bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Mechanisms of Hypersensitivity Phenomena
Authors: Levy David A. , Osler Abraham G.
Published: January 2023

A two-step in vitro reaction system has been described for studies with human sera capable of passively sensitizing human leukocytes for interaction with ragweed pollen antigen. Cells from nonallergic donors are washed and sensitized by incubation in serum from ragweed-sensitive individuals. Following removal of the bulk serum phase from the reaction mixture, the extent of sensitization may be estimated in terms of the amount of histamine released during incubation with the pollen antigen. The following experimental conditions govern the sensitizing process: pH, temperature, time, reaginic serum and divalent cation concentration.

It has also been observed that only one in every five nonallergic individuals provides suspensions of leukocytes suitable for passive sensitization. The basis for this marked specificity of the cell-serum reaction remains unknown. Cells which cannot be sensitized with one potent serum remain nonreactive after incubation with sera of different individuals. Conversely, a serum containing sensitizing antibodies can transfer these antibodies to the cells of different individuals.

The leukocyte-sensitizing activity in human serum is destroyed after heating at 56°C for 2 hr.
The Immunologic Significance of Antigen Induced Lymphocyte Transformation in Vitro
Authors: Mills John A.
Published: January 2023

Lymphocytes from guinea pigs immunized subcutaneously with tuberculin and other protein antigens in Freund's adjuvant will undergo a characteristic morphologic transformation on exposure to the sensitizing antigen in tissue culture. This reaction is strongly correlated with the state of delayed hypersensitivity in these animals. Animals immunized intravenously with large doses of antigen develop circulating antibody to ther antigen or hapten, but lymph node lymphocytes obtained from them fail to show the in vitro reaction. Similarly, lymphocytes from animals immunized with hapten-protein complexes respond to the immunizing conjugate but not to the hapten linked to an indifferent carrier despite the presence of hapten specific antibody in the donors.

The technique may provide a means of studying the relationship between delayed hypersensitivity and the cytologic events leading to antibody synthesis.
A Possible Role of γA-Immunoglobulin in Herpes Simplex Virus Infection in Man
Authors: Tokumaru Tadasu
Published: January 2023

The capacities to synthesize γA in normal subjects and persons with primary and recurrent herpetic infections were analyzed and compared. Complications of primary infections and recurrences appeared to be associated with a deficiency of herpes-specific γA. The threshold protective titer of this γA appeared to be 12 to 20. The initial immune response to herpes infection was characterized by a marked increase in the γM titer, followed after 21 days by a predominance of γA and γG. The protective effect of γA in the mucocutaneous tissues appears to be associated with its high avidity for the herpes simplex virus and its active secretion by such tissues.
Reovirus Infection in Suckling Mice: Immunofluorescent and Infectivity Studies
Authors: Kundin W. D. , Liu Chien , Gigstad Judith
Published: January 2023

When reovirus type 1 was inoculated subcutaneously into suckling mice a generally nonfatal pantropic infection ensued. Infectious virus was recovered from most of the tissues tested from 1 hr to at least 20 days later. The greatest amounts of virus were recovered from 3 to 12 days after inoculation. Similarly, viral antigens were observed by fluorescent antibody staining in numerous tissues from 3 to 12 days after inoculation, with maximal antigenic distribution occurring from the 6th to the 9th days.
Immunogenicity of Trinitrophenyl-Hemocyanin: Production of Primary and Secondary Anti-Hapten Precipitins
Authors: Rittenberg Marvin B. , Amkraut Alfred A.
Published: January 2023

The ability of soluble TNP-KLH conjugates to induce production of precipitating antibody was studied in rabbits early in the immune response. A hapten/carrier mole ratio of 800 to 1000:1 was found optimal. Such conjugates induced an average of 375 µg of anti-TNP antibody and up to 2.5 mg of anti-KLH antibody per ml serum within a week after second injection. Some rabbits produced nearly a mg of anti-hapten antibody/ml. Antibody titers obtained here without adjuvants are thus comparable to those obtained to other haptenated proteins when adjuvants are employed. Primary precipitins also were obtained both to hapten and to carrier, but the frequency of primary anti-hapten precipitin detection was only one-fourth that of the anti-carrier response.

Less heavily haptenated conjugates failed to induce anti-hapten precipitins while heavily substituted KLH was only poorly antigenic for either type of determinant.

Preimmunization with KLH appeared to reduce the anti-hapten response subsequent to injections of TNP-KLH. The depressed anti-hapten response in this case was accompanied by a normal secondary response to the carrier.
Serum Immunoglobulin Levels in Human Malaria and Their Relationship to Antibody Production
Authors: Tobie J. E. , Abele D. C. , Wolff S. M. , Contacos P. G. , Evans C. B.
Published: January 2023

The immunoglobulins IgM, IgG and IgA were quantitated in 12 volunteers infected with Plasmodium vivax and five with Plasmodium cynomolgi. The serum levels in each subject were determined sequentially before, during and after the primary malarial attack and in one case after relapse. Large amounts of IgM globulin were produced in all subjects. However, the vivax volunteers, with parasitemias higher than those of the cynomolgi volunteers, showed greater increases in the macroglobulins, 357% as compared to 125%, respectively. In a vivax case who relapsed, essentially as much IgM globulin was synthesized during the secondary as during the primary response.

Large increases in absolute values for IgG globulin were observed in all volunteers but the percent increases in IgG and IgA globulins were not as striking as for the macroglobulins. Nevertheless, the vivax volunteers showed an increase of 42% for IgG globulin and 55% for IgA globulin. The cynomolgi cases, whose infections were somewhat milder, synthesized less of these two immunoglobulins—19% for IgG and 15% for IgA globulin.

The quantitative determinations of the immunoglobulins IgM, IgG and IgA in the primary attack of vivax and cynomolgi malaria demonstrated that there was an increase in each of the three classes of immunoglobulins which paralleled the increase in antibody formation.
Immunoglobulin Isoantigens (Allotypes) in the Mouse
Authors: Warner Noel L. , Herzenberg Leonard A.
Published: January 2023

Rabbits were immunized with either normal mouse immunoglobulins or isolated mouse myeloma proteins from BALB/c or (BALB/c × NZB)F1 plasma cell tumors. The antisera were tested for antibodies directed to allotypic antigenic specificities by the method of inhibition of precipitation of I125 labeled antigens.

Three γG2a and one γG2b allotypic specificities were detected with one or another of these rabbit antisera. These specificities each corresponded in mouse strain distribution with one of the allotypic specificities previously defined through the use of mouse isoantisera.

The possible nature of the allotypic sites versus the class specific antigen sites was briefly discussed and the potential usefulness of these heterologous antisera in allotypic systems noted.
Studies of Human Intrinsic Factor Auto-Antibodies
Authors: Garrido-Pinson Gerardo C. , Turner Michael D. , Crookston John H. , Samloff I. Michael , Miller Leon L. , Segal Harry L.
Published: January 2023

A study of the sera of 19 patients with pernicious anemia by radioimmunodiffusion, by a charcoal adsorption assay and by gel filtration with Sephadex G100, showed conclusive evidence for the occurrence of two types of antibody to human intrinsic factor in the serum of some of these patients. One type of antibody, the “blocking” antibody, detected by the charcoal adsorption assay, reacted with intrinsic factor to prevent subsequent formation of the B12-intrinsic factor complex. Blocking antibody was unable to react with preformed intrinsic factor-B12 complex. The second type of antibody, “binding” antibody, was shown to react either with the intrinsic factor itself or with the intrinsic factor-B12 complex. Although this antibody reacted with intrinsic factor alone, it did not prevent the subsequent combination of intrinsic factor with vitamin B12 which occurred without displacement of the antibody by the B12. Of the 19 sera studied, eight showed the presence of both antibodies, in two the blocking antibody only was detected, and in one only the binding antibody. The antibodies varied in amount independently of one another. From the small number of patients studied, it did not appear that one occurred much more frequently than the other, and there was no obvious correlation between the presence of antibodies and the age of the patient or the duration of the disease. Instrinsic factor which had formed a complex with the binding antibody could still react with the blocking antibody. This reaction occurred without displacement of the binding antibody, indicating that the intrinsic factor molecule has two distinct antigenically reactive sites.
Adoptive Cutaneous Anaphylaxis: a Technique for Studying Antibody Globulin Synthesis
Authors: Battisto Jack R.
Published: January 2023

Lymph node, spleen and peritoneal exudate cells from immunized guinea pigs produce antibody when deposited in the skin of isologous recipients. Presence of antibody is revealed by injecting recipients intravenously with dye and specific antigen 2 to 7 days after cell deposition. No synthesis was detected in nonisogeneic guinea pigs sensitized against donor-type lymphoid cells or in certain other homologous, nonsensitized recipients.
Synthetic Polypeptide Metabolism
Authors: Carpenter Charles B. , Gill Thomas J. , Mann L. T.
Published: January 2023

The metabolic fate in rabbits of intravenously administered, iodine-labeled poly d-Glu55d-Lys39-d-Tyr6 differs markedly from that of its enantiomorph, poly Glu58Lys36Tyr6 (No. 2). Although both polymers are rapidly cleared from the circulation, 131I is slowly excreted in the urine after d-polymer injection, but quite rapidly excreted after l-polymer injection. Only 32% of the d-polymer is degraded by the 19th day, whereas 83% of the l-polymer is degraded by the 7th day. This delay in the degradation of the d-polymer is reflected in the retention of large amounts of the injected material in the liver and in the kidneys. The amount of d-polymer in the liver slowly declines from a maximum of 16% at 5 days, but the amount in the kidney continues to increase for 2 to 3 weeks and ultimately reaches 32% of the injected polymer.

Radioautographic studies show that both polymers enter the proximal tubular cells of the kidney: the d-polymer persists, whereas the l-polymer is quickly eliminated. Studies with ureteral ligation to stop glomerular filtration demonstrate that the polymers are filtered through the glomerulus and then reabsorbed.

Anephric animals show a slower serum elimination rate for the d-polymer than normal animals. Since the hepatic uptake is unchanged, it is likely that the kidney rapidly extracts a certain population of the d-polymer molecules which are not as readily taken up by the liver. Since ultracentrifugation of the labeled d-polymer prior to injection does not affect its distribution, the basis for this biologic heterogeneity is not aggregation.

Chromatographic analyses of the dialyzable radioactivity in the urine and in the homogenates of the liver and kidney clearly show the presence of labeled peptides derived from the degradation of the d-polymer or of the l-polymer.

A second external label, 59Fe-ferrocene, confirms the serum elimination and urinary excretion patterns obtained with iodine, and, in general, also confirms the organ retention pattern of the d-polymer. However, significant incorporation of the iron from the ferrocene into hemoglobin and other compounds occurs, and this fact limits the usefulness of the ferrocene label, especially for studies of tissue localization.

The prolonged retention of the d-polymer in the organs and its gradual release over a long period of time are postulated to cause immunologic paralysis. This hypothesis explains the apparent lack of immunogenicity of d-polymers under the usual conditions of immunization and the lack of a significant booster effect and the ultimate disappearance of circulating antibody following repeated injections of small amounts of the d-polymer.
Passive Serologic Transfer of Allograft Immunity in Immunologically Suppressed Mice
Authors: Kinne David W. , Simmons Richard L.
Published: January 2023

The administration of a single injection of rabbit anti-mouse lymphocyte serum (RAMLS) to C57 adult male mice results in a profound circulating lymphopenia. The lymphocyte levels return gradually to normal over the succeeding 2 weeks. Coincident with the circulating lymphopenia, the survival of A strain skin grafts on these C57 mice is markedly prolonged. Rejection occurs when the circulating lymphocyte levels are approximately normal. The administration of C57 anti-A immune mouse serum (IMS) to recipients of RAMLS reverses the prolongation of A skin grafts on these mice. The administration of normal C57 mouse serum (NMS) has no effect on graft survival in RAMLS-treated mice. Neither NMS nor IMS has any effect on the pattern of circulating lymphocyte repopulation in RAMLS-treated mice. The survival of Balb/C skin grafts on RAMLS treated C57 mice is not affected by the administration of C57 anti-A IMS. The results support the concept that humoral antibody may act in synergism with lymphocytes in skin allograft rejection.
Nephritogenic Properties of Cross-Reacting Kidney-Fixing Antibodies to Heart, Spleen and Muscle
Authors: Katz David H. , Unanue Emil R. , Dixon Frank J.
Published: January 2023

Cross-reacting kidney-fixing antibodies may cause an immediate (heterologous) nephrotoxic serum nephritis if: a) a sufficient amount of antibody is injected, and b) if the kidney has enough cross-reacting antigenic determinants to allow fixation of a nephritogenic amount of antibody. If these two conditions are met, cross-reacting kidney-fixing antibodies are effective in inducing immediate nephritis. A cross-reacting kidney-fixing antiserum which reacts with only a small number of glomerular antigenic determinants cannot alone cause immediate nephritis. However, if such antisera are injected simultaneously with subnephritogenic amounts of anti-kidney antibody, their combined effect may be immediately nephritogenic. All cross-reacting kidney-fixing antibodies are so anatomically situated in the glomerulus that they can participate in delayed or autologous nephrotoxic serum nephritis. The cross-reacting kidney-fixing antibodies have shorter half-disappearance times from the kidney than true anti-kidney antibodies.
Antibodies against Human Leukemia Cell Lines
Authors: Tanigaki Nobuyuki , Yagi Yasuo , Moore George E. , Pressman David
Published: January 2023

Five groups of antibodies differing in their specificities were characterized in rabbit antisera against two cultured human leukemia cell lines, #6410 and A-LK1D.

These are: 1) antibodies specific to individual leukemia cell lines, 2) antibodies reacting with other leukemia cell lines as well, 3) antibodies reacting as in 2 and in addition with lymphoid organs and with leukocytes, 4) antibodies reacting as in 3 and in addition with liver and kidney and 5) antibodies reacting as in 4 and in addition with nonleukemia cell lines of human origin.

The groups were characterized by the use of a paired label radio-antibody technique adapted to tissue sections or cell smears to test the reactivities of remaining antibodies after exhaustive absorption of antibodies with various organs and cultured cells.
Interaction of Penicillin and Erythrocytes
Authors: Josephson Alan S. , Kaplan Allan P.
Published: January 2023

The previously determined pH dependance of erythrocyte sensitization by penicillin was confirmed. It was also observed that penicillin does not sensitize erythrocytes at 0° or 4°C. The failure of fluoride, iodo-acetate, ouabain and glucose deprivation to block red blood cell (RBC) sensitization indicates that the sensitization process is independent of metabolic activity.

Sensitization of erythrocytes by penicillenic acid was inhibited by serum or molar concentrations of lysine or ε-amino caproic acid. Sensitization of erythrocytes by penicillin was unaffected by the presence of these same agents in the reaction mixture. Treatment of erythrocytes with 1,3-difluoro-4,6-dinitrobenzene or 2,4-dinitro-fluorobenzene prevented sensitization of RBC by penicillenic acid, but did not prevent sensitization by penicillin. These observations suggest that penicillin directly sensitizes erythrocytes without prior transformation to penicillenic acid, and that penicillin may react with a receptor other than the amino group on the red cell surface.
Differentiation of Arboviruses by Immunoelectrophoresis
Authors: Cuadrado Raul R. , Casals Jordi
Published: January 2023

A simple immunoelectrophoresis (IE) method has been shown to be useful and rapid in the antigenic study of arboviruses. Initial evaluation was made by testing viruses of groups A, B, Tacaribe and vesicular stomatitis in their homologous systems by the complement-fixation, hemagglutination-inhibition and IE methods. Seven strains of Sindbis virus were readily differentiated in IE studies, but dengue type 1 virus could not be distinguished from strain TH-Sman nor dengue type 2 from strain TH-36. Results of additional IE tests with a few samples of convalescent and apparently normal human sera suggest that this method may also be useful as a diagnostic procedure in the study of arboviruses.
Effect of Anticoagulants on Delayed Hypersensitivity Reactions
Authors: Cohen Stanley , Benacerraf Baruj , McCluskey Robert T. , Ovary Zoltan
Published: January 2023

Administration of heparin or warfarin to sensitized guinea pigs resulted in diminution or prevention of delayed sensitivity reactions. This effect was found in animals sensitized either to a protein conjugate (DNP-BGG) or to a contact-sensitizing chemical (OCBC). Guinea pigs recovered quickly from the inhibitory effect of heparin, paralleling the return to normal of the coagulation time. The amount of heparin employed in these experiments did not result in depression of serum complement levels.

The administration of chondroitin sulfate, a compound structurally similar to heparin but lacking its anticoagulant action, had no effect on contact sensitivity reactions.

Heparin treatment of contact sensitive guinea pigs did not interfere with the capacity of their lymph node cells to transfer contact reactivity to normal recipients.

Heparin failed to inhibit nonimmunologic inflammatory reactions elicited by bovine fibrinogen or poly-l-lysine, although these reactions bore some gross and histologic resemblance to delayed reactions.

The inhibition of dermal hypersensitivity reactions (DNP-BGG) by heparin was not accompanied by an interference with the booster effect of the skin test on the production of circulating anti-DNP antibodies.

It is concluded that heparin and warfarin exert their inhibitory effect on delayed reactivity through some action on the coagulation mechanism which probably results either in the prevention of accumulation of immunologically nonspecific inflammatory cells or somehow blocks the triggering events initiated by interaction of antigen with sensitized cells.
Similarities between Rabbit Antibodies Produced Following Ingestion of Bovine Serum Albumin and Following Parenteral Immunization
Authors: Rothberg Richard M. , Kraft Sumner C. , Farr Richard S.
Published: January 2023

The immune responses of rabbits fed low concentrations of bovine serum albumin (BSA) have been characterized and compared to the immune responses of rabbits injected with BSA either i.v. or s.c. in oil. The qualities of the antibodies produced were evaluated by the following criteria: 1) the average strength of the antibody-antigen bond as measured by the effect of dilution on the antigen-binding capacity; 2) the changes in strength of the antibody-antigen bond during immunization; 3) the association of BSA binding with heavy and light immunoglobulin fractions; 4) the association of BSA binding with the γA-immunoglobulins; 5) passive hemagglutinating capacities; 6) antigen-precipitating capacities and efficiencies; and 7) alteration of antibody activity by treatment with 2-mercaptoethanol.

Despite possible alteration of the antigen by digestive functions, local initiation of antibody production in lymphoid tissue associated with the gastrointestinal tract and quantitative differences among the three groups, the antibodies present in the sera from orally immunized animals qualitatively were similar to antibodies produced following parenteral immunization, as judged by the above criteria.

Light as well as heavy immunoglobulins with anti-BSA activity were present in the earliest antisera from all three immunization groups.

These findings and the previous demonstration that antibodies produced following oral or s.c. in oil immunization have similar immunologic specificities, suggest that most of the cellular mechanisms of antibody production basic to parenteral immunization are operative during oral immunization.
Autoradiographic Experiments Concerning the Importance of Mononuclear Cells in Experimental Hepatitis
Authors: Warnatz H. , Scheiffarth F. , Wolf F. , Schmidt H. J.
Published: January 2023

Lymphocytes of inbred mice were labeled with H3-thymidine after liver damage was induced by sensitization with homologous liver extract or by poisoning with carbon tetrachloride, respectively. Autoradiographic technique showed that the count of labeled lymphocytes in the liver of recipients was greater when lymphocytes from liver damaged animals were transferred than in control animals receiving lymphocytes from normal mice or mice treated with Freund's adjuvant alone. The percentage of labeled cells in the spleen was the same in all groups. The meaning of these findings for the development of experimental hepatitis is discussed.
The Alteration of Endotoxin by Postheparin Plasma and its Purified Fractions
Authors: Schultz Duane R. , Becker Elmer L.
Published: January 2023

Postheparin plasma from the guinea pig or its euglobulin fraction caused 1) a significant detoxification of the endotoxin from E. coli when assayed for toxicity for 11-day-old chick embryos, 2) a reduction in endotoxin turbidity, and 3) the release of unesterified fatty acids when incubated with endotoxin. The euglobulin fraction required the presence of bovine serum albumin for maximum endotoxin detoxifying activity.

Normal guinea pig plasma or its euglobulin fraction caused little or no detoxification of endotoxin, no reduction in turbidity and no lipase activity.

The addition of endotoxin to a postheparin plasma-chylomicron mixture resulted in the release of more unesterified fatty acids than were released from the same mixture without the addition of endotoxin. The increase was dependent upon the amount of endotoxin and postheparin plasma.

The enzyme lipoprotein lipase was present in each purified fraction of postheparin plasma which detoxified endotoxin. The ability of the lipase to clear fat-containing plasma and to cause a release of unesterified fatty acids from lipid paralleled, but was not necessarily related to similar effects on endotoxin.
Interaction of Rheumatoid Factors with Urea-Denatured Human γ-Globulin and its Subunits
Authors: Hirose Shun-Ichi , Osler Abraham G.
Published: January 2023

Studies on the antigenicity of human γ-globulin, denatured by 6 M urea, stress the association of modified conformational structures with the appearance of antigenic determinants for the human rheumatoid factors. Two types of antigenic determinants have been identified in denatured human γ-globulin. One is apparently due to intramolecular modification, while the second requires the interaction of several γ-globulin molecules.
Serologic Survey of Man for Avian Leukosis Virus Infection
Authors: Piraino F. , Krumbiegel E. R. , Wisniewski H. J.
Published: January 2023

Six current lots of 17 D yellow fever virus vaccine propagated in chicken embryos were found to be contaminated with complement-fixing group antigens of avian leukosis virus.

Bloods of 111 individuals vaccinated with 22 different lots of the 17 D vaccine given up to 54 months before drawing a blood specimen were tested for neutralizing antibody to Bryan standard strain of Rous sarcoma virus. None was found in any of the bloods tested.
Repeated Infections with Respiratory Syncytial Virus
Authors: Beem Marc
Published: January 2023

The occurrence of two symptomatic virus-shedding infections with R.S. virus has been documented in 11 patients. The occurrence of these reinfections could not be attributed to antigenic variation of virus, age of patient at the time of first infection or prolonged interval of time between infections.
Structural Characteristics of Hemolytic Antibodies As Determined by the Effects of Ionizing Radiation
Authors: Rosse Wendell F. , Rapp Herbert J. , Borsos Tibor
Published: January 2023

Some structural characteristics of rabbit IgG and IgM hemolytic antibodies have been deduced by target theory analysis of the relationship between the dose of ionizing radiation and the inactivation of the molecule. The destruction of a single target with a molecular weight of 52,000 in the IgG molecule is sufficient to destroy the hemolytic activity. Our data are consistent with a model of the IgM molecule containing more than three subunits each of molecular weight 1.6 to 1.8 × 105. In this model, each subunit is capable of combining with antigen and two adjacent subunits are required for the fixation of C′ and for hemolytic activity.
Studies of Rickettsia mooseri Cell Walls
Authors: Wood William H. , Wisseman Charles L.
Published: January 2023

Immunologic studies were performed in mice, guinea pigs and man with cell wall and cytoplasmic fractions of Rickettsia mooseri obtained by mechanical disruption. On a weight basis, cell walls were more effective antigens than either whole rickettsiae or cytoplasmic fraction in the following tests: typhus group complement-fixation and hemagglutination tests and stimulation of antitoxic immunity in mice and anti-infectious immunity in guinea pigs. Cell walls also elicited a delayed type skin reaction in hypersensitive human subjects and a toxic skin reaction in nonsensitive subjects. It was concluded that the antigens involved in these tests were located in or on the cell wall.
Adoptive Immunity to Intracellular Infection
Authors: Frenkel J. K.
Published: January 2023

Cells of spleen and lymph node transferred specific immunity to Besnoitia jellisoni and Toxoplasma gondii, both obligate intracellular protozoa. Between isogeneic hamsters, direct transfer was effective. For allogeneic transfer it was necessary to use irradiated or tolerant hamsters as recipients. The bone marrow, thymus, liver and kidney cells of the immune donors were ineffective, as were lysed lymphoid cells, or intact lymphoid cells from immune donors that had been irradiated.

Antiserum showed a slight protective effect, and increased the amount of immunity transferred by cells. Nevertheless, antibody did not appear to account for the transfer of immunity, as cell effects were dependent on cell survival and were not abolished by washing, trypsinization or treatment with rabbit-anti-hamster serum. Cells from heterospecifically immunized hamsters were ineffective by themselves and were not potentiated by specific antiserum.

Both clinical immunity and transferable cellular immunity appeared after 3 weeks. Delayed hypersensitivity and antibody were already present on the 5th day of infection.

Immunity to equine rhinopneumonitis virus infection could be transferred by both cells and antiserum, but not by lysed cells.

Two types of immunity have been shown to be mediated by cells: anti-virus immunity which clears infection, and anti-protozoan immunity of the premunition type, sensitive to hypercorticism.
Reaction Kinetic Studies of the Antigen Antibody Reaction
Authors: Tengerdy Robert P.
Published: January 2023

By the combined use of fluorescence quenching, fluorescence polarization, light scattering, and saturated (NH4)2SO4 precipitation techniques the kinetics of the various phases of the antigen antibody reaction between conalbumin and anticonalbumin was studied. It was shown that the kinetic course of the reaction depended on the mole ratio of antigen to antibody; in the Ab excess zone the reaction consisted of two soluble phases, a rapid primary reaction and a much slower secondary reaction (lattice formation), but in the Ag excess zone there was only one phase. The Q10 of the reaction was 1.25 in the large Ab excess zone and 1.16 in the large Ag excess zone, indicating that temperature had little effect on the kinetics of the reaction either in the Ab excess zone or the Ag excess zone. The optimum pH of the reaction was 7.5, the optimum ionic strength in the range of 0.1 to 0.2.
Regenerative Potential of Immunocompetent Cells
Authors: Nettesheim P. , Makinodan T. , Williams M. L.
Published: January 2023

The principal findings reported in this communication are: 1) the minimum antigen dose necessary to initiate a near maximum antibody response is about 105 times greater for irradiated than for unirradiated spleen cells, and 2) the compartment of immunologically committed progenitor cells (PC2) lacks the potential to recover from an x-ray insult and appears not to have significant self-generating potential.
Protein-Carbohydrate Interaction
Authors: So Lucy L. , Goldstein I. J.
Published: January 2023

The extent to which a number of saccharides inhibit concanavalin A-dextran interaction has been examined by means of the quantitative hapten inhibition technique involving nitrogen analyses of washed precipitates. The results of these studies are in essential agreement with previous studies employing a turbidimetric procedure.

The combining sites of the concanavalin A protein molecule are shown to be complementary to the C-3, C-4 and C-6 hydroxyl groups of α-D-glucopyranosyl and α-D-mannopyranosyl units. Any modification of the C-6 hydroxyl group of methyl α-D-glucopyranoside virtually eliminates the capacity of the resultant sugars to bind to the combining sites of concanavalin A.

On the basis of these data it is concluded that the H-atom of the C-6 hydroxyl group forms a hydrogen bond with the protein.
A Plaque Reduction Test for Dengue Virus Neutralizing Antibodies
Authors: Russell Philip K. , Nisalak Ananda , Sukhavachana Pairatana , Vivona Stefano
Published: January 2023

A technique for performing a plaque reduction test for dengue virus neutralizing antibody is described. Experiments designed to test the accuracy of the antibody measurement are presented and analysed by the method for a parallel line graded response assay. Statistical analysis indicates a high degree of accuracy, and the relative merits of this type of test for dengue neutralizing antibody are discussed.
Effects of Actinomycin D on the Primary Hemolysin Response in Rats
Authors: Ćirković Dimitrije M. , Simić Miroslav M.
Published: January 2023

The initial hemolysin response was studied in 10 series of rats treated with 0.25 or 0.375 mg/kg actinomycin D from 8 hr before to 3 days after one injection of sheep red blood cells. The following results, as compared to an untreated control series, were obtained. The drug, when given early, strikingly prolonged the latent period but not the rate, time or amount of hemolysin formed. The drug, when given at about the midpoint of the latent period, still prolonged the latent period and, in addition, markedly depressed the average rate of accumulation and peak titer. This depressing effect was even more evident when the drug was given after the latent period was completed and the production phase of synthesis was just beginning, but was less evident when the drug was given later, i.e., when the production phase of synthesis was well advanced. These findings are discussed in relation to the various stages of hemolysin formation and indicate that the drug acts more effectively on the proliferation and differentiation of immunologically competent cells and less effectively on antibody synthesis in differentiated Ab-forming cells.
Delayed Contact Sensitivity to Catechols
Authors: Baer Harold , Watkins Roy C. , Kurtz A. Peter , Byck Joseph S. , Dawson Charles R.
Published: January 2023

Catechol as well as the 3-n-alkylcatechols, were shown to be equally good in inducing delayed contact sensitivity in guinea pigs since the majority of animals injected became sensitive. Consequently the capacity to induce sensitization, as measured by the percentage of animals becoming sensitive, is unrelated to the structure of the 3-n-alkylcatechols. The degree of sensitivity induced as well as cross-reactivity depended upon the length of the 3-n-alkyl side-chain. Thus the degree of sensitivity induced is strongly dependent on the structure of the sensitizer (in this instance chain length) and largely independent of sensitizing dose. The data obtained suggested that it was possible to estimate the maximum length of the antigenic determinant. The dermal toxicity of the alkylcatechols was shown to be unrelated to their sensitizing capacity.
Immunoglobulins of the Leopard Shark
Authors: Suran Anita A. , Tarail Mary Hyde , Papermaster Ben W.
Published: January 2023

The rate of antibody production by the leopard shark, Triakis semifasciata was studied. Two immunoglobulins were elicited, first a 17 S macroglobulin and as intensive immunization continued increasing amounts of 7 S immunoglobulin. Both immunoglobulins were active as phage neutralizing antibodies and contained precipitating antibodies as measured by a microprecipitin test using I125 hemocyanin antigen. Shark immunoglobulins were produced at a slower rate than rabbit or mouse antibodies in response to similar antigenic challenge, and on a weight basis shark antibody precipitated or neutralized less antigen. When studied as antigens using rabbit antishark serum the 7 S and 17 S immunoglobulins appear to be identical. Both are inactivated to the same extent by a reducing agent, dithioerythritol. Dithioerythritol splits the 17 S protein to 7 S units which are antigenically identical with the original 17 S and 7 S proteins. The heavy and light chains derived from each of the immunoglobulins are indistinguishable when tested as antigens with rabbit anti-shark serum.
Cross-Reactions of the Group-Specific Polysaccharides of Streptococcal Groups B and G in Anti-Pneumococcal Sera with Especial Reference to Type XXIII and its Determinants
Authors: Heidelberger Michael , Davie Joseph M. , Krause Richard M.
Published: January 2023

Quantitative data are given on the extensive cross-reactivity of the group polysaccharides of streptococcal groups B and G in antipneumococcal type XXIII horse serum and on inhibition-reactions in this antiserum. L-Rhamnose, known to be a principal determinant of the two streptococcal substances, is even more easily split off from the specific polysaccharide of pneumococcal type XXIII. This, and the ready inhibition of both the S XXIII anti-XXIII and group B anti-XXIII reactions by L-rhamnose, show that this sugar, probably in the form of non-reducing end-groups, is also a major determinant of S XXIII. D-Galactose is also involved in the specificity of S XXIII and may reinforce the cross-reaction.
Mixed γG-γM Cold Agglutinin
Authors: Goldberg Leonard S. , Barnett Eugene V.
Published: January 2023

A mixed γG-γM cold agglutinin occurring in a patient with hemolytic anemia associated with infectious mononucleosis is described. Utilizing the technique of quantitative complement fixation, both γG and γM were detected in a 4 to 3 ratio in the eluate. Neither the γM nor γG chromatographically separated fractions of the eluate showed any cold agglutinin activity alone. When these two fraction were mixed, cold agglutinin activity was re-established. The addition of normal γG to the chromatographically separated γM cold agglutinin or the addition of normal γM to the γG cold agglutinin did not result in detectable cold agglutinin activity. The agglutinating activity of the patient's serum against O Rh positive red blood cells sensitized with an incomplete γG-antibody (anti-CD serum Ripley) was 500 times greater at 4°C than at 37°C.

Evidence is presented which suggests that the γG component of the cold agglutinin was directed against red cell antigenic determinants, and that the γM component represented antibody active at 4°C against the γG coating the red cells, i.e., “cold anti-antibody.”.
Biologic Properties of a Non-Precipitating Antigen from Timothy Pollen Extracts
Authors: Malley Arthur , Harris Raymond L.
Published: January 2023

The close antigenic relationship of antigen D and allergen B was demonstrated by inhibition of both passive cutaneous anaphylaxis (PCA) and precipitation in agar gel. The antigenic relationship of allergen A and B was demonstrated by a line of partial identity in microdouble diffusion analysis.

Antigen D possesses haptenic properties as demonstrated by its inhibition of PCA, anaphylaxis and precipitin reactions of either rabbit or guinea pig antisera to timothy pollen antigens.

The antigenic character of antigen D is demonstrated by its direct positive skin reactions in timothy-sensitive patients and by its induction in rabbits with varying amounts of antibody demonstrable with allergen B but not with antigen D.
The Effect of Antibody on the Induction of Tolerance to Human γ-Globulin in Icr Albino Mice
Authors: Havas H. Francis , Senff Kristin
Published: January 2023

Tolerance to human γ-globulin (HGG) was achieved in neonate and adult random-bred ICR mice following a single intraperitoneal injection of 1 to 10 mg of HGG.

The duration of tolerance depended on the amount injected and the age of the animal at the time of injection. Antibody production occurred at times, following antigenic challenge, when detectable amounts of antigen were still present in the serum of the once tolerant animals.

Following recovery from unresponsiveness the initial antibody response had the characteristics of a primary response and antibody levels of the once tolerant mice remained lower than those of immunized mice for several months. Spontaneous antibody production (without prior antigenic challenge) was only rarely observed and it was always transient.

Antiserum had an effect on hastening the loss of tolerance of an older group of adult tolerant mice, but it did not enhance the immune response of younger mice.

When small amounts of high-titered antiserum were administered to neonate tolerant mice at birth, it affected the induction of tolerance, and antibody levels of these mice were higher than those of tolerant mice not injected with antibody. There was no effect on neonate tolerant mice when antiserum was administered during the tolerant state up to the time of recovery.

Since antibody levels were comparable in both the serum and the ascites fluid (obtained by the injection of sarcoma 37 tumor cells), ascites fluid served as the source of antibody.

No precipitating antibody was formed by either immunized mice or those which had lost tolerance. Hence, all antibody levels were tested by the passive tanned cell hemagglutination method.
Effect of Anti-Allotype Sera on Hemolytic Plaque Formation by Single Rabbit Spleen Cells
Authors: Ingraham J. S. , Biegel A. A. , Watanabe M. R. , Todd C. W.
Published: January 2023

Examination of the effects of anti-allotype sera on hemolytic plaque formation by rabbit spleen cells has revealed the following effects: Plaque formation is usually inhibited by the anti-allotype sera if the cells are obtained from rabbits undergoing the initial response to sheep red blood cells.Plaque formation is usually enhanced by the anti-allotype sera if the cells are obtained from rabbits undergoing the secondary response to sheep red blood cells.A single anti-allotype serum directed against an allotypic specificity present on either the H-chain or the L-chain may give either inhibition or enhancement depending upon the source of the PFC as given in 1 and 2 above.Both the inhibition and the enhancement appear to be mediated through the action of the anti-allotype sera on the hemolysin produced rather than directly on the cells producing it.
Synthesis of Immunoglobulins by Human Cell Lines in Tissue Culture
Authors: Finegold Ira , Fahey John L. , Granger Harriet
Published: January 2023

Immunoglobulin synthesis has been demonstrated in 19 of 27 lymphoid cell lines in continuous culture derived from patients with a variety of malignant disorders. Soluble proteins derived from cells grown in media containing C14-amino acids were tested by radioimmunoelectrophoresis with antiserums specific for IgG, IgA, IgM and IgD and κ and λ light polypeptide chains. Immunoglobulins synthesized in vitro ranged from only one light chain type to two heavy chains and two light chain types in individual culture lines.

Physical and immunochemical techniques showed that many of the newly synthesized heavy and light chains were linked to form 7 S or 18 S immunoglobulin molecules. Immunochemical tests indicated that immunogloblins produced by the cultured cell lines were very similar or identical to normal human immunoglobulins. Stability of immunoglobulin formation was assessed by repeat tests of 15 cell lines, and only two cell lines varied in results. The immunoglobulins produced by these cells are electrophoretically homogeneous and thus bear some resemblance to myeloma proteins.

Investigation of serum from patients with Burkitt's lymphoma and chronic myelogenous leukemia, failed to reveal serum immunoglobulin components comparable to the proteins identified in culture. These findings indicate that lymphoid cells producing immunoglobulin in culture may be functionally different from the predominant malignant cell (in vivo) in the donor patients and from the malignant plasma cells of patients with multiple myeloma. It seems possible that the lymphoid cells in culture are derived from a minor part of the malignant cell population or from normal cells.

Herpes-like virus particles are present in most of the cell lines. Immunoglobulin production appeared to be independent of the presence of viral particles.
Chromic Chloride: A Coupling Reagent for Passive Hemagglutination Reactions
Authors: Gold E. R. , Fudenberg H. H.
Published: January 2023

The passive hemagglutination procedure using a chromium chloride solution to bind antigens and antibodies to red cells has been investigated. The CrCl3 method of coating red cells is rapid and simple, and serologic sensitivity and immunologic specificity are retained. The present studies showed that group O human red cells coated with antigen by the CrCl3 procedure can be used in a number of serologic reactions. In particular, use of CrCl3-treated cells as immunoadsorbent provides a rapid method for the preparation of monospecific antisera to human immunoglobulins. The immunoglobulin content of pathologic sera can be estimated by the degree to which the pathologic serum inhibits an appropriate agglutination system consisting of cells coated with γG-, γA- or γM-globulin by the CrCl3 method and of homologous antibody. “Purified” immunoglobulin preparations can be assessed for contamination by similar inhibition of agglutination of red cells coated with immunoglobulins by the CrCl3 method.
Antigenic Variants of Arboviruses
Authors: Henderson J. R. , Levine S. I. , Karabatsos N. , Stim T. B.
Published: January 2023

A method for monitoring variations in antigenic constitution of arbovirus strains has been developed. The technique is based upon the magnitude of cross neutralization of virus strains by antisera prepared against virus fractions obtained from gradient sedimentation of a single strain. At a specific point in time, antigenically distinct Western encephalitis viral populations were found to coexist within various tissues of an infected mouse. The antigenic nature of such populations was found to be unstable and in a continuous state of flux. Eastern encephalitis virus strains had distinct antigenic properties when stocks were examined directly. The antigenic properties also varied when strains were carried from one passage to another in mice or in tissue culture, or when passaged in parallel in mice and tissue culture. The phenomenon of antigenic variation of strains was explained in part by the differential selection and ultimate accumulation of certain antigen subpopulations over others during virus replication in various tissue or cell types.
Antigenic Variants of Arboviruses
Authors: Henderson J. R. , Levine S. I. , Stim T. B. , Karabatsos N.
Published: January 2023

When EE or WE virus strains were serially passaged in tissue culture, constituent antigen properties were expressed at the specific passage level when there occurred an equilibrium in subpopulation antigens. The equilibrium could be recognized only under defined conditions of host passage and was measured by specifically designed serologic techniques. WE virus strains were found to comprise two groups, each with distinct constituent antigen properties. EE virus strains comprised four groups, each with distinct constituent antigen properties. Certain South American type EE strains had constituent antigen properties identical to certain North American type EE strains.
Studies on the Mechanisms of Hypersensitivity Phenomena
Authors: Levy David A. , Osler Abraham G.
Published: January 2023

Passive sensitization, in vitro, of human leukocytes with serum from ragweed-sensitive individuals is enhanced by heparin (ca. 10-6 M). The potentiating effect of heparin is even more evident in the presence of 4 × 10-3 M ethylenediaminetetraacetate (EDTA). The synergistic action of the two compounds on passive sensitization suggests different sites or mechanisms of enhancement. A suggested mode of action involves a net increase in negatively charged membrane sites capable of interaction with cationic residues on the immunoglobulin molecules.

Unlike EDTA, heparin does not influence the cellular histamine release mechanism. The available data suggest that the enhancing effect of heparin may be independent of the blood clotting mechanism. However, the ability of heparin to augment passive sensitization under in vitro conditions, is shared by other mucopolysaccharides with anticoagulant activity.
The Role of Antibody Bivalence in the Neutralization of Bacteriophage
Authors: Klinman Norman R. , Long Carole A. , Karush Fred
Published: January 2023

The neutralization of bacteriophage R 17 was studied with rabbit antibody induced by R 17 and several modified antibody preparations derived from the γG-immunoglobulin fraction of the antiserum. To assess the role of bivalence and the Fc fragment in the neutralization reaction both 7 S and 5 S monovalent and bivalent antibody derivatives were tested as well as monovalent 3 S antibody. The bivalent preparations as a group gave K values at least 30-fold larger than the monovalent antibodies. Within each group there was little if any significant variation. The important role of bivalence, in contrast to the Fc fragment, is attributed to the increased affinity of the antibody for the bacteriophage arising from the bivalence of the antibody and the presence of multiple identical antigenic determinants on the bacteriophage. It is suggested that bivalence was the result of an evolutionary development whose selection was favored because of the increased protection it provided against infectious disease.