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Biomedical subjects

R Kearney

Publications and source records attributed to R Kearney.

At least 37 records · Page 2Linked to original sources
PubMed1983

Binding of murine IgM and monoclonal IgM/A (k) hybrid anti-type III pneumococcal polysaccharide (SIII) antibodies to staphylococcal protein A.

Evidence is produced to show that two specific subclasses of IgM antibodies are formed during the primary immune response to Type III pneumococcal polysaccharide (SIII) in mice. The IgM proteins can be divided into two groups based on different reactivities with protein-A. As with human IgM subclasses, it is proposed to call the two IgM subclasses IgM1 and IgM2, where the latter is defined by the ability to react with protein-A of Staphylococcus aureus. Only the IgM molecule which reacted with protein-A produced passive haemolysis in the presence of guinea-pig complement. Results also show that the IgA anti-SII activity in serum of SIII-immune mice on day 5 of the primary response is due to hybrid IgM/A(k) antibody which is undetected by conventional methods for enumerating antibody-forming cells because cells producing IgM/A antibody develop direct plaques with guinea-pig complement. A monoclonal IgM/A(k) anti-SIII produced from spleen cells 5 days after injection of 10 micrograms SIII plus pertussis vaccine exhibited similar properties to molecules with mu and a-determinants in serum. The IgM/A hybrid antibody reacted strongly with protein-A and produced passive haemolysis of SIII-coated erythrocytes in the presence of guinea-pig, but not mouse, complement. Despite its specificity for the capsular antigen of Type III pneumococci, the IgM/A hybrid antibody conferred only temporary immunity in mice challenged with viable pneumococci. The nature and properties of IgM/A antibodies as well as those of the subclasses of IgM may give important clues to the genetic regulation and expression of antibody production. These findings may provide an explantation for some of the anomalies in various areas of immunological research.

Animals↗
PubMed1980

Potentiation of tumour growth by endotoxin in serum from syngeneic tumour-bearing mice.

The subcutaneous growth of 2 antigenically distinct syngeneic methylcholanthrene-induced murine fibrosarcomas, designated H1 and H7, were significantly augmented by the concomitant administration of E. coli endotoxin (LPS). Amounts as little as 0.2 micrograms i.p. potentiated tumour growth. The weakly antigenic tumour, H1, was more susceptible to provocation by LPS than the more strongly antigenic H7. Maximum provocation of H1 tumour growth occurred when LPS was injected 1 day before the administration of 5000 tumour cells. In contrast, significant anti-tumour resistance resulted if LPS was administered 6 days before the inoculation of tumour cells. Preliminary evidence indicates that low doses of LPS can facilitate the "sneaking through" phenomenon. Enhancement of tumour growth could not be demonstrated with sera or plasma from tumour-bearing mice, unless the samples were contaminated with endotoxin. The results illustrate the importance of excluding endotoxin from solutions used in studies of experimental tumours.

Animals↗
PubMed1980

Specific tumor immunity induced with mitomycin C-treated syngeneic tumor cells (MCT). Effects of carrageenan and trypan blue on MCT-induced immunity in mice.

Mitomycin C treatment of 3-methylcholanthrene-induced syngeneic tumor cells in male mice of the highly inbred strain CBA/WEHI was a convenient and effective method for producing viable but nondividing tumor cells. A single sc injection of 1 x 10(6) mitomycin C-treated syngeneic tumor cells (MCT) induced a specific antitumor immune response that could mediate rejection of small subcutaneous tumor grafts and substantially inhibit growth of larger grafts in normal mice. The response was evident between 3 and 7 days after immunization and persisted for at least 120 days. Adoptive transfer experiments with peritoneal exudate cells from MCT-immunized mice indicated that a cellular basis for resistance was likely in the absence of a detectable humoral component. Administration of MCT to mice with established tumor grafts did not, however, affect tumor growth. Experiments with carrageenan and trypan blue showed that neither induction nor expression of cytotoxic effector cells in MCT-immunized mice was inhibited by these substances, though carrageenan and trypan blue augmented tumor growth in normal mice.

Animals↗
PubMed1979

A method for the induction of a prolonged elevated IgM response without the formation of IgG antibody, by injecting carrageenan-treated mice with multiple doses of sheep erythrocytes.

Carrageenan, a known macrophage toxin and immunosuppressive agent, has been studied for its effect on antibody responses following single doses or multiple daily increasing doses of sheep red blood cells (SRBC) injected intraperitoneally (i.p.) in male CBA strain mice. Results showed that lambda carrageenan administered prior to a single i.p. injection of SRBC markedly suppressed both the IgM and IgG responses. However, when carrageenan-treated mice were injected with multiple daily increasing amounts of SRCB antigen, high titers of specific antibody activities were produced in serum while only IgM plaque-forming cells (PFC) were detected in the spleens up to 8 weeks later. Higher serum titers were obtained if Bordetella pertussis vaccine was administered i.p. shortly before the first antigen dose was injected in the carrageenan-treated mice. Direct PFC (IgM) but not indirect PFC (IgG) were detected in suspensions of spleen cells late in the response of these mice. Such treatment may provide a useful method for raising high titers of cytotoxic IgM antibody to other T-dependent antigens. Evidence is presented to show that pertussis vaccine--a known potentiator of the IgG response--does not reverse the inhibitory effects of carrageenan. Results also provide evidence for the requirement of functional macrophages in the induction of helper-cell activity for the thymus dependent IgG response in vivo.

Animals↗
PubMed1979

Effects of carrageenan, PVP and tumour-bearer serum on immunity induced by excision or mitomycin C-treated tumour cells in mice.

Carrageenan (Cg) was tested for its effects on the growth of, and immunity to, 2 methylcholanthrene-induced syngeneic murine fibrosarcomas (H1 and H2). The tumours were found not to share major tumour-specific transplantation antigens. H2 appeared more immunogenic than H1. In contrast to H1, immunity induced by H2 was not affected by Cg, nor was its growth in Cg-treated normal mice augmented.Postoperative i.p. injections of Cg abolished the weak anti-H1 immunity produced by H1 tumour excision. Furthermore, the subsequent growth of the H1 tumour challenge in the Cg-treated immune mice was significantly greater than the augmented growth in Cg-treated normal mice. The Prior administration of the macrophage-stabilizing agent polyvinylpyrrolidone (PVP) to immune mice significantly reduced the augmenting effect of Cg. The growth-promoting effect of Cg on a secondary H1 tumour challenge in mice immunized by tumour excision was abolished by 10(6) MCT-H1 cells injected s.c. before Cg. In contrast to the immunity induced by tumour excision, Cg did not abolish the immunity induced by the injection of MCT-H1 cells.Passive administration of H1 tumour-bearer serum (TBS) did not enhance the growth of H1 cells in normal mice, nor did TBS abrogate the specific cell-mediated immunity (CMI) induced in vivo by MCT-H1 cells. However, TBS administered to Cg-treated, MCT-H1-immune mice abolished tumour immunity.We propose that TBS does not inhibit CMI in vivo provided that macrophages remain functional, but may do so when macrophages are rendered defective by antimacrophage agents or by products of neoplastic cells. Increasing the levels of specific effector cells can over-ride the inhibiting effects of TBS, even when defective macrophages are present.

Animals↗
PubMed1979

Effect of carrageenan on the non-specific resistance of mice to injected syngeneic tumour cells, alone or in mixtures.

The mechanisms of non-specific resistance to syngeneic methylcholanthrene-induced fibrosarcomas of mice were investigated. Results showed that a small tumour graft of 0.05 X 10(5) cells is greatly enhanced in growth when admixed with large numbers of cell fragments, killed cells or viable non-replicating cells. The enhancement of small tumour grafts in cell mixtures was found to be non-specific. Carrageenan, a known anti-macrophage agent, significantly increased tumour growth in normal mice. However, it did not enhance the increased tumour growth of 0.05 X 10(5) cells mixed with 10(6) viable, non-replicating mitomycin C-treated tumour cells. The latter observation indicates that carrageenan and admixed cells interfere with the same tumour-inhibitory mechanism and therefore cannot produce additive effects. The results give support to the concept of a non-specific macrophage "surveillance" system which appears crucial in controlling tumour growth, since it determines the establishment of small numbers of tumour cells while they can still be easily destroyed.

Animals↗
PubMed1978

Failure of immunogenic tumors to elicit cytolytic T cells in syngeneic hosts.

Immunogenic, methylcholanthrene-induced sarcomas failed to elicit the production of rapidly cytolytic T lymphocytes in syngeneic mice, although they did elicit the production of more slowly cytotoxic cells. They were, however, susceptible to attack by cytolytic T cells from allo-immune mice and, if infected with ectromelia virus, to attack by similar cells from virus-immune, H-2 compatible mice. It is suggested that the failure to elicit cytolytic T cell production may be due to the lack of an appropriate association between tumour-specific antigens and elements of the major histocompatibility complex.

Animals↗
PubMed1976

Macrophages and lymphoid tissues in mice with concomitant tumour immunity.

The growth in mice of subcutaneous isografts of any of 5 methylcholanthrene-induced fibrosarcomas was associated with macrophage stimulation, reflected in an increased incidence of DNA-synthesizing cells among marcophages in the uninjected peritoneal cavity. This occurred at some stage with 4 tumours that induced concomitant immunity and one that did not. Some degree of splenomegaly also occurred with all 5 tumours. The spleens of all the tumour-bearing mice showed histological evidence of increased haemopoietic activity. Histological changes in the lymphoid elements of the spleen were very different with different tumours, ranging from lymphoid stimulation to lymphoid atrophy. The lymph nodes draining the sites of primary isografts which induced concomitant immunity showed signs of stimulation in the paracortical areas, followed by plasmacytopoiesis in the medullary areas. Stimulation of the paracortical areas was not detected in the nodes draining sites of injection of a tumour not inducing concomitant immunity. Nodes draining the sites of challenge isografts in mice exhibiting concomitant immunity showed plasmacytopiesis.

Animals↗
PubMed1975

Comparison of 51Cr release and microcytotoxicity assays against human melanoma cells.

Comparisons of the cytotoxic activity of mononuclear cells from venous blood of human subjects against human melanoma cell lines have been made by means of the 51Cr release assay (CRA) and the microcytotoxicity assay (MCA) of Takasugi and Klein. The relative effectiveness of the two assays in the detection of killing by various sub-populations of effector cells was studied after depletion of monocytes and separation of the blood monocluear cells by SRBC receptor and Fc receptor resetting techniques. Overall, the results showed good correlation. Most differences were the result of low values recorded with the CRA when effector cells were obtained from Hypaque-Ficoll--separated populations which had not been further fractionated. These differences were largely removed when monocytes were depleted by glass absorption and may reflect interference with the CRA by monocytes. No consistent differences were found between the assays in the detection of killing by subfractions enriched for T cells or B cells in this tumour system. The MCA appears to offer the advantage of greater sensitivity and possibly detection of a wider range of cytotoxic mechanisms but the CRA has a number of advantages of a technical nature which make it more applicable to routine assays in clinical studies.

Antigen-Antibody Reactions↗
PubMed1975

Cellular basis for the immune response to methylcholanthrene-induced tumors in mice. Heterogeneity of effector cells.

Immune resistance to methylcholanthrene-induced tumors has two phases, an early specific and a late non-specific phase. Both phases were found to be T-cell-dependent in vivo. Thus, adult thymectomized, irradiated, bone-marrow-protected mice bearing H-1 tumor isografts showed impaired resistance to challenge with homologous (H-1) and heterologous (H-3) tumor cells. In each case resistance was restored by injection of thymus cells. In vitro analysis of the cellular basis of resistance revealed that different mechanisms were involved in the two phases. The cytotoxic effect of immune spleen cells taken during the early specific phase was inhibited by pretreatment with anti-O serum and complement and by removal of macrophages. Neither procedure, however, interfered with the cytotoxic potential of immune spleen cells taken during the late non-specific phage of immunity. Passage of immune spleen cells through rabbit-IgG anti-mouse immunoglobulin-coated columns (which yielded a T-cell-enriched, B-cell-depleted population) resulted in abrogration of cytotoxicity whether the cells were obtained during the early or the late phase of resistance. The inability of late-phase spleen cells to kill was explicable in terms of B-cell removal since T-cells and macrophages had been shown to be ineffective at that time. In contrast, the failure of column-treated cells from the early phase to kill was found to be due to removal of adherent cells rather than B-cells since cytotoxicity (1) was abrogated by passage through control columns coated with rabbit-IgG anti-sheep red blood cell antibody which did not retain B-cells and (2) could be restored by addition of immune macrophages (from anti-O serum-treated spleens). Taken together, these results indicate that the cellular basis of immune resistance to methylcholanthrene-induced tumors is heterogeneous. The early specific phase seems to be mediated by an interaction between T-cells and macrophages; the late none-specific phase, although T-cell dependent in its induction, depends on a different effector mechanism, possibly involving a cell or its products of the B lineage.

Animals↗
PubMed1975

Role of a non-committed accessory cell in the in vivo suppression of a syngeneic tumour by immune lymphocytes.

CBA/J mice bearing a methylcholanthrene-induced sarcoma exhibited concomitant immunity to the tumour. The cellular basis for this immunity was investigated by local transfer of mixtures of lymphoid and tumour cells into the footpads of syngeneic mice. Peritoneal exudate cells obtained from tumour-bearing mice 1 day after intraperitoneal injection of saline had a marked tumour-suppressive effect, whereas normally resident peritoneal cells did not. Peritoneal exudate cells from which adherent cells had been removed ('lymphocytes') had a suppressive effect at high or low lymphocyte: tumour cell ratios in normal recipients. In irradiated (450 R) recipients the lymphocytes were suppressive at high ratios only. At low ratios the lymphocytes were suppressive only if the irradiated recipients had been partially shielded or if the lymphocytes were admixed with peritoneal exudate cells from normal mice. It is concluded that an amplifying mechanism, possibly involving macrophages, can operate in tumour cell suppression initiated by immune lymphocytes.

Animals↗
PubMed1975

Detection of membrane-associated antigens on lymphoid cells by antibody coupled to staphylococcal protein A.

A simple technique is described for the detection of membrane-associated antigens on lymphoid cells. It is based on the observation that the protein A component of staphylococci binds to the Fc pieces of IgG molecules. Lymphocytes from various sources (mouse, rat, and human tissues) were incubated with hyperimmune antisera directed against surface determinants. Subsequent treatment with a suspension of staphylococci containing protein A permitted visualization of both the presence and distribution of determinants on the cell membrane. The method had comparable sensitivity to the fluorescent sandwich technique and could be used to detect a variety of membrane antigens on both T cells and B cells.

Animals↗
PubMed1970

The effect of tumour growth on immune competence. A study of DMBA mammary carcinogenesis in the rat.

Circulating antibody response to flagella antigen has been measured in three groups of Sprague-Dawley rats after feeding with 7.12.DMBA in an attempt to differentiate carcinogen and tumour growth as causative agents in the depression of immune response seen in these animals. DMBA fed female rats developing tumours had progressive depression of both primary and secondary response as compared to control animals, and 7S and 19S antibody fractions were equally affected. Removal of tumours did not result in recovery of response. Attempts to prevent tumour development by mammectomy after DMBA feeding were unsuccessful, but the similar number of tumours found in this group was associated with an equal degree of antibody depression to that seen in the first experiment. Male animals fed DMBA did not develop malignant tumours, and showed no depression of immune response. Results suggest that tumour development plays a part in the depression of circulating antibody response seen in these animals, but that it is not directly related to the number of tumours, and is not reversible by tumour excision.

Animals↗