bluuebunny/crossref_metadata_2025 huggingface dataset:
Hereditary C2 deficiency: Genetic studies and association with the HL-A system.
Authors: Day N K , L'Esperance R , Good R A , Michael A F , Hansen J A , Dupont B , Jersild C
Published: June 2004

Herediatary C2-deficiency has been shown to be transmitted asn an autosomal recessive characteristic. Recent evidence indicates that some genetic factors involved in the control of the complement (C) system in both man and mice are governed by genes localized within the major histocompatibility regionmthis study describes a large pedigree of the paternal family of a C2-deficient patient with systemic lupus erythematosusl It is shown that this condition is transmitted as an autosomal recessive trait, the heterozygous carriers having approximately half normal levels of C2. Furthermore, this trait was shown to be inherited in close linkage with an infrequent HL-A typw, 2,4A2. The maternal, C2-defective chromosome was shown to be transmitted by HL-AW10, W18 haplotypemthis same haplotype was described in a similar study by Fu et al. (6) to be associated with C2 deficiencymfinally, a third haplotype HL-A2,W18 carrying a defective C2 gene was demonstrated in a part of this pedigree.
Multiple individual and cross-specific indiotypes on 13 levan-binding myeloma proteins of BALB/c mice.
Authors: Lieberman R , Potter M , Humphrey W , Mushinski E B , Vrana M
Published: June 2004

13 leven-binding myeloma proteins (LBMP) of BALB/c origin were classified into two groups with different binding specificities; one group of 11 proteins bound beta2 leads to 1 fructosans, a second group of two proteins bound fructosans probably of beta2 leads to 6 linkage. Anti-idiotypic sera prepared to 10 of the proteins in the appropriate strains of mice identified numerous idiotypic determinants. Each protein used for immunization had its own unique individual idiotypic specificities (IdI) and in addition most of the proteins carried two-nine cross-specific or shared idiotypes (IdX) that were found only among LBMP, and not found in 106 non-LBMP. Most of the IdX determinants and only four of the IdI determinants of the beta2 leads to 1 fructosan binding group were located in the antigen-binding site. The multiplicity of antigenic differences in this functionally related group of immunoglobulins reveals an unexpected degree of heterogeneity in V-regions that appears to be unrelated to binding.
Histocompatibility studies in a closely bred colony of dogs. V. Mechanisms of cellular adaptation in long-term DL-A identical radiation chimeras.
Authors: Rapaport F T , Lawrence H S , Bachvaroff R , Cannon F D , Blumenstock D , Mollen N , Ayvazian J H , Ferrebee J W
Published: June 2004

20 Cooperstown beagles of known DL-A genotypes (B" dogs) were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A identical donor (A" dog); the resulting chimeras have survived uneventfully for 882, 1466 days, with no evidence of secondary disease, and have been tolerant to kidney and skin allografts obtained from the donor of marrow. Treatment of "A" dogs with serum obtained from their long-term "B" chimeras had no significant effect upon the ability of the recipients to reject "B" skin allografts...
The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis.
Authors: Calderon J , Kiely J M , Lefko J L , Unanue E R
Published: June 2004

Culture fluids of peritoneal exudate cells rich in macrophages stimulated DNA synthesis of thymocytes and, to lesser extent, of spleen cells. We also investigated the effects of culture fluids from macrophages on the in vitro response to a hapten-carrier protein (fluorescein-menocyanin) using spleen cells from immune mice. Macrophage culture fluids contained an activity that increased the plaque-forming cell response of both IgG and IgM class. This increase was observed in the absence of any added hapten protein to the culture. The helper function of T lymphocytes (as evidenced by challenging with the hapten on the homologous carrier) was also increased by the macrophage culture fluid. However, this enhancement was best observed in conditions of relatively low T-cell activity. Also, the macrophage fluid allowed spleen cells of nude athymic mice to make a plaque-forming cell response to sheep red blood cells of both the IgM and IgG class. The macrophage was the cell source of the stimulatory molecule since it was generated only in cultures of macrophages devoid of significant number of lymphocytes. Stimulatory activity was not found in cultures of lymphocytes, mouse embryo cells, or 3T3 cells. The thymocyte stimulatory molecule did not contain H-2 antigens, was resistant to diisopropylfluorophosphate treatment, eluted from Sephadex with a size ranging from 15,000 to 21,000 daltons, and was sensitive to chymotrypsin and pepsin.
Genetical control of B-cell responses. IV. Inheritance of the unresponsiveness to lipopolysaccharides.
Authors: Coutinho A , Moller G , Gronowicz E
Published: June 2004

The inheritance of B-cell responsiveness to lipopolysaccharide (LPS) was studied in 55 crosses between mice of the low-responder strain C3H/HeJ and the high-responder strains B10.5M and C3H/Tif. F1 hybrid mice between the low-and the high-responder strains, showed in every case responses which were intermediate between the responses obtained with each parent. The responsiveness among F2 hybrid and backcross mice to either high- or low-responder parents, segregated into intermediate, high, or low categories, respectively. The present results are compatible with the hypothesis that responsiveness to LPS is determined by one single, codominantly expressed, autosomal gene. The capacity to develop a specific thymus-independent response to a hapten-LPS conjugate, also under genetical control, was found to segregate together with the capacity to develop polyclonal responses to LPS.
Induction of T-lymphocyte responses to a small molecular weight antigen. II. specific tolerance induced in azebenzenearsonate (ABA)-specific T cells in Guniea pigs by administration of low doses of an ABA conjugate of chloroacetyl tyrosine in incomplete Freund's adjuvant.
Authors: Bullock W W , Katz D H , Benacerraf B
Published: June 2004

The experiments presented in this paper demonstrate that the induction of tolerance on the one hand and the induction of delayed sensitivity on the other hand can be accomplished by administration of similar doses of azobenzene-arsonate conjugated to N-chloracetyl tyrosine (ABA-T) to guinea pigs with the determining factor being the absence or presence, respectively, of activating bacterial products in the adjuvant mixture used. Thus, complete, persistent ABA-T-specific T-cell tolerance can be induced in adult guinea pigs with 20 mug of ABA-T given intradermally in incomplete Freund's adjuvant (IFA) whereas this same dose of ABA-T induces ABA-specific immunity when administered in complete Freund's adjuvant. This tolerance was not reversible by administration of ABA-T and IFA in the presence of bacterial lipopolysaccharide, was generated before the formation of primed T cells, and persisted for at least 3 mo after initiation. Moreover, cell transfer studies performed herein demonstrate that the unresponsiveness resulting from administration of ABA-T in IFA reflects the activity of suppressor cells to induce and maintain a state of unresponsiveness could only be demonstrated in unprimed animals may indicate a severe limitation on the potential clinical usefulness of such an approach to regulation of the immune system.
Secretion of a specific collagenase by stimulated macrophages.
Authors: Werb Z , Gordon S
Published: June 2004

Thioglycollate-stimulated mouse macrophages release a specific collagenase into their medium during in vitro culture. The macrophage collagenase has been characterized as a typical metal proteinase which catalyzes the cleavage of the native collagen molecule into three and one-quarter fragments. The extracellular accumulation and low activity in cell lysates suggest that collagenase is a secretion product of the stimulated macrophage. Prolonged secretion of the enzyme at a constant rate for more than 7 days in culture and its inhibition by cycloheximide provide evidence for biosynthesis in vitro. In contrast, secretion of collagenase is barely detectable from unstimulated macrophages which can, however, be stimulated to secret the enzyme by ingestion and intralysosomal storage of latex particles or dextran sulfate. Macrophages laden with latex, an undigestable particle, continue to release collagenase for at least 20 days. Several established mouse cell lines have also been examined for their capacity to secrete collagenase. Collagenase is one of a class of inducible neutral proteinases by which the activated macrophage can modify its extracellular environment.
The lipoprotein of the outer membrane of Escherichia coli: a B-lymphocyte mitogen.
Authors: Melchers F , Braun V , Galanos C
Published: June 2004

The lipoprotein of the outer membrane of Escherichia coli is a B-cell mitogen in mice. Polyclonal activation of B lymphocytes was measured by an increase in thymidine uptake, by the development of plaque-forming cells against densely coupled trinitrophenylated sheep red cells, and by selectively increased rates of synthesis and secretion of leucine-labeled IgM. Murein-free and muropeptides-containing lipoprotein are effective in B-cell activation, while free murein is inactive. Removal of ester-linked fatty acids from the amino-terminal end of the lipoprotein by alkaline hydrolysis abolishes the mitogenicity of the lipoprotein. B lymphocytes from high responder (C3H/Tif and BALB/c nu/nu) or from low responder (C3H/HeJ) mice to the mitogen lipopolysaccharide (LPS) both respond well to the lipoprotein. Anti-immunoglobulin antibodies inhibit the mitogenic stimulation of B cells by lipoprotein. A complex of structures including the Ig-receptor molecules, the LPS receptor, and the lipoprotein receptor appear involved in the regulation of mitogenic stimulation of B cells to proliferation and differentiation to IgM-secreting cells.
Mixed lymphocyte culture determinants and C2 deficiency: LD-7a associated with C2 deficiency in four families.
Authors: Fu S M , Stern R , Kunkel H G , Dupont B , Hansen J A , Day N K , Good R A , Jersild C , Fotino M
Published: June 2004

Four families with C2 deficiency were studied. Among eight HL-A haplotypes involved with C2 deficiency, five were HL-A 10,W18. Three homozygotes for C2 deficiency from different families were mutually nonreactive in mixed lymphocyte cultures (MLC) and the heterozygotes from the fourth family failed to react to the homozygous cells. It appeared that identical MLC determinants were associated with all the genes from the different families that related to C2 deficiency. Further experiments identified the MLC determinant, LD-7a, as being involved. These results suggest marked linkage disequilibrium between the genes for C2 deficiency and the major histocompatibility complex (MHC). Studies of possible recombinants have offered tentative evidence for the positioning of the locus for C2 deficiency with respect to other segments of the MHC.
Transplantation behavior of A.TH and A.TL T-cell lymphomas in congenic resistant and hybrid strains.
Authors: Goding J W , Warner N L
Published: June 2004

Seven spontaneously arising T-cell lymphomas originating in A.TH or A.TL mice, which are congenic for the immune response gene (I) chromosomal segment were described. When transplanted into partner strains which were incompatible at the I region, the tumors were rapidly rejected. Rejection was proposed to be due to the presence of antigens controlled by I-region genes.
Antieosinophil serum and the kinetics of eosinophilia in Schistosomiasis mansoni.
Authors: Mahmoud A A , Warren K S , Graham R C
Published: June 2004

Mice were exposed to different intensities of infection with Schistosoma mansoni (10, 50, or 200 cercariae) and the kinetics of peripheral and bone marrow eosinophilia was followed for as long as 20 wk. When the schistosomula (immature worms) were migrating from the lungs to the liver there was a mild, transient eosinophilia, but soon after the onset of egg laying by the schistosomes, a major and prolonged increase in eosinophils occurred. This was terminated in the heavier infections by the death of the animals, but showed a spontaneous decline beginning at 18 wk in the lightly infected mice. The effect of S. mansoni eggs on eosinophilia in the blood, bone marrow, and granulomatous lesions was then examined by injecting schistosome eggs into mice intraperitoneally, subcutaneously, and intravenously. While the host response was dependent on the route by which eggs were administered, primary peripheral and bone marrow responses were seen on intravenous injection, and secondary responses occurred on intravenous and subcutaneous injection. In unsensitized and egg-sensitized mice, eosinophils were first seen around eggs injected into the pulmonary microvasculature at 96 and 24 h respectively. When the granulomas were maximal in size eosinophils made up at least 50% of the lesions. Administration of antieosinophil serum profoundly suppressed eosinophils in the peripheral blood, eliminated mature eosinophils and markedly increased eosinophil precursors in the bone marrow, and ablated eosinophils from the tissue lesions, considerably reducing their area.
Inverse relationship between net electric charge on the antigen and that on the sensitized cell in cellular immune response: demonstration with basic encephalitogen of the brain.
Authors: Teitelbaum D , Webb C , Rauch H , Karniely Y , Arnon R , Sela M
Published: June 2004

An inverse relationship exists between the net-electrical charge of immunogens and the antibodies elicited (1). The cellular basis of the net charge phenomenon has been established for both positively and negatively charged immunogens, by cell separation techniques over columns of opposite charge (7, 8). To establish whether this phenomenon can be extended to include cell-mediated immunity, the response to basic encephalitogenic protein (BE) which induces experimental allergic encephalomyelitis (EAE) was now investigated. Lymph node cells from sensitized strain 13 guinea pigs were fractionated over positively and negatively charged columns and compared to unfractionated cell populations in two assay systems: (a) in vitro response to BE in terms of lymphocyte transformation and (b) the passive transfer of EAE to unsensitized syngeneic recipients. The response was found to be confined to the fraction of cells eluted from glass bead columns, namely, the more negative cells. Cells eluted from poly-L-lysine-coated glass bead columns (i.e., positive cells) were devoid of the capacity to respond to this antigen either in vivo or in vitro. It was previously established that thymocytes rather than bone marrow cells account for the inverse charge phenomenon as assayed by T-helper-cell function in in vivo antibody production (8). We have now extended the inverse charge effect to include cell-mediated immune response of the delayed hypersensitivity type.
Kinetic study of T lymphocytes after sensitization against soluble antigen. III. Potentiation and suppression of the PHA response by antigen-activated lymphocytes of low density.
Authors: Bash J A , Durkin H G , Waksman B H
Published: June 2004

Lymph node cells of ovalbumin-sensitized rats were separated on the basis of buoyant density into fractions reciprocally enriched in cells responsive to ovalbumin or phytohemagglutinin (PHA). Recombination of high density and low density fractions in varying proportions resulted in potentiation or suppression of the DNA synthetic response to PHA in culture. The response of cultures containing equal numbers of high and low density cells was markedly greater than the sum of the two populations stimulated separately. However, when decreasing numbers of low density cells were cultured with a constant number of high density cells, profound suppression was observed.
Lymphocyte E rosette inhibitory factor: a regulatory serum lipoprotein.
Authors: Chisari F V , Edgington T S
Published: June 2004

Rosette inhibitory factor, RIF, previously described in serum from patients with hepatitis B virus infection, has been isolated and identified as a minor species of beta-lipoprotein of the low-density (LDL) class. It is unrelated to hepatitis B virus proteins or particles. Although discrete by reference to charge and density (1.050 +/- 0.004 g/cm3), RIF appears to be a complex macromolecular structure containing apolipoproteins A, B, and C. Greater than 400% recovery is achieved upon 300,000-fold purification from RIF+ sera suggesting activation of a precursor form that is not present in normal serum. RIF inhibits E rosette function of T lymphocytes in vitro with a lag period of approximately 4 h and maximal effect at 24 h consistent with a metabolically-induced event. RIF is functionally active at concentrations of 1 X 10(-12) M or greater, rapidly binds to lymphocytes, and has a functionally effective half-life of approximately 1.5 h. Approximately 2,900 receptors for RIF appear to be present per cell and a high mutual affinity is apparent (k approximately to 9 X 10(10) liters/mol). RIF has no detectable effect on mitogen (PHA) responsiveness of lymphocytes, but inhibits the capacity of lymphocytes to respond to histoincompatible cells in vitro at concentrations greater than 10(-8) M. Equivalent RIF- lipoprotein fractions from normal serum are equally inhibitory in the mixed lymphocyte reaction suggesting that this effect is not directly attributable to RIF activity. These data indicate that RIF is a unique and functionally specific species of LDL that represents either an association complex of lipoproteins or a hybrid molecule of unusual composition. The association of this factor with viral-induced hepatocellular injury underscores the need to elucidate its structure and function in greater detail.
Induction of antiphosphorylcholine antibody formation by anti-idiotypic antibodies.
Authors: Trenkner E , Riblet R
Published: June 2004

Anti-idiotypic antibodies have been used to mimic antigen in the mouse antiphosphorylcholine response in order to investigate the induction of precursors of antibody-forming cells. We have shown that interaction of anti-idiotype antibody with receptor antibody molecules induces the formation of antibodies that are specific for phosphorylcholine and carry the idiotypic determinants. This induction is dependent on the recognition of carrier determinants on the anti-idiotype antibody by helper T cells. We conclude that receptor antibody molecules on the surface of the precursors of antibody-forming cells deliver the antigenic signal for the induction of these cells.
The pinocytic rate of activated macrophages.
Authors: Edelson P J , Zwiebel R , Cohn Z A
Published: June 2004

Peritoneal macrophages from mice injected 4 days previously with Brewer's thioglycollate medium have a pinocytic rate, in culture, of 190 ng horseradish peroxidase (HRP)/100 mug cell protein/h, compared to the rate of resident peritoneal cells of 53 ng HRP/100 mug cell protein/h. Mice injected with endotoxin or with only certain of the components of the Brewer's medium show an intermediate level of stimulation. The rate of unstimulated, endotoxin-stimulated, or thioglycollate-stimulated cells shows little change over several days in culture. The pinocytic rate of thioglycollate-stimulated cells can, however, be further increased by exposure of concanavalin A. Although cells may show transient increases in their pinocytic rate in many situations, a sustained increase in pinocytic rate is a sign of the "activated" state of macrophages.
The allogeneic bisection of carrier-specific enhancement of monoclonal B-cell responses.
Authors: Pierce S K , Klinman N R
Published: June 2004

The ability of T cells to enhance the response of syngeneic and allogeneic B cells to thymus-dependent hapten-carrier conjugates was analyzed. This analysis was carried out on individual primary B cells in splenic fragment cultures derived from irradiated reconstituted mice. This system has several advantages: (a) the response of the B cells is entirely dependent on carrier priming of the irradiated recipient; (b) this B-cell response can be quantitated in terms of the number of responding cells; and (c) very small B-cell responses can be readily detected and analyzed. The results indicate that the majority of hapten-specific B cells were stimulated in allogeneic and syngeneic recipients only if these recipients were previously carrier primed. The number of B cells responding in carrier-primed allogeneic recipients was 60-70% of that in syngeneic carrier-primed recipients. The antibody-forming cell clones resulting from B cells stimulated in the allogeneic environment produced small amounts of antibody and antibody solely of the IgM immunoglobulin class, while the larger responses in syngeneic recipients were predominantly IgG1 or IgM plus IgG1. The capacity of collaborative interactions between carrier-primed T cells and primary B cells to yield IgG1 antibody-producing clones was shown to be dependent on syngeny between these cells in the H-2 gene complex. It is concluded that: (a) B cells can be triggered by T-dependent antigens to clone formation through collaboration with T cells which differ at the H-2 complex as long as these T cells recognize the antigen; (b) the immunoglobulin class produced by the progeny of stimulated B cells generally depends on the nature of the stimulatory event rather than the nature of the B cell itself; and (c) stimulation to IgG1 production is dependent on syngeny between the collaborating T and B cells probably within the Ir-1A region. The role of the Ia antigens in the formation of IgG1-producing clones is not yet clear; Ia identity could permit IgG1 production or, conversely, nonidentity of Ia could induce all allogeneic interactions which prohibit IgG1 production.
Identification and characterization of the monoblast in mononuclear phagocyte colonies grown in vitro.
Authors: Goud T J , Schotte C , van Furth R
Published: June 2004

A liquid culture technique for growing mononuclear phagocyte colonies on a glass surface is described. This useful and reliable technique made it possible to study immature mononuclear phagocytes. In the mononuclear phagocyte colonies the cells grow separate from each other in a single layer. Three types of cells are recognized in these colonies, namely nondividing macrophages, and proliferating promonocytes and monoblasts. The macrophage and the promonocyte exhibit the typical characteristics previously demonstrated by the other methods, whereas the monoblast could only be fully characterized by the present liquid culture method. This proliferating cell (labeling index with [3H]thymidine, 92-96%) is almost round (diameters, 10 X 10 mum), has only a small rim of strongly basophilic cytoplasm, almost devoid of granules, and shows a certain degree of ruffling of the cell surface. The monoblast is positive for esterase with alpha-naphthyl butyrate as substrate (91%), for peroxidase (78% in the peroxidase-positive colonies), and lysozyme (43%). The monoblast is able to pinocytize dextran sulphate (15-20%) and to phagocytize opsonized bacteria (20-30%), latex particles (47%), and IgG-coated red cells (96%). IgG receptors (94%) and complement receptors (16%) are present at the cell surface. In these respects the monoblast has the typical characteristics of the mononuclear phagocytes, but its properties show it to be a more immature cell type than the promonocyte. On the basis of these criteria and the sequence of appearance of the different cell types during incubation and during the development of the individual mononuclear phagocyte colony, monoblasts being present before promonocytes appear in the colony, it is concluded that the monoblast is the precursor of the promonocyte. In these cultures granulocyte colonies are also formed, consisting of myeloblasts, (pro)myelocytes, stabs, and polymorphonuclear neutrophils. Besides the typically tight structure of this kind of colony, the granulocytic cells themselves are quite distinct from the mononuclear phagocytes by their morphology, cytochemical characteristics (e.g. all negative for esterase with alpha-naphthyl butyrate, but 96% positive with N-acetyl DL-alanyl 1-naphthylester), functional characteristics (pinocytic index 13-21%; phagocytic index; for opsonized bacteria 15-36%, for latex particles 10%, and for IgG-coated red cells 0%), and their very small number of IgG receptors and lack of complement receptors. On the basis of these criteria, these granulocytic cells are easily distinguished from the immature cells of the mononuclear phagocyte colonies. The present study confirms the conclusion that the mononuclear phagocytes are a separate cell line, quite distinct from the granulocytic series, since even the most immature cells so far identified--the monoblast and the myeloblast--have quite different characteristics.
Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. II. Determination of frequency and characteristics of idiotypic T and B lymphocytes in normal rats using direct visualization.
Authors: Binz H , Wigzell H
Published: June 2004

Anti-idiotypic antibodies made against the antigen-binding receptors of T lymphocytes for a given antigen (Ag-B locus antigens in rats) can be shown to react with IgG antibodies of the same antigen-binding reactivity. Using such anti-idiotypic antibodies, normal Lewis T lymphocytes of B and T type can be visualized by the use of anti-(Lewis-anti-DA) antibodies. Visualization was made possible by the use of direct fluorescent antibody tests or by autoradiography. Using the first technique and naked eye observations 6.2% of normal Lewis T lymphocytes expressed idiotypic markers signifying anti-DA reactivity, whereas anti-DA-reactive B lymphocytes as measured by this approach was in the order of 1.1%. Autoradiography was purified normal Lewis T lymphocytes gave similar figures. When comparing the intensity of fluorescence at the single cell level using quantitative cytofluorometry anti-idiotypic antibodies reactive with T lymphocytes gave a similar degree of intensity as was obtained using anti-Ig antibodies against B lymphocytes.
Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particle-bound ligands to specific receptors on the macrophage plasma membrane.
Authors: Griffin F M , Griffin J A , Leider J E , Silverstein S C
Published: June 2004

These experiments were designed to evaluate the role of macrophage plasma membrane receptors for the third component of complement (C) and for the Fc portion of IgG in the ingestion phase of phagocytosis. Sheep erythrocyte (E) were coated with anti-E IgG [E(IgG)]; these E(IgG) were then attached to cultivated monolayers of mouse peritoneal macrophages under conditions which reversibly inhibit ingestion of E(IgG). The E(IgG)-macrophage complexes were further incubated under similar conditions with an antimacrophage IgG fraction which blocks Fc receptor-mediated ingestion but has no effect upon ingestion mediated by other phagocytic receptors. When these cultures were subsequently incubated under conditions optimal for particle ingestion, phagocytosis of the IgG-coated erythrocytes did not occur; the erythrocytes remained bound to the Fc receptors of the macrophage plasma membrane. To determine whether ligands must cover the entire surface of an attached particle to permit ingestion of that particle, C-coated E [E(IgM)C] were bound to the C receptors of thioglycollate-induced (activated) macrophages at 4 degrees C. E(IgM)C-macrophage complexes were then trypsinized at 4 degrees C, a procedure which resulted in cleavage of erythrocyte-bound C3b molecules to a form of C3 not recognized by the macrophage receptors for C3b. Under the conditions used, trypsin did not affect the attachment of E(IgM)C to the macrophage surface or the macrophage receptors for C3b. When these trypsin treated E(IgM)C-macrophage complexes were incubated at 37 degrees C, the bound E(IgM)C were not ingested; the erythrocytes remained attached to the macrophage plasma membrane via the macrophage's C receptors. These results indicate that attachment of a particle to specific receptors on the macrophage plasma membrane is not sufficient to trigger ingestion of that particle. Rather, ingestion requires the sequential, circumferential interaction of particle-bound ligands with specific plasma membrane receptors not involved in the initial attachment process.
Enhancement of human interferon production by neutral red and chloroquine: analysis of inhibition of protein degradation and macromolecular synthesis.
Authors: Sehgal P B , Tamm I , Vilcek J
Published: June 2004

Two lysosomotrophic drugs, neutral red and chloroquine, enhance polyinosinic:polycytidylic acid-induced interferon production by a strain of diploid human fibroblasts (FS-4). Treatment of cells with neutral red or chloroquine between 2.5 and 3.5 h after induction increases interferon yields 16- to 64- and 4- to 16-fold, respectively, in the subsequent 20.5 h. The two drugs inhibit the rates of protein degradation and of RNA and protein synthesis. In addition, neutral red is a very potent inhibitor of uridine transport into cells. Normalized dose-effect curves show that interferon superinduction is correlated with the inhibition of macromolecular synthesis, but not with that of protein degradation. Treatment of cells with chloroquine at low concentration (25 mug/ml) for a prolonged period of time (24 h) caused approximately 40% reduction in the rate of protein degradation. The usual rapid shutoff of interferon production and the effectiveness of effectiveness of actinomycin D superinduction are not altered by this treatment. This strongly suggests that inhibition of intralysosomal protein degradation does not significantly contribute to interferon superinduction. Degradation of the rapidly and the slowly turning over proteins was unaffected by actinomycin D under conditions of treatment known to enhance interferon production. Treatment with cycloheximide (5 or 50 mug/ml for 5 h) inhibited the rate of degradation of the rapidly turning over component by 10% and the slow component by 30-40%, which suggests that the two components turn over by distinct cellular mechanisms.
Functional characteristics of Peyer's patch cells. III. Carrier priming of T cells by antigen feeding.
Authors: Kagnoff M F
Published: June 2004

Peyer's patch T cells may serve an important role in the interaction of the host with intraluminal gut antigens. Studies presented in this paper demonstrate that T cells in murine Peyer's patches can be carrier primed for helper function in the induction of an antihapten response by feeding antigen. Carrier priming was assessed by measuring the ability of Peyer's patch cells from mice fed heterologous erythrocytes to enhance an antitrinitrophenyl (TNP) response in vitro when added to normal Peyer's patch cells cultured with TNP coupled to the erythrocyte used for feeding. Priming of T helper cells in Peyer's patches was antigen specific and occurred when erythrocytes were administered orally but not when erythrocytes were injected intravenously or intraperitoneally. Murine Peyer's patches are naturally deficient in a cooperating accessory adherent cell type(s) required for B-cell induction to humoral antibody synthesis in vitro and antigen feeding does not result in significant induction of Peyer's patch B cells to humoral antibody synthesis in vivo. Since Peyer's patch T cells can be carrier-antigen primed for helper function in the absence of B-cell induction to humoral antibody synthesis, these studies may indicate that T-cell priming is less dependent than B-cell induction on cooperating accessory adherent cells.
Dominant nonresponsiveness in the induction of autoimmunity to liver-specific F antigen.
Authors: Silver D M , Lane D P
Published: June 2004

The liver-specific F antigen, although not an autoimmunogen, can induce the production of autoantibodies in responder strains. The ability to respond is under the control of two genes, one linked to the H-2 locus of mice, the other not. Responders possessing both genes produce high anti-F titers, while the H-2-linked gene alone permits a significant but low antibody response. (Responder X nonresponder) F1 hybrids derived from parents possessing identical F molecules are nonresponders, in contrast with the dominance of responsiveness in Ir gene systems. The presence of the H-2 locus from nonresponders appears involved in the inability to respond. This is discussed in terms of self-tolerance and suppression.
Binding of monomeric immunoglobulins to Fc receptors of mouse macrophages.
Authors: Unkeless J C , Eisen H N
Published: June 2004

The binding properties of surface receptors of immunoglobulins on mouse macrophages were studied with mouse myeloma proteins and normal peritoneal macrophages, thioglycollate-stimulated macrophages, and a macrophage cell line, P388D1. Primary cultures of mouse embryo fibroblasts served as controls. IgG2a proteins were bound strongly;IgG2b was bound weakly (one-twentieth as well as IgG2a);IgM, IgA, and IgG1 were not bound significantly. The number of binding sites per cell for IgG2a was 4 X 10(5) for thioglycollate-stimulated cells and 1 X 10(5) for normal and P388D1 cells. Binding was exothermal: with decreasing temperature the equilibrium (association) constants increased and dissociation rate constants decreased (at 37degreesC the respective values were 2 X 10(7) M-1 and 0.26 min-1, the latter value corresponds to a half time for dissociation of 2.6 min). From the rapidity of association and dissociation, it appears that the surface of the macrophage is in a dynamic equilibrium with IgG2a molecules in the cell's immediate microenvironment. The receptors for IgG2a are clearly specific for determinants in the immunoglobulin constant domain: two IgG2a proteins with greatly different isoelectric points (determined by isoelectric focusing) were bound with the same affinity to the same receptors; moreover, the Fc fragment was bound and Fab fragments were not. The Fc receptors for IgG2a proteins were readily eliminated by exposing macrophages briefly to trypsin. The receptors were regenerated during subsequent cultivation in serum-free medium; regeneration was inhibited totally by cycloheximide and partially by actinomycin D.
Experimental amyloidosis: the inducer is a polyclonal B-cell activator to which susceptibility is under genetic control.
Authors: Britton S
Published: June 2004

Experimental amyloidosis in mice can be induced by repeated injections of casein. It has now been demonstrated that casein induces strong polyclonal antibody synthesis in mouse B spleen lymphocytes. This effect is much more pronounced in spleen cells from anyloid-susceptible mice (CBA/J) than amyloid-resistant mice (A/J). It is suggested that amyloidosis can be due in some instances to a constant exposure for molecules which induce polyclonal B-cell activation.
Mediation systems in bacterial lipopolysaccharide-induced hypotension and disseminated intravascular coagulation. I. The role of complement.
Authors: Ulevitch R J , Cochrane C G , Henson P M , Morrison D C , Doe W F
Published: June 2004

We have studied the role of complement in lipopolysaccharide (LPS)-induced hypotension and disseminated intravascular coagulation (DIC) by comparing the effects of injection of three preparations of LPS from E. Coli 0111:B4, S. minnesota Re595, and S. marcescens. Injections of nonlethal doses of these LPS preparations into normal rabbits produced decreases in mean arterial blood pressure during a 5-h period. When rabbits treated with cobra venom factor (CoF) to deplete C3 were injected with the various LPS preparations, mean arterial pressures fell at a rate and extent essentially identical to that observed in normal rabbits. Rabbits genetically deficient in C6 also demonstrated LPS-induced hypotensive changes. Only minimal, or no changes in plasma C3 levels or serum CH50 values were detected in normal rabbits after LPS injection. Hypotensive changes were also induced in rabbits when complement was rapidly activated by intravenous injection of CoF. In contrast to the hypotension induced by LPS, the fall in arterial pressure associated with the consumption of complement was short lived and required the rapid consumption of considerable amounts of C3. The occurrence of DIC noted in normal rabbits injected with each preparation of LPS was not inhibited in either rabbits treated with cobra factor or in C6-deficient rabbits. The DIC was most pronounced after injection of Re595 and S. marcescens LPS. Injection of the various LPS preparations produced a rapid disappearance of circulating neutrophils and mononuclear cells, which occurred with the same kinetics and to the same extent in normal, CoF-treated, and C6-deficient rabbits. Injection of either Re595 LPS or S. marcescens LPS produced a biphasic disappearance of circulating 51Cr-platelets. In contrast, injection of 0111:B4 LPS affected only slightly the rate of disappearance of 51Cr-platelets. Depletion of C3 by cobra factor treatment had no effect on the disappearance of platelets in animals injected with 0111:B4. In marked contrast cobra factor treatment greatly reduced the initial rapid disappearance of platelets in rabbits injected with either Re595 or S. marcescens LPS, but had no effect in the secondary disappearance phase.
Hereditary asplenic-athymic mice: transplantation of human myelogenous leukemic cells.
Authors: Lozzio B B , Machado E A , Lozzio C B , Lair S
Published: June 2004

A new animal model characterized by hereditary athymia and asplenia was used as a recipient of chronic myelogenous leukemic (CML) cells with the Philadelphia (Ph1+) chromosome. Transplanted CML cells form solid vascularized tumors containing cells similar to those seen in the patient in a long-term culture. Cells taken from the tumors were nearly triploid, retained all human chromosome markers, and had the same antigenic determinants(s) as cells in culture.
Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells.
Authors: Sassa S
Published: June 2004

The process of erythroid differentiation in mouse Friend leukemia virus transformed cells (T3-C1-2) was examined by following changes in several enzyme activities of the heme biosynthetic pathway and in heme concentration while the cells were undergoing erythroid differentiation after treatment with dimethylsulfoxide. Untreated cells on the one hand, have a limited capacity for spontaneous differentiation. On the other hand, dimethylsulfoxide(DMSO)-treated cells showed an increase in the activities of delta-aminolevulinic acid (ALA) synthetase, ALA dehydratase, uroporphyrinogen-I synthetase, ferrochelatase, and heme concentration by days 1, 1.5, 2, and 4, respectively. The increase of the heme pathway enzymes and heme concentration followed the order of these enzymes or products as they are arranged in the heme biosynthetic pathway. These changes induced by DMSO were effectively inhibited by treatment with actinomycin D, suggesting that continued RNA synthesis is required for the differentiation process. 5-bromo-2'-deoxyuridine (BrdU) (10(-5) M) inhibited the DMSO-induced changes of the heme pathway enzymes. BrdU was most effective when it was present during the first 2 days of cell culture. It gradually lost its inhibitory effect when added after the 3rd day or later. The BrdU-mediated inhibition was completely overcome by the addition of thymidine (7 x 10(-5) M), but not by uridine (7 x 10(-5) M). All these data suggest that a sequential induction of the heme pathway enzyme takes place during erythroid differentiation of Friend leukemia cells, and that the sequential induction of the enzymes may be due to a sequential activation of genes coding for these enzyme activities.
Immune complex orchitis in vasectomized rabbits.
Authors: Bigazzi P E , Kosuda L L , Hsu K C , Andres G A
Published: June 2004

The results of the present study show that bilaterally vasectomized rabbits with high levels of antibodies to sperm antigens frequently develop an orchitis associated with granular deposits of rabbit IgG and C3 in the basement membranes of seminiferous tubules. The immune deposits correspond in location to electron-opaque deposits seen by electron microscopy. The "membranous orchitis" is characterized by thickening of tubular basement membranes, acc-mulation of macrophages and a few polymorphonuclear leukocytes, and destruction of the basal lamina, of the Sertoli and spermatogenetic cells. The pathogenetic role of the immune deposits and the possibility that they contain antigen-antibody complexes is indicated by: (a) selective accumulation of IgG and C3 granular deposits along the basement membranes of seminiferous tubules in rabbits producing high and persistent levels of antibodies to sperm antigens; (b) the elution of immunoglobulins from tissues with chaotropic ion-containing buffers, acid buffers, or heat; (c) the observation that the immuno-globulins accumulated in the testis contain antibody to sperm antigens; and (d) the demonstration of sperm antigens in a location similar to that of IgG and C3. It is postulated that sperm antigen-antibody complexes are formed in the basement membranes of seminiferous tubules when antigens leaking out of the tubules react with specific antibody coming from the circulation. In two rabbits with higher levels of circulating antisperm antibodies and severe orchitis, granular deposits of IgG and C3 were also present in renal glomeruli. Immunoglobulins eluted from the kidneys contained antibody with antisperm activity. These findings are consistent with the hypothesis that in some vasectomized rabbits extratesticular lesions may develop by a mechanism comparable to that of chronic serum sickness.
The role of nonclassical Fc receptor-associated, Ag-B antigens (Ia) in rat allograft enhancement.
Authors: Soulillou J P , Carpenter C B , d'Apice A J , Strom T B
Published: June 2004

The ability of a hyperimmune Lew anti-BN serum (HIS) to induce enhancement of (Lew/BN)F1 kidneys transplanted into Lew recipients was compared to that of the same antiserum that had been depleted of hemagglutinating anti-Ag-B antibodies by absorption with Brown-Norway (BN) RBC-absorbed sera (RAS) or platelet-absorbed sera (PAS). The RAS and PAS were as effective as the unabsorbed HIS in abrogating early rejection as assessed by renal function and promotion of long-term survival. The absorbed sera retained the capacity to block the mixed lymphocyte culture (MLC) between Lew and BN lymphocytes and to a lesser degree the MLC between Lew and BUF, WF, AUG, and ACI lymphocytes; however, strain specificity was clearly evident at high antiserum dilutions. Similarly, these absorbed sera retained the capacity to block the Fc receptor of BN lymphocytes, and this effect was completely strain specific. In contrast, hemagglutinating and cytotoxic antibodies eluted from platelets used for antiserum absorption did not react with Fc receptors as assessed by rabbit antisheep (IgG)-coated SRBC (EA) rosette formation. F(Ab')2 fragments of PAS also blocked EA rosettes. On the other hand, complement rosettes (EAC) were not inhibited by the HIS. The antibodies were therefore directed against the Fc receptor itself or a structure spatially or functionally closely related to it. Both the Fc receptors and the enhancing capacity of the antisera were strictly specific for the BN genotype. It is suggested that the anti-"Fc receptor" antibody could play an important role in the induction of enhancement by impairing host T-B collaboration as a result of its binding to graft allogeneic "Fc receptors" which appear to be analogous to the major histocompatibility complex (MHC)-coded Ia antigens of the mouse.
Synthesis and secretion of alpha2-macroglobulin by cultured human fibroblasts.
Authors: Mosher D F , Wing D A
Published: June 2004

The following observations indicate that cultured human WI-38 fibroblasts synthesize and secrete alpha2-macroglobulin into serum-free medium: (a) after incubation of cultures with [35S]L-methionine, a labeled protein appeared in the medium which was precipitated by antiserum directed against alpha2-macroglobulin; (b) after incubation of cultures with [35S]L-methionine, a major band of radioactivity detected by polyacrylamide gel electrophoresis of the proteins in medium co-migrated with alpha2-macroglobulin; and (c) the amount of alpha2-macroblobulin in the medium, estimated both functionally and immunologically, increased with time in normal but not not puromycin-treated cultures.
Modulation of regulatory mechanisms operative in the cyclical production of antibody.
Authors: Romball C G , Weigle W O
Published: June 2004

Modulation of the cyclical response in rabbits to aggregated human gamma globulin (AHuIgG) was investigated in order to study some of the parameters involved in self-regulation of the immune response. Several mitogens (lipopolysaccharide [LPS], phytohemagglutinin [PHA], and concanavalin A [Con A]), when injected simultaneously with antigen, have been shown to modulate the normal splenic plaque-forming cell (PFC) response in rabbits to a single intravenous injection of AHuIgG. This response to AHuIgG has previously been characterized by the initial appearance of PFC in the spleen 3 days later, with a peak of PFC at 5 days after injection. The number of PFC in the spleen then decreases and remains at a low level until a second increase begins on day 10, peaking on day 13. The 8-day cycle between peak PFC repeats, with a third peak appearing on day 21. In the present studies, injection of LPS with AHuIgG was shown to affect the PFC response by enhancing only the initial peak of PFC, PHA was shown to enhance both the initial and secondary peaks of PFC, while injection of Con A with AHuIgG resulted in a prolonged increase in PFC with no apparent cycling. Irradiation 24 h after injection of antigen resulted in PFC kinetics similar to those observed with PHA, although the increase in PFC was more marked with irradiation. Thus, although LPS, PHA, Con A, and irradiation markedly affected the immune response to AHuIgG, Con A was the only substance which altered the cyclical appearance of PFC to HuIgG. The cyclical nature of the PFC kinetics was shown to occur with either intravenous or intraperitoneal injection of antigen and in both primary and secondary responses, provided that the rabbits were primed with a low dose of antigen. Data were obtained that suggest that the response in distal lymph nodes may be regulated by immunological events occurring in the spleen. Cycling of PFC was not observed in the draining node after subcutaneous injection of AHuIgG in the hind foot. However, if the antigen was also injected intravenously at the same time as the subcutaneous injection, the response in the node became cyclical.