the C′3 inactivator was distributed in a narrow symmetrical peak with an S value of 5.2. Purified preparations of C′3 inactivator gave a single precipitin line in the β1 globulin region in immunoelectrophoresis.

C′3 inactivator has been found to have several biologic functions. This substance inhibits 1) the passive cutaneous anaphylaxis (PCA) reaction, 2) the generation of anaphylatoxin, 3) the rejection of skin homografts, 4) immunophagocytosis and 5) the Prausnitz-Küstner reaction.
Decreased Rate of Synthesis of Immunoglobulin (IgG) in Rats Infected with Moloney Leukemia Virus
Authors: Cure Susan F. , Cremer Natalie E.
Published: December 2022

Rats infected with Moloney virus when newborn and uninfected control animals were injected with IgG prepared from normal inbred Osborn-Mendel rat serum and labeled with 131I. The decline in whole body and blood radioactivity of infected and control animals was measured for a period of 2 weeks and the biologic half-life of the labeled IgG was determined. From these and other data, the synthetic rates for each group of animals was calculated. Infected animals, which had reduced serum IgG levels, had a reduced synthetic ability rather than an increased catabolism of IgG molecules, and this could account for their low serum immunoglobulin levels. The defect in synthetic ability was most pronounced in hyperimmunized animals, resulting in a calculated synthetic rate of 7.5 mg IgG/day in infected rats and 53 mg/day in control rats.
Availability of Transplantation Alloantigens to Circulating Antibodies: Studies with Alloantibodies of Known Specificity
Authors: Witz Isaac , Cudkowicz Gustavo , Pressman David
Published: December 2022

Purified radiolabeled alloantibodies bind specifically to transplantation antigens in vivo following intravenous injection. The antibodies are localized in decreasing amounts by liver, lung, skin, spleen, kidney and brain. However, the ratio between specific and background, i.e., nonspecific, localization of radiolabeled globulins is greatest in the spleen. This reflects a higher concentration of alloantigens on the surface of spleen cells.

Antibodies directed against antigens specified either by the H-2 locus or by other H loci localize with comparable distribution patterns in separate assays in vivo. Localization is measurable even when the reaction of alloantibodies is restricted to single antigens of the H-2 complex.

The results indicate that transplantation antigens are available to humoral alloantibodies in mice and suggest that the paired radiolabeled technique may be used for identifying cells in recipients of foreign grafts and for histocompatibility typing.
Immunoglobulin Production in Cloned Sublines of a Human Lymphocytoid Cell Line
Authors: Takahashi M. , Takagi N. , Yagi Y. , Moore G. E. , Pressman D.
Published: December 2022

In the present study we obtained seven sublines (five diploid and two tetraploid) by cloning LK1D cell line and found that all the sublines contained individual cells which synthesized both α and γ heavy chains along with a single type of light chains, kappa chains. Six of these sublines showed homogeneous karyotypes which were characteristic of each subline, indicating that each subline was most likely to have been derived from a single ancestor cell. Our results show that cells which do not react with anti-immunoglobulin antibodies at a particular time of harvest have the potential to produce immunoglobulins. Moreover, two different heavy chains detected in individual cells are actually synthesized in the same cell and are not due to the transfer of immunoglobulins among the cells.
Antigen-Antibody Reactions in Agar
Authors: Hayden Alonza R.
Published: December 2022

A micromodification of the agar gel precipitin reaction of Oudin is presented; the method uses the optical densities of antigen-antibody precipitate bands formed in reaction tubes for determining the antibody concentration of rabbit antiprotein antisera in absolute weight units, mg N/ml. When microreaction tubes were used, it was possible to obtain standard O.D. vs. antiserum concentration curves (1.56% to 12.5% antiserum) which required only 0.4 ml of antiserum and less than 0.2 ml of 1% antigen in agar.

Optical density values could be obtained at a single antiserum concentration (6.25%) through the use of 0.05 ml of antisera and less than 0.02 ml of 1% protein antigen in agar. These values were used to obtain total precipitate nitrogen values from a standard curve relating O.D. to total precipitate nitrogen at equivalence in liquid media. Total nitrogen values were converted to antibody nitrogen values by substituting them in an equation which expresses antibody nitrogen as a function of total nitrogen and the ratio of antibody to antigen at equivalence.

This method was used to monitor weekly the production of antisera to human serum albumin in 12 rabbits. Optical density measurements made at single antiserum concentrations were used to predict the final antibody content of two pools of antisera.

The mieromodification of the agar gel precipitin reaction offers considerable savings in time and materials, since a complete analysis can be obtained from O.D. measurements at a single antiserum concentration, using a minimum of antigen, antiserum and other reagents after only 2 days of incubation at 25°C.
The Enhancement of Antibody Formation by Escherichia Coli Lipopolysaccharide and Detoxified Derivatives
Authors: Schenck Jay R. , Hargie Martha P. , Brown Mickey S. , Ebert Donna S. , Yoo Agnes L. , McIntire Floyd C.
Published: December 2022

The formation of antibody to human serum albumin (HSA) in rats was greatly enhanced when the protein was linked covalently to E. coli lipopolysaccharide (LPS). The response was less when HSA and LPS were only mixed before injection and nil when they were injected at separate sites subcutaneously. In rats the adjuvant effect of coupling LPS to HSA was comparable to that of using Freund's adjuvant or alum precipitation. In rabbits Freund's adjuvant was significantly the more effective. By the use of two qualitatively different detoxified derivatives, an adjuvant effect approximately equal to that of LPS was obtained with 1000-fold less pyrogenicity. The data suggest that LPS enhances antibody formation by acting directly upon the cells which respond to antigen, and possibly at the antigen-sensitive sites. In this effect both the lipid and polysaceharide portions of LPS appear to play a role, with lipid being the more important.
Immobilizing Antibodies in Pyelonephritis
Authors: Pazin George J. , Braude A. I.
Published: December 2022

Type-Specific immobilizing antibodies were found in serum and urine in the course of retrograde experimental pyelonephritis due to Proteus mirabilis. Serum antibodies were detected 3 to 5 days after infection, reached high levels at 7 to 15 days and persisted until the animals were killed. Six-day serum contained both 2ME-resistant and 2ME-sensitive antibodies, but 13- or 19-day serum antibodies were not affected by 2ME. Upon gradient ultracentrifugation of 19-day sera, the highest immobilizing titer was found in 7 S fractions. Immobilizing antibodies were also demonstrated in dialyzed urine during infection, after infection had been suppressed or eradicated by antibiotics, and after immunization with formalin-treated bacteria by intravenous or intrarenal injection. Urinary immobilizing antibodies correlated well with the location and concentration of 7 S marker on the density gradient and appeared to be stable in infected urine.
The Effect of Antilymphocytic Serum (ALS) on the Reticuloendothelial System (RES) of Mice
Authors: Marshall Villis R. , Knight Peter R.
Published: December 2022

Mice treated with heterologous ALS were found to have a significantly increased clearance of 32P-labeled Salmonella typhimurium C5 particles. This enhanced activity first appeared 24 to 48 hr after injection of the antiserum and persisted in spite of the cessation of ALS treatment.

The ALS used was found to produce hypertrophy of the liver, spleen and lymph nodes. Histologic studies revealed hyperplastic changes in these lymph nodes and spleens with the appearance of large numbers of cells resembling primitive plasma cells, many of which were pyroninophilic.

A correlation between these changes and the time of survival of skin allografts was shown. Allografts were rejected at the time when the phagocytic activity and the histologic changes in lymph nodes and spleen returned to normal.
Immuno-Precipitates of Some Purified and Unpurified Human Plasma Proteins with Monospecific and Polyvalent Human Plasma Protein Antisera
Authors: Ceska M.
Published: December 2022

The formation of immuno-precipitates of purified and unpurified human albumin and transferrin with monospecific and polyvalent human plasma protein antisera was studied. The resolution of immuno-precipitin bands into several components was obtained by infusion with Dextran 250. The dextran infusion method may indirectly show molecular varieties of proteins.
Genetic Control of the Immune Response in Mice
Authors: Gasser David L.
Published: December 2022

The production of agglutinating antibodies to the Ea-1 erythrocytic antigens of Mus musculus appears to be under the control of a single Mendelian recessive factor. There was no evidence that the nonresponding strains, CBA/J and BALB/c, possess antigens capable of absorbing antisera to Ea-1a or Ea-1b red cells, arguing against the hypothesis that these antigens are not foreign to these strains. The locus controlling this response, tentatively designated Ir-2, is linked to the agouti locus in the fifth linkage group.
The Effect of Carrageenan on Delayed Hypersensitivity Reactions
Authors: Schwartz Howard J. , Leskowitz Sidney
Published: December 2022

Administration of carrageenan to tuberculin-sensitive guinea pigs resulted in a dose-dependent suppression of delayed hypersensitivity. Recovery was complete 1 week after drug administration. The suppressive activity was not correlated with anticomplementary or anticoagulant activity. It is suggested that carrageenan exerts its effect as a result of its toxicity for macrophages, acting through lysosomal damage and the release of intracellular enzymes.
Allelic Exclusion and Phenogroup Expression in Individual Molecules of Rabbit Low-Density Lipoprotein Allotypes
Authors: Albers John J. , Dray Sheldon
Published: December 2022

A method for quantitative analysis of lipoprotein allotypes is presented, which is based on indirect precipitation of LDL-125I by an initial reaction with anti-allotype antisera followed by precipitation with goat anti-rabbit γG-Fc fragment.

Essentially all LDL molecules prepared from homozygous rabbits have two allotypic specificities of the Lpq locus—q1 and q3, q2 and q3 or q2 and q4—depending on the genotype of the rabbit.

In heterozygotes, only one of the two allelic genes contributes to the formation of the same molecule; approximately 50% of the molecules have two specificities controlled by one allele, and the other 50% have two specificities controlled by the alternate allele.
Characterization of Human Precipitating Antibody to Inhaled Antigens
Authors: Fink Jordan N. , Tebo Thomas , Barboriak Joseph J.
Published: December 2022

This investigation was carried out to characterize human precipitating antibody against several purified pigeon serum proteins using quantitative and direct isotope precipitin techniques, autoradiographic immunoelectrophoresis and passive cutaneous anaphylaxis. The results indicated that the human sera contained precipitating antibody, presumably only of the IgG class of immunoglobulins, which formed soluble antigen-antibody complexes in the zone of antibody excess. Pigeon γ globulin appeared to be more antigenic in man than pigeon serum albumin.
Studies on the Mechanisms of Resistance to Phylogenetically Diverse Intracellular Organisms
Authors: Ruskin Joel , McIntosh Jean , Remington Jack S.
Published: December 2022

Studies were performed in an attempt to define underlying mechanisms of resistance in mice infected with strains of bacteria or protozoa which confer on the animals resistance against phylogenetically unrelated organisms. The rates of clearance of an intravenously inoculated suspension of carbon particles in resistant and control animals were the same, suggesting that enhanced reticuloendothelial clearance was not involved. Attempts to transfer resistance by injection of “hyper-immune” serum were unsuccessful. In vitro monolayer cultures of peritoneal macrophages from resistant mice were protected against necrotization by bacterial and protozoal challenge when compared with monolayers from normal mice, and there appeared to be a more rapid killing of the intracellular organisms by macrophages from the resistant mice. These findings suggest that the macrophage plays a major role in the heterologous cross-resistance observed in these animals. Continued macrophage “activation” in Toxoplasma and Besnoitia-infected mice is probably due to the continued activity of these parasites during the entire life span of the host.
A Neutrophil Chemotactic Factor Derived from C′5 upon Interaction of Guinea Pig Serum with Endotoxin
Authors: Snyderman R. , Shin H. S. , Phillips J. K. , Gewurz H. , Mergenhagen S. E.
Published: December 2022

Upon activation of the complement system in guinea pig serum by endotoxin, a factor chemotactic for polymorphonuclear leukocytes is generated. This chemotactic factor has an approximate molecular weight (M.W.) of 15,000 and is independent of three minor chemotactic factors (M.W. τ;150,000, ∼68,000 and <4000) present in normal, heat-inactivated or EDTA-treated guinea pig serum. Purified, radiolabeled guinea pig C′3 and C′5 were used to determine whether the 15,000 M.W. chemotactic factor generated in serum was derived from either of these components. Endotoxin was incubated with guinea pig serum to which had been added either 125I C′3 or 125I C′5. Gel filtration elution profiles of the reaction mixtures revealed that both C′3 and C′5 were cleaved in endotoxin-treated serum. Moreover, the 15,000 M.W. chemotactic factor was identified with a cleavage product of C′5 but not of C′3. In addition, rabbit anti-guinea pig C′5, but not anti-C′3, significantly inhibited the activity of the 15,000 M. W. chemotactic factor. We conclude that the majority of chemotactic activity found in whole guinea pig serum after interaction with endotoxin is a product cleaved from C′5.
Differences between Populations of Fresh Water Catfish Defined by Blood Group Antigens and Antibodies
Authors: Kuhns William J. , Nigrelli Ross F. , Chuba Joseph V.
Published: December 2022

The presence of cross-reacting hemagglutinins in fresh water catfish maintained under laboratory conditions enabled a classification of the fish into two distinct groups. The erythrocytes and serum from groups I and II used as reagents in testing other individuals permitted similar distinctions in catfish obtained from several different sources. The agglutinogen in erythrocytes from group I individuals was A-like in nature, based upon agglutination studies using lima bean lectin and human anti-A hemagglutinins; it also possessed Forssman-like activity as inferred from differential absorption studies using guinea pig kidney and bovine erythrocytes. The demonstration that hemagglutinins in group II sera were highly cross-reactive with human erythrocytes, including A1 and A1B, thus suggested a basis for interactions with group I red cells. The basis for a reciprocal effect, namely agglutination of group II cells by group I sera, was less clear, but may be related to the widespread reactivity of these sera against all human erythrocytes tested.
Quantitative Studies of the Specificity of Anti-Pneumococcal Antibodies, Types III and VIII
Authors: Katz Moshe , Pappenheimer A. M.
Published: December 2022

A method has been described for labeling of oligosaccharides, isolated from partial hydrolysates of Type III pneumococcal polysaccharide, by reduction of the terminal hexose units with tritiated borohydride. Interactions of rabbit anti-S3 antibody and its purified Fab fragments, with purified, labeled and reduced hexasaccharides, (T)3A6 and (T)3D6, derived respectively from S3 by acid and by enzymatic hydrolysis, were studied by equilibrium dialysis. Homogeneous binding was observed in each case with association constants exceeding 105 L/mol. Removal of the Fc fragment followed by reduction and alkylation to 3.6 S fragments did not significantly alter the magnitude of the association constants.
Regenerative Potential of Immunocompetent Cells
Authors: Nettesheim P. , Williams M. L. , Hammons Anna S.
Published: December 2022

The experimental data are consistent with the notion that the immune progenitor cell pool initially stimulated in the primary antibody response is distinct from that stimulated in the secondary or anamnestic response. A major factor responsible for the long-lasting immunologic inadequacy of irradiated animals appears to be a chronic deficiency in immunocompetent cells. The capacity to form 7 S antibody was more heavily suppressed by x-irradiation than was the capacity to form 19 S antibody. This preferential suppression of the 7 S response was seen throughout the recovery phase. In thymectomized mice irradiated with 850 r and treated with isologous bone marrow, recovery of the 7 S antibody response was virtually abolished, whereas the 19 S hemagglutinin response recovered substantially. Recovery of antibody-forming capacity from x-ray exposures as high as 1000 r does not require the presence of the thymus; primarily the rate of recovery appears to be thymus-dependent. These observations were made in two different mouse strains with rat and sheep RBC used as test antigens. Recovery from antigen competition was found to be independent of the thymus.
Rabbit Autoantibodies to Aorta
Authors: Intorp Hans W. , Milgrom Felix
Published: December 2022

Antisera of rabbits immunized with antigenic preparations of bovine and human aortic intima reacted also with extracts of rabbit aorta, and two antigens characteristic of this tissue could be detected by these antisera. Two analogous antigens could also be identified by using the antisera of rabbits immunized with pooled rabbit aorta preparations in Freund's adjuvant. One of these antigens was a thermolabile component with fast electrophoretic mobility, presumably a protein; the other was a thermostable ethanol-insoluble component closely related to previously described tissue-specific BE antigens. Reactions with antigenic preparations derived from the antibody-producing animal provided evidence for the autoantibody nature of the antibodies under investigation.
Ultrastructural Identification of Possible Sites of Antigen Processing in Macrophages
Authors: Catanzaro Phillip J. , Graham Richard C. , Schwartz Howard J.
Published: December 2022

Fishman and co-workers first suggested that the primary immune response requires the sequential interaction of antigen and two distinct cell types (1–3). This concept was supported by the finding that an RNA fraction (perhaps containing antigen and/or antigenic fragments) from antigen-stimulated macrophages was capable of inducing specific antibody production in vitro (2–5). To this time, there has been no ultrastructural evidence to elucidate the intracellular site of this antigen “processing,” or the mode of transfer of “processed,”, immunogenic material from macrophages to immunocompetent lymphoid cells. On the contrary, cell biologists, using colloidal gold (6), carbohydrates (7), hemoglobin (8), bovine serum albumin (9), Salmonella adelaide flagella (10) and T2 phage (11), have shown that following uptake by mononuclear phagocytes, these materials enter lysosomes where rapid degradation occurs. The lysosomal compartment seems an unlikely site for antigen to react with or stimulate the formation of immunogenic RNA.
Identification and Genetic Control of the f4 and f5 Rabbit γA Immunoglobulin Allotypes
Authors: Conway Thomas P. , Dray Sheldon , Lichter Edward A.
Published: December 2022

In addition to the three allotypic specificities, f1, f2 and f3 previously described, two new γA immunoglobulin allotypic specificities, f4 and f5, have been identified by immunodiffusion.

Progeny data indicate that the five allotypic specificities are inherited in three phenogroup combinations, f(1,5), f(2,4) and f(3,4) by alleles designated f1,5 f2,4 and f3,4.

The two allotypic specificities f1 and f5, f2 and f4 or f3 and f4 are present on separate γA immunoglobulin molecules in whey or serum.
Recruitment and Proliferation of Immunocompetent Cells during the Log Phase of the Primary Antibody Response
Authors: Perkins Eugene H. , Sado Toshihiko , Makinodan T.
Published: December 2022

The role of cellular proliferation and recruitment was evaluated in the spleens of mice undergoing a primary immune response at 2-hr intervals during the first 96 hr after antigenic stimulation. The response was further analyzed autoradiographically and by the use of vinblastine, a mitotic inhibitor. It was found that: a) antigen-induced cellular proliferation began about 12 hr after antigen injection; b) plaqueforming cells (PFC) began to appear at a level significantly above background following a lag phase of about 24 hr; c) most, if not all, PFC during the log phase of the response are themselves proliferating or are the progeny of proliferating precursor cells; d) the number of PFC increased in a staircase manner, suggesting a considerable degree of synchronous growth; and e) there was a series of recruitment events occurring nonrandomly and in phase with division of PFC. These findings establish the essential and dominant roles of cellular proliferation during the log phase of the primary response. An important and unexpected observation is that there are many recruitment events occurring in a nonrandom manner and that the number of cells recruited increases exponentially. These results indicate that care should be taken in evaluating kinetic indices derived from analysis of data based on the assumption that only one recruitment event is involved and that the growth in the number of antibody-forming cells is random.
Immunofluorescence Studies on the Anatomic Distribution of the Soluble Antigen Responsible for the Production of Nephrotoxic Serum Nephritis
Authors: Nagasawa Toshihiko , Shibata Seiichi
Published: December 2022

Normal human kidney, lung, aorta, heart, muscle and liver were stained with fluorescein-labeled antiserum to intact human ST-GBM (the tryptic-digested ultrasupernatant substance of intact human glomerular basement membrane) for the purpose of elucidating the anatomic distribution of the specific antigen that is responsible for the production of nephrotoxic serum nephritis. These particular organs were investigated because we have previously demonstrated that antiserum against the ST of these organs (rat) could produce typical glomerulonephritis in rats. The characteristic distribution of fluorescence in these organs was as follows: kidney, glomerular basement membrane and tubular basement membrane; lung, alveolar capillary basement membrane; aorta, probably the sarcolemma of muscle cells in the tunica media; skeletal and cardiac muscle, sarcolemma of muscle cells; and liver, sinusoidal walls. Besides this specific distribution, fluorescence was also found in blood vessels and epithelial basement membrane. Further investigation is necessary to clarify the relationship between the antigenic substance in epithelial basement membrane and the production of nephrotoxic antiserum.
Assay for the Immunosuppressive Capacity of Antilymphocyte Serum
Authors: Martin William John
Published: December 2022

In this and the preceding two papers an assay procedure for ALS has been described. It measures the capacity of ALS to opsonize either mouse, human or dog thymus cells. The percentage of mouse thymus cells opsonized by an anti-mouse lymphocyte serum correlates with its ability to depress the immune response of mice to SRBC. Based on this finding, it is postulated that anti-dog or anti-human lymphocyte sera that are capable of opsonizing dog and human thymus cells, respectively, will be immunosuppressive.
Reaginic Antibody against Insulin: Demonstration of Antigenic Distinction between Native and Extracted Insulin
Authors: Patterson Roy , Lucena Guillermo , Metz Robert , Roberts Mary
Published: December 2022

Reaginic antibody against insulin mediated a generalized systemic reaction. The antibody was demonstrated to be against the insulin molecule and not against contaminating non-insulin proteins. The reaginic antibody was consistent with localization in a γE type of immunoglobulin. Reactivity was directed against insulins of several species including human insulin. The antibody reacted with various submolecular units of insulin but not against isolated A- and B-chains. The presence of reactivity against human synthetic insulin and insulin prepared from recombination of polypeptide subunits demonstrated the related antigenicity of these molecules. The reaginic antibody reacted only against extracted insulin including autologous insulin and not against endogenous circulating insulin.
Blastogenesis of Lymphocytes Induced by PPD-Primed X-Irradiated Autologous Lymphocytes
Authors: Kasakura Shinpei
Published: December 2022

Heavily irradiated lymphocytes that were incubated with PPD at 37°C and then washed thoroughly induced blast cell transformation of intact, autologous leukocytes. This did not occur with cells from tuberculin-negative subjects. PPD-primed, 10,000 r-irradiated cells induced blastogenesis. Irradiated cells primed at 4°C also induced blastogenesis. The degree of blastogenesis was affected by the following conditions: (1) the ratio of the number of PPD-primed irradiated cells to the number of intact, autologous leukocytes, (2) the PPD concentration used for priming, (3) the radiation dose, (4) the temperature during incubation with PPD, and (5) the length of incubation with PPD. Our present data suggest that PPD may be bound physically to the surface of cells (probably lymphocytes) and may stimulate intact, autologous leukocytes through direct cell-to-cell contact.