bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen-Induced Deoxyribonucleic Acid Synthesis in Mouse Lymphocytes
Authors: Osborne David P. , Katz David H.
Published: December 2022

The deoxyribonucleic acid (DNA) synthetic response of mouse spleen cell cultures has been studied after stimulation with the soluble antigens, keyhole limpet hemocyanin (KLH) and dinitrophenyl (DNP)-KLH. KLH was capable of inducing mitosis in normal as well as KLH-primed mice, the greater reactivity in primed mice apparently reflecting a specific anamnestic response. The kinetics of KLH antigen-induced DNA synthesis showed an earlier peak response (48 hr) than that induced by the mitogen concanavalin A (72 hr). In contrast, spleen cell cultures from normal mice failed to respond to DNP-KLH while DNP-KLH-primed spleen cells produced a highly significant DNA synthetic response. This response was dose-dependent and required the presence of the intact priming conjugate, since DNP-ovalbumin, DNP-bovine γ-globulin, DNP-lysine, and DNP-ε-amino caproic acid failed to stimulate such DNP-KLH-primed cells. To a great extent, the response was hapten-specific, since dissociated KLH, the form conjugated to DNP, stimulated only low levels of DNA synthesis. Moreover, the DNP-KLH-induced response could be inhibited more than 50% by the presence of the univalent DNP-ligand, DNP-ε-amino caproic acid. Finally, DNP-copolymer of d-glutamic acid and d-lysine, a molecule for which no thymus-derived lymphocytes exist, induced a DNA synthetic response in both normal and DNP-KLH-primed spleen cell cultures, and priming with DNP-KLH failed to increase the level of response to this molecule over that seen in normal spleen cells.
The in Vitro Response of Chicken B Cell Populations to Lipopolysaccharide
Authors: Weber W. T.
Published: December 2022

The ability of B cell populations in the chicken to respond in vitro to LPS was evaluated. Chromosomally marked embryonic bursal cells were transferred to B cell depleted chicks and allowed to differentiate in vitro for several weeks. Subsequent evaluation of host and donor cell proliferation in LPS-stimulated spleen and peripheral blood lymphocyte cultures of cell recipients established that bursa-derived donor cells (B2 cells) in spleen and blood were capable of responding to LPS. The results furthermore suggested a weak response of host T cells to LPS. Lymphocytes within the bursa (B1 cells) failed to respond to this stimulant.
Use of Normal Mouse Serum to Detect Indirect Plaque-Forming Cells
Authors: Silver Donald M. , Winn Henry J.
Published: December 2022

The introduction of a plaque technique for the identification and enumeration of cells synthesizing antibodies capable of lysing erythrocytes marked a major technical advance in immunology (1). The potential of the technique was significantly expanded by the introduction of antiglobulin reagents which permit the detection of additional plaque-forming cells (PFC)2 thought to be synthesizing 7S immunoglobulins (2, 3). However, the precise nature of these so-called indirect plaques was established only with considerable difficulty owing in large part to the problem of preparing anti-heavy chain sera of sufficiently high specificity. Indeed, only a fraction of the available antiglobulin reagents is completely suitable for the positive identification of IgG PFC, and those that have proven useful are reliable only at optimal concentrations that must be determined for individual sera. Of special concern in the selection of antisera is their tendency to inhibit the development of IgM plaques, a phenomenon which is observed frequently even with optimal dilutions of the reagents (3).
Specific Antigenicity of Thymic Reticuloepithelial Cells
Authors: Potworowski Edward F. , Borduas Adrien G. , Lussier Gilles
Published: December 2022

An antiserum was produced in rabbits against a lymphocyte-free extract of chicken thymus. After appropriate absorptions, the serum reacted by immunofluorescence only with thymic reticuloepithelial cells and with perinuclear areas in the cortex.
Presidential Address
Authors: Campbell Dan H.
Published: December 2022

When you so graciously elected me to the Presidency last year, I realized that, according to tradition, I was not expected to give a victory speech but should wait a year and give a Presidential Address when my term in office officially expired. Needless to say, I gave a lot of thought to the problem of what to talk about. I finally came to the rational conclusion that I lacked the ability of my predecessors to present a scholarly discourse on the glorious achievements of immunologists or to paint a speculative rosy picture of the future of immunology.

My thoughts then turned to the problems that have plagued the Association and members since my application for membership was finally approved in 1937, and to consider possible in policies and procedures for the future. The early-day scientists who founded the Association around 1913 could not have envisioned the magnitude and importance which the concepts and methodology of immunology would attain six decades later.
The Role of Thymus-Derived Lymphocytes in the in Vitro Activation of Macrophages to Kill Listeria Monocytogenes
Authors: Krahenbuhl James L. , Rosenberg Leon T. , Remington Jack S.
Published: December 2022

When sensitized spleen cells from guinea pigs chronically infected with Toxoplasma gondii were cultured with normal guinea pig peritoneal macrophages in the presence and absence of Toxoplasma antigen, macrophage monolayers incubated with sensitized spleen cells and antigen were markedly resistant to challenge with Listeria monocytogenes. Experiments were performed to determine the role of thymus-derived lymphocytes in the in vitro activation of macrophages by pretreating the sensitized spleen cells with an antiserum (ATS) prepared in rabbits against fetal guinea pig thymus cells. In the presence of complement, treatment of sensitized spleen cells with ATS completely abolished their ability to activate normal macrophages in the presence of antigen.
A Surface Component in Group A, C, and G Streptococci with Non-Immune Reactivity for Immunoglobulin G
Authors: Kronvall Göran
Published: December 2022

Fifty-seven strains of streptococci belonging to groups A, C, and G were tested for γ-globulin Fc-reactivity with sensitized sheep red cells. Twenty-six per cent of the strains were positive. Forty-four per cent of the strains produced a soluble factor with similar γ-globulin reactivity. With a radioimmunologic assay to detect streptococcal reactivity, human IgG was found to be positive, whereas human IgA, IgM, IgD, and IgE were negative. The reactivity was detected in heavy chain preparations but not in light chains, F(ab′)2 fragments nor in Fc fragments. Experiments using isolated myeloma globulins representing the four IgG subclasses indicated that streptococci might react not only with IgG1-, IgG2-, and IgG4-like protein A but also with IgG3 molecules. One of the two IgG3 myeloma globulins studied did react with a group A streptococcus and both myeloma globulins did react with a group G streptococcus. Serum samples from 14 selected animal species also indicated differences between the γ-globulin reactivity of protein A and streptococci. Marsupials as well as the Rhea bird were non-reactive with streptococci. The results obtained with eleven other species indicated that the group A and G streptococcal reactivities were similar but differed significantly from staphylococcal protein A reactivity.
Long-Term Survival of Mouse Thymic Lymphoid Cells in Vitro: Effect of Human Serum
Authors: Ozato Keiko
Published: December 2022

Long-term survival of mouse thymus cells in vitro was obtained with a medium containing human serum. Almost 90% of floating thymic lymphoid cells continued to live for at least 2 weeks, far longer than the normal life span in vivo. On the contrary, only 0.1% of the cells survived in the medium with fetal calf serum after 2 weeks cultivation. Cultivated thymocytes were markedly stable; the number of viable cells was constant and no proliferation was noted throughout the culture period except during the 1st day. Half of the CBA thymocytes maintained θ isoantigen during the 2-week culture period. They showed very weak responsiveness toward alloantigens which is common in fresh thymocytes. Proliferation was enhanced by either syngeneic or allogeneic stimulation only in neonatal thymocytes after 1-day cultivation but was not observed in fetal or adult thymocytes. The present report also offers evidence that thymocytes specifically stimulate proliferation of allogeneic bone marrow cells.
Presence of Impairment of Humoral Immunity in Nonadherent Spleen Cells of Old Mice
Authors: Heidrick Margaret L. , Makinodan T.
Published: December 2022

Spleen cells from aged mice when cultured in vitro with sheep red blood cells (SRBC) generate fewer antibody-forming cells than do cells from young mice. To define further the nature of the decrease in response with age, we separated spleen cell suspensions from young and old mice into two populations on the basis of their ability to adhere to plastic Petri dishes and their activity was assessed in various combinations with SRBC. Old adherent cells cultured with young nonadherent cells responded fully to the antigen, whereas old nonadherent cells combined with young adherent cells gave a response comparable to unseparated old spleen cells. Similar results were obtained when adherent cells were exposed to SRBC, washed free of the antigen, then recombined with the nonadherent cells. The results demonstrate that the adherent cells of old spleens are indistinguishable from those of young spleens in their ability to initiate antibody response, but the activity of nonadherent cells of old spleens is impaired.
Immune Responses in Vitro
Authors: McIntyre John A. , Pierce Carl W.
Published: December 2022

At various intervals after initiation of Mishell-Dutton spleen cell cultures, cell clusters were separated from non-clustered, single spleen cells by sedimentation through a fetal calf serum gradient at unit gravity. Cell clusters collected at all intervals during the initial 48 hr of culture failed to develop subsequently significant plaque-forming cell (PFC) responses. In contrast, the single, non-clustered spleen cells isolated at these intervals subsequently developed PFC responses equal to or greater than responses in unseparated control cultures. Sequential removal of the cell clusters which reformed when the single spleen cells were returned to culture had little or no effect on the PFC responses generated by the remaining single cells. Thus, it appears that the continuous integrity of cell clusters which form in mouse spleen cell cultures has no direct effect on the immune responses which develop in these cultures.
Thymus Dependence of Reaginic Antibody Formation in Mice
Authors: Michael J. Gabriel , Bernstein I. Leonard
Published: December 2022

Formation of reaginic antibodies in mice has been demonstrated by numerous investigators (1–4). These antibodies were shown to be fixed to homologous skin, being retained there for several days. They were also shown to be heat and mercaptoethanol sensitive. Thus in many of their biologic activities mouse reaginic antibodies resemble human IgE antibodies (5). Availability of genetically thymusless nude mice provided an opportunity to examine the dependence of mouse reaginic antibody formation on the presence of thymus cells. Nude mice (nu/nu) were shown to respond poorly to sheep erythrocytes in respect to formation of IgM and IgG antibodies (6–8). The immune response to sheep erythrocytes was at least partially restored by normal thymus grafts or by injection of normal thymus cells (9). Nude mice (nu/nu) and heterozygous (nu/-) derived from back-crosses to the BALB/c strain (3 to 5 generations) were obtained from Bomholtgaard, Ltd., Ry. Denmark. BALB/c mice (+/+) originated from Jackson Laboratories, Bar Harbor, Maine.
Tissue Typing: An Experimental Solution in the Chicken
Authors: Simonsen Morten
Published: December 2022

The present communication will show that it is possible in the chicken to develop hemagglutinating typing sera which, if applied to an unrelated population, can single out the individuals compatible with a given recipient in terms of the major histocompatibility system. Such a selection is the major point of tissue typing, largely unfulfilled as yet in man and other mammals.

Two analytical tools, 1) hemagglutination, and 2) graft-vs-host (GVH)1 splenomegaly in the embryo have been combined in a special strategy for absorption of iso-antisera with the dual properties of agglutinating red blood cells and of inhibiting lymphocytes in their GVH reaction. Such antisera were produced in inbred chickens of genotypes B1/1 and B2/2 by i.v. injections of washed whole blood cells from heterozygous B1/2 donors. After 4 to 6 weekly injections sera were harvested which showed strong hemagglutination of B2/2 and B1/1 erythrocytes, respectively.
Change in Susceptibility of C3H/HeJ Mice to LCM Virus Infection
Authors: Oldstone Michael B. , Dixon Frank J.
Published: December 2022

Mice infected with lymphocytic choriomeningitis (LCM)3 virus are a useful model for understanding the pathogenesis of disease associated with both acute and chronic virus infections (1, 2). In this model, tissue injury is caused by the interaction of the host's anti-viral immune response with virus or virus-infected cells. In acute infection, injection of adult mice with LCM virus leads either to recovery or death depending on the dose of virus administered, the route of inoculation used, and the ability of the host to mount an anti-viral immune response (3, 4). In chronic infection, the time scale of the response to LCM virus is lengthened and the severity of disease is related to the location and amount of LCM virus carried, the magnitude of the anti-viral antibody response made, and the interaction between virus and antibody (5).

In our initial studies on the pathogenesis of disease associated with LCM virus infection, we studied the susceptibility of different murine strains to LCM virus (5–7).
Intercellular Communication in Stimulated Human Lymphocytes
Authors: Oliveira-Castro Gilberto M. , Barcinski Marcello A. , Cukierman Samuel
Published: December 2022

Microelectrode studies of human lymphocytes after 24 to 48 hr of stimulation by phytohemagglutinin are described. A stable transmembrane potential of about -18 mV was detected. The input resistance of these cells was about 5 megohms.

Clumps of stimulated cells exhibit junctional communication as revealed by coupling coefficients of 0.2 to 0.6. No changes in membrane properties and intercellular communication were detected throughout the observed period.

The results reported here suggest that the establishment of interlymphocyte communication is possibly involved in the control of mitosis.
Immune Complex Glomerulonephritis in One-Year-Old C57BL/6 Mice Induced by Endogenous Murine Leukemia Virus and Erythrocyte Antigens
Authors: Porter David D. , Porter Helen G. , Cox Nancy A.
Published: December 2022

Aging mice frequently develop a glomerulosclerosis; the severity of the lesion varies among mouse strains and increases with age. The kidneys of fifty 1-year-old C57BL/6 mice were examined and 48 had histologic evidence of mild to moderate intercapillary glomerulosclerosis. All fifty mice had glomerular deposits of IgG and 41 had deposits of C3 which were located in the mesangial zone and along glomerular capillary walls. Fifty to 57% of the kidney-bound immunoglobulin which was eluted reacted with murine leukemia virus cell surface antigen, while 8 to 37% of the immunoglobulin reacted with syngeneic erythrocytes. The glomerulosclerosis of aging C57BL/6 mice appears to be an immune complex glomerulonephritis induced by murine leukemia virus antigens, and to a lesser extent, erythrocyte antigens.
Hemolysis of Sheep Erythrocytes in Guinea Pig Serum Deficient in the Fourth Component of Complement
Authors: May Joseph E. , Frank Michael M.
Published: December 2022

The hemolysis of sensitized sheep erythrocytes in serum from guinea pigs with a total genetically controlled deficiency of C4 was studied with purified IgG and IgM anti-Forssman antibodies. It was found that an approximately 20-fold increase in hemolytic antibody concentration was necessary to initiate lysis in C4D serum as compared with normal serum. The kinetic curves of hemolysis in concentrated C4-deficient serum reached a plateau in 30 to 60 min. Lysis in the deficient serum could only be achieved with concentrated serum; hemolytic activity was rapidly lost on dilution. The lytic capacity of C4-deficient serum from individual animals was shown to vary markedly. The cytolytic reaction was specific in that only sensitized sheep erythrocytes were lysed, and there was no lysis of “innocent bystander” cells.
Expression of HL-A Antigens on Cultured Human Fibroblasts Infected with Mycoplasmas
Authors: Brautbar Chaim , Stanbridge Eric J. , Pellegrino Michele A. , Ferrone Soldano , Reisfeld Ralph A. , Payne Rose , Hayflick Leonard
Published: December 2022

A variety of cultured human fibroblast strains with different HL-A phenotypes were infected with non-fermentative and fermentative mycoplasmas. Both short-term and long-term infections were studied. It was found that many more mycoplasmas associated with the cell membranes of long-term infected cultures than of short-term infected ones. Mycoplasma effects on the morphology of long-term infected cultures varied from an increase in cytoplasmic granularity to frank cytopathogenicity. Regardless of the numbers of mycoplasmas associated with the cells, or the condition of the cells, there was no detectable change in the expression of HL-A antigens measured both qualitatively and quantitatively. It is suggested that HL-A antigens are an essential structural feature of the cytoarchitecture of the cells and/or play a role in transport processes and contact phenomena which are crucial to cell survival.
Simultaneous Expression of Hapten Binding and Antibody Secretion by NIP-Primed Lymph Node Cells Early in the Immune Response
Authors: Bankert Richard B. , Wolf Benjamin
Published: December 2022

A combination rosette-plaque assay was used to demonstrate that most (92%) of the plaque-forming cells (PFC) bound hapten to their surface 5 to 8 days after one injection of 3-nitro-4-hydroxy-5-iodophenyl acetic acid (NIP) coupled to diphtheria toxoid, (NIP-TOX). There was a significant decrease in hapten binding by these cells later in the primary response. Rosette formation was observed when NIP-TOX-primed lymph node cells bound NIP-coupled sheep red blood cells stabilized with pyruvic aldehyde (NIP/PASRBC). This suspension of cells was then plaqued on fresh NIP-coupled sheep red blood cells (NIP/SRBC). A rosetted lymph node cell in the center of a plaque clearly demonstrated simultaneous hapten binding and anti-hapten antibody secretion. The specificity of hapten binding and antibody secretion was established by rosette and plaque inhibition with NIP coupled to bovine serum albumin (NIP-BSA). The specificity of each was further characterized by comparative inhibition with analogues of NIP (also coupled to BSA): 3,5-dinitro-4-hydroxyphenyl acetic acid (NNP-BSA), 3,5-diiodo-4-hydroxyphenyl acetic acid (DIP-BSA) and 3-nitro-4-hydroxyphenyl acetic acid (NP-BSA). The homologous hapten NIP was always the best inhibitor of plaques (97.8% inhibition) and rosettes (96.2% inhibition). NNP was always a better plaque and rosette inhibitor than either DIP or NP. This hierarchy of inhibition, and the correlation between rosette and plaque inhibition demonstrated the similarity of receptor and antibody specificity.
Human Antibody to Dengue Soluble Complement-Fixing (SCF) Antigens
Authors: Falkler William A. , Diwan Arwind R. , Halstead Scott B.
Published: December 2022

Soluble complement-fixing (SCF) antigens were prepared to dengue viruses, types 1 to 4, from infected suckling mouse brain. While these non-structural proteins previously had been shown to have group- and type-specific antigenic determinants and to circulate in infected mice, their participation in human dengue infection was never established. Human acute and convalescent sera from primary and secondary dengue infections were tested for antibody to SCF antigens. At two antigen units, one of nine primary convalescent samples had antibody to a single type of dengue SCF, none of 11 secondary acute-phase sera had SCF antibody while all of 22 convalescent-phase samples had relatively high titers to two or more SCF antigens. With higher antigen concentrations, none of eight primary convalescent samples and only one of nine secondary acute-phase sera had antibody to dengue 2 SCF antigen. Sucrose gradient ultracentrifugation showed the antibody activity in the secondary convalescent-phase sera to be of the IgG class, suggesting prior antigenic exposure in these hosts. The inability to detect anti-SCF in the primary convalescent and secondary acute samples was not due to IgM interference as demonstrated with ethanethiol reduction experiments. This study has demonstrated that SCF antibody is produced in humans allowing for the possibility, as postulated, that these antigens participate in dengue immunopathogenesis. The inability to detect antibody during the acute phase of secondary dengue infections and in the convalescent sera from primarily infected humans requires further study.
Leukemia Virus-Induced Immunosuppression
Authors: Mortensen Richard F. , Ceglowski Walter S. , Friedman Herman
Published: December 2022

An examination of cell-mediated immunity (CMI) in susceptible mice infected with Friend leukemia virus (FLV) revealed a marked depression of the delayed hypersensitivity response and its in vitro correlate, macrophage migration inhibition. Spleen lymphocytes from mice sensitized with complete Freund's adjuvant (CFA) and infected with low doses of FLV rapidly lost their ability to produce a migration inhibitory factor (MIF) in response to PPD. With both direct and indirect assays for MIF it was shown that there was a significant decrease in the production of MIF in response to mycobacterial antigens by 3 days post-infection. The degree of suppression correlated with both the infecting dose of FLV and the time post-infection. Mice were protected from FLV induced immunosuppression of CMI by vaccination with FLV. In vitro spleen lymphocyte stimulation with the thymus derived (T) cell specific mitogen, ConA, and with antigen (PPD) was also rapidly suppressed after FLV infection. Macrophages from leukemic mice were able to respond to MIF-rich culture supernatants, but nonadherent spleen lymphocytes from the same mice were not able to generate MIF. Antagonists or inhibitors of MIF were not detected in the supernatants of leukemic spleen lymphocyte cultures. The development of delayed hypersensitivity to tubercle bacilli could be abrogated by infecting with FLV up to 14 days after injection of CFA. These observations indicate that FLV not only inhibits the bone marrow-derived cell function of antibody formation, but also the cell-mediated immune functions which are mediated by T cells and which have been implicated as the surveillance mechanism responsible for controlling the emergence of neoplasia.
Rosette Formation by Guinea Pig Thymocytes and Thymus Derived Lymphocytes with Rabbit Red Blood Cells
Authors: Stadecker Miguel J. , Bishop Gene , Wortis Henry H.
Published: December 2022

Rabbit red blood cells (RRBC) can bind to guinea pig lymphocytes forming rosettes. Ninety-five per cent of thymocytes, about 50% of lymph node cells, 15% of spleen cells, 30% of peripheral blood lymphocytes and <1% of L2C (B cell) leukemic lymphocytes form rosettes. Lymphocytes with binding sites for complement (EAC rosetting cells) do not rosette with RRBC. Cells sensitive to the cytotoxic activity of anti-thymus derived (T) cell sera plus complement are the same cells that form RRBC rosettes. Anti-T cell sera (even in the absence of complement) inhibit RRBC rosetting. Rosette formation requires a live lymphocyte and is blocked by sodium azide, but not EDTA. It is concluded that the ability to bind to RRBC is a characteristic of living guinea pig T cells and not of B cells.
Restricted Rabbit Antibodies: Amino Acid Sequences of Rabbit H Chains of Allotype a1, a2, and a3 in the Region 80 to 94
Authors: Jaton Jean-Claude , Braun Dietmar G. , Strosberg A. Donny , Haber Edgar , Morris James E.
Published: December 2022

The partial amino acid sequence of rabbit heavy (H) chains of allotype a1, a2, and a3 was determined. The H chains were derived from restricted antipolysaccharide antibodies which were shown to be precipitated quantitatively by antiallotype sera raised against pooled immunoglobulins.

The N-terminal half of the H chains (C1 fragment) was isolated from a CNBr digest and subjected to automated Edman degradation. Extended homology with known sequences from rabbit pooled H chains indicated that C1 fragments were cleaved between residues 34 and 35 and/or 79 and 80. One additional cleavage site was observed at position 110 in two H chains.

Section 80 to 94 of a1, a2, and a3 restricted H chains showed little sequence variation. No simple correlation between the identity of a single amino acid residue and the allotype of the H chain could be determined.
Decreased Epinephrine Response of Adenylate Cyclase Activity of Lymphoid Cells from Immunodeficient Pituitary Dwarf Mice
Authors: Kemp Robert G. , Huang Yung-Chen , Duquesnoy Rene J.
Published: December 2022

Although basal activities of adenylate cyclase in lymphoid cells and liver cells were similar in suckling and weaned Ames pituitary dwarf mice and normal littermates, the cyclase from the thymus and spleen of weaned dwarfs was not stimulated by 10 µM epinephrine. Thymus cyclase from normal mice was stimulated by about 300% and spleen cyclase by 150% by epinephrine. Similar results were obtained with weaned Snell-Bagg dwarf mice, although the lymphoid cell adenylate cyclases responded somewhat better to epinephrine. The significance of these observations is discussed in relation to the pathogenesis of the endocrine immunodeficiency syndrome of the weaned dwarf mouse.
Immunochemical Studies of the Intramolecular Heterogeneity of the Carcinoembryonic Antigen (CEA) of the Human Digestive System
Authors: Gold J. M. , Banjo C. , Freedman S. O. , Gold P.
Published: December 2022

Previous studies have shown that in addition to the tumor-specific site on the carcinoembryonic antigen (CEA), this molecule also contains a blood group A-like grouping. To study the A-like site on the CEA molecule, we devised a radioimmunoassay in which anti-A antibodies were coupled to either Sepharose or Sephadex beads. The following observations were made. 1) The monosaccharide, N-acetyl-D-galactosamine was capable of inhibiting the interaction between 125I-CEA and a preparation of anti-A antibodies. 2) A glycopeptide (GP-1), containing the tumor-specific antigenic site of the CEA, which was obtained by the enzymatic degradation of the CEA molecule was capable of binding to anti-A antibodies. The ratio, by weight, of GP-1 to N-acetyl-D-galactosamine required to achieve equivalent binding was 10-3 to 10-4 to 1. GP-1 has a molecular weight of about 4000 daltons, and although it contains N-acetyl-D-glucosamine, D-mannose, D-galactose, and L-fucose, the glycopeptide is apparently devoid of N-acetyl-D-galactosamine.
The Immune Response of Tetraparental Mice to Two Synthetic Amino Acid Polymers: “High-Conjugation” 2,4 Dinitrophenyl-Glutamic Acid57-Lysine38-Alanine5 (DNP-GLA5) and Glutamic Acid60 Alanine30 Tyrosine10 (Gat10)
Authors: Warner Carol M. , Fitzmaurice Maryann , Maurer Paul H. , Merryman Carmen F. , Schmerr Mary Jo F.
Published: December 2022

Allophenic (tetraparental) mice of the following types were produced: C57BL/6J ↔ C3H/HeJ, C57BL/6J ↔ DBA/1J, C3H/HeJ ↔ CF1, C3H/HeJ ↔ DBA/1J, C57BL/6J ↔ BALB/cJ, SJL/J ↔ C3H/HeJ, SJL/J ↔ DBA/2J, SJL/J ↔ C57BL/6J, and DBA/1J ↔ A/J. These mice were immunized with 35 or 77 µg of “high-conjugation” (50 to 75%) 2,4 dinitrophenyl-poly (glu57 lys38 ala5), DNP-GLA5, or with 10 µg of poly (glu60 ala30 try10), GAT10. The primary and secondary antibody responses to the DNP group or GAT10 were tested. Many of the mice expressing the presence of “responder” cells, as shown by coat color phenotype, failed to respond to these antigens. We suggest two possible explanations: 1) An allophenic mouse may need a minimum number of responder lymphoid cells in order to respond to an antigen. 2) Cross-tolerance may be responsible for the non-response to some antigens in some strains of mice.
A Comparison of the Cytolytic Action of Guinea Pig and Rabbit Complement on Sensitized Nucleated Mouse Cells
Authors: Koene Robert A. P. , McKenzie Ian F. C.
Published: December 2022

The efficiency of guinea pig complement (GPC) and rabbit complement (RC) was compared in a cytotoxic assay by the 51Cr release method, and with the DBA/2 leukemia L1210 as target. Alloantisera and heteroantisera, containing antibodies of defined specificity and shown to be IgG (2ME resistant), were used. When there were limiting amounts of either alloantibody or heteroantibody present, RC was clearly more efficient than GPC. In the presence of excess antibody, however, both RC and GPC behaved similarly, except that in the presence of GPC, fewer cells were lysed. This finding is related to the target cells containing a population of cells resistant to lysis with GPC, rather than to the amount of 51Cr released from each cell. When alloantisera were mixed, variable effects occurred: a) blocking or antagonistic effects occurred in all combinations in the presence of RC; with GPC, this effect was only seen in the presence of antisera to two private specificities (H-2D.4 + H-2K.31). b) Synergistic effects were noted only with GPC when there was a mixture of antibody to a private (H-2D or H-2K) specificity with that to a public specificity. In the presence of heteroantibody, either not absorbed, or absorbed to remove species-specific antibody and leave antibody to H-2.31, the ratio of the effectiveness of RC:GPC remained unaltered, indicating little or no synergism between these two antibodies and GPC. All of these findings are in substantial agreement with the concept that GPC requires the activation of two adjacent cell surface sites for cytolysis, but that RC requires only the activation of one such site.
Immunopathology of the Renal Complications of Babesiosis
Authors: Annable C. R. , Ward P. A.
Published: December 2022

Histologic examination of kidneys from rats infected with the hemosporidian protozoan Babesia rodhaini demonstrates the presence of a moderate, acute proliferative glomerulitis. Immunofluorescent studies establish that this renal complication is associated with glomerular deposits of IgG and the third component of complement (C3) in a pattern that is diagnostic for soluble, immune complex-induced nephritis. Acid elution of proteins from involved kidneys leads to the recovery of IgG that is reactive with babesial antigen. In the course of rat babesiosis hypocomplementemia develops, coincident with the parasitemia, severe anemia and glomerular deposits of IgG and C3.
Immunochemical Studies on Blood Groups
Authors: Feizi Ten , Kabat Elvin A.
Published: December 2022

Two anti-I cold agglutinins with different specificities have been linked to Sepharose to make insoluble adsorbents to isolate blood group I glycoproteins from sheep hydatid cyst fluid (HCF) and from human milk. One was anti-I Ma (group 1) whose ability to precipitate with human milk I substance distinguishes it from the other anti-I Step (group 3) which precipitates with HCF. The I antigens were absorbed to the columns at 4°C and elution occurred at 37°C without resort to dissociating agents.

Specific separation of I active material from inert material was achieved using the insoluble anti-I Ma adsorbent. With the insoluble anti-I Step adsorbent, and I + P1 blood group active fraction was separated from P1 and from the other inert materials in HCF. The I antigen eluted from the Ma column, in contrast to that eluted from the Step column, had strong reactivity with type XIV anti-pneumococcal horse serum. This is in accord with previous evidence for the βDGal(1 → 4)βDGlcNAc(1 → 6)—specificity of anti-I Ma and of its distinct difference from the determinant of anti-I Step.
The Molecular Dimensions of Guinea Pig Lymphotoxin
Authors: Gately Maurice K. , Mayer Manfred M.
Published: December 2022

The molecular dimensions of guinea pig lymphotoxin were studied by means of gel filtration, sucrose density gradient ultracentrifugation, and CsCl isopycnic ultracentrifugation. Lymphotoxin was produced by stimulating immune lymph node cells with the specific antigen, ovalbumin, and was assayed by means of a Coulter counter microassay. The D20,w of guinea pig lymphotoxin was estimated by gel filtration on Sephadex G-100 to be (8.0 ± 0.2) × 10-7 cm2/sec, and the apparent S20,w of guinea pig lymphotoxin was estimated to be 4.2 ± 0.1S by sucrose density gradient ultracentrifugation. The buoyant density of guinea pig lymphotoxin was determined to be 1.302 ± 0.002 g/ml by CsCl isopycnic ultracentrifugation. From these values the molecular weight of guinea pig lymphotoxin was calculated to be 45,000, and the frictional ratio was calculated to be 1.1. No evidence was found to indicate that more than a single factor was involved in producing the cytotoxic effect attributed to lymphotoxin.
Anti-Inflammatory Effects of Tartar Emetic and Niridazole: Suppression of Schistosome Egg Granuloma
Authors: Mahmoud Adel A. F. , Warren Kenneth S.
Published: December 2022

Treatment of cerebral schistosomiasis japonica with tartar emetic produces a remarkable and rapid improvement which cannot be explained on the basis of worm destruction alone. In dracunculiasis, niridazole appears to have an anti-inflammatory effect facilitating the extraction of the adult worms. In addition to their antischistosome effects these drugs may serve to suppress the response to schistosome eggs which has been demonstrated to be a form of delayed hypersensitivity. Niridazole and tartar emetic were administered, in their recommended therapeutic doses, to mice. In unsensitized animals granulomas appeared by the 4th day and reached their peak at 16 days. Treatment with the drugs resulted in no reaction at 4 days, minimal reaction at 8 days, and marked suppression at 16 days. Mice sensitized by the prior injection of eggs developed large reactions 1 day after intravenous egg injection and massive reactions by 8 days. No reaction was seen at 24 hr in the treated animals and, at 8 days, the reactions were 50% smaller than in the controls. In egg-sensitized mice both drugs suppressed delayed footpad swelling to soluble egg antigens, another parameter of delayed hypersensitivity. The degree of inhibition of granuloma formation by niridazole and tartar emetic was similar to that of many of the major immunosuppressive drugs, neonatal thymectomy and antimacrophage serum. The rapid amelioration of cerebral schistosomiasis, the ease of guinea worm extraction, and some of the other effects of these drugs, may be explained by these observations.
The Percentage of Monocytes among “Mononuclear” Cell Fractions Obtained from Normal Human Blood
Authors: Zucker-Franklin Dorothea
Published: December 2022

Human peripheral blood “mononuclear” cell fractions obtained by Ficoll-Hypaque centrifugation contained 44% of cells able to phagocytose latex particles. Such cells could be removed magnetically following their incubation with iron filings. Glass wool column filtration was less effective. Very few phagocytic cells were found among cells obtained from patients with CLL. It is concluded that the percentage of monocytes in normal blood is at least twice as high as is commonly recognized on routine smears. These observations point up the need for further purification steps whenever “mononuclear” cells are used in studies concerned with the function of lymphocytes.
Specificity of Autoantibodies to Tubular and Glomerular Basement Membranes Induced in Guinea Pigs
Authors: Lehman David H. , Marquardt Hans , Wilson Curtis B. , Dixon Frank J.
Published: December 2022

All twenty-eight guinea pigs immunized with a variety of bovine renal basement membrane (RBM) preparations developed similar interstitial nephritides, with minimal glomerular abnormalities. Direct immunofluorescence revealed linear deposition of IgG along the tubular basement membranes (TBM) of all guinea pigs and along the glomerular basement membranes (GBM) of 13 of them. Elution of renal-bound IgG demonstrated that all guinea pigs had antibodies against both TBM and GBM, although anti-GBM activity was usually not detectable at low concentrations of IgG in the eluates. Absorption of pooled eluates with a variety of guinea pig RBM immunoabsorbents revealed the following: 1) approximately three-fourths of the eluted IgG comprised antibody to RBM; 2) all of the eluted autoantibody reacted with TBM, while only 36 to 46% crossreacted with GBM; 3) TBM appeared to have antigenicities both separate from and shared with GBM; 4) guinea pigs immunized with whole bovine TBM appeared to form antibodies to both the collagenous and noncollagenous portions of RBM.
Successful Treatment of Experimental Allergic Encephalomyelitis (EAE) in Guinea Pigs with Homologous Myelin Basic Protein
Authors: Driscoll Bernard F. , Kies Marian W. , Alvord Ellsworth C.
Published: December 2022

Homologous myelin basic protein has been used successfully for treatment of experimental allergic encephalomyelitis (EAE) in NIH and strain 13 guinea pigs. Response of strain 13 guinea pigs to both induction and treatment of EAE was more consistent than response of outbred, NIH guinea pigs. Serum levels of antibasic protein antibody were related to the amount of mycobacteria used for sensitization rather than to disease severity or success of treatment.
Antibody-Dependent Lymphoid Cell-Mediated Cytotoxicity: Role of Complement
Authors: van Boxel John A. , Paul William E. , Green Ira , Frank Michael M.
Published: December 2022

Unsensitized lymphoid cells have the capacity to destroy antibody-coated target cells in vitro. Definitive studies to rule out the participation of complement (C) components in this reaction require a system with a complete absence of C components and with no possibility of endogenous synthesis of C by cells in culture. Such a system is provided by using lymphoid effector cells from animals genetically deficient in certain C components and serum from these C-deficient animals to support the cultures. Lymphoid cells from animals genetically deficient in C4, C5 or C6 were found to be fully capable of destroying antibody-coated target burro erythrocytes. Direct C-mediated hemolysis of target cells via the classical or alternate pathways is thus ruled out. Furthermore, serum depleted of C3-9 by cobra venom factor treatment fully supported target cell lysis suggesting that the late C components derived from the serum are also not important. The role of the C3 receptor in promoting the binding of the effector cells to the antibody-coated targets was examined by competitive inhibition experiments. Whereas an excess of unrelated target cells coated with IgG inhibited cytotoxicity by competing for the aggregate receptor on the effector cell, coating of such competing cells with C in addition resulted in no further inhibition. Moreover an excess of unrelated target cells coated with IgM and C was not inhibitory. These findings indicate that the C3 receptor does not have a major role in this reaction in vitro.
Regulation of the Antibody Response to Type III Pneumococcal Polysaccharide
Authors: Baker Phillip J. , Stashak Philip W. , Amsbaugh Diana F. , Prescott Benjamin
Published: December 2022

The present study was conducted primarily to obtain information concerning the mechanism by which suppressor thymic-derived (T) cells influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III). This was accomplished by examining the effects of treatment with antilymphocyte serum (ALS) and Velban, a mitotic inhibitor, on the kinetics for the appearance of plaque-forming cells (PFC) in mice immunized with SSS-III. Without ALS-treatment, the kinetics were essentially biphasic. First, there was a phase during which PFC appeared at a relatively rapid rate; this was followed by a phase during which the rate of appearance of PFC gradually declined until maximal numbers were attained. In contrast, similar rate changes were not noted for mice given ALS; here, PFC increased at a uniform exponential rate throughout the 1st 5 days of the antibody response. Velban completely arrested the development of additional PFC in ALS-treated but not non-ALS-treated mice. These findings indicate that suppressor T cells act primarily by limiting the extent to which antibody-forming bone marrow-derived cells proliferate following immunization.
Circulating Immune Complexes in Mycoplasma Pneumoniae Infection
Authors: Biberfeld Gunnel , Norberg Renee
Published: December 2022

Immune complexes were detected by the platelet aggregation technique in the sera of 16 (41%) out of 39 patients with acute respiratory illness due to M. pneumoniae. Immune complexes were demonstrable during the first 2 weeks after onset of illness and then rapidly disappeared. The size of the immune complexes was 19S or larger.
Blocking Activity Induced by Solubilized Alloantigens
Authors: Zighelboim Jacob , Bonavida Benjamin , Rao V. Srinivasa , Fahey John L.
Published: December 2022

In recent years, several investigations have been directed toward delineating the biologic role of transplantation and tumor-associated antigens present on cell membranes. One approach has been the solubilization of these antigens and the study of their immunologic and biochemical characteristics. Medawar (1) was the first to report that mice injected with crude membrane preparations derived from allogeneic mouse lymphoid tissue induced prolonged skin allograft survival. Since then, contradictory results have been reported in which either accelerated rejection (2) or prolonged survival of skin allografts (3) were observed after injections of different forms of soluble alloantigens into the recipient mice. Recently, Von Hachen et al. (4) have demonstrated active enhancement of rat kidney allografts and weak GVH in recipients which were pretreated with soluble transplantation antigens. The observed biologic effects induced by solubilized membrane antigens are considered to be of an immunologic nature.
Stimulation of Early Protein Synthesis as an Assay of Immune Reactivity: Analysis of the Cells Responding to Mitogens and Alloantigens
Authors: Gorczynski Reginald M. , Rittenberg Marvin B.
Published: December 2022

Spleen cells from nonimmune mice were cultured for 24 hr in the presence of phytohemagglutinin (PHA), lipopolysaccharide (LPS), or alloantigens. Data are presented to show that within this time period all three stimuli caused an increase in protein synthesis. The response to PHA and alloantigens was defined as a T cell response by virtue of the effects of anti-θ antibody, adult thymectomy, and velocity cell sedimentation. Similarly, the response to LPS was determined to be a B cell response since it was unaffected by anti-θ antibody or adult thymectomy but was abolished by treatment of responder cells with anti-Ig antiserum and complement. Furthermore, the cells responding to LPS were physically separable from those responding to PHA and alloantigens and sedimented with a velocity characteristic of B lymphocytes.
Separation of T and B Lymphocytes and Their Role in the Mixed Lymphocyte Reaction
Authors: Boehmer Harald v.
Published: December 2022

Electrophoretic separation was used to purify mouse spleen T and B lymphocytes for a study of the stimulating and proliferating cells in mixed lymphocyte reaction. In one-way mixed lymphocyte studies with mouse lymphocytes it is shown that mitomycin C-blocked T cells as well as 100% pure mytomycinblocked B lymphocytes can induce high and significant stimulation when cultured together with allogeneic T lymphocytes. Exclusively T lymphocytes have the ability to recognize allogeneic lymphocytes and, as a consequence to this event, to initiate proliferation in MLR. Mitomycin C-treated T cells can, after allogeneic recognition, stimulate lymphocytes which by themselves are not able to proliferate in response to an allogeneic stimulus. The implication of these findings in regard to experiments published elsewhere, in which non-T cells “responded” in mixed lymphocytes, is discussed.
Decline in Suppressor T Cell Function with Age in Female NZB Mice
Authors: Barthold David R. , Kysela Susan , Steinberg Alfred D.
Published: December 2022

Type III pneumococcal polysaccharide (SSSIII) did not cross-react with the nucleic acid antigen polyinosinic · polycytidylic acid when tested in NZB or CBA mice. Neither antigen requires thymic helper cells for the induction of an antibody response. The antibody response to each antigen, given alone or together, was increased by simultaneous administration of antithymocyte serum.

Studies of the immune response to SSSIII were conducted in NZB mice since it was felt that this autoimmune strain might represent a natural model for the loss of suppressor T cells. The number of plaque-forming cells to SSSIII following immunization increased with age in female NZB mice. No such age-associated increase was observed in non-autoimmune BALB/c mice, suggesting that NZB mice might have a loss of suppressor function with age. This was supported by the reduction in the high PFC response to SSSIII of 10-month-old NZB mice by transfer of thymocytes from 4-week-old NZB mice.
Determination of Soluble Immune Complex Molar Composition and Antibody Association Constants by Ammonium Sulfate Precipitation
Authors: Arend William P. , Mannik Mart
Published: December 2022

The interaction between rabbit IgG anti-HSA and HSA was studied by ammonium sulfate precipitation of the complexes formed throughout a wide range of antigen excess. The Ag/Ab molar ratio varied between 0.85 and 1.20 in the range of five to 60 times antigen excess. In greater degrees of antigen excess (up to 500-fold) the molar ratio of the complexes remained at a plateau between 1.20 and 1.25. Identical results were obtained using antibodies isolated by immunoadsorbent techniques or using antibodies in antiserum. The molecular composition of the limiting complexes was primarily Ag2Ab2 and Ag1Ab1, but a small amount of Ag2Ab1 could have been present.

The association constant between anti-HSA and HSA was determined with isolated antibodies and with anti-HSA in antiserum. The association constants were similar, ranging from 2.19 × 107 to 3.20 × 107 liters/mole. However, the values for the association constant were partially dependent upon the absolute amounts of antigen and antibodies present and upon the relative amounts of each.
Production of Augmented Experimental Autoimmune Thyroiditis Lesions by Combined Transfer of Antiserum and Lymph Node Cells
Authors: Sharp Gordon C. , Mullen Helen , Kyriakos Michael
Published: December 2022

Combined transfer of thyroid-sensitized lymph node cells and hyperimmune rabbit antiserum to guinea pig thyroglobulin in inbred strain 13 guinea pigs resulted in a higher incidence and greater severity of experimental autoimmune thyroiditis than that which followed transfer of cells or serum alone. The lesions produced by combined transfer of cells and antiserum were comparable to lesions induced by active immunization of strain 13 animals. These data provide evidence for the participation of both cellular and humoral factors in the pathogenesis of autoimmune thyroiditis.