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Biomedical subjects

C I Smith

Publications and source records attributed to C I Smith.

At least 307 records · Page 17Linked to original sources
PubMed1979

Detection of albumin-secreting hepatocytes at the single cell level by a protein A plaque assay.

In a complement-dependent assay, using protein A-coupled erythrocytes as target cells and anti-albumin immunoglobulin (Ig) as a developing serum, it was possible to detect single albumin-secreting hepatocytes as plaque-forming cells. Plasmacytoma cells were detected using anti-Ig antibodies and did not form plaques with anti-albumin Ig. This method can potentially be used for detecting any cell-secreting products in sufficient amounts.

Albumins↗
PubMed1979

Lipopolysaccharide and lipid A-induced human blood lymphocyte activation as detected by a protein A plaque assay.

Various purified cell wall lipopolysaccharides (LPS) from gram-negative bacteria and derivatives of these LPS were tested for their stimulatory capacity for human peripheral blood cells. Immunoglobulin (Ig) production was tested by an indirect plaque-forming cell assay using Staphylococcus aureus protein A-coupled erythrocytes and specific anti-Ig as developing serum. This method allows the detection of the majority of cells secreting Ig of a single class, and the number of plaque-forming cells detected are approximately 100-1000 times the amount obtained using normal sheep red cells as targets. LPS containing the O antigen-specific chain, as well as mutant products only containing lipid A and ketodeoxyoctonate trisaccharide, could induce cell division and antibody synthesis. The polypeptide antibiotic polymyxin B was found to inhibit LPS-induced activation. Furthermore, purified lipid A, complexed with bovine serum albumin, was also found to activate human peripheral blood B cells. These findings demonstrate that human peripheral blood lymphocytes can be activated by LPS and also indicate that lipid A is the active part of these molecules.

DNA↗
PubMed1979

Con-A-activated T cells secrete factors with polyclonal B-cell-activating properties.

Concanavalin A induced polyclonal antibody synthesis in normal spleen cells in vitro. Optimal responses were obtained by Con A concentrations lower than those optimal for induction of DNA synthesis. T cells, but not macrophages, were necessary for the effect. Spleen cells from nude mice were not activated, whereas cells from the LPS non-responder stain C3H/HeJ were activated to polyclonal antibody synthesis by Con A. Supernatants from Con A activated spleen cells could by themselves induce polyclonal antibody synthesis in untreated spleen cell cultures, even when Con A had been removed by absorption with Sephadex G-50 and when alpha-methyl-mannoside was present in the secondary cultures. T cells produced the active supernatants, which were competent to induce polyclonal antibody synthesis, but not DNA synthesis, in both H-2-incompatible and compatible strains. When the supernants were absorbed with erythrocyte antigens, they specifically induced an enhanced response, in secondary cultures, to the antigen used for absorption. Possible mechanisms of this specific effect are discussed.

Animals↗
PubMed1979

Regulation of lymphocyte activation by serum factors.

The effect of autologous normal mouse serum on activating properties of the polyclonal B cell activators lipopolysaccharide and purified protein derivative was studied. 'Low' concentrations (0.1-1%) were found to be slightly stimulatory, whereas 'high' concentrations (greater than 10%) were clearly inhibitory both for the induction of plaque-forming cells and for the DNA synthetic response. Similar effects were recorded in unstimulated cultures. Absorption of normal mouse serum with the erythrocytes used as target cells in the plaque assay resulted in less suppression or sometimes even in enhanced responses.

Absorption↗
PubMed1979

The immunodepressive effect of human glucoproteins and their possible role in the nonrejection process during pregnancy.

Human chorionic gonadotrophin (HCG) and human chorionic somatomammotrophin (HCS) were shown to suppress the proliferative T and B cell response induced by different mitogens in human and mouse lymphocytes. Thyroid stimulating hormone (TSH), sharing the alpha-chain subunit with HCG was devoid of effect suggesting that the immunosuppressive entity is localized within the beta-chain subunit. Human growth hormone (HGH) which is partly biologically cross-reactive with HCS did not impair mitogen responsiveness. HCG was also able to inhibit the differentiation of cells since the induction of antibody-formation was depressed. Expression of plaque forming cells was also reduced by addition of HCG directly in the PFC assay possibly reflecting the anti-complementary effect of this hormone, since cell mediated lysis of target cells by Con A activated lymphocytes, which is not complement-dependent, was unaffected by adding HCG in the assay system.

Animals↗
PubMed1979

Pokeweed mitogen induced differentiation of human B cells: evaluation by a protein A haemolytic plaque assay.

Using the protein A plaque assay, the number of human cells secreting immunoglobulin of various classes after pokeweed mitogen stimulation was determined. At optimal response (on day 5-7) a mean of 58,354 IgM PFC/10(6), 34,207 IgG PFC/10(6) and 10,525 IgA PFC/10(6) cells was found when using peripheral blood lymphocytes. In spleen cells, peak values which were slightly higher than in blood, were obtained at day 4-6. The proportions of cells secreting light chains of either type were found to be comparable to those of unstimulated cells thus supporting the notion of the polyclonality of the response. Pokeweed mitogen stimulation of peripheral blood lymphocytes was found to be totally T-cell dependent whereas the response of spleen cells was not. When assayed for antigen-specific precursor cells in cultures stimulated by mitogen, the frequency of SRBC-specific IgM producing cells was found to be 1.3/1000 cells. This frequency was regularly found to be independent of medium supplement.

Antibody-Producing Cells↗
PubMed1979

Species restriction of the mitogenicity induced by lanatoside C. Lymphocyte activation by digitalis glycosides is confined to cells from digitalis resistant species.

Activation of Na+, K+-ATPase has previously been suggested to be the triggering signal in mitogen-induced cell activation. Using a digitalis glycoside known to be a potent polyclonal B-cell activator, this hypothesis could be tested since digitalis activates ATPase at different concentrations in various species, depending on the degree of sensitivity to the toxic effects of glycosides. Lanatoside C was found to stimulate lymphocytes from glycoside resistant species such as rat, mouse and hamster. The possible involvement of Na+, K+-ATPase was made less likely by the similarity in dose--response profile in these cells although they have been reported to display varying degrees of glycoside resistance. Furthermore, using lymphocytes from digitalis-sensitive species such as man, guinea-pig or rabbit, no mitogenicity could be recorded, strongly suggesting a lack of correlation between glycoside-induced effects on Na+, K+-ATPase and cell activation.

Adenosine Triphosphatases↗
PubMed1978

B-cell activating properties of polymyxin B.

Polymyxins are known to be inhibitors of certain polyclonal B cell activators such as lipopolysaccharide and dextransulphate. However, increased specific responses to hapten-coupled mitogens have been reported after the addition of polymyxins to superoptimal conjugate doses. In this paper we have studied the effect of polymyxin B on superoptimal polyclonal doses of lipopolysaccharide. Results similar to those reported for hapten-lipopolysaccharide conjugates were obtained. Polymyxin B was also found to exert adjuvant properties for a primary immune response to sheep erythrocytes and to be a thymus-independent antigen.

Animals↗
PubMed1978

Role of suppressor T cells in autoimmune responses induced by polyclonal B cell activators.

In order to investigate a possible role of suppressor T cells in the maintenance of self tolerance, we compared the autoimmune response induced by LPS in cultures of untreated spleen cells with the one of anti-theta treated spleen lymphocytes. It was constantly found that T cell depletion never resulted in an increase in the number of plaques directed against autologous albumin coupled SRBC. The same finding was also apparent when the autoimmune response given by spleen cells of old, normal or thymectomized and young untreated animals was compared. In order to exclude the possibility that lack of increase of the autoimmune response in animals with T cells deficiency was due to long-lived suppressor functions, cells or factors, we compared the response to autologous albumin, as induced by LPS, in spleen cells of nude mice with the one given by their normal littermates. Since even in this instance no significant increase could be detected, we conclude that suppressor cells do not play an active role in the maintenance of self tolerance.

Animals↗
PubMed1978

Effect of membrane stabilizing agents on induction of the immune response. II. Inhibitory effects on lymphocyte activation by B-cell mitogens parallel toxicity.

The effect of three membrane stabilizing compounds, chlorpromazine, imipramine and lidocaine, on mouse spleen cells was investigated. Cellular activation by the B-cell mitogen lipopolysaccharide (LPS) was found to be inhibited. Suppressing doses also inhibited back ground DNA-synthesis and the number of background plaque forming cells. However, the degree of suppression caused by all three of the membrane stabilizing agents tested, parallelled the decline of viable cells in the cultures. It is concluded that the drug induced inhibition of LPS activation was due solely to the toxicity of the compounds.

Animals↗