bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Specific Substances in the Alcohol Extract of the Bacillus of Tuberculosis
Authors: Dienes L. , Schoenheit E. W.
Published: December 2022

In a table are given the amounts extracted with the successive use of different lipoids solvents from 31 grams of tubercle bacilli and the effectiveness of the extracts as antigens in the complement fixation test.

With the separation of the ether and alcohol soluble and acetone insoluble fraction of the extracts and in several cases with washing them with water, we obtained from all extracts examined (5 ether, 1 ethyl and 1 methyl alcohol extract) preparations which were active as antigens very closely in the same amount, 0.00020 to 0.00030 mgm. being the antigen unit. We did not succeed with continued purification in enhancing more the potency of the preparation.

The chemical examination of the purified products, as far as could be made, has shown them to be closely similar to each other. Carbohydrates are present in large amounts in the non-purified alcohol extracts and from 12 to 26 per cent of them were found in the preparations obtained both from the alcohol and ether extracts in different phases of the purification process. The amount of carbohydrates in the most effective preparations and their eventual connection with the specific properties of the preparations has not yet been examined. The purified product has a chemical composition widely different from the well studied phosphatides.

The very high potency of the preparations, the close uniformity of the potency and chemical composition of the preparations obtained from different extracts, constitute a certain probability that our preparations consist in a large part of the specific substance.
Anaphylaxis
Authors: Sherwood Noble P. , Stoland O. O.
Published: December 2022

In 1920 (1) and again in 1923 (2) we reported the results of our work on bacterial anaphylaxis. Unfortunately we over-looked several papers which had more or less bearing on our work. Zinsser and Mallory (3) (1924) have recently called attention to these omissions in a very kindly way which we much appreciate.

Our work was a study of the smooth muscle reaction of Dale in actively and passively sensitized animals where the antigens used were Bacillus typhosus, paratyphosus “A” and “B”, and Bacillus enteritidis. The work of Weil (4) (1917) and also of Smith (5) (1922) dealt with the reaction in tubercular infected guinea pigs using tuberculin as an antigen. The paper of Zinsser and Parker (6) (1917) was on passive sensitization with anti-typhoid serum and with the use of typhoid protein as an antigen. They did not attempt active sensitization.
Observations on the Specific Part of the Heterogenetic Antigen
Authors: Landsteiner K. , Levene P. A.
Published: December 2022

The following are some preliminary results of studies on the heterogenetic antigen. It is known that the specific part of the antigen can be extracted with alcohol from the organs of various animals. The chemical nature of this substance has been studied by Kurt Meyer (1), and by Wernicke and Sordelli (2). Kurt Meyer regarded the active substance as one of the group of unsaturated phosphatides (lecithin, cephalin), whereas Wernicke and Sordelli considered it a cerebroside. In a recent communication, however, Sordelli, Wernicke and Deulafeu (3) report that after purifications with pyridine and afterwards with diluted acetone, the fractions correponding to the cerebrosides—phrenosine and cerasine—were the less active ones.

In connection with these contentions, two facts are of interest. These are: In the first place the generally weaker content in heterogenetic substance of the white substance of the brain, as compared with the content of several other organs (4, 5), and second, the failure of the pure cerobrosides phrenosine and cerasine and of pure sphyngomyelin to react with Forssman's heterogenetic antibodies in the same manner as the active extracts.
Antigenic Character of Heated Protein
Authors: Furth J.
Published: December 2022

When the first studies on precipitin were made, investigation of its thermoresistance was begun. In Nuttall's book on Blood Immunity and Blood Relationship (1) there is a table containing the early observations on the destruction of the precipitable substance by heat made by Tchistovich, Eisenberg, Nuttall, Linossier and Lemoine. Nuttall writes: “The precipitable substances in normal serum possess about the same resisting power as the precipitins. The results with milk are in flat contradiction.” At the suggestion of Nuttall, G. S. Graham-Smith tested the thermoresistance of the precipitinogen employed in his own experiments and came to the conclusion that “an antiserum can be exposed to a greater degree of heat than its corresponding serum without injury and the precipitum producing property is completely destroyed in the latter at a lower temperature.”
Studies in Specific Hypersensitiveness
Authors: Walzer Matthew , Kramer Sidney D.
Published: December 2022

In testing the skin for conditions of atopic hypersensitiveness, the clinician, whether he employs the scratch or intradermal method, is often confronted with numerous difficulties. He is especially handicapped in the testing of infants and small children, where the patient's coöperation is usually lacking, and the danger of constitutional reactions is always imminent. At times, an irritable skin, or the presence of dermographia or a diffuse eczema, erythema, or lichenification, seriously interferes with the performance and interpretation of the tests. It is in the hope of avoiding some of these difficulties that the method to be presently described is offered, as an alternative procedure to the direct testing of these types of cases.

In 1921, Prausnitz and Küster (1) first demonstrated passive transfer of local sensitivity by injecting into the skin of a normal individual the serum of a fish-sensitive case, and subsequently eliciting a specific positive skin test for fish at this site.
Selection of Cell Populations in Induction of Tolerance: Affinity of Antibody Formed in Partially Tolerant Rabbits
Authors: Theis Gail A. , Siskind Gregory W.
Published: December 2022

Induction of partial tolerance to a haptenic determinant, by the neonatal injection of antigen, resulted in a decrease in the affinity of the antibody formed. Thus, tolerance was more readily induced in those cells capable of synthesizing high affinity as opposed to low affinity antibody. The results are interpreted in terms of a thermodynamically driven selection of cell populations participating in immunologic reactions.
The Antigenic Determinants of the Variable Half of a Bence-Jones Protein of Type L
Authors: Ruffilli A.
Published: December 2022

The antigenic determinants of a fragment of a Bence-Jones protein of type L corresponding to the NH2-terminal variable half of this protein were studied. Information about the number of these antigenic determinants, their distribution among Bence-Jones proteins of type K and L and their presence in human IgG immunoglobulin was obtained. The best experimental conditions for identifying these immunologic “markers” in the variable half of the light chains of immunoglobulins were described.
Nephrotoxic Serum Nephritis in Mice with a Genetic Deficiency in Complement
Authors: Lindberg Lois H. , Rosenberg Leon T.
Published: December 2022

Complement-containing progeny from the hybridization of B10.D2-old line females with B10.D2-new line males were used to study the role of the complement system in immune tissue injury. Small differences in the severity of nephrotoxic serum nephritis were found following the injection of nephrotoxic serum which implicate the late acting complement components as intensifiers of tissue injury.
Immune Lytic Transformation: A State of Irreversible Damage Generated as a Result of the Reaction of the Eighth Component in the Guinea Pig Complement System
Authors: Stolfi Robert L.
Published: December 2022

Data presented here indicate that during the sequential complement reaction a state of irreparable cellular damage is reached after the reaction of the eighth component, but before the reaction of the ninth component, in the guinea pig complement system. Spontaneous lysis of the EAbC′—8 complex was shown to be similar to the lysis of the classical E* complex (EAbC′—9) in that it proceeded to a greater extent during a fixed incubation in buffer at 0.15 M rel NaCl than in buffer of lower ionic strength; and also in that it was completely inhibited in 0.086 M EDTA. The rate of lysis in an EAbC′—8 population remained almost constant during 180 min at 37°C, whereas, the rate of lysis in a population containing very small numbers of C′9 sites was very much higher at the beginning of the incubation period and decreased rapidly so that by 90 min it was indistinguishable from that of a population of EAbC′—8. This difference in lytic pattern indicates that the lysis of EAbC′—8 is not a reflection of contaminating C′9 sites. The EAbC′—8 complex did not manifest increased lytic susceptibility compared with other stable intermediate complexes in buffers of low osmotic pressure, on subjection to mechanical trauma, or in buffers at pH between 5.0 and 7.5. The EAbC′—8 complex was found to be specifically more susceptible to lysis in the presence of low concentrations of sodium desoxycholate. Further, the lysis of this intermediate in the presence of sodium desoxycholate was found to be similar to its lysis in the presence of C′9 in that it was temperature dependent, and inhibited in buffer of low ionic strength. Under carefully controlled conditions of sodium desoxycholate concentration and incubation time, the amount of lysis of EAbC′—8 was proportional to the average number of C′8 sites per cell in the population.
Differentiation of Antibody-Forming Cells
Authors: Kind Phyllis , Campbell Priscilla A.
Published: December 2022

Male LAF1 mice, 10 hr after irradiation with 750 r, were injected intravenously with normal LAF1 spleen cells followed 1 day later by an intravenous injection of sheep red blood cells. The recipient mice were sacrificed 6 days after antigen injection and their spleens separated in vitro into two portions: a portion showing precursor cell activity and therefore containing a large number of plaque-forming cells (positive areas), and a portion showing no precursor cell activity and therefore containing very few plaque-forming cells (negative areas). The number of antibody-forming cells and precursor cells in each portion was measured. The ratio of plaque-forming cells to precursor cells was 32:1 in the positive areas and 5.4:1 in the negative areas. These data suggest that all precursor cells are not stimulated maximally by antigen.
A Proposed Mechanism for Natural Immunity to Enterobacterial Pathogens
Authors: Chedid Louis , Parant Monique , Parant Francine , Boyer Fernand
Published: December 2022

The bactericidal effect of normal mouse serum, generally ascribed to natural “O” antibodies, can be removed by absorption with rough microorganisms. Passive hemagglutination tests disclose the presence of thermolabile, non-agglutinating “R” antibodies in normal mouse serum; titers in germ-free animals are much lower. Horse hyperimmune serum against rough S. typhimurium protects mice against infection with unrelated virulent smooth K. pneumoniae. Provided the Klebsiellae are preincubated in normal mouse serum bactericidal activity can also be demonstrated in vitro. This activity does not require the presence of complement and can be removed either by the same Klebsiella strain or by rough strains of Salmonellae but not by the smooth strain of Salmonellae from which these mutants originate. Although these effects would most easily be accounted for by specific antibodies it is also possible that they are instead attributable to a serum protein capable of charge interaction with rough antigens. In any event these findings, together with previous observations concerning degradation of somatic antigen and phenotypic modification of Klebsiellae recovered from endotoxin-treated mice, have led to the development of a new concept of natural immunity to Enterobacteriaceae. In this hypothesis, enzymatic factors capable of attacking cell wall components unmask R antigenic sites common to many bacterial strains and species. Thereafter the presence of a few types of “R” antibodies or of serum factors reacting with rough antigens have the capability of coping, like masterkeys, with a very wide range of infections due to serologically unrelated organisms.
Neutralization of Sensitized Lactic Dehydrogenase Virus by Anti-γ-Globulin
Authors: Notkins Abner Louis , Mage Michael , Ashe Warren K. , Mahar Suellen
Published: December 2022

Incubation of lactic dehydrogenase virus (LDV) with mouse anti-LDV resulted in the formation of an infectious virus-antibody complex (sensitization). Virus sensitization preceded neutralization and the more highly sensitized the virus became the more resistant it was to neutralization. Sensitized virus, in contrast to unsensitized virus was readily neutralized by goat antimouse serum or goat anti-mouse γ-globulin. Neutralization of sensitized virus by anti-γ-globulin occurred within 1 min at 4°C. The amount of virus neutralized was related to the degree of sensitization, the concentration of anti-γ-globulin and free γ-globulin in the reaction mixture and the specificity of the anti-γ-globulin. Anti-γF, anti-γG and anti-γA neutralized sensitized virus, whereas anti-γM had no effect. The Fab fragments of papain-digested goat anti-mouse serum partially neutralized the sensitized virus and blocked further neutralization by undigested anti-mouse serum. The Fc fragment had no effect. These findings point to the potential usefulness of sensitized virus as a tool for detecting and studying various immunoglobulins.
Skin-Fixing Antibody in Experimental Allergic Encephalomyelitis
Authors: Falk George A. , Heinze Robert G. , Kies Marian W. , Alvord Ellsworth C.
Published: December 2022

The antibody response of guinea pigs to purified encephalitogenic myelin basic protein (BP) has been examined by passive cutaneous anaphylaxis (PCA) in the guinea pig. This technique is known to be a sensitive measure of 7S-γ1 antibody. Serum from animals developing experimental allergic encephalomyelitis (EAE) following a single injection of guinea pig BP in Freund's complete adjuvant contained no PCA activity. Animals protected by multiple injections of guinea pig BP in Freund's incomplete adjuvant developed variable antibody titers. Two protected animals produced no detectable antibody. 7S-γ1 antibody is thus not required for either induction or prevention of EAE with BP. PCA activity in guinea pigs was confined to the serum fraction containing γ1 but not γ2-globulin, as previously reported in other antigen-antibody systems.

Experiments were also performed with bovine BP in a study of antigenic cross-reactivity. Serum from guinea pigs hyperimmunized with guinea pig BP had identical titers to guinea pig BP and bovine BP. Serum from guinea pigs hyperimmunized with bovine BP, however, had significantly higher titers against bovine BP than against guinea pig BP, indicating the presence of both shared and species-specific antigenic determinants in the bovine encephalitogen. Bovine BP showed cross-reactivity with pooled bovine serum, but not with bovine serum albumin, α-, β- and γ-globulins, hemoglobin, or fibrinogen.
Distribution of Antibodies Within 19 S and 7 S Immunoglobulins Following Infection with Mycoplasma Pneumoniae
Authors: Biberfeld Gunnel
Published: December 2022

Sera from cases of pneumonia with serologic evidence of Mycoplasma pneumoniae infection were fractionated by sucrose gradient centrifugation and gel filtration. The distribution of complement-fixing (CF), indirect hemagglutinating (IHA) and tetrazolium reduction-inhibiting (TRI) antibodies within the 19 S and 7 S immunoglobulins was determined at different times after onset of illness. The proportion of 19 S to 7 S antibodies varied considerably between individuals even when compared at the same time after clinical onset. However, in the majority of cases there was an increase of 7 S relative to 19 S CF antibodies with time after onset. Yet, most cases still had some 19 S CF antibodies after 5 to 12 months.

TRI antibodies also showed a temporal shift in their distribution between 19 S and 7 S globulins.

IHA antibodies were predominantly 19 S globulins. In half of the cases studied there was an increase of 7 S relative to 19 S IHA antibodies with time after infection while the remaining cases showed 19 S IHA antibodies exclusively even after 5 to 12 months.

In some cases both CF and IHA antibodies showed a partial temporal shift from 19 S to 7 S immunoglobulins whereas in other cases this trend was noted with only one of the antibodies.

No difference was found in the CF antigen requirement of sera collected in the early and late phase of infection or between 19 S and 7 S antibodies.
Development in Hamsters of Antibodies against Surface Antigens Present in Cells Transformed by Papovavirus SV40
Authors: Tevethia Satvir S. , Couvillion Lynda A. , Rapp Fred
Published: December 2022

Newborn hamsters inoculated with SV40 and later challenged with the homologous virus in the latent period developed antibodies which reacted specifically with antigens at the surface of hamster cells transformed by SV40. Regression of tumors induced by SV40 was consistently related with the development of this antibody. Adult hamsters vaccinated with SV40 and subsequently resisting a transplant of SV40 transformed cells developed similar antibody in their sera which could be detected as early as the 2nd week after the challenge. The evidence indicates that the S antibodies elicited by the techniques employed may be directed against SV40-specific transplantation antigens.
Relationship between Molecular Size and Intra- and Extravascular Distribution of Protein Antigens
Authors: Nakamura Robert M. , Spiegelberg Hans L. , Lee Sun , Weigle William O.
Published: December 2022

Plasma proteins varying in molecular weight from 50,000 to 950,000 were radiolabeled and injected into rabbits and the lymph to plasma concentration ratios (CL/CP) of the various proteins were measured 3 days following injection. The amount of protein in the extravascular fluid spaces after equilibration, as measured by the CL/CP, correlated exponentially with the effective hydrodynamic diffusion radius of the protein. An exponential relationship also was observed between CL/CP and molecular weight for globular proteins, whereas fibrinogen, which is a spindle-shaped protein, showed only a correlation with the effective hydrodynamic diffusion radius and not with the molecular weight. No correlation between the intra- and extravascular distribution and half-lives of the various homologous and heterologous proteins was observed. The immunoglobulins of similar molecular size, but different chemical structure, as human γA-monomer, human γG and rabbit γG, showed a similar lymph to plasma concentration ratio following equilibration.

Following intravenous injection, a larger percentage of bovine serum albumin (BSA) complexed with Fab fragments from purified anti-BSA remained in the intravascular fluid spaces than of BSA alone after complete equilibration.

Similar to the CL/CP, the calculated extravascular lymph space occupied by the various proteins correlated exponentially with the effective hydrodynamic diffusion radius of the protein.

The importance of the in vivo distribution and the behavior of protein antigens in relation to immunologic phenomena is discussed. With a given blood concentration, the concentration of serum protein antigens in the extravascular fluid space varies considerably with antigens of different molecular sizes.
The Effect of Carbamylation and Amidination of Rabbit γG-Antibody on its Ability to Fix Complement
Authors: Cohen Stanley , Becker Elmer L.
Published: December 2022

The effect of carbamylation or amidination of rabbit γG-antibody on its ability to fix guinea pig complement has been studied. These procedures, which result in the conjugation of lysine groups, cause a reduction in complement-fixing ability without significant loss in the antibody's ability to combine with antigen. Although heavy carbamylation can reduce the ability of antibody to precipitate antigen, this effect was not observed with amidination. At least a 55% loss in fixing ability, produced by light conjugation by means of either carbamylation or amidination, is probably due to the inactivation of specific complement-fixing sites; with increasing degrees of conjugation, further loss in fixing ability results, due to nonspecific alterations of the antibody molecule. These losses are associated with, but not caused by a diminution in the rate of antigen-antibody aggregation.

Preformed complexes of antigen and unconjugated antibody are less effective at fixing complement than immune complexes formed in the presence of complement. Both amidination and carbamylation abolish this difference.
Immunology of the Mycoses
Authors: Marcus Newberry W. , Chandler John W. , Chin Tom D. Y. , Kirkpatrick Charles H.
Published: December 2022

The transformation of lymphocytes in vitro in the clinical types of histoplasmosis was studied by stimulation of peripheral blood lymphocytes with histoplasmin. Lymphocytes were obtained from five healthy histoplasmin-positive and five histoplasmin-negative donors as well as five patients who had acute histoplasmosis and five patients who had chronic histoplasmosis. The measurement of incorporation of radioactive thymidine into DNA was a more sensitive indicator of lymphocyte transformation than morphology.

The uptake of thymidine, as expressed by a ratio of the radioactive counts from the antigne stimulated tubes and the unstimulated tubes (E′C), was greater for the healthy histoplasmin-positive donors (median E/C 66.7) than for the histoplasmin-negative donors (median E/C 4.9). Acute histoplasmosis patients (median E/C 51.1), as a group, reacted similarly to the healthy histoplasmin-positive donors. The chronic histoplasmosis patients (median E/C 22.6), on the other hand, reacted more like the histoplasmin-negative donors. The lymphocyte transformation, appeared to be depressed according to the severity of the clinical illness as well as by the presence of serum antibodies. Also, the transformation was depressed by heating serum at 56°C in a water bath for 30 min. No antibody against histoplasmin could be demonstrated in the culture fluid by means of the C-F test even when there was strong lymphocyte transformation.
Serum Complement in the Rejection of Sarcoma I Ascites Tumor Grafts
Authors: Phillips Mildred E. , Rother Ursula , Rother Klaus
Published: December 2022

The reactivity of sarcoma I, isoantibody, and complement (C′) was studied in vitro and in vivo. C′ activity was needed in the cytotoxic reaction in vitro. When inoculated into the peritoneal cavity of presensitized mice, tumor cells bound mouse γ-globulin and C′ (β1C protein) within 2 min. Tumor growth resulted in decreasing serum C′ titers. There was a positive relation between the number of tumor cells implanted, loss of C′ activity and death of the recipient animals. B10D2/new line mice which possess a lytic C′ system were at least 10 times more efficient in the destruction of tumor implants than B10D2/old line mice which lack C′5 activity.

It is concluded that C′ participates in the rejection reaction against allografted sarcoma I tumor and that biologic functions dependent on the activity of C′5 are preeminent in the graft destruction. A second mechanism was independent of C′5 and less efficient.
Inhibition by Cardiolipin of the Antibody Response to Bacterial Antigens
Authors: Whang H. Y. , Neter E.
Published: December 2022

A study of the effects of eardiolipin on the immune response of rabbits to bacterial antigens revealed the following results. 1) Cardiolipin, when injected together with common bacterial antigens of enterobacteriaceae or of Gram-positive bacteria, inhibited the production of circulating antibodies, but did not interfere with immunologic priming. 2) Separate injections of antigen and inhibitor resulted in undiminished immune response. 3) The inhibitor did not affect the antigenic determinant of the antigens in vitro, nor did it interfere with antigen attachment to erythrocytes. 4) Cardiolipin did not inhibit the antibody response to O antigen. 5) The effects of cardiolipin on the immune response to common bacterial antigens resembled those produced by lipopolysaccharide and its lipoid A component.
The Immune Response in the Hamster
Authors: Coe John E.
Published: December 2022

A fast (7 S γ1) and slow (7 S γ2) 7 S γ-globulin system in the hamster has been described. Specific antisera to hamster 7 S γ1 and 7 S γ2 were prepared, and the antigenic relationship of the papain and pepsin digests of 7 S γ2 were compared to each other and to the 7 S γ1-globulin. Antigenic determinants common to the 7 S γ1- and 7 S γ2- globulins were located in the Fab and F(ab')2 piece of 7 S γ2, whereas antigenic determinants unique for the 7 S γ2 whereas antigenic determinants unique for the 7 S γ2 molecule were in the Fc piece of 7 S γ2. The molecular size of 7 S γ1-globulin was shown to be similar to that of the 7 S γ2-globulin (s020, w 7.2) and the antigen-binding capacity of the 7 S γ1-antibody was not detectably affected by 2-mercaptoethanol or heat treatment.
Production of Fe Fragments of IgM
Authors: Yakulis Vincent , Schmale John , Costea Nicolas , Heller Paul
Published: December 2022

Stable Fc fragments were obtained by incubation of human or rabbit IgM with sodium borohydride (NaBH4). Hydrolysis of IgM with papain yielded only small amounts of Fc fragment. Treatment of rabbit IgG with NaBH4 resulted in the formation of Fc fragments which were identical to those obtained by papain digestion. NaBH4 appears to be more suitable than papain for obtaining Fc fragments of IgM.
Studies on the Ontogeny of the Mouse Immune System
Authors: Tyan Marvin L.
Published: December 2022

The presence of potential immunologically competent cells in the various tissues of embryonic, newborn and adult mice was demonstrated by means of a modified γgraft-vs.-host” method and by the injection of chromosomally marked cells into irradiated recipients. The results indicate that lymphoid stem cells which have the potential to participate in cell-bound immune reactions appear in the placenta and liver by the 9th or 10th day of gestation. Throughout pregnancy they are found in the liver. During the 11th to 14th days of gestation these stem cells are present in the upper trunk or in the thymus. On about the 15th day they appear in the lung and toward the end of the pregnancy in the fetal bone marrow and spleen. There was little or no evidence of the presence of lymphoid precursors capable of maturation to cells which mediate cell-bound immune responses in the gut prior to birth.

Following parturition lymphoid stem cells were present in the liver, Peyer's patches, lung, bone marrow, lymph nodes, spleen, blood and thymus. However, by 6 weeks after birth the bone marrow appeared to be the major or sole source of these cells.
Antigens of Rickettsia Prowazeki
Authors: Barker Lewellys F. , Patt Judith K.
Published: December 2022

Antigenic activities of intact rickettsiae, cell walls, protoplasm and soluble antigens of Rickettsia prowazeki were compared on the basis of weight in complement fixation and mouse protection tests. All of the materials were active in both systems. The protoplasm antigens showed the greatest specificity and heat lability in the CF test. Cell walls and soluble antigens as well as intact rickettsiae contained more heat-stable CF antigens and tended to be more active than protoplasm in the mouse protection test although differences in this activity were not statistically significant. Heating the antigens provided evidence of dissociation between heat-labile mouse-protecting antigens and heat-stable CF antigens.
The Detection of Antibody-Containing Cells in the Blood Stream during the IgM Cellular Antibody Response
Authors: Hiramoto Raymond N. , Hamlin N. Marlene , Harris Holland L.
Published: December 2022

Evidence is presented that during the IgM response to sheep erythrocytes, significant numbers of plaque-forming cells (PFC) are circulating in the blood. The total number of PFC in the circulation did not exceed the total number in the spleen.

Comparative studies between the spleen and peripheral blood indicate that as much as 15.8% of the antibody synthesis may be taking place directly in the blood stream during a particular period. However, the response in the blood was transient: cells in the circulation did not persist for more than a few days after reaching their peak level.
Passive Hemagglutination Procedures for Protein and Polysaccharide Antigens Using Erythrocytes Stabilized by Aldehydes
Authors: Hirata Arthur A. , Brandriss Michael W.
Published: December 2022

Chicken, sheep and rabbit erythrocytes were stabilized with formaldehyde, pyruvic aldehyde or both, for use in passive hemagglutination reactions. Bovine serum albumin, insoluble BSA, ovalbumin, rabbit γ-globulin, chicken γ-globulin, bovine γ-globulin, E. coli endotoxin, acetylated endotoxin, de-esterified endotoxin, de-esterified and bromacetylated endotoxin, succinylated endotoxin and synthetic polyglucose were found to adsorb firmly on the stabilized cells.

For optimal coating of stabilized cells with antigens, critical factors included pH, antigen concentration and the duration of contact with antigen. These conditions differed somewhat from one antigen to another.

Coated cells could be stored frozen or lyophilized.

Approximately 1 × 10-7 to 1 × 10-8 mg of anti-BSA antibody were detected by using rabbit erythrocytes coated with BSA. This level of sensitivity compares favorably with tannic acid or BDB procedure for cell coating.

Antiglobulin tests were applicable in all of the cases tested and were found to increase the hemagglutination titers 10- to 30-fold.
Immune Response to Anti-Lymphocyte Globulin
Authors: Jasin Hugo E. , Lourie Seth H. , Currey H. L. F. , Ziff Morris
Published: December 2022

The appearance of antibodies to rabbit IgG in rats injected with the IgG fraction of rabbit anti-lymphocyte serum was examined. While 13 of 24 animals injected with ALG developed significant anti-rabbit IgG titers, only 2 rats of 18 injected with comparable amounts of normal rabbit IgG developed antibody, and in these it was present in relatively low titer. Evidence of immunosuppression was observed in the ALG treated animals in a reduction of antibody formation to sheep erythrocytes and a suppression of Freund's adjuvant-induced arthritis.

In a group of animals simultaneously injected with bovine γ-globulin, the immune response to this protein was similar in both the experimental and control groups. The enhancement phenomenon observed, therefore, appeared to be specific for IgG with anti-lymphocyte activity.
A Demonstration of the Coprecipitation of β-Lipoproteins with Specific Precipitates of Chicken Antibodies and Human Serum Albumin
Authors: Van Orden Dianna E. , Treffers Henry P.
Published: December 2022

The coprecipitation of β-lipoprotein with specific precipitates of HSA and chicken antibodies (8% NaCl) has been demonstrated by gas chromatography. The precipitin curves obtained with the β-lipoprotein-depleted sera in the presence of EDTA were reproducible despite aging at refrigerator or freezer temperature. The curves for the depleted sera had the same macroglobulin-type contour as the untreated serum, but had lower values throughout the antigen range tested. β-Lipoprotein depletion produced no change in equivalence point, but it appeared to decrease the sensitivity of the antibody to 2-ME.
Localization of 11 S External Secretory IgA by Immunofluorescence in Tissues Lining the Oral and Respiratory Passages in Man
Authors: Rossen Roger D. , Morgan Councilman , Hsu Konrad C. , Butler William T. , Rose Harry M.
Published: December 2022

The tissue localization of cells containing 11 S external secretory IgA was investigated using rhodamine- or fluorescein-labeled antisera specific either for the heavy polypeptide chain of 7 S serum IgA (anti-IgA) or for the characteristic extra-antigenic determinants of 11 S secretory IgA (anti-Piece). Both anti-Piece and anti-IgA caused fluorescence of: 1) cells at the periphery of lymphoid follicles and lining the crypts of the pharyngeal and palatine tonsils, and 2) scattered interstitial and serous acinar cells of the compound alveolar glands in the nasal submucosa and in the submaxillary and parotid salivary glands. Anti-IgA alone stained occasional cells in the lymphoid follicles of spleen and of lymph nodes taken from the lung, submandibular tissue and periaortic chain. Anti-Piece stained none of the latter tissues, and neither anti-Piece nor anti-IgA caused fluorescence of liver, pancreas or pulmonary alveolar cells.

When anti-IgA and anti-Piece, one labeled with fluorescein and the other with rhodamine, were applied to the same tissue sections, cells stained by anti-Piece were also stained by anti-IgA. Occasional cells in all tissues stained with anti-IgA alone when both conjugates were applied to the sections. These findings suggest that the complete 11 S external secretory IgA is formed in many cells lining the oral and respiratory passages. It is not necessary to postulate selective transport of 7 S serum IgA either from the interstitial fluid surrounding nasal and salivary glands or from the plasma to account for the high concentrations of 11 S IgA in external excretions.
The Enhancing Effect of Bone Marrow Cells on the Immune Response of Irradiated Mice Reconstituted with Spleen Cells from Normal and Immunized Donors
Authors: Radovich Jevrosima , Hemingsen Helen , Talmage David W.
Published: December 2022

The injection of 5 million normal bone marrow cells into cobalt-60 irradiated mice produced a striking effect on the size of the spleen and greatly enhanced the number of antibody-forming cells found in the spleen 6 days after the injection of sheep RBC and small numbers of spleen cells from normal or preimmunized mice. The experiments are interpreted as indicating a nonspecific effect of bone marrow cells on the localization or proliferation of antibody-forming cells. They negate previous claims that bone marrow enhancement can be considered evidence for a multipotential antibody-forming cell precursor.

Note Added in Proof: In the Proc. Nat. Acad. Sci., 59: 296, 1968, G. F. Mitchell and J. F. A. P. Miller reported experiments indicating that in the thymus-bone marrow interaction the antibody was made in a cell derived from the bone marrow. That is indeed a remarkable nonspecific effect. If it can be shown that in the interaction between normal bone marrow and immune spleen cell the antibody is made in the bone marrow cell, then this would raise the question of how the memory was transferred.
Communications
Authors: Scott David W. , Waksman Byron H.
Published: December 2022

Recent studies of immune responses induced in vitro suggest that close contact between phagocytic cells and immunologically competent cells, phagocytosis of antigen, and possibly a “processing step” may be necessary elements of the immunologic induction mechanism (1–3). Several workers have proposed that, in the absence of a phagocytic step, antigen may interact directly with immunologically competent cells and produce tolerance (4, 5). If this is the case, it should be possible to induce tolerance in vitro by exposing lymphoid cells to a non-phagocytizable antigen. We present here data which test this hypothesis and describe some of the conditions under which tolerance can be produced in vitro.

Male Lewis rats were thymectomized as young adults, irradiated (900 r, central axis dose) 3 weeks later, and injected intravenously with 7 to 10 × 108 viable, syngeneic lymph node (LN) and spleen (S) cells, treated in various ways.
Structure of Human Immunoglobulin M
Authors: Kishimoto Tadamitsu , Onoue Kaoru , Yamamura Yuichi
Published: December 2022

Pepsin fragmentation of a purified IgM obtained from a patient with macroglobulinemia was studied.

Three fragments were obtained. These fragments were all related structurally to the Fab-(IgMs) fragment obtained by papain digestion of the subunit of IgM. The first, 5.6 S fragment (F(ab′)2(IgM)), was converted quantitatively to 4.2 S fragments (Fab′(IgM)) by mild reduction and alkylation. No change in antigenicity was observed by this treatment. Thus the 5.6 S fragment seemed to be a dimer in which two monomeric 4.2 S fragments were linked by a disulfide bond.

The second, 3.3 S fragment (Fab pep(IgM)), was similar to the Fab(IgM) obtained by papain digestion of the IgM or its subunit. It lacked a part of the µ chain portion (Fd′µ) of F(ab′)2(IgM) on which the particular disulfide bond linking the two Fab′ fragments seemed to be located. It was noted that the part of Fd′µ mentioned carried some antigenic determinants of the µ chain.

The third, 2.4 S fragment (Fab piece(IgM)), was a part of the Fab pep(IgM) consisting of a part of κ chain and a part of µ chain. It seemed to lack a part of the Fab pep(IgM) on which the disulfide bond(s) linking a κ chain and a µ chain portions are located.

Time study of the digestion showed that pepsin first cleaved off the Fc portion of the IgM and yielded the 5.6 S dimeric fragment, F(ab′)2. Then the F(ab′)2 was degraded to the 3.3 S monomer, Fab pep, and further to the 2.4 S fragment, Fab piece.
Modification of the Amino Groups of Rabbit γG-Globulin
Authors: Ljaljevic M. , Ljaljevic J. , Parker C. W.
Published: December 2022

Conditions which led to inactivation of rabbit γG-globulin in direct passive cutaneous anaphylaxis (PCA) experiments in guinea pig skin also produced inactivation in reverse PCA experiments. Thus acetylation, carbamylation, picrylation and phthylation of reverse PCA antigens (rabbit Fc or dinitrophenylated rabbit γ-globulin) caused loss of skin-sensitizing activity whereas amidination did not. These results strongly favor the possibility that inactivation of skin-sensitizing activity is due to loss of fixation in guinea pig skin. In further support of this view no correlation was seen between complement-fixing activity and skin-sensitizing activity. Amidinated preparations of rabbit antibody which retained their ability to sensitize guinea pig skin fixed very little complement.
The Immune Response of Random-Bred Hartley Strain Guinea Pigs to 2,4-Dinitrophenyl Conjugates of a Copolymer of l-Glutamic Acid and l-Lysine
Authors: Lamelin Jean-Pierre , Paul William E. , Benacerraf Baruj
Published: December 2022

A study of the role of the PLL gene in controlling the anti-DNP antibody response to DNP-GL was performed. Equilibrium dialysis of serum globulin against 3H-DNP-EACA demonstrated a binding capacity corresponding to less than 0.55 µg/ml of serum antibody in guinea pigs lacking the PLL gene. The binding capacities of serum globulin from these animals did not differ appreciably and consistently from that observed with control serum globulin fractions from guinea pigs immunized with unconjugated GL. On the other hand, guinea pigs possessing the PLL genetic factor had serum anti-DNP antibody concentrations of from 0.18 to 2.20 mg/ml at 2 weeks after DNP-GL immunization. These data are compatible with the dependence of a significant antibody response to DNP-GL on the presence of the PLL genetic factor.
Studies of the Proteins of Lacrimal Secretions
Authors: Josephson Alan S. , Weiner Roy S.
Published: December 2022

The major immunoglobulin of tears is IgA globulin, which is recovered in the external volume when subjected to Sephadex G 200 gel filtration. This protein contains “transport” or “secretory” piece as does the IgA globulin of other secretions.

Another protein in tears, the anodal tear protein, is not related to albumin but is electrophoretically a “prealbumin.” It has gel filtration characteristics consistent with a molecular weight intermediate between that of serum albumin and of lysozyme, and has not been identified in serum, spinal fluid, saliva or urine.

The protein content of tears shows an inverse relationship to the volume of lacrimal fluid obtained during a collection period of less than 5 min.
The Agglutinating and Bactericidal Activity of IgM and IgG Antibodies to the 9 and 12 Factors of Salmonella Typhi O 901
Authors: Daguillard Fritz , Edsall Geoffrey
Published: December 2022

By the methods of absorption, elution and column chromatography separation, IgM and IgG antibodies to either one or both 9 and 12 O factors of S. typhi O 901 were isolated. On a molar basis IgM antibodies were always more active than IgG. IgM antibodies directed against the 12 antigenic sites were more active in both agglutination and complement-dependent bactericidal killing. Mixture of preparations containing antibodies to different specific sites of the bacterial cell wall did not react synergistically in bactericidal reactions. In all tests the different antibody preparations reacted more strongly with the homologous antigen than with the cross-reacting organisms. A prozone, i.e., a pronounced inhibition of the bactericidal activity, was elicited by both types of immunoglobulins at higher concentrations, and was attributed to antibodies specifically attached to either one or both antigenic sites.
Equine Antibodies to Human γG-Globulin
Authors: Johnston Sarah L. , Allen Peter Z.
Published: December 2022

Several antisera to human γG-globulin obtained from a single horse and isolated γ1- and γ2-antibody fractions prepared from these antisera were compared in complement fixation studies. C′-fixing ability of each successive bleeding progressively increased, paralleling an apparent increase in the proportion of γ2-antibody in the whole serum. Isolated γ2-antibody fractions fixed complement when tested at a level of 1 µg antibody N and greater. There were no significant differences in complement-fixing ability on an antibody N weight basis among γ2 fractions from the same or different bleedings. Isolated γ1-antibody fractions possessed no complement-fixing ability but could inhibit fixation by the γ2-antibody.

Both γ2 and γ1 preparations exhibited similar end points (0.04 µg antibody N) when employed as anti-globulin reagents in the Coombs test. In comparison, the γ1-antibody fractions gave a prozone in the antibody excess region, whereas no prozone was noted with the γ2 fractions. The specificity of antisera and antibody fractions from successive bleedings for antigenic determinants on the human γ-globulin molecule was established by reacting these preparations with several antigens related to the heavy and light chains of human γ-globulin.
Relative Stabilities of Complexes of Measles Soluble and Viral Hemagglutinins with 19S and 7S Immunoglobulins
Authors: Schluederberg Ann
Published: December 2022

Studies of hemagglutination-inhibition reactions of the antigenically related measles soluble (SDA) and envelope-integrated viral (HA) hemagglutinins have shown the following: Eighty units of SDA failed to compete with 4 units of HA for HI antibodies, although in the same experiment SDA required, unit for unit, an antibody concentration of the same magnitude for inhibition as that required by HA.A negative Danysz effect was demonstrated with SDA and a positive effect with viral HA, which indicates that SDA forms a less stable union with antibody than does HA. Reversibility of SDA-antibody combination was proposed as an explanation for the result above.The ratios of SDA inhibition titer to HI titer varied under different circumstances. Factors included time of serum collection relative to disease onset, class of immunoglobulin predominating, and average size and state of aggregation of the HA preparation used for the comparison.
In Vivo and in Vitro Properties of Intact and Pepsin-Digested Heterologous Anti-Mouse Thymus Antibodies
Authors: Riethmüller Gert , Riethmüller Doris , Stein Hans , Hausen Peter
Published: December 2022

Rabbit anti-mouse thymus globulin (AMT-IgG) had a strong inhibitory effect of IgM antibody-forming spleen cells of mice when injected prior to the antigen. No effect was observed when AMT-IgG was injected after or simultaneously with the immunizing dose of sheep red cells. Pepsin-digested bivalent antibody did not inhibit formation of antibody-synthesizing spleen cells nor did it prolong survival of allogeneic skin grafts. AMT-IgG as well as the bivalent fragment F(ab')2 stimulated uridine incorporation of thymocytes in vitro. The F(ab) fragment, however, had no stimulatory effect though it protected the cells when exposed to complete cytotoxic antibodies in the presence of complement. The possible mechanism of immediate immunosuppression by which AMT-IgG acts in vivo is discussed. Biologic properties of the Fc fragment are implicated in this action.
Thermostable Kidney Antigen and Its Excretion into Urine
Authors: Intorp Hans W. , Milgrom Felix
Published: December 2022

Fractions of bovine and human kidneys obtained by extraction at 100°C followed by ethanol precipitation (BE fractions) were used for immunization of rabbits. Untreated antisera contained many antibodies to bovine or human tissue extracts. Following proper absorption, anti-bovine kidney BE serum detected a kidney-specific antigen in BE preparations of bovine kidney and anti-human kidney BE serum detected a similar antigen in human kidney BE. There was, however, no cross-reaction between these two antigens. The antigens under investigation had an electrophoretic mobility comparable to serum α-globulin. They were demonstrated in separated cortical and medullary portions of kidneys, but were virtually absent from glomeruli isolated by the method of Krakower and Greenspon. Urinary excretion of the kidney-specific thermostable antigen was demonstrated in calves with experimentally induced tubular damage, and in a human patient suffering from acute tubular necrosis.
Studies of the Chicken Immune Response
Authors: Abramoff Peter , Brien Nancy B.
Published: December 2022

New Hampshire Red chickens (10 to 12 weeks old) were immunized with an intravenous injection of SRBC. By 13 hr, morphologic differentiation was detected in the spleen cell population as indicated by an accumulation of pyroninophilic cells. Differential staining of the nucleic acids indicated that the percentage of plasmacytic cells continued to increase in the spleen for 72 hr, at which time they comprised 17% of the population. The first significant amounts of antibody released by spleen cells were detected by the Jerne plaque technique at this same time suggesting that morphologic differentiation was complete before antibody was released. Maximum antibody-plaque formation occurred at 96 hr and the greatest amount of humoral antibody was detected 72 hr later.

Morphologic changes in the cellular population of the bursa similar to those found in the spleen also occurred after antigenic stimulation. However, no antibody was detected in the bursa. The morphologic changes in the bursa preceded those in the spleen. The possible immunologic implications of these results are discussed.
Enterovirus Immunodiffusion Reactions: A Comparison of Results Obtained in Agarose and Agar Using Two Different Microdiffusion Systems
Authors: Styk Bohumil , Schmidt Nathalie J.
Published: December 2022

Two different microdiffusion systems and agar and agarose gels were compared for suitability in immunodiffusion reactions with certain enterovirus types (coxsackievirus type B2 and echovirus type 9) which had given poor resolution in previous immunodiffusion studies. The use of agarose, rather than agar, gels facilitated diffusion of these antigens and permitted resolution of two or more antigen-antibody systems. The “chamber” technique, employing a plastic template over a thin layer of gel, was more sensitive for immunodiffusion tests with these virus types than was the “slide” technique utilizing a thicker layer of gel. Results of tests with echovirus type 9 antigen in an agarose gel suggested the existence in human and monkey sera of “group” antibodies reacting with this antigen type. No “group” reactivity was noted with the other echovirus antigens studied. Guanidine treatment (3.4 molar) abolished precipitating activity of coxsackievirus antigens, but not of echovirus types 9 and 11 antigens, although the “group” reactivity of echovirus type 9 antigen was destroyed by treatment with 4.6 M guanidine.