bluuebunny/crossref_metadata_2025_split huggingface dataset:
CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE
Authors: Shearer G. M. , Cudkowicz G. 
Published: June 2004

Marrow cell suspensions of unprimed donor mice have been transplanted into X-irradiated syngeneic hosts. 5–46 days later, bone cavities and spleens contained regenerated cells of the immune system which required interaction with thymocytes (from intact donors) and antigen (SRBC) to form antigen-sensitive units (ASU) and to generate mature immunocytes. These cells were capable of differentiating either into direct or indirect hemolytic plaque-forming cells (PFC). The precursors of PFC regenerated earlier than the other cell type necessary for immunocompetence, the antigen-reactive cell (ARC). The latter was not found until 10 or more days after transplantation. Availability of ARC was inferred from PFC responses elicited by grafted mice challenged with SRBC at varying intervals.
In a second series of experiments, graded numbers of marrow cells (ranging from 107 to 5 x 107) were transplanted with 5 x 107 or 108 thymocytes into irradiated mice, and SRBC were given 18 hr later. After 9–12 days the recipient spleens contained all or some of the following immunocytes: direct and indirect PFC, and hemagglutinating cluster-forming cells. The frequency of each immune response varied independently of the others, but in relation to the number of marrow cells grafted. This was interpreted to indicate that ASU formed in irradiated mice by interaction of marrow and thymus cells were similar to those of intact mice. In particular, they were specialized for the molecular class (IgM or IgG) and function (lysis or agglutination) of the antibody to be secreted by their descendent immunocytes. Hence, class-differentiation appeared to be conferred upon ASU by their marrow-derived components.
REGULATION OF THE IMMUNE RESPONSE
Authors: Sinclair Nicholas R. StC. 
Published: June 2004

The ability of 7S and F(ab')2 antibody fragments to suppress priming with low doses of antigen was compared. The 7S preparation was approximately 100–1000 times more potent than the F(ab')2 preparation when the agglutinin titers of the two preparations were the same. The presence of any ability to suppress priming in the F(ab')2 preparation may reflect an inherent capacity of the F(ab')2 antibody or contamination with small amounts of 7S antibody.
The difference between 7S and F(ab')2 antibody in ability to suppress priming is attributed to the lack of the Fc portion on the F(ab')2 antibody. The Fc portion may be needed to prevent rapid excretion of antibody from the body, to induce rapid phagocytosis of antigen-antibody complexes with consequent breakdown and elimination of antigen, or to inactivate or suppress the antigen-sensitive cells from reacting to antigenic determinants. More detailed studies will permit a better assessment of the importance of these three possible regulatory roles of the Fc portion of the immunoglobulin in the immune response.
INDIVIDUAL ANTIGENIC SPECIFICITY OF HUMAN MACROGLOBULINS
Authors: Harboe M. , Solheim B. G. , Deverill Johanna 
Published: June 2004

The localization of individually specific antigenic determinants on the monoclonal γM Mö was studied in gel diffusion experiments with 19S γM Mö and its 7S subunit. Various types of such determinants were delineated. Some were demonstrable both on the intact macroglobulin molecule and on the subunit. The latter was often unable to precipitate with the corresponding antibody, but combined with it and inhibited precipitation. Immunization of rabbits with purified γMs Mö was the most useful way to obtain antisera demonstrating individually specific antigenic determinants on the subunit by direct precipitation. Still other determinants were apparently destroyed by mild reduction of the γM molecule.
Reduction and reassociation of mixtures of two monoclonal γM-globulins resulted in formation of hybrid molecules containing subunits of different origin. Individually specific antisera against the two components were useful for demonstrating hybrid formation. Serological activity, i.e., cold agglutinin activity, was present in the hybrid molecules.
ANTIBODY AND IMMUNOGLOBULIN PRODUCTION AT THE CELLULAR LEVEL IN BURSECTOMIZED-IRRADIATED CHICKENS
Authors: Alm Gunnar V. , Peterson Raymond D. A. 
Published: June 2004

The effect of bursectomy combined with sublethal X-irradiation in the newly hatched chicken on the immunoglobulin and antibody producing capacity in later life was investigated. The previous findings of a significant incidence of hypogammaglobulinemia in such animals were confirmed. Spleen cells from severely hypogammaglobulinemic animals synthesized and secreted little or no immunoglobulin. Such spleen lymphoid cells contained fewer immunoglobulin antigenic determinants than spleen cells from irradiated control animals as evidenced by their relative inability to respond by an increased DNA synthesis after in vitro culture with rabbit antiserum to chicken immunoglobulin. Therefore, the deficiency in the immunoglobulin synthesis extends not only to actively secreting cells such as plasma cells, but to the entire lymphoid cell population.
As expected, most irradiated-bursectomized chickens, irrespective of plasma immunoglobulin levels failed to produce detectable amount of circulating antibodies to Brucella abortus antigen in the primary immune response. Severely hypogammaglobulinemic animals were completely unable to elaborate any plaque forming cells (PFC) in the primary response to sheep red blood cells (SRBC). The results of this investigation support the contention that in the severely hypogammaglobulinemic bursectomized-irradiated chicken the entire antibody producing and immunoglobulin producing cell line is absent. The possibility remains that precursor or stem cells are present but are not appropriately directed to antibody synthesis by other cell types.
BIOLOGICAL PROPERTIES OF CELL WALL MUCOPEPTIDE OF HEMOLYTIC STREPTOCOCCI
Authors: Rotta Jiři , Bednář Blahoslav 
Published: June 2004

Several of the toxic properties of streptococcal mucopeptide have been studied in detail. Intravenous injection of as little as 1 µg of mucopeptide, solubilized by ultrasonic treatment, elicits a reproducible febrile response. Rabbits which are made tolerant to Escherichia coli endotoxin are only partially tolerant to the subsequent injection of streptococcal mucopeptide. Soluble mucopeptide was successfully employed to prepare and provoke the localized Shwartzman reaction.
Intravenous injection of 80 µg of solubilized mucopeptide leads to diffuse cellular infiltration as well as focal areas of myocardial necrosis, surrounded by inflammatory cells.
THE LOSS OF PHENOTYPIC TRAITS BY DIFFERENTIATED CELLS
Authors: Chacko S. , Abbott J. , Holtzer S. , Holtzer H. 
Published: June 2004

A single, functional, mitotically quiescent chondrocyte may be induced to reenter the mitotic cyde, and produce a progeny of over 1011 cells. Sessile, adherent, polygonal cells deposit matrix, whereas amoeboid, dispersed, flattened fibroblastic cells do not. The prior synthetic history of a cell is of greater importance in determining whether the characteristic chondrogenic phenotype will be expressed, rather than growth in "permissive" or "nonpermissive" medium. Clonal conditions select for stem-like cells, some of whose progeny may become polygonal chondrocytes. The retention of the characteristic chondrogenic phenotype in vitro is favored by pruning the dedifferentiated chondrocytes which arise in these cultures. Dedifferentiated chondrocytes interfere with the deposition and synthesis of chondroitin sulfate by neighboring functional chondrocytes. Possible mechanisms are proposed to explain this type of cell-cell or cell exudate interference.
If the progeny of a single, genetically programmed chondrocyte may or may not synthesize chondroitin sulfate, then extragenic sites in the cytoplasm or cell surface must influence the decision as to which cluster of "luxur" molecules the cell will synthesize.
THE PATHOGENESIS OF ALEUTIAN DISEASE OF MINK
Authors: Porter David D. , Larsen Austin E. , Porter Helen G. 
Published: June 2004

Mink inoculated with 1 x 105 ID50 of Aleutian disease virus revealed very high virus titers in the tissues 8–18 days later. The highest virus titers observed were 5 x 108 ID50 per g of spleen and 1 x 109 ID50 per g of liver 10 days after inoculation. Concomitant with the increase in infectious virus titers, viral antigen(s) was found in the cytoplasm of macrophages in the spleen and lymph nodes and in Kupffer cells in the liver. Antiviral antibody was assayed by indirect immunofluorescence, using sections of infected liver as the source of antigen. A few mink infected for 9 days and all those infected 10 days or more developed antibody to Aleutian disease virus antigen(s). By 60 days after infection, when hypergammaglobulinemia was marked, the mink had an exceptionally high mean antibody titer of 100,000.
The pathogenesis of the glomerulonephritis of Aleutian disease is apparently related to formation of viral antigen-antibody-complement complexes which lodge in glomerular capillaries. No evidence was found that viral infection of the kidney took place, and no autoimmune responses were found.
In this "slow-virus" disease the virus replicates rapidly and the morphologic and biochemical manifestations of disease are apparently due to the continuing interplay between a replicating antigen and the host immune response.
SPECIES SPECIFICITY OF LEUKOCYTIC PYROGENS
Authors: Bornstein Donald L. , Woods James W. 
Published: June 2004

Polymorphonuclear neutrophilic leukocytes of the dog, cat, and goat release leukocytic pyrogen under the same conditions as the heterophile polymorphonuclear leukocytes of the rabbit. The characteristics of the febrile response to an intravenous injection of homologous leukocytic pyrogen in all four species are very similar: a brisk monophasic fever reaching a peak between 30 and 50 min with smooth defervescence to the baseline by 3 hr. Shivering, which is not obvious in the rabbit, is noted in the dog, cat, and goat during the first 30 min. Quantitative differences in response reveal the cat to be the most sensitive of of these species to homologous leukocytic pyrogen, followed by the rabbit, dog, and goat.
The response to heterologous pyrogen is in most cases markedly diminished compared to that after equal doses of homologous protein, suggesting the operation of species specificity, although canine and feline pyrogen behaved very similarly in all tests. Species specificity of leukocytic pyrogen is probably related to amino acid substitutions in different species of a common mammalian protein effector molecule.
STUDIES ON ANTIGENIC COMPETITION
Authors: Brody Neil I. , Siskind Gregory W. 
Published: June 2004

Antigenic competition was studied in a haptenic system. It was found that: (a) The extent of competition is greater when larger doses of antigen are employed. (b) Antigenic competition appears to be independent of the carrier molecule. (c) The affinity of the antibody produced in antigenic competition is approximately equal to the affinity of antibody formed by animals immunized with only one antigen. (d) Antigenic competition only occurs when both antigens are injected so as to drain into the same regional lymph nodes.
The results suggest that antigenic competition occurs locally at the site of antigen stimulation and is not mediated by a circulating factor, by tolerance induction, or by suppression due to synthesis of cross-reacting antibodies.
REGULATION OF THE SECONDARY ANTIBODY RESPONSE IN VITRO
Authors: Ambrose Charles T. 
Published: June 2004

Two opposite effects of actinomycin D on antibody synthesis have been studied in organ cultures of rabbit lymph node fragments. These cultures were prepared from previously primed rabbits and stimulated with antigen(s) on day 0 to yield a secondary response, whose inductive phase extended to about day 9 and whose productive phase may last for several months in the serum-free medium described here.
Concentrations of actinomycin D above 0.01 µM (0.012 µg/ml) produce inhibition of antibody synthesis during both phases of the response. However, antibody synthesis is about 10 times more sensitive to inhibition by this drug when it is added during the inductive phase than during the productive phase. During the latter phase, synthesis is more rapidly terminated as the drug level approaches 10 /µM (12.5 µg/ml). At this level the 50% synthesis time is about 2.8 hr, which is identical with that found when 5–10 µM puromycin is added to the medium of parallel cultures.
Transient enhancement of antibody synthesis is frequently produced by a brief exposure to low levels of actinomycin D (generally less than 0.01 µM). Enhancement appears in precise temporal association with actinomycin pulses added for 2 days or less only between days 6 and 16. This apparent enhancement of antibody synthesis resembles the increased enzyme synthesis described by Garren et al. (6) and led to a search for an antibody-inhibitory material (AIM) whose synthesis might be stopped preferentially by low levels of the drug.
Stimulated lymph node cultures produce between days 6 and 15 a nondialyzable material which inhibits antibody synthesis during the productive phase of heterologous antigen-antibody culture systems. Just as enhancement with low levels of actinomycin D appears within 2 hr after the drug has been added to cultures, so inhibition occurs within 4 hr of adding AIM to cultures during their productive phase. These observations suggest that AIM is analogous to the translational "repressor" postulated by Garren et al. (6). AIM has relevance in two areas of immunology: (a) it may be the explanation for many examples of antigenic competition, and (b) it may represent a normal control mechanism for the productive phase.
HEAT LABILE OPSONINS TO PNEUMOCOCCUS
Authors: Smith Mary Ruth , Wood W. Barry 
Published: June 2004

Heat labile opsonins (HLO) in normal rat serum to both encapsulated and unencapsulated pneumococci (a) have the same heat lability as complement (C); (b) are active at 37°C but not at 0°C; (c) are inactivated proportionately to hemolytic C by the addition of immune aggregates to the serum; (d) are adsorbed from serum nonspecifically by bacteria at 37°C but not at 0°C; (e) are Ca++- and/or Mg++-dependent in their action; and (f) are inactivated by zymosan and a purified cobra venom factor, and in the case of encapsulated pneumococci, at least, by NH4OH. Like other opsonins, HLO to pneumococci act primarily on the bacteria rather than on the phagocytes. Their combined properties indicate that they involve multiple components of the hemolytic C system.
Since HLO are immunologically polyspecific, they presumably play a broad protective role in the early (preantibody) phase of acute bacterial infections.
STUDIES ON THE MIGRATORY BEHAVIOR OF MELANOCYTES IN GUINEA PIG SKIN
Authors: Billingham R. E. , Silvers Willys K. 
Published: June 2004

Pigment spread is the natural or experimentally procured (through grafting) progressive encroachment of pigmentation from black or red skin areas into juxtaposed white skin areas, or from black skin areas into red skin areas in spotted guinea pigs and other mammals. So far as spread from black into white skin is concerned, it had previously been shown that migration of epidermal melanocytes into skin lacking homologues of these cells was responsible. However, since red skin already has its own complement of phenotypically "red" melanocytes, the intriguing possibility remained that when black pigment encroaches upon red, rather than melanocyte migration being responsible, phaeomelanin (red)-producing melanocytes are transformed into eumelanin (black)-producing cells by some kind of serially transmissible factor derived from contiguous eumelanotic melanocytes.
By utilizing two isogenic strains (Nos. 2 and 13) of spotted guinea pigs and their F1 hybrids, the mechanism underlying the spread of pigment from black into red skin has been analyzed, employing cellular transplantation antigens as melanocyte "markers." The findings demonstrate unequivocally that a physical migration of pigment cells is responsible.
By comparing the extents of pigment spread from black ear skin grafts, or from epidermal cell suspensions prepared therefrom, from parental strain or from F1 hybrid donors in white host skin areas of F1 hybrid guinea pigs, it has been possible to evaluate the influence of the intimate contact of melanocytes with alien transplantation antigens on their survival and migratory behavior. No evidence was forthcoming that pigment spread takes place less readily when the cells responsible are confronted by epidermal cells bearing foreign antigens than when they are confronted by cells of their own antigenic constitution. These findings are contrary to expectation if the phenomena of allogeneic inhibition or contact-induced cytotoxicity apply to normal cells in in vivo situations.
SPECIFIC ANTIBODY WITHIN LYMPHOID GERMINAL CENTER CELLS OF MICE AFTER PRIMARY IMMUNIZATION WITH HORSERADISH PEROXIDASE: A LIGHT AND ELECTRON MICROSCOPIC STUDY
Authors: Sordat Bernard , Sordat Martine , Hess Max W. , Stoner Richard D. , Cottier Hans 
Published: June 2004

The appearance in mice of specific antibody within newly formed germinal centers in lymph nodes was demonstrated by light and electron microscopy after regional primary antigenic stimulation with horseradish peroxidase (HRP).
Lymphoid germinal center cells containing anti-HRP antibody in the perinuclear space and in the cytoplasm were detected from 17 to 26 days after antigenic stimulation. Extracellular anti-HRP antibody within germinal centers, localized between dendritic reticular cells and lymphoid elements, could not be found before the appearance of intracellular antibody. These findings strongly suggest antibody formation by lymphoid germinal center cells. Both antigen and corresponding antibody persisted in intercellular spaces up to 35 days after primary stimulation.
The concomitant presence in a given lymph node of germinal centers which are positive or negative with regard to specific antibody provide evidence in favor of monospecificity of individual centers. The mechanisms of antigen-trapping within germinal centers are discussed in the light of the present observations.
REACTIVE LYSIS: THE COMPLEMENT-MEDIATED LYSIS OF UNSENSITIZED CELLS
Authors: Lachmann P. J. , Thompson R. A. 
Published: June 2004

It has been shown that the "activated reactor" that is produced in certain human sera by complement activation is a stable complex of the fifth and sixth component of complement (C56). On interaction with C7, the indicator factor, a complex C567 is formed which for a short time (half-life less than 1 min) has an activated binding site and can attach itself to normal red cell membranes, conferring on them the hemolytic properties of the "heat stable" complement intermediate EC 1 ∼ 7, the capacity to be lysed by C8 and C9. These cells have neither antibody nor the complement components up to C3 bound on them.
The binding site—activated C567c—can similarly bind to other hydrophobic surfaces, including agarose gel where it forms a "stainable line".
If the complex is not bound to a surface, the binding site decays and the resulting complex will no longer give rise to lysis. However it will still inactivate C8 and C9 in solution. The sera that can generate activated reactor apparently do so because they have an excess of C5 and C6, compared to their content of C7.
The phenomenon of reactive lysis thus represents complement-mediated lysis of unsensitized cells initiated at the C5 stage by a stable complex (C56) which was generated by complement activation at a distance.
The immunochemistry of the phenomenon is described and some of its implications discussed.
EVIDENCE FOR TRANSFORMATION OF SPLEEN CELLS ONE DAY AFTER INFECTION OF MICE WITH FRIEND LEUKEMIA VIRUS
Authors: Rossi Giovanni B. , Cudkowicz Gustavo , Friend Charlotte 
Published: June 2004

Proliferation and erythroid differentiation of transplanted DBA/2 marrow cells and Friend virus-induced leukemic cells were assessed in syngeneic, allogeneic (H-2 compatible), and (BALB/c x DBA/2)F1 hybrid mice (CDF1). Measurements were made 5 days after transplantation of donor cells into nonirradiated or X-irradiated mice by the spleen colony or the 125IUdR-59Fe uptake methods. Growth of DBA/2J (Jackson subline) marrow grafts was poor in irradiated CDF1J hybrids as compared with growth in syngeneic and allogeneic hosts. The DBA/2J transplants proliferated, however, without impairment in irradiated CDF1 hybrids which were the progeny of DBA/2 male parents of other sublines, e.g. DBA/2Ha, DBA/2Cr, and DBA/2Cum. In contrast, tissue-cultured Friend leukemic cells of DBA/2J origin grew deficiently in all CDF1 hybrids tested, regardless of irradiation and of the DBA/2 parent's subline. The growth pattern of transplanted DBA/2J cells was a manifestation of hybrid resistance. The results with DBA/2J and other DBA/2 subline grafts suggested that hybrid histocompatibility alleles were expressed to a greater extent in leukemic than in normal marrow cells, for the former were consistently recognized as "nonself" by CDF1 mice, but not the latter cells.
The property of deficient growth in irradiated CDF1Ha hybrids was acquired by DBA/2J hemopoietic cells within 6 hr from infection in vivo with Friend leukemia virus, and persisted during the following 8 days. It was ascribed to enhanced expression of hybrid histocompatibility gene(s) (Hh) induced by the virus. Autonomous growth potential of hemopoietic cells, manifested by proliferation in nonirradiated recipients, was first detected 24 hr from infection, and likewise persisted at the later intervals. At the same time, the infected cells grew deficiently also in nonirradiated CDF1Ha mice. The two irreversible cellular changes were regarded as the earliest signals of virus-induced transformation.
THE FIXATION OF COMPLEMENT AND THE ACTIVATED FIRST COMPONENT (C1) OF COMPLEMENT BY COMPLEXES FORMED BETWEEN ANTIBODY AND DIVALENT HAPTEN
Authors: Hyslop N. E. , Dourmashkin R. R. , Green N. M. , Porter R. R. 
Published: June 2004

Hapten-antibody complexes prepared at equivalence with the bivalent hapten bis-DNP-octamethylene-diamine and purified rabbit anti-DNP antibody were fractionated by Sepharose gel-filtration and the fractions examined by electron microscopy. Individual fractions were tested for whole-complement fixation and C1 fixation. Dimer forms did not show this type of biological activity, while fractions containing tetramers and larger polymers exhibited both C and C1 fixation, which could be inhibited by prior exposure of the complexes to the univalent hapten epsilon-DNP-caproic acid. The dose-response result indicated that the C-fixation observed was not due to interpolymeric cooperative effects.
It was concluded that in the generation of biological activity by soluble antigen-antibody complexes made with complement-fixing antibody, quaternary structural changes following specific combination with antigen may be as important as any tertiary structural alterations that occur in the individual immunoglobulin molecule.
INTERACTIONS OF THE COMPLEMENT SYSTEM WITH ENDOTOXIC LIPOPOLYSACCHARIDES IN IMMUNOGLOBULIN-DEFICIENT SERA
Authors: Gewurz H. , Pickering R. J. , Snyderman R. , Lichtenstein L. M. , Good R. A. , Mergenhagen S. E. 
Published: June 2004

Bacterial lipopolysaccharides (LPS) derived from a variety of organisms effectively induced C consumption in humans, bovines, and porcines with developmental agammaglobulinemia; birds with experimental agammaglobulinemia; and humans with agammaglobulinemia syndromes. This interaction proceeded even in precolostral piglet sera which contained less than 2.5 x 10–6 mg/ml gamma globulin, and led to generation of neutrophil chemotactic factor and anaphylatoxin in these sera. Hence, the LPS-C interaction can proceed in sera markedly deficient in immunoglobulin.
The question of whether immunoglobulins can be bypassed in the LPS-C interaction, or whether they are regularly utilized in a way so efficient that their participation is masked, was considered.