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Biomedical subjects

R J Scheper

Publications and source records attributed to R J Scheper.

At least 289 records · Page 16Linked to original sources
PubMed1981

Lymphokine-mediated stimulation of eosinophil migration in the guinea-pig.

Guinea-pig lymphokines were shown to stimulate the migration of eosinophils from capillary tubes. Eosinophil migration stimulatory activity was produced by Freund's complete adjuvant (FCA)-sensitized lymph node or peritoneal exudate lymphocytes in the presence of purified protein derivative (PPD), as well as by Con A-stimulated lymph node lymphocytes. Like murine and human eosinophil-stimulation promoter lymphokine (ESP), the guinea-pig lymphokine activity is T cell-derived, non-dialysable and resistant to heating at 56 degrees. In contrast to the migration inhibition factor (MIF) which could be adsorbed by macrophages, eosinophil migration stimulatory activity could not be removed by pre-adsorption to macrophages or eosinophils.

Adsorption↗
PubMed1980

Accumulation of T cells and local anti-PPD antibody production in lymphokine-mediated chronic peritoneal inflammation in the guinea pig.

The role of lymphokines in chornic peritoneal inflammation in the guinea pig has been investigated. A model of chronic inflammation was used in which a large intraperitoneal accumulation of macrophages and lymphocytes occurred, following repeated local injection of PPD into FCA-immunised animals. Activity attributable to the lymphokine, MIF could be demonstrated in chronic peritoneal exudate fractions even after several weeks of continuous stimulation. Characterisation of the lymphoid infiltrates revealed a large predominance of T cells. Very high percentages but low absolute numbers of T lymphocytes were also found in chronic peritoneal exudates of non-preimmunised, continuously stimulated guinea pigs. Ectopic lymphoid foci were found only in the peritoneal lining tissue of the preimmunised animals and were shown to contain many anti-PPD antibody producing cells. These lymphoid foci may have been induced by the continuous local generation of lymphokines. Their presence suggests that significant local, specific antibody production is particularly likely to occur in chornic inflammation with a delayed hypersensitivity component.

Animals↗
PubMed1980

Chronic inflammatory reactions in the guinea-pig peritoneal cavity induced by continuous local PPD stimulation. Immune status dependency of the accumulation of lymphocytes and eosinophils.

A chronic inflammation model is described which allows the study of the relationship between the level of specific cell-mediated and humoral immunity to the triggering antigen, and the presence of cells or mediators in the inflammatory exudate. In the present study special attention is paid to the participation of lymphocytes and eosinophils. Normal or FCA-pre-immunized guinea-pigs received repeated intraperitoneal injections with PPD for periods up to 21 weeks. In non-pre-immunized animals the inflammation was characterized by a strong accumulation of eosinophils, whereas only a few lymphocytes were present. In contrast, the FCA-pre-immunized guinea-pigs showed a strong lymphocytic accumulation in the absence of eosinophils. Both peritoneal inflammations were shown to remain dependent on the continuous PPD administration. Therefore, the participation of either lymphocytes or eosinophils could be directly correlated to differences in the specific immune status. Both experimental groups developed similar strong anti-PPD antibody responses as assessed by haemagglutination and passive cutaneous anaphylaxis. Only the FCA-pre-immunized guinea-pigs, however, showed strong cell-mediated immunity. The development of CMI to the continuously administered antigen appears to be a prerequisite for the accumulation of lymphocytes, while it seems to prevent antibody-mediated eosinophil accumulation.

Animals↗
PubMed1980

Hapten-cell conjugates in DNCB contact sensitivity. In vitro stimulation with DNP-conjugates optimally inducing contact sensitivity in vivo.

Until now in vitro stimulation tests have failed to detect DNCB contact sensitivity in guinea-pigs sensitized epicutaneously without the use of adjuvants. In this study DNP-conjugates optimally inducing contact sensitivity in vivo were tested for their capacity to detect DNCB contact sensitivity in vitro in a lymphocyte transformation assay. In vivo contact sensitivity measurements in guinea-pigs which had been immunized with different hapten-cell conjugates, showed that (1) living cells should be used for conjugation with the allergen, (2) macrophages are optimal carriers and (3) syngeneity is not required. Therefore, DNFB-coated peritoneal macrophages (viable when conjugated) were used as an antigen for in vitro stimulation. Using this conjugate, a highly reproducible antigen-specific increase in DNA synthesis could be obtained in lymph node lymphocytes from guinea-pigs that had been sensitized to DNCB by epicutaneous application of the allergen without the use of adjuvants.

Animals↗
PubMed1980

Suppression of antibody-mediated accumulation of eosinophils in chronic inflammatory lesions by concomitant delayed hypersensitivity reactions.

Studies were carried out in order to explain the often small contribution of eosinophils to immunologically mediated chronic inflammatory reactions. A chronic inflammation model was used in which large numbers of eosinophils accumulated in the peritoneal injections with PPD or ovalbumin (OA). Eosinophil accumulation could be strongly suppressed by pre-immunization with a mycobacteria-containing adjuvant, which induces delayed hypersensitivity to the stimulating antigen. Suppression of OA-induced eosinophil accumulation could be obtained in a non-specific way by concomitant delayed hypersensitivity reactions to PPD. The absence o eosinophil accumulation was not related to a lack of relevant antibodies. Histological studies suggested that similar numbers of basophils were locally available in both non-pre-immunized and pre-immunized groups to allow for the attraction of eosinophils by the expression of basophil anaphylactic reactivity. Skin tests and macrophage migration inhibition measurements provided further support for the hypothesis that local lymphokine release may suppress the accumulation of eosinophils in chronic inflammatory lesions.

Animals↗
PubMed1978

Production and traffic of B lymphocytes in the extracortical central area of the guinea pig thymus.

Lymphocytes in the stroma and lymphatics of the extra-cortical central area (ECCA) of the guinea pig thymus have been studied with light microscopy, quantitative microscopy, colchicin-induced mitotic arrest, EA (IgG) and EA (IgM) C adherence, surface immunoglobulins (Ig total, IgM, IgG), alkaline phosphatase activity and the effect of cyclophosphamide administration. The results suggest, that AP-positive, SIg-positive EAC-negative lymphocytes in the ECCA proliferate and maturate into AP-negative, SIg-positive, EAC-positive lymphocytes. The latter leave the thymus through the lymphatics. Calculations show that daily 8-9 X 10(6) B lymphocytes are produced in the ECCA and leave this area through the lymphatics. As this number is more than 10% of the number of T cells which daily leave the thymus, we conclude that in the ECCA a considerable number of B lymphocytes is produced.

Alkaline Phosphatase↗
PubMed1978

Interference of simultaneous skin tests in delayed hypersensitivity.

The interference of two simultaneous skin test reactions of intermediate strength has been studied in the guinea-pig, using four different antigens, i.e. ovalbumin, horse cytochrome c, PPD and oxazolone. Skin test reactions were evaluated at 4, 24 and 48 h by measuring three parameters: increase in skin thickness, diameter of erythema and intensity of erythema. When an Arthus reaction was elicited simultaneously with a delayed hypersensitivity (DH) reaction, no effect on the DH reaction was observed. When two simultaneous DH reactions were elicited with different antigens, the risk of interference appeared to be rather small. When, however, the same antigen was used for both skin tests, suppression of at least one parameter of a DH-reaction was found in almost all experiments. Suppression of one skin test by another one could not be reduced by introducing a large distance between the two skin tests. As complete inhibition of either of the parameters never occurred, multiple skin testing may allow one to obtain a qualitative impression of the state of delayed hypersensitivity; when, however, reliable quantitative data are needed, the performance of more than one skin test at a time should be avoided.

Animals↗
PubMed1977

Histopathology of acute and chronic inflammation.

Inflammation, defined as local reaction to injury, is basically a homeostatic process-loop system with morphological and biochemical components. If this homeostatic loop is uncomplicated a normal situation is reached soon after injury. Morphologically different patterns of inflammation can appear, depending on the character and intensity of the injury. Furthermore, the contributions made by hyperaemia, exudation of fluid, infiltrates carrying inflammatory cells, and cell proliferation not only vary with the type of injury but also depend on the time after injury. Some of the histopathological changes can be seen as essential for the restoration of the normal situation, whereas others damage the tissue more than seems desirable. The morphological aspects of different types of inflammation are discussed in relation to the homeostatic nature of the inflammatory process.

Acute Disease↗
PubMed1977

The value of an assessment of erythema and increase in thickness of the skin reaction for a full appreciation of the nature of delayed hypersensitivity in the guinea pig.

Delayed type skin reactions in guinea pigs have been assessed by measuring three parameters: increase in skin thickness, diameter of erythema and intensity of erythema. Some groups of animals were immunized with different protein antigens in Freund's complete adjuvant with or without cyclophosphamide (CY) pretreatment; others received a single high dose of antigen intravenously at the time of immunization. The results emphasize the importance of measuring all three parameters for several days after skin testing. The intensity or erythema was found to be an especially useful parameter for assessing CY-induced modification of delayed hypersensitivity (DH) reactions. The increase in skin thickness, which can be measured objectively, was also valuable as both immediate and DH reactions are characterized by induration. The diameter of erythema could only be measured accurately for a short time after skin testing. Furthermore, the effects of intravenous antigen and CY pretreatment were not reflected by that parameter.

Animals↗
PubMed1977

The relation between B-cell stimulation and delayed hypersensitivity. The effect of cyclophosphamide pretreatment on antibody production.

Cyclophosphamide (CY), which can enhance some forms of delayed-type hypersensitivity if given 3 days before immunization, is also a potent suppressor of most antibody mediated 4-h skin reactions to protein antigens. However many haemagglutinating antibodies, which are present in serum at the time of skin testing, are not similarly suppressed. Antibody titres in some sera recovered from CY-pretreated guinea-pigs differ little from titres in control sera. This resistance to CY suggests that long-lived precursors characterize the B-cell lines that produce many haemagglutinating antibodies, whereas the CY-sensitive precursors of skin reactive antibodies, which mediate Arthus-type reactions, are probably rapidly dividing, short-lived cells. Furthermore, the novel appearance of BGG antibodies in sera from CY-pretreated animals immunized with DNP50-BGG indicates that haemagglutinating antibody responses to some antigens are regulated by CY-sensitive mechanisms.

Animals↗
PubMed1977

The relation of immune depression and B-cell stimulation during the development of delayed hypersensitivity to soluble antigens.

A comparison has been made of the effects of cyclophosphamide (CY) pretreatment and i.v. injection of a high dose of antigen on delayed hypersensitivity induced by proteins in Freund's incomplete and complete adjuvants. Five antigens have been studied: obalbumin (OA), bovine serum albumin (BSA) bovine gammaglobulin (BGG), DNP 5-BGG and DNP 50-BGG. A spectrum of reactivity has been detected depending upon the ability of the antigen to stimulate B-cell as well as T-cell activity. Bovine serum albumin and BGG behave as relatively weak antigens in which the T-cell response, measured by delayed hypersensityity, is easily suppressed by i.v. antigen and the B-cell modulating system, revealed by CY sensitivity, is poorly stimulated. These proteins, injected i.v., are weak stimulators of antibody-dependent Arthus reactions. On the other hand, OA, DNP 5-BGG and DNP 50-BGG behave as strong antigens, resisting suppression of the T-cell response by soluble antigen and exhibiting (in Freund's incomplete adjuvant) a strongly developed CY sensitive, B-cell modulating system. Strong Arthus reactivity is readily demonstrated following i.v. administration of these antigens. A dissociation has been demonstrated between B-cell modulation of T-cell function and unresponsiveness induced by i.v. antigen. The failure to reverse the latter type of unresponsiveness by cyclophosphamide pretreatment suggests that separate mechanisms are involved in these systems.

Animals↗
PubMed1976

Effects of contact sensitization and delayed hypersensitivity reactions on immune responses to non-related antigens. Modulation of Immune responses.

Guinea pigs were immunized intracutaneously into the ears with sheep red blood cells (SRBC). Application of a sensitizing dose of the contact allergen dinitrochlorobenzene (DNCB) onto the same ears was shown to suppress or enhance the humoral response to SRBC depending on the time of application. When guinea pigs were sensitized to a contact allergen, application of a sensitizing dose of a non-related allergen on the same ears either had no effect or caused a clear enhancement of the development of delayed type hypersensitivity (DTH). Strongest enhancement was found when both sensitizations were performed on the same day. Further experiments on the effects of a concomitant DTH reaction elicited at the site of application of a contact allergen showed a strong potentiation of DTH when B-cell suppression was minimized by pretreatment with cyclophosphamide (CY). It was considered that CY-DTH-immunopotentiation might be a useful tool for achieving a higher level of sensitivity after epicutaneous sensitization.

Allergens↗
PubMed1976

Direct macrophage migration inhibition test in DNCB contact sensitized guinea pigs.

Using dinitrochlorbenzene contact-sensitized guinea pigs, several DNP conjugates have been assayed in the direct macrophage migration inhibition test (MMIT). Although no significant differences could be observed between the carriers used, conjugates prepared from serum proteins and epidermal extracts tended to give the strongest inhibition of macrophage migration. Conjugates prepared from cells cultured in vitro in the presence of hapten did not cause more inhibition than control conjugates prepared in the absence of cell metabolism. The direct MMIT showed statistical differences between sensitized and nonsensitized groups of guinea pigs. However, none of the conjugates permitted conclusions to be drawn with regard to individual animals.

Animals↗
PubMed1976

E and EAC rosette-forming cells in healthy donors and cancer patients.

The influence of age and sex on the lymphocyte count and numbers of E and EAC rosette-forming cells (RFC) was investigated using peripheral blood of healthy donors. In the female donors we found a lower total lymphocyte count and percentage of EAC RFC than in male donors. The percentage and total number of E RFC appeared to be low in younger donors. Total lymphocyte count and numbers of E and EAC RFC were investigated in untreated and treated patients with advanced solid tumors and in patients with untreated malignant lymphomas. The lymphocyte count in all these groups was decreased, but the E/EAC RFC ratio was normal, except in the group with untreated solid tumors, where we found an increased percentage of E RFC. It is suggested that in these patients a nonspecific impairment of bone marrow function might be expressed in numbers of peripheral T and B cells.

Adolescent↗
PubMed1976

Central and peripheral action of suppressor cells in contact sensitivity in the guinea-pig.

Suppressor cells were demonstrated in the spleen of guinea-pigs made specifically unresponsive to dinitrofluorobenzene (DNFB) with dinitrobenzene sulphonic acid (DNBSO3). Transfusion of these cells at the same time as sensitization with DNFB, produced a significant reduction in the immunoblasts proliferating in the draining lymph node 4 days later. Transfusion on the day of skin testing produced no greater suppression of skin reactivity than cells taken from animals made hypo-reactive to DNFB by contact with dinitrothiocyanate benzene (DNTB). It is concluded that there are at least two sites that suppressor cells can act. In the case of total unresponsiveness induced by DNBSO3, action is both central and in the periphery. In the case of hyporeactivity induced by DNTB, in which there is no defect in proliferation of T cells in response to antigen, the action of these cells is confined to the periphery. results of spleen weight studies suggest that suppressor cells homing in the spleen respond by proliferation to epicutaneously applied DNFB.

Animals↗
PubMed1975

RRBC and EAC rosette formation after DNCB contact sensitization and cyclophosphamide treatment of guinea-pigs.

Rabbit erythrocyte (RRBC) and EAC rosette formation, for detection of T and B lymphocytes respectively, was studied in thymus, lymph nodes and peripheral blood of guinea-pigs. Using two different methods for preparation of RRBC rosette-forming cells (RFC) it was found that, without an incubation period at 37 degrees, a smaller part of the pool of T cells is detected which is particularly sensitive to cyclophosphamide (cy). RRBC rosette formation was studied for 2 weeks after treatment with one high dose of cy and appeared to be minimal in the thymus after 1 week and maximal in the lymph nodes at about day 3. EAC rosette formation was completely blocked by cy treatment. Four days after contact sensitization with 2,4-dinitrochlorobenzene (DNCB) no percentual increase was found in RRBC-RFC, suggesting a parallel increase of B and T cells in stimulated lymph nodes. Cytological screening of the rosettes at day 4 after DNCB showed that of the RRBC-RFC approximately 17 per cent were blast cells, while no difference was detected in the number of blast cells participating in EAC rosette formation as compared to the unstimulated lymph nodes. In contrast to RRBC-RFC the percentage of EAC-RFC in draining lymph nodes is increased after contact sensitization. The mechanism of this increase is discussed.

Animals↗