bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE LYMPHATIC STATUS OF HAMSTER CHEEK POUCH TISSUE IN RELATION TO ITS PROPERTIES AS A GRAFT AND AS A GRAFT SITE
Authors: Barker Clyde F. , Billingham R. E. 
Published: June 2004

Hamster cheek pouch skin, transplanted to the side of an isogenic host's chest wall, retains its immunologically privileged status as evidenced by the prolonged survival of inlaid homografts of ordinary skin.
Various findings sustain the premise that exemption from rejection by otherwise susceptible homografts in both intact pouch tissue and in established pouch skin isografts is due to an impediment in the afferent pathway of the immunologic reflex, i.e., to deficient lymphatic drainage. Although lymphatics were not apparent when dye was injected into pouch skin grafts or into grafts of ordinary skin sustained by them, lymph vessels were readily and consistently revealed by dye injected into intact trunk skin or established isografts of trunk skin. When suspensions of viable lymph node cells from specifically sensitized parental strain donors were injected superficially into either the intact skin or established grafts of normal skin on F1 hybrid hamsters, a striking hypertrophy of the regional lymph nodes occurred, due to graft-versus-host reactivity. However, similar cell suspensions inoculated into intact pouch tissue or into pouch skin grafts on F1 hamsters incited no regional lymphadenopathy, indicating the lack of appropriate pathways to the nodes.
When skin homografts were inlaid eccentrically into pouch skin isografts, so that they were in contact with host skin at one edge, rejection occurred. Furthermore, rejection of long-established intrapouch skin homografts resulted if the hosts received: (a) small homografts of ordinary skin transplanted to conventional beds; (b) suspensions of donor strain pouch skin epidermal cells, injected intracutaneously; (c) lymph node cells from specifically sensitized donors of the same strain, i.e. adoptive immunization; or, (d) if a portion of the target homograft's perimeter was surgically approximated to body skin.
Treatment of normal hamsters with two closely spaced pulses of ALS, although only marginally effective in prolonging the lives of homografts of trunk skin, enabled pouch skin homografts to survive for very long periods. The influence of this brief treatment with immunosuppressant was still demonstrable if challenge of hosts with the weakly immunogenic pouch skin homografts was delayed for 100 days.
MACROPHAGE PLASMA MEMBRANE
Authors: Nachman Ralph L. , Ferris Barbara , Hirsch James G. 
Published: June 2004

Rabbit alveolar macrophages were incubated in vitro with radioactive protein precursors. Plasma membranes were isolated from these cells, dissolved in phenol-urea-acetic acid, and separated by acrylamide gel electrophoresis. 3H-leucine was rapidly incorporated into membrane protein. The rate of labeling with 3H-leucine was markedly different from one protein band to another, indicating heterogeneous or multistep synthesis and assembly of proteins in the alveolar macrophage plasma membrane.
Cells incubated with 3H-choline incorporated this compound into membrane lecithin. On gel electrophoresis the label derived from choline was located in the two bands migrating most rapidly towards the cathode. Studies on cells incubated with 3H-glucosamine revealed incorporation of label into two protein bands, one located near the origin and the other migrating rapidly towards the cathode.
The in vitro techniques were also employed for pulse-chase studies to gain information on rate of turnover of macrophage plasma membrane proteins. This turnover rate was rapid, with a half-life of approximately 8 hr. The radioactivity disappeared from the several protein bands at the same rate, suggesting bulk removal of membrane rather than catabolism of the individual proteins in situ. Endocytosis seems a likely mechanism to account for a major part of the plasma membrane removal.
Studies on the protein components of phagolysosomal membranes from cells which had been labeled with 3H-leucine revealed the presence of all of the major labeled protein bands characteristic of the plasma membrane except one, thus confirming the bulk interiorization of large segments or units of plasma membrane by endocytic processes.
AUTOSENSITIZATION IN VITRO
Authors: Cohen Irun R. , Globerson Amiela , Feldman Michael 
Published: June 2004

Autosensitization of rat or mouse lymphoid cells against syngeneic fibroblast antigens was induced in cell culture. Rat lymphoid cells autosensitized by this method were able to produce immunospecific lysis of syngeneic target fibroblasts in vitro or GvH reactions in newborn rats. Autosensitized mouse spleen cells mediated similar GvH reactions when injected into newborn mice.
The nature of the system used to induce immunity in vitro appears to argue against the possibility that lymphocytes capable of reacting against self-antigens could arise by mutation in cell culture. Hence, it is likely that cells potentially reactive against self-antigens preexisted in the lymphoid cell donors. The ability of autosensitized cells to mediate immune reactions in vivo suggests that the immunogenic self-antigens present on sensitizing fibroblasts also were accessible in the intact animals.
Loss of natural self-tolerance in vitro, therefore, can be explained most simply by the existence of lymphocytes which are reversibly tolerant to self. Hence, ontogenic elimination of potentially self-reactive cells may not be the only basis for natural tolerance. Regulatory mechanisms, such as antigen excess, may have to function in vivo to prevent differentiation of self-tolerant lymphocytes. These regulatory mechanisms appear to be annulled in the cell-culture system. The present system thus may offer a new approach to studies of tolerance and regulation of cellular immunity.
IMMUNOGLOBULINS ON THE SURFACE OF LYMPHOCYTES
Authors: Unanue Emil R. , Grey Howard M. , Rabellino Enrique , Campbell Priscilla , Schmidtke Jon 
Published: June 2004

Immunofluorescent studies using live cells from antibody-forming organs and anti-immunoglobulin antibodies demonstrate two populations of small lymphocytes which are differentiated by the presence or absence of Ig on their surface membranes. Most of the lymphocytes with detectable surface Ig appear to derive from cells of the bone marrow, while most of the Ig-negative lymphocytes derive from the thymus. Thus, adult mice thymectomized, lethally irradiated, and transplanted with bone marrow cells showed a normal number of lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes. Injection of thymocytes into these mice did not result in an increase in the number of lymphocytes with surface Ig in spleen and lymph nodes. Most of the injected thymocytes could be identified by means of histocompatibility markers. Also, the spleen and lymph nodes of neonatally thymectomized mice contained lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes.
Attempts were made to identify light chains on thymocytes by a sensitive radioimmunoassay. In some experiments no light chains were detected and in others a small amount, i.e. no more than 2.6% of the amount present on spleen lymphocytes, could be detected. Whether these low figures are significant or represent a small amount of serum contamination is not clear as yet.
IMMUNE RESPONSE TO CHEMICALLY MODIFIED FLAGELLIN
Authors: Parish C. R. 
Published: June 2004

Flagellin (mol. wt. 40,000) from S. adelaide organisms was acetoacetylated to varying extents with diketene (acetoacetic anhydride). Chemical studies demonstrated that the amino groups of flagellin were more readily acetoacetylated than the hydroxyl groups. Several antigenic tests revealed that as flagellin was acetoacetylated to increasing extents there was a steady decline in the affinity of the molecule for anti-flagellin antibodies.
Loss in antigenic activity following acetoacetylation was not related to the number of acetoacetyl groups attached but was determined by the type of residue substituted. Reactive lysine residues were much less important anti-genically than easily substituted hydroxyl groups.
Acetoacetylation very readily destroyed the antibody-forming capacity of flagellin in rats. This fall in immunogenicity was related to the antigenic activity of the preparations. In fact, only a 40% reduction in the antigenic activity of flagellin produced a 90–95% reduction in primary antibody formation. The more heavily acetoacetylated flagellins produced no detectable antibody and, in fact, rendered adult rats tolerant (in terms of antibody formation) to a subsequent challenge of flagellin. Tolerance was induced by acetoacetylated flagellins which had drastically reduced affinities for anti-flagellin antibodies.
These results were interpreted as indicating that the affinity of antigen for receptors on cells appears to be of crucial importance in determining whether antibody formation or immunological tolerance (antibody suppression) occurs.
THE ANTIGENS AND AUTOANTIGENS OF THE SEMINAL VESICLE
Authors: Orsini Frank , Shulman Sidney 
Published: June 2004

Guinea pig vesicular fluid was characterized both biochemically and immunologically. Biochemical analyses showed this fluid to be homogeneous by ultracentrifugal analyses, revealing a single boundary with a sedimentation coeflicient of 1.5 S. In contrast, electrophoretic separation methods revealed six components, of which three were major components, of approximately equal proportions. They were termed I, II, and III. One of these components (II) was shown to be strongly antigenic in heteroimmunization, whereas components I and III failed to show any antigenicity, even after diverse attempts. This antigen (component II) was found to be highly tissue specific and species specific.
Through procedures of isoimmunization, component II was also found to be immunogenic, giving rise (in male animals) to autoantibodies, A high proportion of injected guinea pigs showed positive skin tests and many revealed tissue lesions when the seminal vesicles were examined histologically. It is therefore concluded that experimental autoimmune disease of the seminal vesicle has been induced.
CONTRIBUTION OF BONE MARROW CELLS AND LACK OF EXPRESSION OF THYMOCYTES IN GENETIC CONTROLS OF IMMUNE RESPONSES FOR TWO IMMUNOPOTENT REGIONS WITHIN POLY-(PHE,GLU)-POLY-PRO--POLY-LYS IN INBRED MOUSE STRAINS
Authors: Mozes Edna , Shearer G. M. 
Published: June 2004

Previous cellular studies on the genetic regulation of immunological responsiveness for two immunopotent regions within the branched chain synthetic polypeptide (Phe, G)-Pro--L demonstrated a direct correlation between the number of detectable immunocompetent splenic precursor cells and the response patterns of SJL, DBA/1, and F1 mice (21). In order to establish the cellular origin(s) of the genetic defect, the present study first demonstrated that thymus and bone marrow cell cooperation was required for (Phe, G)- and Pro--L-specific immune responses. Secondly, limiting dilution experiments, in which several graded and limiting inocula of marrow cells were mixed with a non-limiting number of 108 thymocytes and injected into irradiated, syngeneic recipients, indicated that the low responsiveness of the SJL and DBA/1 strains to the (Phe, G) and Pro--L specificities, respectively, could be attributed to a reduced number of precursor cells found in bone marrow. About five times more marrow precursors were detected in SJL mice for Pro--L than for (Phe, G), whereas about five times as many precursor cells were estimated for (Phe, G) as for Pro--L in the DBA/1 strain. These differences are similar to those obtained using spleen cells from unimmunized SJL and DBA/1 donors (21), and indicate that these genetically determined variations in responsiveness can be accounted for by differences in the frequencies of monospecific populations of immunocompetent cells present in bone marrow.
In contrast, limiting dilution transfers of thymocytes or thymus-derived cells with an excess of syngeneic marrow cells resulted in equally frequent (Phe, G) and Pro--L responses for both SJL ad DBA/1 strains. This finding in conjunction with the observation that the generation of (Phe, G)- and Pro--L-specific responses were associated in individual recipients injected with limiting inocula of thymocytes indicated that a single population of thymocytes was stimulated by (Phe,G)-Pro--L. Therefore, it is improbable that the thymic population of immunocompetent cells contributes to expression of these genetically controlled defects.
CHARACTERIZATION OF IMMUNOGLOBULIN STRUCTURES FROM THE SURFACE OF CHRONIC LYMPHOCYTIC LEUKEMIA CELLS
Authors: Eskeland Trond , Klein Eva , Inoue Masaharu , Johansson Bo 
Published: June 2004

Chronic lymphocytic leukemia cells with relatively large amounts of mu and kappa immunoglobulin structures on the surface, and apparently very small amounts intracellularly, were subjected to homogenization or washing after freezing and thawing. After a light centrifugation, which sedimented the nuclei and unbroken cells, most of the immunoglobulin structures were found in the supernatant. Ultracentrifugation, which was performed to remove the membranes from the supernatant, sedimented only half the amount of the immunoglobulin structures.
By sucrose density gradient ultracentrifugation and Sephadex G-200 filtration, the unsedimented immunoglobulin structures were shown to consist of 7S IgM and free kappa chains. About 80,000 7S IgM molecules were calculated to be present on each cell. The amount of kappa chains not associated with IgM was estimated to be equal to the amount of kappa chains in IgM. Inhibition of passive hemagglutination was used to detect and quantitate the immunoglobulin structures.
CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE
Authors: Miller J. F. A. P. , Sprent J. 
Published: June 2004

Collaboration between thymus-derived lymphocytes and nonthymus-derived antibody-forming cell precursors occurs in the primary antibody response of mice to heterologous erythrocytes and serum proteins. The purpose of the experiments reported here was to determine whether collaboration took place in an adoptive secondary antibody response.
A chimeric population of lymphocytes was produced by reconstituting neonatally thymectomized CBA mice soon after birth with (CBA x C57BL)F1 thymus lymphocytes. These mice could be effectively primed to fowl immunoglobulin G (FγG) and their thoracic duct lymphocytes adoptively transferred memory responses to irradiated mice. The activity of these cells was impaired markedly by preincubation with CBA anti-C57BL serum and to a lesser extent by anti-θ-serum. Reversal of this deficiency was obtained by adding T cells in the form of thoracic duct cells from normal CBA mice. Cells from FγG-primed mice were at least 10 times as effective as cells from normal mice or from CBA mice primed to horse erythrocytes. These results were considered to support the concept that memory resides in the T cell population and that collaboration between T and B cells is necessary for an optimal secondary antibody response.
Poor antibody responses were obtained in irradiated mice given mixtures of thoracic duct cells from primed mice and of B cells from unprimed mice (in the form of spleen or thoracic duct cells from thymectomized donors). In contrast to the situation with T cells, the deficiency in the B cell population could not be reversed by adding B cells from unprimed mice. It was considered that memory resides in B cells as well as in T cells and that priming probably entails a change in the B cell population which is fundamentally different from that produced in the T cell population.
ANTIGENIC PROMOTION
Authors: Wu Chin-Yu , Cinader Bernard 
Published: June 2004

Rabbits were immunized with p-azobenzene arsonic acid derivatives of human serum albumin (HA-As) or of dissociated keyhole limpet hemocyanin. The IgM response to the hapten was evaluated in terms of the number of hapten-specific plaque-forming cells in the lymph node draining the injection site. In some experiments, antibody was measured by agglutination of tanned and sensitized erythrocytes.
The hapten response of animals immunized with HA-As was increased (promoting effect) when the animals were injected with one of several structurally unrelated macromolecules: keyhole limpet hemocyanin (KLH), horse spleen ferritin (HSF), lysozyme (Lys), alum-precipitated human gamma globulin (alum-precipitated HGG). Different macromolecules differed in the magnitude of the promoting effect they induced, e.g., promotion by the associated form of KLH was greater than that by the dissociated form; alum-precipitated HGG was a better promoter than was soluble HGG. The relative magnitude of promotion by different macromolecules (associated vs. dissociated KLH, alum-precipitated vs. soluble HGG) correlated with the relative magnitude of the carrier effect, as judged by the hapten response induced by p-azobenzene arsonic acid conjugated to various proteins. Promotion was detected by agglutination assay of circulating antibody, by plaque assay of cells from the popliteal lymph node draining the site of preinjection, but not by plaque assay of cells from the contralateral lymph node. Promotion was dependent on the dose of the promoting macromolecule and on the dose of the hapten-protein conjugate. It was not observed in animals tolerant to the promoting macromolecule. Inhibition (i.e. antigenic competition), rather than promotion, was observed upon a secondary response to the preinjected macromolecule or when the hapten-protein conjugate was incorporated in Freund's adjuvant.
RESPONSE OF CULTURED MACROPHAGES TO MYCOBACTERIUM TUBERCULOSIS, WITH OBSERVATIONS ON FUSION OF LYSOSOMES WITH PHAGOSOMES
Authors: Armstrong J. A. , Hart P. D'Arcy 
Published: June 2004

The cytological response to the ingestion of tubercle bacilli by cultured mouse peritoneal macrophages has been studied by electron microscopy. Methods included a quantitative assessment based on systematic surveying of cell profiles, and of phagosomes and their contained bacteria, encountered in thin sections; classification of the sectioned bacteria into visibly damaged and apparently intact categories; prelabeling of dense granules (secondary lysosomes) with ferritin as an aid to identifying the occurrence and frequency of phagosome-lysosome fusion; and monitoring of bacterial growth and viability by light microscopy and cultural counts. The situations studied were as follows: progressive infection with the multiplying virulent strain H37Rv; ingestion of the same strain previously inactivated by gamma radiation; infection with an attenuated strain (BCG); and a stabilized virulent infection induced by the surfactant Macrocyclon.
In the bacterial suspensions used routinely for inoculation, about half the bacilli were viable, matching closely the proportions of intact and damaged organisms identified with the electron microscope. In the inoculated macrophages, some phagosomes containing intact bacilli and others containing damaged bacilli were always to be found; but the proportion of organisms scored as damaged increased, and that of intact organisms decreased, in situations where the population as a whole had been rendered nonviable before inoculation, or where they became so intracellularly as in the late stages of a BCG infection.
Evidence of fusion of ferritin-marked lysosomes with some bacterium-containing phagosomes was obtained in all experiments, but a significant difference was regularly observed according to whether the bacilli were damaged or intact. Virtually all phagosomes containing damaged bacilli showed signs of fusion; but when many phagosomes were present containing apparently intact organisms (as with actively multiplying strain H37Rv or with this strain held at a steady level of viability by Macrocyclon, and also with strain BCG at an early stage of that infection), signs of fusion of lysosomes with these phagosomes were infrequent.
From these findings it is inferred that intracellular survival of M. tuberculosis in cultured macrophages is associated with a tendency to nonfusion of dense granules with the phagosome, thus avoiding direct exposure of the bacilli to the contents of these organelles. It is suggested, further, that fusion of dense granules with the phagosome, leading to digestion, is determined by recognition of the bacillus as nonviable. The possibility is discussed that the cytological response to different mycobacterial infections may reflect differences of a basic nature between facultative and obligate intracellular parasitism.
ANTIBODY-MEDIATED ACTIVATION OF A DEFECTIVE ß-D-GALACTOSIDASE
Authors: Celada Franco , Ellis John , Bodlund Kerstin , Rotman Boris 
Published: June 2004

Two closely related protein antigens were used to study immunogenic competition. Namely, normal ß-D-galactosidase of Escherichia coli (Z) and a genetically defective ß-D-galactosidase (AMEF) which seems to differ from the normal in one amino acid substitution. A unique characteristic of this pair of antigens is that, although they are indistinguishable in precipitation and absorption tests with antibodies, the enzymatic activity of AMEF is specifically increased several-hundredfold in the presence of antibodies directed against Z. The following results show that Z and AMEF also differ in their immunogenic ability: (a) antibodies directed against Z activated AMEF; antibodies directed against AMEF did not activate, but competed specifically with activating antibodies. (b) Animals immunized with AMEF failed to produce activating antibodies when they were subsequently challenged with Z, although the presence of some cells primed to produce activating antibodies could be demonstrated by adoptive transfer. (c) Animals preimmunized with Z were stimulated in their production of activating antibodies by AMEF challenge, although not as efficiently as with Z.
A model explaining these observations by competition for the immunogenic site among antigen-sensitive cells carrying cross-reacting receptors is presented.
QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES
Authors: Spring Susan B. , Schroeder Kenneth W. , Nisonoff Alfred 
Published: June 2004

The effect of challenge by antigen on persistence of clones of antibody-producing cells and on the induction of new clones was investigated through quantitative measurements of idiotypic specificities.
In each of nine rabbits idiotypic specificities present in the earliest bleedings were completely replaced after a few months; subsequent changes occurred much more slowly. On a quantitative basis the population of molecules used as immunogen always reacted most effectively with the homologous anti-idiotypic antiserum.
Little effect of increased antigen dose on the rate of change of idiotype was observed. Even large amounts of antigen administered every 2 wk caused only gradual changes in idiotypic specificities. This was attributed either to more effective capture of antigen by memory cells, as compared to precursor cells, or to the induction of tolerance in those clones that were not expressed. In two of three rabbits on a monthly injection schedule, the idiotypic specificities identified underwent very slow changes over a period as long as 17 months. Changes occurred more rapidly when antigen was administered every 2 wk.
In each of four rabbits investigated, all idiotypic specificities identified before a 5 month rest period were still present afterwards, indicating the survival of essentially all clones of antibody-producing cells during that interval. Quantitative inhibition data indicated that some new clones of cells were initiated.