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J L Turk

Publications and source records attributed to J L Turk.

At least 163 records · Page 9Linked to original sources
PubMed1982

In vivo macrophage suppression of delayed hypersensitivity in the guinea-pig.

The nature of the suppressive activity in the peritoneal exudate cells (PEC) of guinea-pigs immunized with dinitrophenyl bovine gamma globulin (DNP50-BGG) was investigated. A method was developed to isolate from the peritoneal exudate large numbers of macrophages. Using density gradient centrifugation on Percoll it was possible to obtain a population of cells which contained over 90% macrophages. This macrophage preparation was found to respond to lymphokine but to be incapable of passively transferring delayed hypersensitivity reactions. When these immune macrophages were transferred into antigen immunized animals, which had been pretreated with cyclophosphamide (CY), the skin reactions were suppressed to the same extent as when the total PEC was transferred. PEC from guinea-pigs immunized with ovalbumin in Freund's incomplete adjuvant did not suppress the skin reactions in CY-pretreated DNP50BGG immunized animals. However, in contrast, macrophages from these animals did suppress the skin reactions in the recipient guinea-pigs indicating that the macrophage suppression was not antigen specific.

Animals↗
PubMed1981

Experimental mycobacterial granulomas in guinea pig lymph nodes: ultrastructural observations.

A systematic ultrastructural study has been performed of the mononuclear phagocytes in granulomas induced by different types of mycobacteria, e.g. live BCG (Pasteur), irradiated M. leprae and irradiated BCG (Pasteur) in guinea pig lymph nodes. Live BCG (Pasteur) induces a granuloma which peaks at 2-3 weeks and by light microscopy, a large number of the infiltrating cells have the appearance of epithelioid cells. Ultrastructurally a large proportion of these cells have a distinct appearance. They are characterised by the presence of very large nuclei, and prominent nucleoli, paucity of cytoplasmic organelles and swollen rough endoplasmic reticulum. Cells from 2 week granulomas induced by live M. kansasii and BCG (Glaxo), has a similar ultrastructural appearance. BCG (Pasteur) granulomas slowly resolved and by light and electron microscopy fibrosis and collagen deposition was seen by 7 weeks and was very extensive in some nodes at 10 weeks. The nodes from M leprae injected animals showed peak infiltration at 5 weeks and by light microscopy the infiltrating cell population was more mixed, with most of the cells having a macrophage appearance. Electron-microscopy showed these infiltrating cells to be mainly activated macrophages, containing phagocytosed organisms. Nodes from irradiated BCG (Pasteur) injected animals had peak infiltration at 1 week. The light and electron microscopic appearance showed areas consisting mainly of fibroblasts and mononuclear phagocytes. Thus, the granulomas induced by M. leprae are very different from those induced by BCG in the guinea pig. It is suggested that lymph nodes draining areas of local injection of BCG and irradiated M. leprae could respectively form a good model in the guinea pig for cellular and biochemical studies of the granulomas of tuberculoid and lepromatous leprosy.

Animals↗
PubMed1981

The monocyte-macrophage system in granulomatous inflammation.

Granulomas may be immunologically induced or non-immunologically induced. In immunologically induced granulomas cells of the monocyte-macrophage series take on the appearance of epitheloid cells. Ultrastructurally epithelioid cells may have a secretory appearance with much rough endoplasmic reticulum or take on highly degenerate vesicular appearance. Other epithelioid cells look like activated macrophages. Secretory epithelioid cells may be found associated with acute local inflammation as in borderline tuberculoid leprosy in reaction, the lepromin reaction, following injection of BCG vaccine and in experimental zirconium granulomas. In these situations there may also be strong histological and biochemical evidence of increased fibroblast activity and collagen synthesis. It is suggested that these cells are actively secreting a fibroblast-activating factor. Epithelioid cells may lose their Fc receptors, undifferentiated macrophages in lepromatous leprosy can lose their C3 receptors. It is suggested that in a number of situations granuloma formation may be associated with complement activation through the alternative pathway as in the case of mycobacterial granulomas. Toxic granulomas produced by metals may be caused by C3 being split by plasmin after conversion from plasminogen by activation of the Hageman factor.

Animals↗
PubMed1981

The effect of photochemotherapy (PUVA) on cell mediated immunity in the guinea pig.

Guinea pigs were injected intraperitoneally with 8-methoxypsoralen (8-MOP) and afterwards the shaved right flank was irradiated with UV-A. This treatment was performed daily for 14 days. Seven days after treatment started they were immunized with ovalbumin in Freund's complete adjuvant and 7 days later skin tested with ovalbumin on the unirradiated left flank. Photochemotherapy (8-MOP plus UV-A) did not alter the total white blood cells or the proportion of lymphocytes or granulocytes. However, this treatment significantly depressed the delayed hypersensitivity reaction to ovalbumin; nonspecific inflammation, induced by intradermal turpentine, was not altered. In addition, treatment with 8-MOP alone suppressed the skin reaction to ovalbumin, but not to the same extent as treatment with 8-MOP and UV-A. 8-MOP plus UV-A had no effect on macrophage migration inhibition factor but it did significantly depress mitogen and antigen specific lymphocyte transformation.

Animals↗
PubMed1981

Immediate hypersensitivity in the guinea pig conjunctiva. III. long-term persistence of the hypersensitive state and characterization of antibodies.

The ocular immediate hypersensitivity reaction in guinea pigs to topically applied normal rabbit serum can be evoked as long as 4 years after sensitization. The reaction was as severe and tended to persist for longer than that evoked 6 months after sensitization. Passive cutaneous anaphylaxis tests showed that very high titres of homocytotropic antibodies were present and that both IgE- and IgG1-like antibodies were involved. Sensitization with one set of injections instead of two was not consistently successful and the response on challenge was mild to moderate. Pretreatment of eyes with Isoptocarpine before antigenic challenge had no effect on the response. The addition of bacterial lipopolysaccharide to the first set of sensitizing injections produced hypersensitivity in animals which were otherwise refractory to sensitization.

Animals↗
PubMed1981

The effect of cyclophosphamide and role suppressor cells in the desensitization of delayed hypersensitivity.

Desensitization of guinea-pigs with ovalbumin (OA) or bovine gamma globulin (BGG) induces strong specific desensitization and is associated with a non-specific energy to tuberculin--PPD. Similarly, it was found that animals receiving desensitizing injections of PPD have suppressed delayed hypersensitivity reactions to OA or BGG. PPD also induced strong specific desensitization. Cyclophosphamide (CY) given in one large dose (300 mg/kg) 3 days before immunization failed to affect the specific desensitization induced by all three antigens. However, if CY was given 1 day after immunization, it was not possible to induce specific desensitization. The induction of non-specific desensitization was prevented in all three antigen systems if CY was given either 3 days before or 1 day after immunization. Desensitization with either OA or BGG markedly suppressed the specific 4 hr Arthus reactions.

Animals↗
PubMed1981

Suppression of delayed hypersensitivity to tuberculin by antigenic competition. A positive immunoregulatory mechanism sensitive to cyclophosphamide.

Effector mechanisms that produce delayed hypersensitivity reactions to tuberculin are subject to positive immunoregulation. Two different immunoregulatory mechanisms can be demonstrated. One is specific and the other, antigenic competition, is non-specific; both are sensitive to cyclophosphamide (CY). Delayed hypersensitivity to purified protein derivative PPD in guinea-pigs can be enhanced by the administration of cyclophosphamide 3 days before but not after immunization. The enhanced response seems to result from the reduced influence on effector cells of CY-sensitive suppressor cells. Passive transfer of delayed hypersensitivity to PPD is facilitated by the use of cells from CY treated animals. The response to both immunization and skin testing with ovalbumin in animals immunized with this antigen in Freud's complete adjuvant (FCA) produces a marked, non-specific reduction in the delayed hypersensitivity response to PPD. CY given 3 days before or 1 day after immunization prevents this suppression of the PPD response by antigenic competition. The data suggests that in the generation of both the specific suppressor cells for tuberculin and the non-specific suppressor cells of antigenic competition, that can influence effector cells for tuberculin, a period of rapid cell proliferation occurs that renders both mechanisms sensitive to cyclophosphamide.

Animals↗
PubMed1981

A lack of correlation between antigen-specific cellular reactions and resistance to Mycobacterium lepraemurium infection in mice.

Following infection subcutaneously in the footpad with 10(7) Mycobacterium lepraemurium organisms C57BL mice were able to limit multiplication of organisms at the infection site for the 6 months studied and to limit organism spread to the draining lymph node. Large numbers of organisms were present in the footpad and draining lymph node of BALB/c mice at 6 months. In spite of this difference in local immunity the changes in cellular reactivity to specific antigen as assessed by the delayed footpad response and the in vitro proliferative response of draining lymph node cells were similar in the two strains over the time studied.

Animals↗
PubMed1981

Differences in cell-mediated immune responses of 'high-resistance' and 'low-resistance' mice to a nonpathogenic mycobacterium.

The kinetics of the footpad response of bacillus Calmette-Guérin (BCG)-infected mice to soluble BCG antigens were compared in two strains of mice with different degrees of susceptibility to Mycobacterium lepraemurium. For the first 21 days the responses of the 'high-resistance' C57BL and the 'low-resistance' BALB/c to the nonpathogenic BCG were similar to that produced when the pathogenic mycobacterium was used. After 4 weeks the kinetics of the BALB/c mice changed and resembled that of the C57BL mice. The change in kinetics was compared with circulating antimycobacterial antibody levels and the response of draining lymph node cells in the antigen-specific lymphocyte transformation test. A dissociation was found between the kinetics of the delayed footpad response and the lymphocyte transformation response. Since both strains of mice are equally resistant to BCG, it appears that the delayed footpad response cannot be used as an indicator of host resistance in all mycobacterial infections.

Animals↗
PubMed1981

Absorption of macrophage aggregating factor by guinea-pig peritoneal exudate cells.

Lymphokine (LK)-induced aggregation of peritoneal exudate cells (PEC) has been measured using a quantitative technique. Aggregating activity could be removed from LK preparations by absorption of these with PEC and, in addition, the absorbing PEC, on further incubation themselves aggregated. Absorption of aggregating activity to PEC was rapid, being easily measurable at between 2-5 and 10 min although it was difficult to demonstrate at 30 min. Trypsinized PEC were as effective as normal PEC in absorbing aggregating activity. alpha-L-fucose inhibited LK-induced PEC aggregation and this inhibition showed some specificity in being significantly greater than that obtained with D(+)galactose. However, measurement of the subsequent aggregation of PEC which had been pulse exposed to LK, in the presence of alpha-L-fucose, showed that alpha-L-fucose had no effect on this aggregation. It is concluded that the measurement of aggregating activity can be used to study LK binding to PEC, although the relationship of this binding to the inhibition of aggregation obtained with alpha-L-fucose is not clear.

Animals↗
PubMed1980

Ultrastructure of cells of the mononuclear-phagocyte series (MPS) across the leprosy spectrum.

A systematic ultrastructural study of cells of the MPS across the spectrum of leprosy has been carried out. Graded changes in macrophage ultrastructure from the lepromatous to the tuberculoid poles have been shown. Mycobacteria-filled macrophages in lepromatous leprosy are characterised by long cell processes, whereas in borderline tuberculoid leprosy these cells have a rounded appearance and are mainly characterised by numerous intracellular vacuoles. In borderline leprosy, macrophages have an intermediate appearance. Cells of the MPS containing abundant endoplasmic reticulum were only seen in typical "epithelioid cell" tuberculoid granulomas in "BT in reaction" and in the Mitsuda reaction. Epithelioid cell granulomas in other forms of BT leprosy contained activated macrophages.

Cell Nucleus↗
PubMed1980

Lymphokine-induced Macrophage aggregation: the possible role of cyclic nucleotides.

The possible role of cyclic nucleotides in guinea pig macrophage aggregation, induced by human lymphokine (LK) has been investigated. Small increases were found in guanosine 3'5'-cyclic monophosphate (cGMP), but not adenosine 3'5'-cyclic monophosphate (cAMP), levels of lymphokine aggregated macrophages. Addition of exogenous dibutyryl (DB) cAMP, L-isoproterenol, or theophylline did not induce macrophage aggregation. By contrast, both exogenous DBcGMP and carbamyl-choline induced a macrophage aggregation; although DBcGMP was more effective. In addition, both L-isoproterenol and DBcAMP in the presence of theophylline decreased LK-induced macrophage aggregation, whereas D-isoproterenol and DBcGMP had no effect. The results obtained here are discussed in the context of the previously reported effects of cyclic nucleotides on migration inhibitory factor (MIF) activity and the possible role of these agents in the mechanism of action of MIF.

Bucladesine↗
PubMed1980

Immunologic and nonimmunologic activation of macrophages.

Cells of the mononuclear phagocyte system take on different morphological features and appear to have different functions in immunological and nonimmunological granulomas. In immunological granulomas the appearance is of epitheliod cells. Epitheliod cells are of 2 types. In borderline tuberculoid leprosy granulomas, the appearance is of activated macrophages. Similar activation can be induced by lymphokine which increases respiratory enzyme activity. Other types of epithelioid cell are found in experimental zirconium granulomas. These cells contained rough endoplasmic reticulum, indicating that they may play a secretory role. It is suggested that these cells could play a part in stimulating fibrosis. Other substances that produce nonimmunological granulomas, such as aluminum containing compounds, are directly toxic to macrophages in vitro resulting in the rapid release of cytoplasmic enzymes. These compounds also activate complement, causing C3 conversion and anaphylatoxin production. C3 conversion may be through pathways other than the classical and alternative pathways and does not occur in the absence of plasminogen. Mycobacteria can activate complement through the alternative pathway, suggesting a mechanism for granuloma formation in lepromatous leprosy. Loss of C3 membrane receptors from macrophages in lepromatous leprosy could be produced by feeding peritoneal exudate macrophages with mycobacteria in vitro. This was not just due to phagocytosis, as a similar receptor loss was not obtained when the cells were fed latex particles or zymosan. Epithelioid cells in tuberculoid leprosy and sarcoidosis lose Fc membrane receptors but retain C3 receptors. Thus epithelioid cells can be readily distinguished from other cells of the mononuclear phagocyte series.

Animals↗
PubMed1980

Activation of the alternative pathway of complement by mycobacteria and cord factor.

The ability of a number of mycobacteria and some of their components to activate complement was examined. Mycobacterium bovis BCG (Glaxo strain), Mycobacterium leprae, Mycobacterium lepraemurium, and cord factor activated the alternative pathway of complement in normal human serum and normal and C4-deficient guinea pig sera and generated biologically active products. BCG (Pasteur strain) and muramyl dipeptide did not activate complement. The relevance of activation of complement by mycobacteria to their induction of granulomas is discussed.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Preparation of antisera specific for guinea pig B cells.

Heterologous antisera against guinea pig B lymphocytes have been prepared in rabbits. Sera, obtained 1 week after a third injection of cells from a guinea pig leukemic B cell line (L2C), were absorbed with guinea pig and sheep erythrocytes and guinea pig thymocytes. In the presence of complement, selected antisera killed both L2C cells (85%) and B cells from Hartley outbred guinea pigs (85%). Normal rabbit serum kills guinea pig thymocytes and this ability was enhanced in the sera obtained from rabbits immunized with L2C cells. After three absorptions with thymocytes the antisera retained their cytotoxicity for B cells but did not kill guinea pig thymocytes or peripheral T lymphocytes. The antigenic determinants on the L2C cells that simulate anti-B cell activity are unknown but surface membrane immunoglobulins were excluded. The development of methodology for obtaining a potent and specific anti-guinea pig B cell serum should significantly improve the usefulness of guinea pigs as animals for in vitro studies.

Animals↗