bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Biosynthesis in the Spleen
Authors: Selawry Helena S. , Starr Jason L.
Published: December 2022

Spleen microsomes and ribosomes are more efficient for the incorporation of amino acids after primary immunization. Studies undertaken in an attempt to elucidate the mechanism responsible for this observation demonstrated that the functional change is not an integral part of the ribosomal unit, since it can be altered with salt washes. It was postulated that the process of immunization affects the concentration of factors in close association with the ribosomes and thus exerts a control at one of the steps in the mechanism of protein synthesis.
Immunologic Deficiency Associated with Mammary Tumor Virus (MTV) Infection in Mice: Hemagglutinin Response and Allograft Survival
Authors: Blair Phyllis B. , Kripke Margaret L. , Lappé Marc A. , Bonhag Rose S. , Young Larry
Published: December 2022

Mice infected with the mammary tumor virus (MTV) are less vigorous in their humoral antibody response and cell-associated immune response to unrelated antigens than are isogenic MTV-free controls. The deficiency in both types of immunologic reactivity is most pronounced in the older MTV-infected animal, at 10 months of age and later, but statistically significant differences in hemagglutinin titers can be obtained even in young adult females. Immunologic deficiency can be detected not only in animals neonatally infected with MTV but also in young adult and mature adult females within several days after the introduction of the virus.
Isolation of Rabbit Anti-Rhesus Lymphocyte Antibody Using a Specific Immunoadsorbent
Authors: Wilson B. J. , Malley A. , Cook M. W. , Mackler B. F.
Published: December 2022

This report describes a rapid, one-step method of purifying both anti-rhesus and anti-human lymphocyte antibodies using a specific immunoadsorbent. The immunoadsorbent was prepared by chemical conjugation of rhesus lymphocyte stroma to Sephadex G-100. Specifically purified antilymphocyte antibody eluted from the immunoadsorbent represented 6% to 9% of the total protein applied to the column. The antibody preparations showed a 10- to 15-fold increase in specific activity (leukoagglutinins/milligram IgG).
The Antigen Receptor in Delayed-Type Hypersensitivity
Authors: Hill William C. , Nissen Barbara
Published: December 2022

Low molecular weight fractions from sensitive lymphoid cells were shown to sensitize normal guinea pigs by three different routes. Two antigens were used, one of which was an artificial contact-sensitizing agent (dinitrofluorobenzene) and the other a protein antigen from mycobacteria.
The Effect of Physical and Chemical Properties of the Sensitizing Substance on the Induction and Elicitation of Delayed Contact Sensitivity
Authors: Godfrey H. P. , Baer Harold
Published: December 2022

The quantitative relationship between induction and elicitation of delayed contact sensitivity by chemically reactive sensitizers and some of the physicochemical properties of these compounds was investigated. Guinea pigs were sensitized with 5 µmols of compound in complete Freund's adjuvant and skin tested to determine specific and cross-reactivity. The plot of specific sensitivity against a calculated reactivity coefficient was a parabola. Similar plots of specific sensitivity against nonaqueous solubility or oil-buffer partition coefficients were less significant. For a restricted group of sensitizers, the halodinitrobenzenes and dinitrobenzene thiocyanate, specific sensitivity was negatively proportional to chemical reactivity, solubility, and the atomic parameters of the 1-substituent of the benzene ring (atomic number, atomic weight, radius, surface area, volume). Cross-reactions between substituted 2,4-dinitrobenzenes were extensive but not reciprocal, delayed reactions often being elicited best by heterologous compounds. 3,5-Dinitrobenzoyl chloride was a poor sensitizer and showed little cross-reactivity with 2,4-dinitrobenzene derivatives. The mechanisms underlying these observations may be the interaction between the amount of reactive chemical lost from sensitizing depot or skin test site into the blood by solution in plasma and/or reaction with serum protein and the amount remaining capable of reacting with body cells or tissues. The material lost from the sensitizing depot or skin test site may be or become tolerogenic and influence induction and elicitation of delayed hypersensitivity.
The Fifth Component of the Guinea Pig Complement System
Authors: Shin Hyun S. , Pickering Richard J. , Mayer Manfred M.
Published: December 2022

The mechanism of the reaction between EAC1̄, and C5 has been studied by kinetic analysis of C5 consumption and formation of SAC1̄,,5b with variation of the concentration of reactants, temperature, pH and ionic strength. The results are compatible with the hypothesis that EAC1̄, enzymatically cleaves the C5 molecule into two fragments, one of which, C5b, then becomes fixed to the cells. The minimal hemolytic efficiency of purified guinea pig C5 is about 10%. As expected, the rate of C5 consumption by EAC1̄, and that of formation of SAC1̄,,5b diverge as temperature or ionic strength are allowed to vary. N-acetyl-l-tyrosylethylester blocks C5 consumption and SAC1̄,,5b formation; on the other hand, phloridzin inhibits SAC1̄, formation but not C5 consumption. Cell-bound C2 and C3 are required for consumption of C5 and these components have to be located on the same cell, probably in close proximity to one another.
Correlation of Lymphocyte Transformation with the In Vivo Immune Responsiveness of Rabbits
Authors: Jevitz M. A. , Ekstedt R. D.
Published: December 2022

A comparative study of in vitro induced lymphocyte transformation with cultures of peripheral blood cells from rabbits immunized to favor delayed sensitivity or antibody production was done. Cultures made at intervals during the animals' primary, secondary, or hyperimmune in vivo response to the C-RBC antigen were studied for the transformation phenomenon morphologically and by monitoring the incorporation of tritiated thymidine and uridine. The responses as judged by these characteristics indicate that the transformation process correlates with both types of distinct immune responsiveness. The appearance of large transformed cells with characteristic pyroninophilic cytoplasm and increased thymidine incorporation upon specific stimulation can be taken as evidence for immunologic activation. Animals minimally immunized to produce antibody alone or to exhibit delayed hypersensitivity without detectable humoral antibody incorporated less isotope into lymphocyte cultures than did either hyperimmune or boosted delayed sensitive animals. That these boosted animals were also exhibiting a single immune state was shown as definitively as possible by hemagglutinin titers and skin testing done at times of culture. Stimulation of cell cultures could be evoked with chicken erythrocytes or a urea extract but not with homologous erythrocytes. Cells cultured for prolonged periods in vitro and with varied concentrations of both the cellular and soluble forms of the antigen reflect differences in the transformation response of delayed and antibody-producing animals.
DNA Degradation in Mammalian Cells Following Complement-Mediated Cytolysis
Authors: Shipley William U. , Baker Alan R. , Colten Harvey R.
Published: December 2022

Immune cytotoxic damage of Chinese hamster cells in tissue culture leads to enzymatic degradation of target cell DNA, which results in a greater than 10-fold reduction in molecular weight of the single-stranded DNA fragments. The amount of DNA degradation is a function of antiserum concentration and correlates with lethal injury as measured by loss of colony-forming ability.
Modification of Bone Marrow Induced GVH Disease with Heterologous Antisera to γ Globulin or Whole Serum
Authors: Tyan Marvin L.
Published: December 2022

Recent clinical successes in organ transplantation have reawakened interest in the use of bone marrow grafts for the production of chimerism and specific homograft tolerance, and, perhaps more importantly, for the treatment of aplastic and genetically determined anemias, leukemias and congenital and acquired immunologic deficiency states. It has been found to be relatively easy to induce chimerism and specific tolerance in mice and rats with acute whole-body irradiation (1, 2) or short-term immunosuppressive therapy (3) coupled with the transfusion of allogeneic hemopoietic and lymphoid stem cells obtained from bone marrow. However, bone marrow from adult donors contains mature lymphoid cells that are able to recognize and react against foreign transplantation antigens of the host, producing a syndrome of delayed deaths as a result of the graft-vs-host (GVH) immune reaction (4). In primates and in man the transfusion of foreign bone marrow cells results in an acute and severe form of GVH disease (5, 6).
A Study of Mixed Cell Interactions between Sensitized and Allogeneic Mouse Spleen Cells in Vitro Using the Hemolytic Plaque Assay
Authors: Hirano Shinji , Uyeki Edwin M.
Published: December 2022

By using the in vitro production of PFC (plaque-forming cells) as an indicator of cytotoxic potency, allogeneic spleen cell interactions were investigated. Dispersed spleen cells from two allogeneic mouse strains were mixed at the beginning of the culture period, and a wide range of interaction was observed (i.e., suppression or stimulation of PFC production). The degree of suppression of PFC was generally related to the disparity of the H-2 allele. In some combinations of normal allogeneic lymphoid cells, moderate stimulation of PFC production was observed and was associated with allogeneic strains of weak histoincompatibility. Suppression of PFC production in mixed cultures by effector cells (spleen cells from pre-sensitized animals) had the following characteristics: a) marked suppression of PFC production was observed only when effector cells were combined with specific donor cells, b) initial cell-cell contact was necessary and c) the factor(s) responsible for the suppression of PFC production did not depend on the action of complement and was not detectable in aqueous extracts from effector cells. This factor(s) appeared earlier than humoral antibodies in mice sensitized against target lymphoid cells.
Passive Serologic Transfer of Allograft Immunity in Immunologically Suppressed Mice
Authors: Kinne David W. , Simmons Richard L.
Published: December 2022

The administration of rabbit anti-mouse lymphocyte serum (RAMLS) plus cortisone to secondary C57 hosts prolonged the survival of A skin grafts transferred from untreated C57 primary hosts 48 hr after initial grafting. The administration of C57 anti-A immune mouse serum (IMS) to the primary C57 hosts reversed the RAMLS-cortisone induced prolongation in the secondary C57 hosts. The prolonged survival of BALB/c grafts on RAMLS plus cortisone-treated secondary C57 hosts was not influenced by administration of C57 anti-A IMS to the primary C57 hosts. A circulating lymphopenia of similar degree was noted in RAMLS plus cortisone-treated secondary C57 hosts after receiving A grafts from either IMS-treated or untreated C57 primary hosts. The administration of IMS to primary C57 hosts resulted in the rejection of a significant number of A skin grafts which had been transferred to A secondary hosts. The results support the thesis that humoral antibody bound to the graft can participate in allograft rejection, perhaps in synergism with a nonspecific cytotoxic effect of lymphocytes.
Alterations in Isotypic and Allotypic Immunoglobulin Antigens Induced by Chemical Modification
Authors: Messner Ronald P. , Natvig Jacob B. , Ein Daniel , Williams Ralph C.
Published: December 2022

Gamma G myeloma and Bence Jones protein were modified by amidination, a treatment specific for ε-amino groups of lysine, and tested before and after modification for their serologic reactivity with antisera against defined γ and light chain antigens. Gm(a), “non-a”, Gm(z), Inv(a), and Oz(+) reactivity but not that of Gm(f), (b0), (g) or “non-g” were inactivated by this treatment. Lysine residues are known to be directly involved or lie immediately adjacent to the amino acid positions responsible for expression of all the antigens altered by amidination. It is suggested that the use of chemical probes specific for various amino acid resides may be of benefit in defining the structures responsible for the serologically-defined antigens of human immunoglobulins.
Use of Leukocyte Chemotaxis in Vitro to Assay Mediators Generated by Immune Reactions
Authors: Horwitz David A. , Garrett Martha Anne
Published: December 2022

Polycarbonate (Nuclepore) filters were used to develop a rapid, reproducible technique to measure simultaneously mononuclear and polymorphonuclear leukocyte chemotaxis in vitro. Both cell types, obtained from guinea pig peritoneal exudates, showed a chemotactic response to an Escherichia coli filtrate. Neutrophils showed a faster, stronger response than did mononuclear cells and seemed to inhibit mononuclear chemotactic activity. Peritoneal exudate stored for 4 days did not lose its chemotactic responsiveness. This technique may be used to detect chemotactic activity generated by humoral and cellular immune reactions and to study the relative responsiveness of various leukocytes to the same agent.
Detection of Antibody-Like Structures on Cell Surfaces with Chemically Modified Bacteriophages
Authors: Sulica Andrei , Haimovich Joseph , Sela Michael
Published: December 2022

Antibody-like structures present on cell surfaces may be detected by means of an assay using chemically modified bacteriophages. Guinea pig spleen and peritoneal cells bound specifically the chemically modified bacteriophage T4. The reaction occurred at low temperatures and in the presence of inhibitors of protein biosynthesis and of pinocytosis. Upon exposure to the corresponding hapten, the dinitrophenyl (DNP)-phages or the penicilloyl (Pen)-phages could be released from cells and subsequently counted. The specific binding of DNP-bacteriophage T4 was almost abolished after prior treatment of cells with an affinity labeling reagent.

The ability of peritoneal macrophage cells to bind the modified phage was due to the cytophilic antibodies passively adsorbed in vivo or in vitro. No such reaction occurred when cells from normal guinea pigs were used. In the spleen suspension, most of the modified phages were bound to non-adhering lymphocytes. Spleen cells from both normal and immunized guinea pigs were capable of interacting specifically with DNP-phage or Pen-phage. This ability was probably due to the receptor sites present on surfaces of lymphoid cells.
Genetic Control of the Immune Response of Mice to Hemocyanin
Authors: Cerottini Jean-Charles , Unanue Emil R.
Published: December 2022

There were marked differences in the immune responses of inbred strains of mice to keyhole limpet hemocyanin (KLH). Genetic control of the response was best demonstrated after immunization with small doses of KLH. Differences in antibody titers were not related to differences in class of immunoglobulin or relative avidity of antibody. High responsiveness to KLH appeared to be under control of an autosomal dominant gene(s). High and low responsiveness to KLH was observed among strains of mice which had similar histocompatibility (H-2) antigens. No significant differences were found in the uptake and catabolism of KLH by macrophages from low or high response mice. Moreover, F1 hybrid crosses between low and high response strains responded equivalently to KLH transferred in live macrophages from either parental strain. These findings indicated that the genetic control of the immune response to KLH was not exerted at the level of the cells responsible for antigen handling.
Reappearance and Relative Importance of Immunocompetent Cells in the Thymus, Spleen and Lymph Nodes Following Lethal X-Irradiation and Bone Marrow Reconstitution in Mice
Authors: Blomgren Henric , Andersson Birger
Published: December 2022

The development of the hemolysin response to sheep erythrocytes (SRBC) was studied in mice irradiated with 800 R and reconstituted within 2 hr with 107 isologous Studied in mice irradiated with 800 R and reconstituted within 2 hr with 107 isologous bone marrow cells (800 R:BM) as compared with untreated controls. The hemolysin response was absent in 800 R:BM mice when injected with SRBC on day 0 and was appreciably increased by adding thymic cells with the SRBC on day 0. Thereafter, it progressively reached higher peak titers during recovery of the animals from irradiation, as tested by the injection of SRBC alone on days 10, 14 and 25 after irradiation, and reached somewhat higher peak titers by adding thymic cells with the SRBC on the same days after irradiation. The humoral antibody response against SRBC of mice which had previously been thymectomized, 800 R irradiated and bone marrow reconstituted was absent 14 days after treatment. Their hemolysin response could be restored by the injection of cells from thymus, spleen or lymph nodes from normal donors. After 800 R:BM of the cell donors this type of reactivity reappeared first in the thymus and thereafter in spleen and lymph nodes. It was concluded that immunocompetent cells of this type are generated within the thymus and are later seeded into other lymphoid organs.
Evidence for Thymic Dependence of Pha-Reactive Cells in Spleen and Lymph Nodes and Independence in Bone Marrow
Authors: Blomgren Henric , Svedmyr Erik
Published: December 2022

The influence of the thymus on the in vitro phytohemagglutinin (PHA) response of spleen, lymph node and bone marrow cells was investigated in lethally irradiated, bone marrow-protected (800 R:BM) mice. Reactivity of the cells was measured by studying their incorporation of 3H-thymidine in vitro. Nucleated cell content of the various sites during recovery was also obtained. In 800 R:BM mice, the PHA-response first appeared in cells of the bone marrow and later in those of the thymus, lymph nodes and spleen. It was markedly impaired in lymph node and spleen cells, but not in bone marrow cells during recovery (25 to 35 days after irradiation) when the mice were thymectomized 3 to 4 weeks prior to irradiation and protection by BM cells or fetal liver cells, as compared to similar cells during similar recovery in sham-thymectomized mice or in 800 R:BM mice given thymic cells with the bone marrow or fetal liver cells. Moreover, treatment of lymph node or bone marrow cells with an antiserum directed against an antigen specific for thymic lymphocytes or their descendants reduced the PHA-response of lymph node cells but not that of the bone marrow cells. These results suggest that the PHA-responses of lymph node and spleen cells are thymus-dependent while that of the bone marrow cells is thymus-independent.
Blocking Effect of Serum from Tumor-Bearing Animals on Macrophage Migration Inhibition with Tumor Antigens
Authors: Halliday W. J.
Published: December 2022

Peritoneal cells were obtained from unstimulated mice which had been exposed to tumor antigens (regression of a Moloney virus-induced tumor or removal of a transplanted MCA-induced tumor). The migration of these cells in culture was inhibited specifically by tumor extracts. The inhibition was reversed specifically by serum from mice bearing the corresponding tumor.
Specific Immunologic Unresponsiveness Induced in Adult Guinea Pigs with the Aid of p-Azobenzenearsonate Hapten Coupled to Autologous Red Cells
Authors: Borek Felix , Battisto Jack R.
Published: December 2022

Repeated intravenous injections of adult guinea pigs with p-azobenzenearsonate-coupled autologous erythrocytes induced immunologic unresponsiveness specific for the p-azobenzenearsonate hapten.
Regulation of Homocytotropic Antibody Formation in the Rat
Authors: Okumura Ko , Tada Tomio
Published: December 2022

Adult rats about 3 months old were splenectomized or thymectomized and then immunized with dinitrophenylated Ascaris suum extracts (DNP-As) plus Bordetella pertussis 3 to 10 days after the operation. Homocytotropic antibody (HTA) formation against DNP-As was examined by passive cutaneous anaphylaxis (PCA) over a period of 45 days. HTA formation was found to be greatly enhanced and prolonged by splenectomy and thymectomy. Virtually no termination of HTA formation occurred. Combined extirpation of the spleen and thymus in adult rats had the same enhancing effect. Passive hemagglutination tests with sera treated or untreated with 2-mercaptoethanol showed that the production of γG and γM antibodies was unchanged. In contrast to adult thymectomy, neonatal thymectomy caused a loss, or at least a marked reduction, of the ability to produce HTA. The results suggest that adult splenectomy and thymectomy cause regulatory disturbances of HTA formation in the rat.
Immunochemical Comparison of Human Erythrocyte Membrane Proteins
Authors: Howe C. , Blumenfeld O. O. , Lee L. T. , Copeland P. C.
Published: December 2022

Water-soluble glycoprotein (virus receptor substance, VRS) obtained by phenolic extraction of human erythrocyte membranes was compared with a sialic acid-rich protein fraction derived from pyridine-extracted membranes. In double diffusion analysis, electrophoretically pure VRS gave reactions of identity with a major component of the sialoprotein fraction. Quantitative precipitin analyses also showed the close similarity of the two antigens. The amino acid profile of the sialoprotein resembled that of VRS and differed significantly from that of pyridine soluble proteins from which the bulk of the sialoprotein was separable by chromatography on G-200 Sephadex in 33% pyridine. The capacity of the sialoprotein fraction to inhibit influenza virus hemagglutination was significantly less than that of purified VRS.
A Study of the Afferent and Efferent Limbs of the Immune Response in Opossums
Authors: Marx James J. , Burrell Robert , Fisher Silvia Q.
Published: December 2022

The immune response of the North American opossum (Didelphys virginiana) was investigated to define further the possibilities of using this species as a subject for in utero examinations of immune tolerance and related phenomena. Experiments were designed in an attempt to discern the proposed disparity between the immune response of the opossum and that of other laboratory animals. The ability of the opossum to clear bacterial antigens from the circulation was comparable to that of a rabbit. This ability reached levels comparable to those of adults in pouch young about 11 weeks after birth. The efferent limb was investigated using techniques for the detection of antibody-producing cells. Plaque assays revealed a distinct but decreased ability to respond to sheep red blood cells (SRBC) in terms of plaque-forming units. This ability first appeared in pouch young between 70 and 120 days. In comparison with mice the cell density in the opossum spleen was low, and there was a proportionally lower percentage of immunocompetent cells capable of responding to SRBC stimulation; this explained the observation that the levels of humoral antibody production and of plaque-forming units were lower than those seen in more conventional animals. The decrease in number of antigen-responsive cells and the slower antibody production suggest that the weakness in the immune system of this animal is centered in both the central and efferent limbs of the immune response.
Relationship of Germinal Centers in Lymphoid Tissue to Immunologic Memory
Authors: Durkin H. G. , Thorbecke G. J.
Published: December 2022

A study was made of the primary and secondary immune responses in 3- to 4- week-old rabbits that received prednisolone treatment on days 5 to 13 after primary injection of alum-precipitated bovine γ globulin into the hind footpads. The treatment did not affect the primary response but completely inhibited preparation for a secondary response induced by challenge with soluble bovine γ globulin 14 days after the primary injection. Histologic examination of popliteal lymph nodes demonstrated that prednisolone treatment interfered with germinal center production, which may have been related to the inhibition of priming for the secondary response.
Lack of Correlation between the Net Charge of Antigen and Antibodies in Guinea Pigs Immunized with Some Charged Antigens
Authors: Nussenzweig Victor , Green Ira
Published: December 2022

Anti-dinitrophenyl (DNP) antibodies were specifically isolated from guinea pigs immunized with DNP-conjugates of polyamino acids with different net electrical charges. The distribution of the antibodies in the γ1 and γ2 classes of immunoglobulins (which have different charges) and in two DEAE-cellulose chromatographic fractions of γ2 globulin was studied. No consistent relationship was found in either case between the net charges of the DNP-conjugates used for immunization and the anti-DNP antibodies which they elicited.
Hormone-Influenced Serum Protein (HIP): Anti-Protein System in the Chicken
Authors: David C. S.
Published: December 2022

A hormone-influenced serum protein (Hip) has been detected in some laying hens, and a “naturally” occurring anti-Hip antibody has been found in some hens lacking Hip. Hip has a molecular weight of about 150,000 and migrates as a β globulin in immunoelectrophoresis. Anti-Hip is an IgG antibody. Hip occurs with high frequency in certain families, indicating a possible genetic influence or expression. Treatment with progesterone induced synthesis of Hip in both females and males, but anti-Hip was produced only in females. Several factors that may be responsible for this “protein-anti protein” system are discussed.
Attempts to Abolish Tolerance of Skin Homografts in Mice with X-Irradiated Plasma from Specifically Sensitized Donors
Authors: Lubaroff David M. , Silvers Willys K.
Published: December 2022

The ability of plasma from sensitized, lethally x-irradiated mice to abolish tolerance of skin homografts was investigated. The graft was destroyed in only 1 of 12 tolerant mice that received plasma. A somewhat higher incidence (4/10) occurred in mice inoculated with serum from unirradiated donors. In contrast, all mice injected with sensitized lymphoid cells rejected their grafts.
Antibodies to Denatured IgE and New Antigenicity of the IgE Acquired during Heating
Authors: Ito Kohi , Wicher Konrad , Arbesman Carl E.
Published: December 2022

Antibodies that reacted with heat-aggregated IgE were observed in a goat but not in rabbits when both were immunized with the Fc fragment of IgE. Using goat antiserum that contained antibodies to native and denatured IgE, it was shown that heating the IgE at 56°C for less than 1 hr caused antigenic changes. After heating for 4 hr the protein lost its precipitability with classspecific antibodies to native IgE, but continued to react with antibodies to the denatured IgE.
Isolation of Heavy and Light Chains of Immunoglobulin from the Surfaces of Lymphoid Cells
Authors: Baur Sonia , Vitetta Ellen S. , Sherr Charles J. , Schenkein Isaac , Uhr Jonathan W.
Published: December 2022

Discussion and Summary

The experimental results indicate that lactoperoxidase-catalyzed iodination of viable lymphoid cells is limited to the plasma membrane. Radiolabeled molecules from the cell surfaces of myeloma, lymphoma and normal spleen cells can be specifically precipitated with anti-Ig sera. Reduction and alkylation of these precipitates yield H and L chains. Gamma chain is present on P3K cells and µ chain on Daudi cells, as expected. Mµ chain was the predominant H chain found on spleen cells, consistent with recent experiments of others using lymphocytes (5, 10, 13, 16). Ig on the surface was not adsorbed to the plasma membrane and therefore presumably was synthesized by the cells. These findings provide evidence that Ig molecules on the plasma membrane, whether antigen-specific receptors or molecules destined for secretion, can be isolated and studied by conventional methods of immunochemistry and biochemistry.
Oxidative Sulfitolysis of Human IgM
Authors: Zikan Jiri , Bennett J. Claude
Published: December 2022

Oxidative sulfitolysis as a method for disruption of disulfide bonds was first applied to proteins by Swan (1). More recently this method has been used with immunoglobulins (2).

In the present study oxidative sulfitolysis of IgM, followed by chromatography in 5 M guanidine HCl, resulted in high yields of H and L chains. Quantitative data provided additional evidence for the four-chain model of IgM subunits consisting of two H and two L chains. Determination of disulfide bonds and cysteic acid residues indicated disruption of three interchain disulfide bonds per H chain, mutually connecting H chains, and one other disulfide bond connecting H and L chains. The H chain was found to contain five and the L chain two intrachain disulfide bonds.

In comparison with reduction and alkylation, oxidative sulfitolysis has the advantage of producing no side reactions and of providing highly soluble chains.

Materials and Methods. Waldenström's IgM (Dau) was prepared as described previously (3).
Transfer of Experimental Autoimmune Thyroiditis of the Mouse by Serum
Authors: Vladutiu Adrian O. , Rose Noel R.
Published: December 2022

The problem of the participation of cellular and humoral factors in the pathogenesis of experimental autoimmune diseases has been discussed for more than two decades without arriving at a definite conclusion. The lack of correlation between the intensity of tissue damage and titer of humoral antibodies (1, 2) in the fact of the existence of such a correlation with delayed skin reactions (3) suggested that autoimmune damage is a delayed type of hypersensitivity. Thereafter, the successful transfer of autoimmune disease by lymphoid cells (4, 5) and the failure of transfer by serum (1,6) enforced the belief that circulating antibodies do not play a causative role in the pathogenesis of autoimmune diseases. However, in recent years, successful serum transfers of autoimmune diseases have been reported. In these experiments rather special procedures were used for inducing the tissue damage: injection of the serum into the target organ (7, 8), the removal of the target organ from donors (9), x-irradiation of donors (10) or recipients (11), and pretreatment of recipients with Freund's adjuvant or 131I (11).
A Study of Tumor Allograft-Sensitized Lymph Nodes in Mice
Authors: Irvin George L. , Eustace John C.
Published: December 2022

The activity of lymph node cells sensitized to a tumor allograft was studied by adoptive transfer into recipient mice syngeneic with the lymph node cell donors. The results depended upon the time interval between sensitization and transfer. Lymph node cells harvested early (3, 5 and 7 days) after sensitization caused accelerated tumor allograft rejection, whereas cells harvested on days 12 and 14 transferred tumor graft enhancement. The peak activity of accelerated rejection was found in cells sensitized for 5 days and the peak of enhancement activity was transferred with 14-day immune cells. At a time intermediate between the peaks of opposing activities a dose-related dual function was discovered. Large doses of lymph node cells caused rejection, and smaller doses produced enhancement. Humoral antibodies against the tumor allograft in lymph node cell donor and recipient mice were assayed by the in vitro cytotoxicity method. Negative or low antibody levels were found in the sera of mice that donated or received lymph node cells capable of transferring rejection. High antibody levels were found in the sera of donors or recipients of lymph node cells that mediated enhancement. A correlation of the rise of humoral antibody titers in donor mice with increased enhancement activity suggests that lymph node cells mediate this activity by continued synthesis of enhancing antibody in recipient mice.
Genetic and Cellular Factors in the Immune Response
Authors: Gill Thomas J. , Kunz Heinz W.
Published: December 2022

Further breeding studies were carried out to test the polygenic model for the control of the antibody response to a synthetic polypetide antigen and to examine more closely the nature of the sex influence on the antibody response. The backcrosses of reciprocally mated F1 hybrids into both the highly responding ACI strain of inbred rats and the poorly responding F344 strain yielded offspring with low, moderate and high responses in a ratio compatible with that predicted by the polygenic model. The backcrosses having a low antibody response bred true with inbreeding and with second backcrossing, as predicted, so they apparently have only those genetic factors that lead to a low antibody response. Limited inbreeding studies with the highly responding backcrosses indicated that they also bred true. Inbreeding of moderately responding backcrosses with moderately or highly responding backcrosses gave offspring that showed the whole spectrum of antibody responses, as would be expected for control by multiple genetic factors. Pedigree analyses of the antibody responses to poly(Glu52Lys33Tyr15) in a variety of hybrids of the ACI and F344 strains were performed in order to search for unexpectedly high responses (mean of the parental responses + three standard deviations) or for minimal responses (≤50 µg of antibody/ml) in the offspring of parents that made moderate amounts of antibody. Such unexpected antibody responses were found in all of the crosses examined: F1 hybrids, F2 hybrids, F1 backcrosses, inbred F1 backcrosses, second F1 backcrosses and F2 backcrosses. These findings indicate that multiple genetic factors are involved in the control of the antibody response. Furthermore, they strongly suggest that genetic recombination has occurred in the animals with the very high or very low antibody responses. In addition to the major genes controlling the antibody response, there appears to be a sex influence which causes differences in the responses of males and females. The nature of this sex influence was investigated by comparing the distribution and magnitude of the antibody response in the offspring of reciprocal matings and in males and females of the same mating. The data suggest that there are additional genetic factors active in the female which lead to a more heterogeneous antibody response in all and to a higher response in the females of the ACI strain.
Molecular Immunogenicity of Bacterial Lipopolysaccharide Antigens: Establishing a Quantitative System
Authors: Rudbach Jon A.
Published: December 2022

Primary injection of lipopolysaccharide (LPS) from Escherichia coli sensitizes mice for a heightened immunologic response to a constant secondary dose of the same LPS. The lower dose limit for primary sensitization is a few tens of molecules and the height of the secondary response is proportional to the size of the dose of LPS over a 1012-fold range. Linear dose-response curves can also be established for the secondary injection of LPS, but over a much smaller range. A minimum of 10 to 14 days is required between injections of LPS to obtain consistently maximum titers, and the capacity of mice to give a secondary response is maintained for at least 12 weeks following the primary injection of LPS. The results suggest that this system provides a sufficiently sensitive and reproducible test for continuing studies on the molecular immunogenicity of LPS antigens.
“In Situ” Visualization of a Graft-vs-Host Reaction
Authors: Gengozian Nazareth , Hübner Karl F.
Published: December 2022

Mice were lethally irradiated (950 R) and injected with xenogeneic (rat) or allogeneic spleen or bone marrow cells. Spleens were removed daily during the 1st week after treatment and tested for the presence of a graft-vs-host (GvH) or host-vs-graft (HvG) reaction using a modification of the Jerne hemolysis-in-agar technique. With either red blood cells or thymocytes as target cells, hemolytic and cytolytic foci indicative of a GvH reaction were detected within the first few days after treatment; peak activity was reached on day 6 in animals given xenogeneic spleen cells and on day 5 in those given allogeneic spleen cells. Injection of xenogeneic bone-marrow cells also yielded GvH foci, although the peak activity was delayed 1 day and was quantitatively less than with spleen cells. In the allogeneic model, bone marrow injection did not yield hemolytic or cytolytic foci. Control studies indicated that the foci obtained were mediated by a humoral factor, presumably an antibody, and were a result of complement-dependent specific antigen-antibody reactions. Although a pathogenic role of the humoral factor in GvH reactions is still to be defined, the ability to detect directly the presence of a GvH reaction represents a potentially important adjunct to further understanding of this disease process in man and animals.
Antibodies Produced After Immunization with Substituted Meta-Dinitrobenzenes
Authors: Godfrey H. P. , Baer Harold
Published: December 2022

The serum antibodies induced in guinea pigs after immunization with 5 µmols of a series of substituted meta-dinitrobenzenes in Freund's adjuvant were investigated. The frequency of induction of precipitating and anaphylactic antibodies was directly related to the chemical reactivity of the immunizing material; no such relation was found for induction of hemagglutinating antibodies. The most reactive chemicals and one preformed conjugate (DNP37BSA) induced antibodies in more than 80% of the animals but the types of antibody varied. 2,4-Dinitrofluorobenzene induced high titers of anaphylactic antibodies, high levels of γ1 immunoglobulins and an antibody of γ1 mobility whose precipitation was complement-dependent. 3,5-Dinitrobenzoyl chloride induced high titers of hemagglutinating antibody, high levels of γ2 immunoglobulins and a γ2-precipitating antibody whose precipitation was complement-independent. The conjugate induced equal titers of anaphylactic and hemagglutinating antibodies and equal amounts of γ1 and γ2 precipitins. The antibodies induced were extensively cross-reactive, in contrast to the great specificity shown earlier for the delayed response to these chemicals.
Hapten Binding Studies on Mouse IgA Myeloma Proteins with Antibody Activity
Authors: Sher Alan , Tarikas Helgi
Published: December 2022

Five mouse IgA myeloma proteins (S23, S63, S107, S129, J539) with antibody specificities for either phosphorylcholine, ε-DNP-caproic acid or galactoside derivatives were studied in terms of their binding of these ligands. The immunoglobulins appeared to be homogeneous with respect to their affinity for hapten and had association constants between 2 × 103 and 105 liters/mol as determined from equilibrium dialysis measurements. Binding activity was associated with the Fab fragment of each IgA. By means of a membrane filter assay, unfractionated S107 protein in serum as well as the reduced and alkylated monomer purified by immunoadsorption was shown to have two sites per 156,000 unit molecular weight. Digestion of the monomer with trypsin gave a Fab fraction in 64% yield with one site per 53,000 molecular weight. However, protein purified by procedures involving chromatography, gel filtration and repeated dialysis steps gave fractional numbers of binding sites, a finding which suggests that mouse IgA's are unusually sensitive to denaturation.
The Evolution of the Immune Response
Authors: Frommel D. , Litman G. W. , Finstad J. , Good R. A.
Published: December 2022

18.5S and 7S immunoglobulins were purified from sera of horned sharks immunized with Brucella abortus. Both preparations had antibody activity, which was abolished more readily by reduction with dithiothreitol than with cysteine. Chromatography on Sephadex G-100 columns, in 6 M guanidine-HCl, disclosed that partial reduction with dithiothreitol cleaved all interchain bonds, whereas cysteine mainly affected the inter-subunit disulfide linkages of the 18.5S antibody molecules. Although high reactivity of sulfhydryl groups toward reducing agents was found in these immunoglobulins, the non-covalent bonds linking their chains appeared more resistant to dissociation than those of mammalian IgM. These studies suggest that in the immunoglobulins of elasmobranchs, the interchain disulfide bridges are of greater importance for stabilization of the antibody-combining sites than they are in the immunoglobulins of more recent evolutionary stages.
Destruction of Rabbit Platelets in the Allergic Response of Sensitized Leukocytes
Authors: Siraganian Reuben P. , Osler Abraham G.
Published: December 2022

The interaction of antigen with sensitized rabbit leukocytes results in histamine release and is cytotoxic for platelets in the reaction mixtures. The destruction of the platelets requires no exogenous serum factors and is proportional to the number of sensitized leukocytes in the reaction mixtures. Destruction of the platelets follows the release of one or more soluble intermediate(s) when the sensitized leukocytes react with antigen. The release of this factor(s) from leukocytes requires Ca2+ (optimal at 3 × 10-4 M) and is inhibited by Mg2+. The action of this factor on platelets is temperature sensitive and is essentially complete in 5 min. The activity required for platelet destruction is also mediated by Ca2+ and is not inhibited by Mg2+. These observations suggest that the histamine release from sensitized rabbit leukocytes is associated with extracellular appearance of other, as yet unidentified substances whose activity is both temperature and calcium dependent.
Primate Respiratory Mast Cells
Authors: Patterson Roy , Suszko Irena M.
Published: December 2022

Mast cells were obtained from the bronchi of a group of monkeys with varying degrees of cutaneous and respiratory hypersensitivity to purified ascaris antigen. The respiratory tissue biopsies were repeated many times on the same subjects. The mast cells were identified in both fixed and living preparations of respiratory mucosa which were maintained under short-term tissue culture conditions. The living mast cells in respiratory tissue exposed to rabbit anti-human IgE and Compound 48/80 underwent morphologic changes of degranulation. Respiratory mast cells from rhesus monkeys with a sufficient degree of in vivo respiratory and cutaneous reactivity to ascaris antigen had similar loss of granules after exposure to antigen in vitro. The loss of granules resulted from their intracellular disappearance rather than extrusion from the mast cells. Treatment of the cells with anti-IgG caused some degranulation of mast cells, but to a lesser extent than was observed with anti-IgE, ascaris antigen or Compound 48/80.
Regain of Homogeneous Binding Activity after Recombination of Chains of “Monofocal” Antibody
Authors: Klinman Norman R.
Published: December 2022

Chain recombination studies were carried out with two purified “monofocal” anti-DNP antibody preparations and purified serum anti-DNP antibody. The results indicated that after separation and recombination of H and L chains the “monofocal” antibodies completely regained their hapten-binding capacity whereas serum antibody showed a 10-fold decrease in the association constant of its binding with hapten. The regain in activity of “monofocal” antibodies is attributed to their homogeneity, and the loss of activity upon separating and recombinating chains of serum antibody is the result of chain mispairing rather than of denaturation. These results serve as further evidence for the homogeneous nature of “monofocal” antibodies and their probable monoclonal origin.
The Stimulation of Splenic Foci in Vitro
Authors: Klinman Norman R. , Aschinazi Gila
Published: December 2022

The “splenic focus” technique has been extended to an analysis of the focal response in vitro to both carrier and haptenic determinants of the 2,4-dinitrophenylhemocyanin (DNP-Hy) molecule. The response was shown to depend on the use of previously immunized donor cells and was directly related to the number of such cells injected. While anti-DNP foci could be stimulated with the hapten on heterologous carriers, the number of foci was maximized by the use of DNP-Hy, the complex used for primary immunization of the donor cells. Foci producing anti-DNP antibody were detected in fragments producing no detectable anti-Hy antibody; however, more fragments were found with foci producing both anti-DNP and anti-Hy antibody than would have been expected if stimulation were by two determinants which were independent of one another.
The Effect of Acute Radiation Exposure Rates on Formation of Hemagglutinating Antibody in Mice
Authors: Carlson Donald E. , Gengozian Nazareth
Published: December 2022

The acute radiation exposure rate is a critical determinant for suppression of the hemagglutinin response in irradiated mice. It was found that this exposure-rate dependence of the immune response varied with: a) the total radiation dose, b) the time of radiation exposure relative to antigen injection, and c) the antigenic challenge, either as antigen dosage or species (red blood cell) of antigen. Maximum radiation-rate antibody sensitivity occurred 12 hr after antigen injection. Under these conditions, 700 R at either 40 R/min or 72 R/min suppressed the response by a factor of 68 below the same total dose at 8 R/min. This highly significant difference in the exposure-rate-dependent period together with the kinetics of killing curves for transferred spleen cells suggested that one or more populations of immunocytes may be differentially inactivated. The absence of a correlation between mortality rate and the hemagglutinin response as a function of exposure rate suggested that radiation-death itself is not a measure of immune incompetence.
Immunoglobulins on the Surface of Lymphocytes. III. Bursal Origin of Surface Immunoglobulins on Chicken Lymphocytes
Authors: Rabellino Enrique , Grey Howard M.
Published: December 2022

Immunoglobulins (Ig) have recently been found to be present on the surface of small lymphocytes in the peripheral organs of mouse, human and rabbit by autoradiographic and immunofluorescence techniques using radiolabeled or fluorescein-labeled anti-immunoglobulin antisera (1–3). However, not all lymphocytes contain detectable amounts of immunoglobulins. Whereas approximately 50% of spleen cells and the majority of bone marrow lymphocytes contain surface immunoglobulins in the mouse, only 10% to 20% of the lymphocytes in peripheral blood and lymph nodes, and less than 1% of thymic lymphocytes contain detectable immunoglobulin (3). The lowest concentrations of lymphocytes with surface immunoglobulin were found in areas in which thymic-derived cells are thought to predominate (4). This suggested that the Ig positive cells were of bone marrow origin and that the negative cells were thymus-derived.
Restriction of Surface Immunoglobulin Determinants to Lymphocytes of the Plasma Cell Line
Authors: Kincade Paul W. , Lawton Alexander R. , Cooper Max D.
Published: December 2022

With widespread acceptance of selective theories for antibody formation, intense interest has focused on the identification and characterization of antigen recognition sites on immunocompetent cells. Immunoglobulin determinants have been demonstrated on the surface of lymphoid cells by a variety of techniques (1–5); these determinants have been related to the antigen-binding properties of the cells (5–7). Since the relative proportion of lymphocytes bearing detectable surface Ig determinants is lowest in the thymus, it has been suggested that these cells belong exclusively to the thymus-independent population of lymphocytes (8, 9).

This hypothesis can be readily tested in the chicken because of the feasibility of eliminating selectively either the thymus-dependent or the plasma cell lines of differentiation (10). In this report evidence is presented that heavy chain determinants of immunoglobulins which are detectable on a large percentage of lymphocytes in normal chickens are absent from the lymphocytes of birds in which the plasma cell line has been selectively eliminated.