bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOMEOSTASIS OF ANTIBODY FORMATION IN THE ADULT RAT
Authors: Rowley Donald A. , Fitch Frank W. 
Published: June 2004

Passive immunization of rats with homologous anti-sheep erythrocyte serum markedly inhibited the primary antibody response to various doses of sheep erythrocytes. Inhibition was "specific" and apparently produced by either "19S" or "7S" antibody to the antigen. Passive immunization inhibited splenic hyperplasia associated with the primary antibody response. Passive immunization 24 hours after active immunization effectively inhibited the primary antibody response.
The markedly suppressive effect of specific antibody on the primary antibody response contrasted sharply with the absence of this effect on the secondary response. Antigen-antibody complexes formed in vitro elicited no measurable primary antibody response but did elicit a high secondary response. Exposure of normal spleen cells to the antibody in vivo or in vitro suppressed their response to the antigen in x-irradiated recipients. In contrast, cells from previously immunized animals transferred to x-irradiated animals produced antibody in the presence of passively given antibody. Thus, "potential antibody-forming cells" from normal animals were unresponsive to the antigen in the presence of specific antibody, while "antibody-forming cells" from previously immunized animals responded to the antigen in the presence of antibody. Presumably, antibody actively produced in small quantities by a few antibody-forming cells might inhibit antibody formation by potential antibody-forming cells. Confirmation of this suggestion was obtained by showing that some animals initially injected with small doses of antigen failed to produce measurable antibody to subsequent injections of larger doses of the antigen. Low doses of antigen capable of inducing unresponsiveness produced no measurable circulating antibody, but these doses did produce increased numbers of plaque-forming (antibody-releasing) cells in spleens of rats. Thus, the formation of specific antibody may provide a homeostatic or "feed-back" mechanism which controls or limits production of specific antibody to the portion of the antibody-forming system previously stimulated by the antigen. This mechanism may account in part for immunological unresponsiveness produced in certain other related experimental systems.
THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Authors: Cohn Zanvil A. , Benson Belinda 
Published: June 2004

The in vitro differentiation of homogeneous populations of monocyte-like cells from the unstimulated mouse peritoneal cavity is described. Under the conditions employed, a progressive increase in cell size occurs without significant cell division. This process is characterized morphologically by the accumulation of phase-dense and neutral red-positive granules, mitochondria, and lipid droplets. The phase-dense granules react strongly for acid phosphatase. Biochemical determinations indicate marked increases in the total content and specific activity of acid phosphatase, cathepsin, and ß-glucuronidase. The production of acid phosphatase is more rapid and extensive than that of the other two hydrolases. From these data it appears that the conversion of a monocyte-like cell to a mature macrophage is accompanied by the formation of increased numbers of lysosome-like cytoplasmic organelles.
Mouse peritoneal phagocytes stimulated in vivo with a bacterial lipopolysaccharide undergo a similar series of morphological and biochemical events.
A NEW CLASS OF HUMAN IMMUNOGLOBULINS
Authors: Rowe David S. , Fahey John L. 
Published: June 2004

The unique myeloma protein from S. J., a patient with multiple myeloma, was isolated and characterized. It resembled other myeloma proteins in many respects. The S. J. myeloma protein migrated in a distinct peak in the slow ß-globulin region on zone electrophoresis, appeared as a single band on starch gel electrophoresis, and sedimented at 7.04S in the ultracentrifuge. Papain and cysteine treatment produced Fc (fast) and Fab (slow) fragments. Reduction and alkylation of the myeloma protein produced heavy and light chains in a ratio of approximately 3:1. The S. J. myeloma protein had type L (type II) light chains. These were antigenically similar to the Bence Jones protein also found in this patient.
The S. J. myeloma protein was unique in the properties of its heavy chains. The myeloma protein (and its heavy chains and Fc pieces) did not contain antigenic determinants specific for IgG, IgA, or IgM. The myeloma protein (and its heavy chains), however, did contain antigenic determinants which are characteristic of a new class of immunoglobulin. The S. J. myeloma protein was unusual also in its effect on the metabolism of normal IgG and in the electrophoretic mobility of the Fc fragment produced by papain digestion.
No evidence was obtained to indicate that the entire heavy polypeptide of the S. J. protein was a grossly abnormal product of malignant cell metabolism. The unique properties of the S. J. myeloma protein (and its heavy chains) are believed to represent, in large measure, properties to be found in a small part of the normal immunoglobulin population.
A NEW CLASS OF HUMAN IMMUNOGLOBULINS
Authors: Rowe David S. , Fahey John L. 
Published: June 2004

A new class of immunoglobulin, IgD, was identified in normal human serum by immunochemical technics. Antiserums prepared against the unique S.J. myeloma protein facilitated recognition of the related normal protein. IgD was shown to possess type K (I) and type L (II) light chain determinants, similar to those present in other classes of immunoglobulins. IgD does not possess determinants which are specific to IgG, IgA, or IgM. The IgD proteins possess their own specific antigenic determinants. IgD migrates in the fast γ-region on immunoelectrophoresis. The properties on sephadex gel filtration and DEAE cellulose chromatography are described.
IgD was found to have a median level of 0.03 mg/ml in 100 normal serums. The range of concentrations found in individual normal serums is much wider, however, than that of other classes of immunoglobulins. IgD, on the average, accounts for less than 1 per cent of the normal serum immunoglobulins.
BOUND COMPLEMENT AND IMMUNOLOGIC INJURY OF BLOOD VESSELS
Authors: Ward Peter A. , Cochrane Charles G. 
Published: June 2004

Rats and guinea pigs were depleted of complement (C') by treatment with heat aggregated human γ-globulin (agg HGG), zymosan, anti-ß1C globulin, and carrageenan. Although antigen and antibody were bound to vascular structures, Arthus reactions were inhibited. This inhibition was characterized by the lack of C' binding to walls of vessels, the lack of polymorphonuclear (PMN's) cellular infiltrates, and the lack of significant vascular damage. When the same animals were followed for several hours thereafter, levels of serum C' began to rise, C' was bound in tissues, PMN infiltrates appeared, and immunologic vasculitis developed. Blood counts, chemotaxis of PMN's induced by lysates of PMN granules, together with studies on motility and phagocytosis by PMN's obtained from C' depleted rats, failed to establish any abnormality in these cells which would account for inhibition of Arthus reactions.
The specificity of C' depletion in terms of effects in the first four reacting components of guinea pig C' was studied. Treatment with agg HGG led to loss of activity in all components, whereas zymosan and anti-ß1C globulin predominately affected the third component (C'3c). Carrageenan mainly affected the first two reacting components of C'. Thus, the availability of the 3c component, or a subsequently reacting component, correlated with the attraction of PMN's to immune reactants in vivo.
Various antibodies with different C' fixing capacities in vitro were tested for their ability to induce immunologic vasculitis in normal animals. In rats, only those antibodies which fixed C' in vitro possessed biological activity, whereas in guinea pigs, all antibodies tested, regardless of C' fixation in vitro, induced Arthus reactions. For a given antibody in rats the vasculitis-inducing property was reflected in its ability to bind C' in vascular structures.
Rats depleted of circulating PMN's by specific antibody were tested for Arthus activity. Although concentrations of immune reactants and C' were readily detected in vascular structures, no PMN infiltration occurred and significant vascular damage was averted.
IMMUNOGLOBULIN ISOANTIGENS (ALLOTYPES) IN THE MOUSE
Authors: Herzenberg Leonard A. , Warner Noel L. , Herzenberg Leonore A. 
Published: June 2004

Eight antigens of 7S γ2-immunoglobulins controlled by alleles at a single locus Ig-1, have been identified in mice. This locus has previously been shown to determine antigenic specificities on the F fragments of 7S γ2a-globulins. The reactions of these antigens with various isoantisera have shown that the antigens all cross react with one another.
New methods for the analysis of antigenic specificities of soluble proteins are presented in detail. A sensitive method for detecting in the order of 0.01 µg of these isoantigens has been developed, based on the quantitative inhibition of precipitation of I125-labeled antigen.
Cross-reactions of the antigens were analysed in inhibition assays and the data is compatible with the existence of a minimum of eight antigenic specificities. Each of the antigens is composed of different combinations of these specificities, with only one antigen having a specificity not present in any other.
Sixty-eight mouse strains have been tested with specific isoantisera, and on the basis of the results, have been placed into the eight allele groups.
Evidence for close genetic linkage of the Ig-1 locus and 11 chromosome markers has been sought and not found.
HISTOCHEMICAL STUDIES OF LYSOSOMES AND LYSOSOMAL ENZYMES IN VIRUS-INFECTED CELL CULTURES
Authors: Allison A. C. , Mallucci L. 
Published: June 2004

The appearance of lysosomes and the distribution of lysosomal enzymes have been studied in a number of cell cultures exposed to viruses. Lysosomes were shown by fluorescence microscopy after vital staining with aminoacridines and light microscopy after vital staining with neutral red. The lysosomal enzymes studied histochemically in unfixed and fixed cells were acid phosphatase and 5-bromo-4-chloro-indoxyl acetate esterase.
Activation of lysosomal enzymes was found to take place in three stages. The first is characterized by permeability of lysosomal membranes without release of enzymes. This is demonstrable by staining of lysosomal enzymes in unfixed cells and by increased uptake of aminoacridine fluorochromes and neutral red into lysosomes. In cell sheets initially stained with neutral red this gives rise to red plaques. This stage can be fully reversible; cells infected with, and yielding, the red-plaque strain of NDV, recover fully afterwards.
In the second stage lysosomal enzymes are released into the cytoplasm, the cells round up and there is decreased uptake of aminoacridines and neutral red into lysosomes. In cell monolayers this results in the formation of white plaques. In the third stage, not usually seen in cell cultures, lysosomal enzymes are released from or inactivated in the cells and are not seen in either fixed or unfixed preparations.
The possible roles of lysosomal enzymes in production of cytopathic effects, polykaryocytosis and malignant cell transformation are discussed.
INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS
Authors: Grey Howard M. , Mannik Mart , Kunkel Henry G. 
Published: June 2004

The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled γ-globulin and for the localization of these determinants on the γ-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of γ-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum.
The antigenic determinants responsible for the individual specificity were localized in all cases studied solely to the Fab fragment produced by papain digestion. After reductive cleavage, three patterns of localization were observed. Individual specificity could be localized either to; (a) isolated heavy chains, (b) isolated light chains, (c) antigenic determinants present only when light and heavy chains were recombined.
After immunization with whole myeloma proteins, individual specificity was localized in part at least to the isolated heavy chain in four of six proteins studied. It was localized to the light chains in three of five type L proteins but in none of six type K proteins. In the instances where individual specificity of the myeloma protein was present on the light chains, it was shown that the Bence Jones protein from the same patient also contained the individual specificity. Immunization with isolated heavy or light chains furnished further evidence for the individual specificity of both types of chains.
These studies on myeloma proteins furnished evidence concerning the portions of the γ-globulin molecule subject to individual antigenic variation. The light chains, particularly the L type and the Fd portion of the heavy chains were primarily involved. Evidence for the importance of the quaternary structure was also obtained from the necessity in some instances for light and heavy chains to be associated in order for individual specificity to be observed. The Fc fragment of the heavy chains on the other hand showed very limited variation which was related to subgroup specificity.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Bentwich Zvi , Harris T. N. 
Published: June 2004

The relationship of the streptococcal hemolysin which is recognized on incubation of RBC with streptococcal cells (cell-bound hemolysin, CBH), to RNA hemolysin, a representative of oxygen-stable hemolysin (streptolysin S) has been studied. A number of similarities have been found in the conditions for optimal production of each of these hemolysins, a requirement for cysteine, Mg++, and glucose; maximal production by streptococci in the stationary phase; similar curves of pH-dependence. In both systems, the production of hemolysin was inhibited by certain antibiotics, by ultraviolet irradiation, and by sonic disruption and was absent in the same streptococcal mutant strain. The hemolytic activity of both systems was inhibited by lecithin, trypan blue, and papain. Similarities were also found in relative susceptibilities to the two hemolytic systems of erythrocytes of a number of animal species.
These data support a suggestion advanced in an earlier study that a streptococcal hemolytic moiety, which can be induced by, and carried on, a number of diverse agents to comprise the group of oxygen-stable hemolysins, serves, in its original attachment to a component of the streptococcal cell, to produce the hemolytic effect recognized as the cell-bound hemolysin.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Harris T. N. 
Published: June 2004

In studies of the mechanism of lysis of red blood cells by washed streptococci with hemolytic activity (cell-bound hemolysin, CBH) no components released spontaneously by RBC or streptococci, or by interaction between these cells, could be found to induce the formation of soluble hemolysin by the streptococci. It was also found that separation of RBC from streptococci even by Millipore filter or a very thin layer of agar could prevent their hemolysis.
By means of cellulose columns it was possible to separate RBC from streptococci after a short incubation. RBC thus separated from streptococci with which they had been incubated underwent hemolysis on subsequent incubation at 37°C. By varying the period of incubation prior to separation it was possible to demonstrate the transfer of increasing amounts of hemolysin from streptococci to RBC with increasing periods of incubation. A considerable part of this appeared to be at a constant rate.
A theory is presented on the relationship between the streptococcal cell-bound hemolysin and the group of oxygen-stable streptococcal hemolysins, in terms of a transferable hemolytic moiety and binding sites for this moiety on the streptococcal cell, on various molecular species which can act as inducers of the oxygen-stable hemolysins, and on the RBC, with the affinity of the respective binding sites for the hemolytic moiety increasing in that order.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Unanue Emil R. , Dixon Frank J. 
Published: June 2004

A direct correlation between the amount of kidney-fixing antibody and the degree of associated renal injury was demonstrated for rabbit and duck nephrotoxic antibodies. No evidence for a qualitative difference among nephrotoxic antibodies of a given type was obtained. It appeared that duck nephrotoxic antibody was directed against a wider spectrum of rat renal antigens than was rabbit nephrotoxic antibody. In order to produce immediate proteinuria an amount of rabbit or duck gamma-2 kidney-fixing antibody capable of occupying approximately 45 per cent or more of the capillary filtration surface was needed. For immediate proteinuria an amount of rabbit gamma-2 kidney-fixing antibody capable of reacting with more than one-half of the available antigenic sites was needed. Less than twice that amount of rabbit antibody completely saturated available antigenic sites in the kidney. Virtually all nephrotoxic antibodies in hyperimmune rabbit nephrotoxic sera were of the gamma-2 variety while nephrotoxic antibodies in comparable duck nephrotoxic sera were found in gamma-2 (with 5.8 and 7.4S sedimentation coefficients) and gamma-1M fractions.
Gamma-1M duck nephrotoxic antibody was 60 times more potent a nephritogen than gamma-2 duck nephrotoxic antibody on a molecular basis. Mercaptoethanol abolished the nephrotoxicity of gamma-1M duck antibody and reduced that of gamma-2 duck antibodies but had no effect on rabbit gamma-2. In no case did mercaptoethanol treatment have an effect on the kidney-fixing properties of the antibodies involved.
After injection of nephrotoxic antibodies there appeared to be a prompt fixation of a majority of the antibody to tissue antigens primarily in the kidney. However, a small amount of potentially kidney-fixing antibody remained in the circulation for a considerable period apparently reflecting a dissociation of less avid antibodies with an equilibrium between fixed and free antibody. The role of this more easily dissociable antibody in the progression of nephrotoxic nephritis is not certain but it is possible that it could play a role in the early progression of the disease.
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Greisman Sheldon E. , Woodwards William E. 
Published: June 2004

Bacterial endotoxins were administered by continuous intravenous infusions at constant rates to normal man and rabbits. An initial progressive febrile reaction was followed by progressive defervescence to baseline. The resulting pyrogenic refractory state was characterized as follows: (a) reticuloendothelial blockade with thorotrast neither prevented nor reversed its course; (b) passive transfer was unsuccessful with refractory phase plasma; (c) infusions of normal plasma or fresh whole blood failed to restore responsiveness; (d) a minimum of 4 hours of continuous endotoxin infusion was required for full development of unresponsiveness; (e) circulating antibody titers to endotoxin remained unaltered; (f) peripheral leukocytosis appeared; (g) infusion of febrile phase plasma reevoked an immediate, monophasic fever; (h) endotoxinemia could be demonstrated by pyrogen bioassay; (i) 10-fold increases in endotoxin infusion rates reevoked fever; (j) impaired responsiveness extended to heterologous endotoxins; (k) dermal inflammatory responses to endotoxin were suppressed in man while tuberculin reactivity remained unimpaired; dermal inflammatory responses to endotoxin were enhanced in rabbits; and (l) pyrogenic reactivity to endotoxin reappeared within 24 hours in man; refractoriness persisted in rabbits.
It is concluded that the pyrogenic refractory state reflects an inability of the host to continue to mobilize endogenous pyrogen during sustained endotoxinemia. Such observations, together with previous studies, are consistent with two distinct immunologic mechanisms of resistance to endotoxin pyrogenicity: (a) desensitization at the cellular level; and (b) elaboration of circulating antibodies which assist reticuloendothelial clearance and destruction of endotoxin. Whereas both such mechanisms may contribute to pyrogenic tolerance, the characteristics of the pyrogenic refractory state suggest the participation only of the former.
ANTIGENS IN IMMUNITY
Authors: Nossal G. J. V. , Ada G. L. , Austin Caroline M. 
Published: June 2004

Flagellar antigens from S. adelaide bacteria were labelled with carrier-free 125I so as to achieve a substitution rate of 0.1 to 2.1 radioactive iodine atoms per flagellin molecule. Lymph nodes from rats injected with small amounts of these antigens were teased into a single cell suspension. Single antibody-forming cells were identified and submitted individually to autoradiography so as to measure their content of iodine 125I. The study was confined to the 7S phase of the primary response.
Grain counts over 216 single antibody-forming cells were no higher than counts over equivalent background areas in the emulsion. This finding suggested that the cells contained little or no macromolecular antigen, and it was considered very unlikely that there were sufficient macromolecules of antigen in a plasma cell to act as a direct template on polysomes for the formation of antibody. The question of the possible presence, in such cells, of fragments of antigen was considered. This possibility, while not supported by the present results, cannot be excluded at present.
ANTIBODY SYNTHESIS AT THE CELLULAR LEVEL
Authors: Möller Göran , Wigzell Hans 
Published: June 2004

The suppressing activity of passively transferred antibodies on antibody synthesis against sheep red cells was investigated at the cellular level by the agar-plaque technique developed by Jerne. Humoral antibodies injected prior to the antigen suppressed the appearance of plaque-forming spleen cells producing 19S antibodies completely. Antibodies given during the first 4 days after antigen injection also showed such action, but only after a latency period of 40 hours. The inhibiting efficiency of 7S antibodies was about 100 to 200 times greater than that of 19S antibodies. The results support the conclusion that humoral antibodies inhibit the immune response by removing the stimulus for the proliferation of the antibody producing cells and not by directly depressing antibody synthesis in already committed cells.
Passively transferred antibodies inhibited the 7S response if given prior to, or 24 hours after the antigen injection, in analogy with previous results concerning 19S response. In contrast to these previous results on 19S synthesis, antibody transfer had no detectable effect during the early exponential phase of 7S production (5 to 7 days after antigen injection). Only limited inhibition was observed 3 days after the antigen. One possible explanation of this difference is that 7S-producing cells do not divide, or divide at a slow rate. Antigen injection would stimulate the proliferation of 19S-producing cells. Subsequently these would switch to the synthesis of 7S antibodies. These would inhibit the initiation of new 19S-producing cells by combining with the antigen. They would thus suppress the recruitment of their own precursors. A steady state of 7S antibody production by cells with a long lifetime would be the result. This hypothesis ascribes an important regulatory function to 7S antibodies. They would be parts of a feed-back system preventing excessive cell multiplication in response to a single antigen.