bluuebunny/crossref_metadata_2025 huggingface dataset:
Subgroup-Specific Antigenic Marker on Immunoglobulin λ Chains: Identification of Three Subtypes of the Variable Region
Authors: Tischendorf Frank W. , Tischendorf Margrit M. , Osserman Elliott F.
Published: December 2022

Three distinct classes of human k light polypeptide chains have been detected immuuochemically (1). The three antigenic types correspond to the three basic variable sequences designated as ki, kii and kiii (2). In previous reports (3, 4) we described two specificity region subgroups of human λ chains tentatively called (St+) and (St-), differing in antigenic determinants localized on the variable (V) or NH2- terminal region of the λ molecule.

In the course of studies on the delineation of the (St-) subgroup with various antisera, several rabbit antisera were encountered which showed differences among (St-) type Bence Jones proreins and λ chains of myeloma proteins in immunodiffusion analysis. Similar differences were found for the (St-) type proteins of normal serum. The antigens involved correlate with certain structures of the V region of the λ polypeptide chain.

Myeloma proteins and Bence Jones proteins were isolated and typed with respect to subgroup (4).
Enhancement by Reducing Agents of the Transformation of Human and Rabbit Peripheral Lymphocytes
Authors: Fanger Michael W. , Hart David A. , Wells J. Vivian , Nisonoff Alfred
Published: December 2022

Lymphocytes may be stimulated to undergo transformation into blast cells by a variety of nonspecific chemical agents, or by antiglobulin or antilymphocyte antisera. Antigens act as mitogenic agents on lymphocytes from sensitized animals (1-3).

We have now observed that the action of various mitogens on human and rabbit peripheral lymphoeytes is markedly enhsnced in the presence of the reducing agents, l-cysteine, glutathione, or sulfite.

Rabbit peripheral lymphocytes were isolated, purified on a cotton-wool column and cultured as described previously (4). Human leukocytes were obtained from the blood of normal individuals by allowing the cells to settle in 10% Plasmagel (Laboratoire Roger Bellon, Neuilly, France). The leukocyte-rich layer was removed and the cells were washed several times with 20% decomplemented fetal calf serum in Eagle's minimal essential medium (MEM). Leukocytes were cultured (4) at a concentration of 106 cells/ml. Rabbit lymphoeytes were cultured for 48 hr and human leukocytes for 108 hr; 24 hr before harvest, 5 µCi of 3H-thymidine (6.7 Ci/mM) was added to the rabbit lymphocyte cultures and either 5 µCi or 2 µCi of 3H-thymidine to the human leukocyte cultures. Radioactivity incorporated into DNA was determined as described previously (4).
Predominant Contribution of IgA Antibody-Forming Cells to an Immune Response Detected in Extraintestinal Lymphoid Tissues of Germ-free Mice Exposed to Antigen by the Oral Route
Authors: Bazin H. , Levi G. , Doria G.
Published: December 2022

Germ-free mice exposed to sheep RBC by the oral route displayed an immune response in extraintestinal lymphoid tissues. Such a response in the spleen and mesenteric lymph nodes was characterized by a high percentage of PFC of the IgA class, and is at variance with that found after parenteral immunization.
Passive Hemagglutination
Authors: Wolberg Gerald , Liu Chi Tan , Adler Frank L.
Published: December 2022

Aggregates of mildly denatured bovine serum albumin (BSA) present antigenic determinants which are not found in native or denatured but unaggregated BSA. Antibody against these determinants appears early and often transiently in rabbits immunized with denatured or native BSA emulsified in Freund's incomplete adjuvant. Using agglutination of tanned red cells, coated by exposure to native or denatured BSA, to detect and measure antibody activity against BSA, it was shown that adding trace amounts of gelatin to the coating solution significantly reduces the sensitivity of the test. This effect is related to gelatin's highly efficient adsorption to tanned red cells. The degree of reduction in sensitivity varies with the antiserum tested.
Immunochemical and Biologic Properties of Rat IgE
Authors: Stechschulte Daniel J. , Orange Robert P. , Austen K. Frank
Published: December 2022

An electrophoretically fast, antigenically unique rat immunoglobulin with hapten specificity has been identified and termed IgE. Monospecific antiserum for rat IgE removed from rat antiserum the biologic activities attributed to rat homocytotropic antibody. Thus, the immunoglobulin class of rat homocytotropic antibody is IgE.
Role of Lymphoid Cells in Passive Transfer with Plasma of Delayed Hypersensitivity in Guinea Pigs
Authors: Dupuy J. M. , Good R. A.
Published: December 2022

Specific skin reactions to purified protein derivatives could frequently be transferred with plasma or serum from heavily irradiated sensitized guinea pigs. Splenic lymphocytes from a non-sensitized animal that had been incubated for 90 minutes with plasma capable of transferring sensitivity became able to effect such a transfer. Latex particles, red blood cells, or thymocytes could not effect the transfer nor could spleen cells treated in vitro with large amounts of mitomycin C. It is concluded that only certain lymphoid cells may have receptors at their surfaces for attachment of the factor that is responsible for transferring sensitivity, and that the viability and the ability of these cells to replicate are essential for the passive transfer of delayed hypersensitivity.
Activation of Normal Rabbit Macrophage Monolayers by Supernatants of Antigen-Stimulated Lymphocytes
Authors: Mooney John J. , Waksman Byron H.
Published: December 2022

Tuberculin- or HSA-sensitized rabbit lymph node cells, harvested at 10 to 14 days, and normal rabbit lymph node cells were incubated for 24 hr alone or in the presence of specific or heterologous antigen. The supernatants prepared from these lymph node cell cultures were added to duplicate or triplicate monolayer cultures of peritoneal macrophages from normal rabbits, each macrophage being exposed to soluble products released in vitro by 10 lymph node cells. After 24 and 48 hr of continuous exposure to the undiluted supernatants, 150 to 300 cells in each flask were scored for adherence and ameboid activity. Macrophages exposed to supernatants from mixtures of sensitized cells with specific antigen had two to five times greater numbers of ameboid cells at 24 and 48 hr than did monolayers of the same macrophages exposed to control supernatants, and twice as many cells remained adherent at 48 hr. Thus, factors released by sensitized lymphocytes cause activation of normal macrophages. It is suggested that a similar mechanism may be responsible for cell-mediated immunity in systems involving microbial antigens.
Structural and Antigenic Relationships Between Avian Immunoglobulins
Authors: Leslie Gerrie A. , Benedict Albert A.
Published: December 2022

Ring-necked pheasants, Japanese quail and chickens have 7S immunoglobulins that are antigenically related to each other. It was demonstrated that the cross-reactions were due to similar antigenic determinants on the H and L chains and Fab and Fc fragments. The L chains of the chicken and pheasant were antigenically identical whereas the quail L chains reacted only weakly with the other two. It was concluded that the antigenic structure of QG was much more different from either CG or PG than CG or PG were from each other. The H chains of each of the IgM's shared antigenic determinants.
Hypersensitivity to Ascaris Antigens
Authors: Strejan Gill , Campbell Dan H.
Published: December 2022

Rabbits immunized with soluble, crude Ascaris extracts, or with extracts adsorbed on Al(OH)3 produced homocytotropic (Hc) antibodies after both primary and secondary antigenic stimulations. The antigen emulsified in complete Freund's adjuvant proved ineffective. While reduction and alkylation inactivated most of the antibody preparations, heating of the antisera at 56°C indicated that both heat resistant and heat sensitive Hc antibodies are being produced and may coexist in the same serum.
Specific Inhibition of an Anti-Hapten Immune Response by Chemical Modification of Cells
Authors: Naor David , Mishell Robert I. , Wofsy Leon
Published: December 2022

Reaction of mouse spleen cells with 2,4,6-trinitrophenyl sulfonate (TNPS) resulted in suppression of an in vitro anti-TNP antibody response without diminishing the response to carrier sheep red blood cells (SRBC). The anti-TNP response of unreacted spleen cells could also be inhibited specifically by addition of small fractions of TNPS-reacted cells, indicating that the specific inhibition is not primarily due to direct chemical modification by TNPS of anti-TNP cellular receptor sites. These results illustrate some of the considerations involved in applying affinity labeling to the problem of antigen receptors on lymphocytes. They also suggest a general procedure for suppressing a particular antibody response with appropriately modified homologous cells.
Interspecies “Transfer” of Delayed Hypersensitivity In Vitro with Rna Extracts
Authors: Paque Ronald E. , Dray Sheldon
Published: December 2022

When nonsensitive guinea pig peritoneal exudate cells (PEC) were incubated in vitro with RNA extracts from rhesus monkeys with delayed sensitivity to purified protein derivative (PPD) alone, or PPD and coccidioidin, the PEC were inhibited in their migration from capillary tubes in the presence of specific antigen. These data suggest that interspecies conversion of “nonsensitive” guinea pig PEC to “sensitive” cells was accomplished with monkey RNA extracts.
Mechanisms of Endotoxin Tolerance
Authors: Greisman Sheldon E. , Woodward Celeste L.
Published: December 2022

Immunologic mechanisms contribute to the development of pyrogenic tolerance to bacterial endotoxins. The present studies test the concept that the hepatic Kupffer cell is the “target” tissue protected by these immune mechanisms.

The pyrogenic response of healthy acclimatized New Zealand rabbits to a purified Escherichia coli endotoxin administered by ear vein was characterized by a classic biphasic febrile response, an initial early phase (60- to 90-min peak) and a later second phase (180-min peak). Tolerance induced by repetitive daily ear vein administration of the endotoxin resulted in ablation of the second febrile phase, but only minimal reductions of the early phase. These responses were then contrasted with those induced when the E. coli endotoxin was presented directly to the hepatic Kupffer cell by perfusion through chronically implanted hepatic portal venous cannulae.

Direct hepatic perfusion with endotoxin resulted in diminution or ablation of the early phase of fever in both non-tolerant and tolerant animals. This effect was seen in 3 of 12 non-tolerant and all of 21 tolerant animals. Reticuloendothelial blockade with thorotrast consistently restored the early fever phase following portal vein administration of the endotoxin in the tolerant animals. In contrast to the early febrile response, direct hepatic perfusion with endotoxin enhanced the second febrile phase in the non-tolerant animals; the second febrile phase, however, remained markedly inhibited in 17 of the 21 tolerant animals tested.

Analysis of these findings indicates: 1) extra-hepatic mechanisms dominate the first phase of the biphasic febrile response to bacterial endotoxin in the rabbit, 2) hepatic mechanisms dominate the second phase of the biphasic febrile response to endotoxin, 3) the liver of the tolerant rabbit clears directly perfused endotoxin more efficiently than the liver of the non-tolerant animal and 4) despite the more efficient uptake of directly perfused endotoxin by the liver of the tolerant rabbit, the second phase of fever usually remains markedly inhibited.

The findings fully support the concept that tolerance to the pyrogenic activity of bacterial endotoxin is based upon increased uptake of the toxin by hepatic Kupffer cells which have become refractory to further release of endogenous pyrogen.
Partial Purification and Characterization of a Dengue Virus Soluble Complement-Fixing Antigen
Authors: Brandt Walter E. , Chiewsilp Dumrong , Harris Donald L. , Russell Philip K.
Published: December 2022

Rate-zonal centrifugation of dengue-2 infected mouse brain or cell culture has revealed two hemagglutinins (HA) and a non-hemagglutinating soluble complement-fixing (CF) antigen (1, 2). A rapidly sedimenting HA (RHA) consists of infectious particles measuring 48 to 50 nm in diameter and a slowly sedimenting HA (SHA) contains small doughnut structures measuring 14 nm in diameter. The third antigen was described as a soluble CF antigen (SCF) since it could not be readily removed from suspension by ultracentrifugation. Subsequent studies suggested that SCF is a nonstructural antigen which can be distinguished from the structural polypeptides of the virion by coelectrophoresis in polyacrylamide gels (R. D. Cardiff, W. E. Brandt, T. G. McCloud and P. K. Russell, to be published). SCF was also found to be the only antigen unaffected by exposure to sodium lauryl sulfate (SLS) and 2-mercaptoethanol (2-ME) (3); further, exposure of standard dengue-1 and dengue-2 sucrose-acetone antigens to SLS and 2-ME or 8M urea reduced the level of cross-reactions with other dengue serotypes.
C3 in High Molecular Weight Complexes: Separation from Plasma of Nephritic Patients and Normal Subjects by a Method that Avoids in Vitro Artifacts
Authors: Askenase Philip W. , Leonard Edward J.
Published: December 2022

The demonstration of host γ globulin and complement components in glomeruli of patients with post-streptococcal glomerulonephritis (1–3) or the nephritis associated with systemic lupus erythematosus (2, 4, 5) supports the view that the inflammatory lesions are caused by deposition of circulating complement-fixing soluble antigen-antibody complexes (6). Immune complexes, therefore, might be present in the circulation during active disease and, given sufficient assay sensitivity, should be detectable. When immune complexes activate complement, the third component (C3) becomes bound to the complex and can, therefore, be used as a marker of immune complexes. Since C3 has a molecular weight of about 185,000 (7) and in an immune complex behaves like a much larger molecule, separation of unreacted from complexed C3 on the basis of size is possible by gel filtration on Sephadex G-200.

The proteins of normal whole serum are eluted from Sephadex G-200 in three main peaks.
Immunoglobulin E-Type Antibodies Induced by Ascaris Suum Infections in Guinea Pigs
Authors: Dobson C. , Morseth D. J. , Soulsby E. J. L.
Published: December 2022

An IgE-type anaphylactic antibody, analogous to human IgE antibody, is described in guinea pigs infected with Ascaris suum. It differs from other guinea pig anaphylactic antibodies by virtue of its greater molecular weight, its sensitivity to heat and 2-mercaptoethanol and its ability to sensitize homologous skin sites for prolonged periods of time in greater dilution.
The Reaction of Immunoglobulin-Coated Bentonite and Radioiodinated Antigen
Authors: Cheng W. C.
Published: December 2022

The antigen-binding properties of purified antibodies to the 2,4-dinitrophenyl, 2,4,6-trinitrophenyl and 2,4-dinitro-5-aminophenyl groups were studied by employing microgram quantities of purified antibody adsorbed onto a colloidal suspension of bentonite particles and measuring the binding of an 125I-labeled hapten protein complex. The results indicated that the antigen-binding affinity of antibodies obtained from late antiserum is greater than that of antibodies from early antiserum. Differential binding of the antigen by selectively isolated antibody populations of the same antiserum pools was also observed. The data also indicated that, in general, a selectively isolated antibody population having high affinity for a structurally related cross-reacting antigen still exhibited a greater degree of binding for the antigen used to elicit the antibody response than for the cross-reacting antigen used for its isolation. One fraction of anti-2,4-dinitro-5-aminophenyl antibodies, however, was found to bind the cross-reacting DNP-RSA antigen better than the homologous DNAMP-RSA antigen. The possible significance of this exceptional case was discussed.
The Isolation and Biologic Activities of Purified Secretory IgA and IgG Anti-Salmonella Typhimurium “O” Antibodies from Rabbit Intestinal Fluid and Colostrum
Authors: Eddie David S. , Schulkind Martin L. , Robbins John B.
Published: December 2022

Direct contact of external secretory tissue with living, but not with dead, Salmonella typhimurium stimulated formation of high concentrations of anti-“O” antibodies in the small intestinal fluid and colostrum. Purified IgG and IgA anti-S. typhimurium “O” antibodies were isolated from these fluids and their activities measured on a molar basis. Serum and exocrine IgG molecules had identical complement-dependent bactericidal, opsonization and PCA reactions. Exocrine IgA antibodies showed little or no activity in these biologic assays but did exert a similar suppressive effect upon antibody formation after intravenous injection or oral administration, as did exocrine IgG antibodies. Both IgA and IgG molecules had similar specific agglutination activities.
The Immune Response of the Pigeon (Columba Livia)
Authors: Guttman Ralph M. , Tebo Thomas , Edwards John , Barboriak Joseph J. , Fink Jordan N.
Published: December 2022

Pigeons were immunized with bovine serum albumin and the subsequent antibody responses were characterized by several immunologic techniques. The antibody responses were delayed in onset, and 6 of 17 pigeons failed to produce detectable hemagglutinating antibody until after a second or third injection. Only 4 of 17 birds produced precipitating antibody. Mercaptoethanol-sensitive antibody persisted after the primary stimulus as the hemagglutination titers of some sera collected after the third injection could still be reduced by treatment. Immunoelectrophoresis and autoradiography revealed the presence of antibodies with mobilities similar to human IgG and IgM. A heat labile skin-sensitizing antibody was detected and had a minimum latent period of 24 hr and other characteristics similar to human homocytotropic antibody.
Immunoferritin Study of the Distribution of HL.A Antigens on Human Blood Cells
Authors: Kourilsky François M. , Silvestre Danielle , Levy Jean Paul , Dausset Jean , Nicolai Marie Gabrielle , Senik Anna
Published: December 2022

The localization and distribution of human histocompatibility antigens of the HL.A system was studied in the membranes of a variety of peripheral blood and bone marrow cells, using an indirect ferritin-labeled antibody technique. The distribution of specific HL.A ferritin labeling at the cell membrane was found to be discontinuous, forming “patches” similar to those described for H-2 antigens in mice with indirect immunoferritin methods. The importance of the HL.A labeling at the cell surface varied considerably according to the spectrum of specificity of the anti HL.A antisera used. The cell prolongations were never labeled. The HL.A antigens were localized on all nucleated cells studied, including lymphocytes, monocytes, polymorphonuclear leukocytes, granulocyte precursors, stem cells, erythroblasts, leukemic cells and cultured lymphoid cells. However the comparative evaluation of the labeling suggested that the concentration of HL.A antigens is much lower at the membrane of immature cells. HL.A antigens were never detected on mature erythrocytes, but are still present on reticulocytes. These results suggest a heterogeneity of the human cell membrane with regard to the HL.A antigenic expression, and important variations of the concentration of these antigens according to the cell type and degree of differentiation.
Mechanism of Histamine Release from Mast Cells by Cationic Protein (Band 2) from Neutrophil Lysosomes
Authors: Ranadive N. S. , Cochrane C. G.
Published: December 2022

Studies have been conducted on the mechanisms of release of histamine from isolated mast cells by a purified basic protein of neutrophilic leukocytes. Release was inhibited in the cold, by 2,4-dinitrophenol (DNP) (5 × 10-5) in the absence of glucose, by iodoacetic acid (2 × 10-3), and by heating the cells to 45°C. Organophosphorus esterase inhibitors also prevented release of histamine when added simultaneously with the neutrophilic basic protein. Mast cells activated in the presence of DNP inhibitor and then washed released histamine upon addition of glucose. This release was not affected by diisopropylfluorophosphate, but was inhibited by chelation. Mast cells exposed at 37°C to basic protein in the presence of DNP for varying times, and then washed and added to glucose-containing medium, demonstrated increasing inability to release histamine over a 30-min period of initial exposure. These cells would not respond to fresh addition of the basic protein. In contrast, cells held at 10°C in the presence of basic protein would still respond after washing to the fresh addition of basic protein. The data provide evidence for distinct intracellular steps in the process of activation of mast cells and release of histamine.
Secretory IgA, A Major Immunoglobulin in Most Bovine External Secretions
Authors: Mach Jean-Pierre , Pahud Jean-Jacques
Published: December 2022

Bovine secretory IgA (SIgA), recently identified in colostrum, was shown to be homologous to human SIgA by immunologic cross-reaction. A quantitative study indicated that bovine SIgA, a minor component of colostrum, is a major immunoglobulin in most other external secretions including saliva, spermatic fluid, lacrimal, nasal and gastrointestinal secretions. SIgA was isolated from saliva. The free form of secretory component was found to be abundant in milk. A normal lactating cow produces about 1.2 g of this protein per day. Two forms of IgA were identified in serum: a normal serum IgA with no secretory antigenic determinant, and a small amount of SIgA. In vitro synthesis of SIgA by the salivary gland was studied by tissue cultures with incorporation of labeled amino acids.
Electron Microscopic Recognition of Surface Antigen by Direct Reaction and Ferritin Capture with Guinea Pig Hybrid Antibody
Authors: Knüsel A. , Bächi Th. , Gitzelmann R. , Lindenmann J.
Published: December 2022

We have recently reported the results of electron microscopic studies of rabbit small intestinal mucosa in which sucrase was identified as a part of the epithelial cell surface by virtue of its reactivity with ferritin-labeled anti-enzyme (1). In the specific reaction with mucosal villi, the periphery of antibody-bound ferritin molecules was separated from the membrane by a minimal distance of 85 Å. This latter observation might be explained in part by the possibility that ferritin molecules were attached to the immunoglobulin sufficiently close to the specific combining site to causesome degree of steric hindrance and hence limit the approximation of antibody and antigen. Hybrid antibodies (anti-enzyme/anti-ferritin) first bound to the cell surface antigen might on subsequent reaction with ferritin bring the label into closer apposition with the membrane. Experiments to test this hypothesis are reported here.

Materials and Methods. Immunoglobulin G was obtained from guinea pigs immunized (2) against rabbit intestinal sucrase or horse spleen ferritin.
The Mechanism of Induction of Cold Agglutinins by Mycoplasma Pneumoniae
Authors: Costea Nicolas , Yakulis Vincent J. , Heller Paul
Published: December 2022

Cold agglutinins with specificity to the I-erythrocyte antigen (CAI) were detected in serum of rabbits injected intravenously with live or killed Mycoplasma pneumoniae, Streptococcus MG or Listeria monocytogens. Similar antibody responses were elicited in CF1 but not in SWJ mice suggesting genetic variability of these immune responses. CAI synthesized in response to M. pneumoniae were found to cross-react with other bacterial antigens (Streptococcus MG and L. monocytogenes) whereas CAI following injection of L. monocytogenes reacted only with this micro-organism. The heterogeneity of these antibodies with specificity to the I-antigen was demonstrated by their inhibition with disaccharide ligands of α and β configuration.
Allotypic Determinants on the Fab Fragment of Rabbit Aa Locus Negative IgG-Immunoglobulin
Authors: Knight K. L. , Gilman-Sachs A. , Fields R. , Dray S.
Published: December 2022

Immunization of rabbits with a locus negative IgG immunoglobulin molecules obtained from an Aa2Aa2 rabbit suppressed in utero with anti-Aa2 resulted in isoantibodies directed against the a negative IgG molecules. The allotypic specificities are located on the Fab fragment of IgG and are absent on the Fc fragment. Peptide maps of tryptic digests of the Fab and Fc fragments of Aa negative and Aa positive IgG revealed no differences between the Fc fragments but four to five peptide differences between the Fab fragments. Subgroups of rabbit γ chains are thus identified by antigenic differences in the Fd region and these subclasses appear to have identical Fc regions.
Changes in Phospholipid Metabolism Which Occur as a Consequence of Mitogenic Stimulation of Lymphocytes
Authors: Lucas David O. , Shohet Stephen B. , Merler E.
Published: December 2022

Streptokinase-streptodornase (SKSD) was found to stimulate the turnover of phosphate in phosphatidyl inositol (PI). Stimulation of phosphate incorporation into PI by phytohemagglutinin (PHA) in lymphocytes obtained by fractionation on a gradient of BSA correlated with stimulation of DNA synthesis which occurred after 3 days of culture with PHA. The results obtained with lymphocytes separated on gradients of bovine serum albumin suggest the presence of two populations of lymphocytes responding to PHA. The experiments demonstrate that the PHA-induced turnover of phosphate in PI in lymphocytes is not the result of agglutination, but rather a consequence of mitogenic stimulation. In contrast to the stimulation induced by PHA and SKSD in PI, tetanus toxoid was found to stimulate the incorporation of phosphate into phosphatidyl choline and phosphatidyl ethanolamine. This difference argues further for the specificity of the response to mitogens observed in lymphocyte phospholipids.
Ontogenesis of Cell-Mediated Immunity in Murine Thymocytes and Spleen Cells and its Acceleration by Thymosin, a Thymic Hormone
Authors: Goldstein Allan L. , Guha Arabinda , Howe Michael L. , White Abraham
Published: December 2022

The ontogenesis of the cell-mediated immunologic capacity of spleen cells and thymocytes of CBA/Wh mice was studied from day 19 of embryonic life through 60 days of age. Two indices of immunologic competence were used, namely, the capacity of donor CBA/Wh cells to elicit a graft-vs-host (GVH) response in adult, lethally irradiated B6AF1/J mice and the mixed lymphocyte interaction (MLI) in vitro. In addition, the influence of a thymic humoral factor (thymosin) on the rate of maturation of cells from spleens of neonatal CBA/Wh mice and from bone marrow of adult CBA/Wh mice was investigated. The results of this study indicate that the capacity of thymocytes to elicit a GVH response and their ability to participate in a MLI developed within the first hours after parturition. Spleen cells, however, did not acquire the capacity to elicit positive responses in either one of these assays until 3 or 4 days postnatally. Administration of thymosin in vivo to newborn CBA/Wh mice or in vitro incubation of lymphoid stem cell populations with thymosin significantly accelerated the development of the capacity of spleen cells to elicit a GVH response. The ability of thymocytes to elicit a GVH response, once developed with a given number of cells, remained constant throughout the study period of 60 days. In contrast, the marked response of newborn CBA/Wh thymocytes to (CBA/Wh × C57BL/6)F1 spleen cells in the MLI decreased rapidly with age, suggesting a loss of recognition capacity or an alteration in cell types within the thymic population. The data support the concept of an endocrine role for the thymus in the development and maturation of lymphoid cells that participate in cell-mediated immune responses.
Toxicity of Streptococcal Mucopeptides in Vivo and in Vitro
Authors: Heymer Berno , Bültmann Burckhard , Haferkamp Otto
Published: December 2022

In view of recent clarification of the chemical and antigenic structure of streptococcal cell-wall mucopeptides (1), the biologic properties of these substances have become a matter of increasing interest to immunologists (2–6). Streptococcal mucopeptides have been demonstrated to elicit an acute dermonecrotic reaction in rabbits and guinea pigs (2), to induce fever, shock, and myocardial lesions in rabbits (3, 4), to enhance non-specific resistance in mice (3), and to initiate the local Shwartzman phenomenon in rabbits (4). Hence this fundamental constituent of the streptococcal cell wall shares several characteristics of the endotoxins of Gram-negative organisms. The question that remains unanswered, however, is whether these biologic effects are due to an intrinsic toxicity of streptococcal mucopeptides or whether they are the consequences of a humoral or cellular hypersensitivity reaction (7).
The Immune Response in the Hamster
Authors: Haakenstad Alan O. , Coe John E.
Published: December 2022

An immunoglobulin (Ig) class, analogous to IgA in other mammals, was identified in hamster serum and secretions. This protein was the main Ig in saliva and colostrum and the only Ig in enteric contents. Specific antisera to hamster IgA were readily prepared by inoculating rabbits with a precipitate produced after reacting rabbit anti-hamster 7Sγ-2-F(ab′)2 with hamster saliva. Hamster IgA migrated as a β-protein on electrophoresis and shared Fab determinants with the other three Ig classes, but it also had unique antigenic determinants. Specific antibody activity was best induced in serum IgA by a combination of oral and parenteral immunization. A heterogeneity of IgA molecular sizes (7S and larger) existed in serum, saliva and enteric contents although salivary IgA sedimented most rapidly on sucrose density gradient analysis. After mild reduction and alkylation, the IgA of serum and enteric contents sedimented as 7S proteins.
Immunoglobulin Synthesis in Mixed Cultures of Syngeneic Cells of Different Lymphoid Tissues
Authors: Mikhailova A. A. , Petrov R. V. , Zakharova L. A.
Published: December 2022

The intensity of antibody and nonspecific γ globulin synthesis was studied in mixed cultures of syngeneic spleen and lymph node cells by a radioisotopic method with the help of immunosorbents. The results showed that an increased rate of synthesis of antibodies (300% to 600%) and nonspecific γ globulins (150% to 200%) occurred when spleen cells taken from non-immunized animals were cultured for 22 hr together with syngeneic spleen or lymph node cells taken from immune mice. It is suggested that lymphocytes activated by antigen somehow attract certain types of spleen cells into the process of immunoglobulin synthesis.
Human Anti-insulin Antibodies
Authors: Faulk W. Page , Karam John H. , Fudenberg H. Hugh
Published: December 2022

Sera from 50 insulin-treated diabetics were studied for antibodies against insulin. Antiinsulin titers were measured by the degree of insulin 131I binding, and biochemical classes of anti-insulin antibodies were defined using radioimmunoelectrophoresis. The most common type of anti-insulin immunoglobulin was IgG (40 patients). Nine patients had IgA anti-insulin antibodies, and the rarest antibody was IgM. IgG antibodies correlated with anti-insulin titers, but IgA and IgM did not. Insulin-anti-insulin immune complexes were demonstrated in the sera of four patients. Antigen-antibody complexes are suggested to be a pathogenetic factor in the microvasculitis of diabetes.
Valence and Association Constant of Rat Macroglobulin Antibody
Authors: Oriol R. , Binaghi R. , Coltorti E.
Published: December 2022

Fractions containing 19S and 7S antibody were obtained by gel filtration from specifically purified rat anti-DNP antibody and from whole immune serum. The valence and the association constants (K0) of the antibodies in each fraction were determined employing the monovalent hapten DNP-ε-aminocaproic acid. Ten binding sites per molecule were found in the 19S antibody. The sites were distributed into two populations in which K0 differed more than 100-fold. Each population consisted of about 50% of the sites in both native and specifically purified 19S antibodies. The binding data with the 7S antibody indicated a valence of two and a single population of sites that showed some heterogeneity.
Malignant Transformation in Vitro by “Non-Oncogenic” Variants of Defective SV40 (PARA)
Authors: Butel Janet S. , Tevethia Satvir S. , Nachtigal Maurice
Published: December 2022

Four variants of PARA (defective SV40)-adenoviruses which appear to be “nononcogenic” in newborn hamsters were found to be able to transform Syrian hamster lung and kidney cells in vitro. All the transformed cell lines contained SV40 T antigen. With one exception, the transformed cell lines were transplantable in syngeneic weanling hamsters. However, a wide spectrum of transplantability was observed. Some of the cell lines transformed by “non-oncogenic” variants of PARA were highly transplantable and others induced only rare tumors with long latent periods. In contrast, all the cell lines established following transformation by oncogenic variants of PARA were readily transplantable in vivo. These results indicate that these “non-oncogenic” variants of PARA possess the potential for malignant transformation of cells.
Metabolism of Asparagine, Aspartate, Glutamine, and Glutamate in Lymphoid Tissue: Basis for Immunosuppression by L-Asparaginase
Authors: Prager Morton D. , Derr Ina
Published: December 2022

Metabolic properties of lymphoid tissue were examined with a view to elaborating a mechanism by which l-asparaginase acts as an immunosuppressive agent. The study consisted of a) examining the ability of lymphoid tissue to incorporate asparagine, aspartate, glutamine, and glutamate from an exogenous source into cell protein, and b) determining the capacity of the tissue to synthesize these amino acids endogenously. All four amino acids were incorporated into cell protein during shortterm incubations. Under the conditions of study glutamine and glutamate were incorporated to the same degree, but depending on cell density, asparagine was incorporated from 1.3 to 6.3 times as readily as aspartate. The most marked difference was in the biosynthetic capacity of lymphoid tissue with respect to the four amino acids. Asparagine synthetase, as an indicator of the capacity to make asparagine, was barely detectable (0.01 milli-international units (mIU)/mg protein). In contrast, the capacity for glutamine (GSase) was 2200 times as high and for aspartate and glutamate (GOT) 7000 times as great. The limited capacity for asparagine formation implies that it must be supplied from the circulation, and since asparaginase destroys circulating asparagine, immunosuppression results.
In Vitro Effects of Measles Virus on Proliferating Human Lymphocytes
Authors: Zweiman Burton
Published: December 2022

Addition of measles virus to human lymphocytes cultured with phytohemagglutinin-P or antigen in medium containing fetal calf serum depressed the usual proliferative response in cells of both measles-immune and measles-susceptible subjects. When antologous serum was used in the medium, measles virus-induced depression of proliferation was seen only in cells of measles-susceptible individuals. The latter finding suggests inhibition of the measles virus effect by anti-measles antibodies or other humoral factors in the serum of measles-immune individuals.
Frequency of Antibody to Hepatitis-Associated Antigen As Measured by a New Radioimmunoassay Technique
Authors: Lander Jerrold J. , Alter Harvey J. , Purcell Robert H.
Published: December 2022

A modification of the radioimmunoassay procedure for measuring antibody to hepatitis-associated antigen (HAA) using a double antibody precipitation method in a microtiter system is described. The test is 2,000 to 500,000 times more sensitive than complement fixation and is reproducible and specific for anti-HAA.

The frequency of anti-HAA was 14.4% in voluntary blood donors, 22.6% in commercial blood donors, 14.8% in blood bank personnel, 11.4% in laboratory personnel and 82.6% in persons given multiple transfusions.

The high frequency of anti-HAA in persons with no history of hepatitis or parenteral exposure to blood suggests that HAA-positive hepatitis is endemic in the United States and that it is transmitted by a non-parenteral route.
Purification and Analysis of “Monofocal” Antibody
Authors: Klinman Norman R.
Published: December 2022

“Monofocal” antibody against the 2,4-dinitrophenyl (DNP) haptenic group was obtained from the culture fluids of splenic fragments stimulated in vitro. The antibody was purified and compared with purified serum anti-DNP antibody. The “monofocal” antibodies were shown to bind hapten homogeneously and to have a more restricted electrophoretic mobility than serum antibody. These “monofocal” antibodies differed markedly from one another in their electrophoretic mobilities, affinity for hapten and ease of purification from an immunoadsorbent. From these results it was concluded that serum antibody represents a pool of the products of a variety of clones each producing a homogeneous antibody population.
Enzyme-Activation by Antibody
Authors: Cinader B. , Suzuki T. , Pelichová H.
Published: December 2022

Conformational alteration of antigen by antibody has been deduced from antibody-induced enhancement of the catalytic activity of bovine pancreatic ribonuclease. Further support for this conclusion is adduced from the effect of ribonuclease A antibody on the activity of ribonuclease S', which consists of two enzyme fragments. These fragments, S-peptide and S-protein, are enzymically inactive when separated and active when mixed. The molar ratio (S-peptide:S-protein) at which maximum restoration of activity occurs is reduced when S-protein is allowed to combine with ribonuclease A antiserum or with activating-antibody fractions. Antibody also changes the relative effect of ribonuclease S' on different substrates.
Cyclophosphamide Treatment of Experimental Allergic Encephalomyelitis in Lewis Rats
Authors: Paterson Philip Y. , Drobish Diane G.
Published: December 2022

Cyclophosphamide (CY) treatment (daily doses of 5 or 8 mg/kg for 10 days or less) of Lewis rats with paralytic experimental allergic encephalomyelitis (EAE) results in clinical remission and reversal of histologic evidence of disease in a high proportion of animals. Continued administration of CY is required to maintain these beneficial effects. CY treatment diminishes but does not abolish cutaneous reactivity to tuberculoprotein in Lewis rats sensitized to mycobacteria. On the basis of these and other observations, CY is believed to exert therapeutic effects in EAE by inhibiting proliferation of inflammatory cells and release of injurious factors within the sites of EAE lesions in brain and spinal cord.
The Early Immune Response to the Dinitrophenyl and Folate Determinants: Weight Estimates of Serum, 19S and 7S Immunoglobulins
Authors: Revoltella Roberto , Adler Louise T. , Osler Abraham G.
Published: December 2022

The hapten-binding capacity procedure has been applied to the estimation of anti-dinitrophenyl and anti-folate antibodies during the early immune response of rabbits. Serum antibodies were readily detectable and estimated during the 1st week after immunization. Approximately equal weights of 19S and 7S immunoglobulins were found in virtually every serum specimen assayed during the first postimmunization week.
A New Specific Humoral Viral Resistance Factor, Serum Protective Factor—Some Biologic and Physical Properties
Authors: Thind Inderjit S. , Price Winston H.
Published: December 2022

Serum protective factor (SPF) is a new specific humoral viral resistance substance found in mice following certain experimental arbovirus infections. This factor occurs with or without the use of the immunosuppressant drug cyclophosphamide. A further characterization of its physical and biologic properties is presented. SPF, a protein with an estimated molecular weight of between 67,000 and 150,000, persists for a longer period of time than neutralizing antibody and interferon following primary Langat virus infection of mice. SPF is different from the well characterized imunoglobulins as suggested by Sephadex G-150 column fractionation, and has no in vitro virus neutralizing activity in contrast to neutralizing antibody. Unlike neutralizing antibody, SPF requires living cells to protect in vivo and does not protect mice younger than 14 days of age on passive administration against subsequent viral challenge. Thus in recovery from viral infections, humoral substances such as SPF, interferon and neutralizing antibody may have a synergistic action since the former two protect by their action on the cells and the latter acts directly on the virus to provide protection.
The Effect of Bursectomy on the Recovery from Immunologic Tolerance
Authors: Peterson Raymond D. A. , Alm Gunnar V. , Michalek Suzanne
Published: December 2022

The role of the bursa of Fabricius of the chicken in the recovery from immunologic tolerance was studied. Newly hatched, sublethally x-irradiated chickens were injected twice weekly intra-abdominally with physiologic saline or large doses of bovine serum albumin (BSA) until they were 5 weeks old. At this time the BSA-injected animals were specifically tolerant. After intravenous challenge with BSA very few spleen cells forming antibody to BSA could be detected with a modified Jerne hemolytic plaque assay. Good responses to sheep erythrocytes were obtained. Surgical bursectomies were performed on half the animals after the injections were stopped. Bursectomy had no effect on the subsequent responsiveness to BSA in the saline-injected chickens. The tolerant chickens had recovered their responsiveness to BSA after 10 weeks. Bursectomy impaired this recovery. These results suggest that the antibody-forming bursa-dependent line of lymphoid cells may be made specifically tolerant. The bursa of Fabricius may serve as an important, if not exclusive, source of new immunocompetent cells in the process of recovery from immunologic tolerance.
The Detection of Antibody to Hemocyanin by Direct Solid-Phase (Polystyrene) Radioimmunoassay and Gel Filtration
Authors: Kotoulas Angeliki O. , Moroz Leonard A.
Published: December 2022

A sensitive, relatively simple method is described for the direct solid-phase radioimmunoassay of antibody to a macroglobulin antigen, keyhole limpet hemocyanin (KLH). Antibody is adsorbed to polystyrene tubes (antibody-binding phase), reacted with 125I-KLH (antigen-binding phase) and excess 125I-KLH removed by washing, the residual radioactivity providing a measure of antibody activity. The sensitivity of the method (5 to 10 ng antibody protein) is comparable to other primary antibody assays, and is markedly dependent on ionic strength and total protein concentration during the antibody-binding phase. The assay is equal to or slightly less sensitive than passive hemagglutination for detecting 19S antibody, and consistently more sensitive for detecting 7S antibody. A method of similar sensitivity is also described for the detection of anti-KLH antibody by gel filtration on agarose columns. Both methods are potentially applicable to the detection of antibody to other, particularly macroglobulin, antigens.
Tolerance Following Immunity, with Loss of Serum Specificity, in Adult Rabbits Injected Repeatedly with HeLa Cells
Authors: Miller Gail Lorenz
Published: December 2022

Transition from immunity to tolerance was followed during the course of repeated intravenous injection of rabbits with graduated doses of HeLa cells as antigen. Cytotoxic antibody titer was used as the measure of the immune response. The tolerance was not total, however, as residual antibody persisted in the sera of the treated animals. The initial injections led to production of antisera which were relatively specific for the HeLa cells. Repeated injections led to eventual loss of specificity. Possible explanations for the loss are considered.
Effect of Adult Peritoneal Cells on the Antibody Response of Newborn Mice to Sheep Red Blood Cells
Authors: Bendinelli M. , Senesi S. , Falcone G.
Published: December 2022

The findings that grafts of adult peritoneal cells enhance the antibody response of newborn mice (1, 2), rats (3) and rabbits (4) have suggested that the immunologic immaturity of newborns might partly be due to a functional deficiency of macrophages.

The results reported here show that unstimulated peritoneal cells (PC), but not peritoneal cells induced by thioglycolate (IPC), are endowed with the property of potentiating the antibody response of newborn mice to sheep red blood cells (SRBC).

Inbred BALB/c mice were used throughout the experiments. PC and IPC were collected from mice of both sexes aged 8 to 12 weeks, the latter cells 3 days after i.p. inoculation of 3 ml thioglycolate medium (Difco Laboratories. Detroit, Mich.), by washing the peritoneal cavity with 5 ml of Eagle's minimal essential medium containing 5 i.u./ml of heparin. Litters of 6 to 8 mice were divided into four groups.
Guinea Pig Leukocytes: In Vivo and in Vitro Infection with a Herpes-Like Virus
Authors: Hsiung G. D. , Fong C. K. Y. , Lam K. M.
Published: December 2022

Herpes-like virus (HLV) particles have been observed in cultured human cells derived from Burkitt's lymphoma (1), from patients with leukemia and lymphoma (2), from peripheral blood of patients with infectious mononucleosis (3), and from normal healthy human leukocytes (4). Although virus particles have been observed in cells after in vitro cultivation, the presence of the HLV particles in tissues and leukocytes taken directly from humans has not been reported. The pathogenesis of these HLV in human cells and their relationship to the associated clinical diseases is not clear.

As part of the studies on the pathogenesis and persistence of a HLV in guinea pigs (5), we noted the following: 1) failure to demonstrate HLV particles in leukocytes taken directly from infected guinea pigs; 2) appearance of the HLV particles in leukocytes taken from inoculated animals but only after in vitro cultivation; and 3) evidence of enhanced proliferation of guinea pig leukocytes infected in vitro with the HLV.
Kinetics of Bovine Complement
Authors: Fong Jack S. C. , Muschel Louis H. , Good Robert A.
Published: December 2022

Although bovine serum is non-hemolytic in standard hemolytic complement assays, it reacts with sensitized sheep erythrocytes to form an intermediate which can be lysed with EDTA-treated guinea pig serum. The optimum condition for the formation of EACBo consists of incubating sensitized sheep erythrocytes and bovine serum at 2°C for 10 min in a low ionic strength buffer (glucose-gelatin-barbital-buffered saline r/2 = 0.075) containing calcium 0.00015 M and magnesium 0.0001 M. In constrast to the corresponding human, guinea pig or equine intermediates, the maximum formation of the bovine lytic intermediate is inversely associated with incubation temperature and is enhanced to a greater extent by magnesium ions. The formation of a bovine lytic intermediate with sheep cells sensitized by rabbit antibody suggests that there is no incompatibility of interaction between early-acting bovine complement components and guinea pig terminal complement components or sensitized sheep cells. Thus the inability of bovine serum to lyse sheep erythrocytes probably is a functional difference of the bovine terminal complement components.