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Biomedical subjects

C I Smith

Publications and source records attributed to C I Smith.

At least 289 records · Page 16Linked to original sources
PubMed1982

Characterization of human lysozyme (muramidase)-releasing cells. Organ distribution and functional properties as analyzed in a protein A plaque assay.

Using a modification of the protein A plaque assay, human lysozyme-releasing cells were detected as plaque-forming cells (PFC). Blood and bone marrow contained higher numbers of muramidase secretors compared to adenoid and tonsil cell suspensions. Human peripheral blood cell cultures were found to contain cells detected as PFC in the presence of antimuramidase immunoglobulin as a developing agent. Lysozyme-producing cells were also found in human bone marrow cultures. High cell densities and a short culture period were optimal conditions for lysozyme release in bone marrow cell cultures. Addition of the activating ligand lipopolysaccharide directly into the plaque assay altered the number of muramidase-secreting cells.

Antibody-Producing Cells↗
PubMed1981

In vitro induction of human suppressor T cells by a chorionic gonadotropin preparation.

Human chorionic gonadotropin (hCG) in physiological retroplacental concentration has been shown to possess the capacity of inducing human lymphocytes which are subsequently competent to depress an antibody response induced by purified protein derivative of tuberculin, phytohemagglutinin, lipopolysaccharide and pokeweed mitogen. These suppressor cells inhibited the T cell-dependent mitogen-induced activation of lymphocytes synthesizing IgM, IgG and IgA. No suppression by hCG-induced cells was observed in Epstein-Barr virus activated cell cultures, indicating a T cell origin of the target cell. It is suggested that this may represent a mechanism for the cellular basis of an hCG-induced immunosuppressive effect in pregnancy.

Adult↗
PubMed1981

Concanavalin-A-induced suppressor lymphocytes in normal individuals.

Suppressor lymphocytes are now known to play an important role in the control of immune responses. It has been demonstrated that lymphocytes stimulated by the mitogen concanavalin A (Con A) have the ability to suppress the normal lymphocyte response to antigens. It has further been shown that this suppressive action is reduced when the suppressing lymphocytes are derived from patients with disorders (e.g. systemic lupus erythematosus) in which it has been suggested that suppressor cell function is abnormal. In this study we have examined several aspects of the Con A-induced suppression. The induction of suppression required viable cells, and both the induction and the action of the suppressor cells were radio-resistant. The induction of suppressor cells by Con A was independent of DNA synthesis but not of protein synthesis. The action of these suppressor cells was enhanced by the addition of prednisolone to the cultures. This latter observation is of interest in view of the action of steroids in diseases in which a defect of suppressor cells is suggested to be present and lends support to the importance of suppressor cells in the aetiology of these disorders.

Cell Survival↗
PubMed1981

Polyclonal human T lymphocyte activation results in the secondary functional activation of the human B lymphocyte.

The polyclonal T lymphocyte activators Con A and PHA were demonstrated to induce secretion of IgM and IgG as well as IgA antibodies in cultures of human peripheral blood lymphocytes. A similar response was seen in one-way mixed lymphocyte cultures and the kinetics, dose-response characteristics and optimal culture conditions are presented. The presence of functional T lymphocytes is a prerequisite for in vitro B lymphocyte activation in response to T lymphocyte mitogens. A narrow dose-response profile is a characteristic for both Con A and PHA and polyclonal B cell activation occurred at what have been previously regarded as suboptimal concentrations of these agents. The use of higher doses of these activators failed to generate immunoglobulin-secreting cells despite the presence of early and optimal levels of DNA synthesis in the cultures.

Adult↗
PubMed1981

Functional studies on B cells in human bone marrow: in vitro mitogen stimulation of normal and malignant B cells.

Using the protein A plaque assay, bone marrow cells from normal donors were shown to secrete spontaneously immunoglobulins mainly of the IgG and IgA class. After mitogenic activation, a marked increase in IgM production was observed with kinetics and cell density requirements similar to that of blood lymphocytes. In Morbus Waldenström patients, IgM was the predominant Ig class secreted spontaneously by bone marrow cells. The high in vitro background proliferation of these cells could be abolished by addition of the appropriate anti-idiotypic antiserum. After stimulation with mitogens, differentiation of cells within the malignant clone to immunoglobulin-secreting lymphocytes was evidenced, suggesting a retained responsive capacity of the transformed cells.

Aged↗
PubMed1981

Detection of IgD-secreting human lymphocytes at the single cell level by a protein A plaque assay.

By the use of Staphylococcus aureus protein A-coupled erythrocytes as target cells, and anti-Ig antibodies as a developing serum, immunoglobulin-secreting cells can be detected as plaque-forming cells in a complement-dependent haemolytic plaque assay. This method is based on the fact that the Fc portion of IgG will bind to protein A molecules. Using a rabbit anti-human IgD immunoglobulin as a developing serum we were able to detect secretion of IgD molecules from human cells. In a patient with an IgD myeloma, 6% of the bone marrow cells were found to form plaques. Bone marrow cells and blood lymphocytes from healthy donors as well as human tonsil cells were also examined for delta chain secretion. In some donors, a low increase in plaque numbers was obtained when anti-IgD Ig was used as a developing agent. In spite of the fact that the antisera used were highly specific we cannot rule out the possibility that the increase was due to cross-reactivity. However, these findings clearly demonstrate that the release of IgD from normal human lymphoid cells occurs at a much lower level as compared to secretion of IgM, IgG or IgA.

Adult↗
PubMed1981

Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B.

Hepatitis B virus associated DNA polymerase activity, hepatitis b surface antigen (HBsAg), and serum aspartate aminotransferase were followed in 21 patients with chronic active hepatitis while immunosuppressive therapy (prednisone +/- azathioprine) was being withdrawn. In every case, DNA polymerase activity fell within 6-10 wk of decreasing treatment and became undetectable in 8 patients. This was usually accompanied by a fall in HbsAg titer and a transient rise in serum aspartate aminotransferase activity. Four additional patients with previously untreated HbsAg positive chronic active hepatitis were placed on prednisone for 12 wk. There was a rise in DNA polymerase activity and HBsAg titer with a fall in serum aspartate aminotransferase values during treatment. Upon discontinuing therapy, DNa polymerase activity fell dramatically in all 3 patients who completed their course of prednisone and became undetectable in 1. These findings suggest that immunosuppressive therapy has a potentiating effect on hepatitis B viral replication in patients with chronic active hepatitis.

Adult↗
PubMed1980

T-cell functions in nude mice: proliferation of spleen cells from athymic mice in the one-way xenogeneic mixed leucocyte reaction.

Spleen cells from nude mice proliferate in vitro when stimulated with xenogeneic (human) lymphoid cells rendered unresponsive by addition of digitalis glycosides. In digitalis-sensitive species, such as humans, DNA, RNA, carbohydrate, and protein synthesis is completely blocked by addition of low concentrations of glycoside, whereas no impairment is found in digitalis-resistant species such as mouse. Since T cells have been implicated to be the cells responding in the mixed leucocyte reaction, this finding may suggest the occasional existence of "T-like" cells in the spleens of nude mice.

Animals↗
PubMed1980

Mitogenic activation of human lymphocytes: a protein A plaque assay evaluation of polyclonal B-cell activators.

Using the protein A plaque assay, the capacity of various polyclonal B cell activators to induce differentiation in human B lymphocytes was investigated. Dextran sulphate and native dextran were both virtually devoid of mitogenic properties. Lipopolysaccharide, however, was found to be a potent mitogen in human cells that, although giving rise to low DNA synthetic response, induced high numbers of immunoglobulin-synthesizing cells. Mean plaque-forming cell (PFC) numbers in healthy blood donors assayed on the optimal day (days 5-7) were 23,493 IgM/10(6) cells, 11,288 IgG/10(6) cells, and 2643 IgA/10(6) cells. Values obtained in spleen cells, peaking at days 4-6, were slightly higher. Purified protein derivative (PPD) was equally or even more effective than lipopolysaccharide (LPS) in generating PFC of different subclasses in peripheral blood with mean of 29,241 IgM/10(6), 21,269 IgG/10(6), and 3681 IgA/10(6). PPD furthermore induced a marked DNA synthetic response in human lymphocytes. These data suggest that LPS and PPD may both be used as functional markers in human cells when analysing patients with a suspected immunodeficiency state. It is suggested that cultures should be assayed using the protein A plaque assay, thereby being able not only to investigate the individual immunoglobulin classes but also to avoid the possible hazards involved in measuring antigen-specific responses in patients whose prior immunization to the antigen tested can never be totally excluded.

B-Lymphocytes↗
PubMed1980

Detection of muramidase (lysozyme)-secreting leucocytes at the single-cell level by a protein A plaque assay.

Using a modification of the protein A plaque assay, muramidase (lysozyme)-producing leucocytes were detected as plaque-forming cells. In the presence of anti-muramidase Ig and complement the secreted lysozyme resulted in lysis of protein-A-coated target erythrocytes. By the use of a monolayer technique individual plaque-forming cells could be identified by staining procedures. Granulocytes as well as monocytes were found to produce muramidase and thus to form plaques. This method could serve as a useful tool when studying lysozyme secretion. Furthermore, by the use of appropriate antisera, this method could be employed for the study of any cell type (any secretion), provided enough molecules are being secreted.

Cells, Cultured↗
PubMed1980

In vitro induction of murine suppressor T-cells by human chorionic gonadotropin.

Human chorionic gonadotropin (HCG) has previously been considered to be immunosuppressive and, thus, by prohibiting maternal rejection of the fetal transplant, to be one of the factors responsible for the successful outcome of pregnancy. The mechanism by which HCG exerts its pregnancy retaining effect is, however, as yet unknown. The present study shows that HCG has the capacity in mice of inducing lymphocytes which are subsequently competent to depress a polyclonal antibody response induced by different B cell mitogens. It is therefore suggested that HCG may exert its feto-protective action by inducing suppressor T cells. These lymphocytes would thus prevent the activation of cells which are responsible for transplant rejection.

Animals↗
PubMed1980

The protein-A plaque assay: a new system for the detection of cells secreting a given idiotype.

With a modification of the protein-A plaque assay, cells secreting a given idiotype could be detected. Different anti-idiotypic antisera raised against the M-component of macroglobulinemia Waldenström patients were used. The antibodies did not cross-react with cell clones of other patients or normal controls. Spontaneous plaques, without prior cultivation, were mainly shown to be of IgM class, the majority being idiotype specific, in blood and bone marrow lymphocytes from these patients. This is in contrast to the predominance of Ig or IgA found in normal blood donors. A low but recognizable stimulation of the malignant clone may be observed when cells were stimulated by certain polyclonal B cell activators.

Antibody-Producing Cells↗
PubMed1980

Cell-mediated immunity to liver antigen in toxic liver injury. II. Role in pathogenesis of liver damage.

The possible pathogenetic role of lymphocytes sensitized to liver antigens was investigated in CBA mice in which sublethal hepatic necrosis had been induced by carbon tetrachloride (CCl4). Sensitized lymphocytes from CCl4-treated mice were administered to syngeneic recipients. The recipients developed sensitivity to liver antigens but showed no evidence of liver damage. The cell mediating the immune response both in the donor and the recipient was a T cell. This was demonstrated further by studies involving mice rendered T cell deficient. These mice did not develop sensitized lymphocytes when they were treated with CCl4 but the extent of liver damage was similar in both T cell-depleted and intact animals. These findings suggest that T cell sensitization to liver antigens occurs as a result of toxic liver damage and does not play a role in the pathogenesis of the hepatic necrosis.

Animals↗
PubMed1980

Cell-mediated immunity to liver antigen in toxic liver injury. I. Occurrence and specificity.

To investigate the possible role of cell-mediated immunity in the pathogenesis of liver disease lymphocyte function was studied in CBA mice in which predictable sublethal liver necrosis had been included by the administration of the hepatotoxin carbon tetrachloride (CCl4). Non-specific lymphocyte function, as assessed by the response to the mitogen phytohaemagglutinin (PHA) was normal in over 90 percent of the animals. Forty-three per cent of the treated mice demonstrated specific lymphocyte sensitivity to liver antigen preparations. Such specific sensitivity was transient and apparent in only one case for more than 2 weeks after the CCl4 treatment. The lymphocyte sensitization was not reproduced by the addition of CCl4 to the lymphocyte cultures. There was no correlation between the severity of the liver disease and the detection of sensitized lymphocytes. Although these data may not be extrapolated directly to human liver disease, they demonstrate that cell-mediated immune reactivity to liver-derived antigens can occur as a result of non-immunological toxic liver injury.

Animals↗