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D G Colley

Publications and source records attributed to D G Colley.

At least 91 records · Page 5Linked to original sources
PubMed1987

Anti-idiotypic T lymphocyte responsiveness in murine Schistosomiasis mansoni.

Pooled sera from CBA/J mice infected for greater than or equal to 16 weeks with the blood fluke Schistosoma mansoni were immunoaffinity purified using soluble schistosome egg antigens (SEA) coupled to Sepharose 4B. The bound and then eluted fraction was shown to contain only immunoglobulins and to have anti-SEA activity. These anti-SEA antibodies stimulated proliferation of lymph node cells from mice infected with S. mansoni for 8, 12, or greater than or equal to 16 weeks but not from uninfected mice. The cells stimulated by anti-SEA antibodies were nylon wool adherent, Thy-1.2+, L3T4+, Lyt-2-lymphocytes. Immunoglobulins without anti-SEA activity isolated from the sera of syngeneic uninfected mice were not stimulatory for cells from normal or infected animals. Thus the responding T cells appear to be stimulated by the idiotypes expressed on the syngenic anti-SEA antibodies. These data present evidence for anti-idiotypic cellular reactions in murine schistosomiasis that could play important immunoregulatory roles in this disease.

Animals↗
PubMed1987

Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. I. Granuloma formation and modulation around polyacrylamide antigen-conjugated beads.

We have developed an in vitro model of granuloma formation for the purpose of studying the immunological components of delayed type hypersensitivity granuloma formation in patients infected with Schistosoma mansoni. Our data show that 1) granulomatous hypersensitivity can be studied by examining the cellular reactivity manifested as multiple cell layers surrounding the antigen conjugated beads; 2) this reactivity is a CD4 cell dependent, macrophage dependent, B cell independent response and 3) the in vitro granuloma response is antigenically specific for parasite egg antigens. Studies designed to investigate the immune regulation of granulomatous hypersensitivity using purified populations of either CD4 or CD8 T cells have demonstrated the complexity of cellular interactions in the suppression of granulomatous hypersensitivity. The anti-S. mansoni egg immune responses of individual patients with chronic intestinal schistosomiasis can be classified either as soluble egg antigen (SEA) hypersensitive with maximal granulomatous hypersensitivity or SEA suppressive with activation of the T cell suppressor pathway with effective SEA granuloma modulation. Our data suggest that T cell network interactions are active in the generation of effective granuloma modulation in chronic intestinal schistosomiasis patients.

Animals↗
PubMed1987

Immunoregulation in human schistosomiasis by idiotypic interactions and lymphokine-mediated mechanisms.

Anti-idiotypic (anti-Id) T cells from schistosomiasis patients or former patients proliferate upon exposure to polyclonal or monoclonal anti-soluble egg antigen (SEA) antibodies. Chloroquine does not inhibit, the response, which is induced by F(ab')2 (but not soluble Fab) fragments of these antibodies. Purified T cells from former patients require macrophages or exogenous IL-1 to respond to anti-SEA Ids and can respond to matrix-bound Fab fragments in the presence of IL-1. These anti-Id T cells recognize the Ids directly. Chronic schistosomiasis patients immunoregulate the production of a non-IL-2 lymphokine that stimulates IL-2 receptor expression on resting T cells. This regulation is reversed upon chemotherapeutic cure.

Animals↗
PubMed1987

Modulation of Schistosoma japonicum pulmonary egg granulomas with monoclonal antibodies.

We have examined the ability of various Schistosoma japonicum egg antigens to sensitize mice for subsequent secondary pulmonary egg granuloma formation. Further, we produced monoclonal antibodies (Mabs) specific for egg antigens and evaluated their abilities to modulate pulmonary granuloma formation and inhibit soluble egg antigen (SEA)-stimulated lymphocyte blastogenesis. A homogeneous, 140 Kd egg glycoprotein, SJe; 140-GP was nearly as effective as intact eggs in sensitizing for egg-focused pulmonary granuloma formation, while SEA, or the heterogeneous immunoaffinity (IA)-purified C10 antigens were ineffective. The in vivo administration of chronic infection serum (CIS) or Mabs reactive with SJe; 140-GP, to egg-sensitized/egg-challenged mice, modulated pulmonary granuloma formation. Two of these modulatory SJe; 140-GP-specific Mabs (1 A1-1 or 14B3-8), an IgG1, and an IgG3, respectively, did not alter the responses of SEA-stimulated lymph node cells from mice with acute or chronic schistosomiasis japonica. In contrast, another SJe; 140-GP-specific IgG3 Mab (7A6-5), CIS, immunoaffinity purified anti-SEA from CIS, or the non-SEA-binding fraction of CIS, all resulted in dose-related inhibition of SEA-induced proliferation. These data confirm the antibody-driven nature of some immunoregulatory networks in murine schistosomiasis japonica, and extend these observations to include certain Mabs. The immunogenic nature of SJe; 140-GP, and the modulatory and inhibitory activities of Mabs specific for this glycoprotein, indicate it may play a central role in granuloma formation and modulation in this infection.

Animals↗
PubMed1987

Stimulation of peripheral blood mononuclear cells from patients with schistosomiasis mansoni by living and fixed schistosomula, and schistosomular membrane extracts and vesicles.

Several antigenic preparations derived from Schistosoma mansoni schistosomula were compared as immunogens in proliferation assays utilizing peripheral blood mononuclear cells (PBMN) from patients with chronic intestinal schistosomiasis mansoni. Living and fixed schistosomula, either irradiated or nonirradiated, and freshly transformed or 24 hr cultured worms were found to induce very similar proliferative responses of patients' PBMN. Two schistosomulum surface membrane preparations were also compared. Membrane vesicles from schistosomula were found to elicit mean proliferative responses similar to those stimulated by a CaCl2-extracted tegument preparation and to do so at lower total protein concentrations. However, the responses to membrane vesicles were somewhat more variable. When saline extracts from schistosomular bodies submitted to these two treatments were used as stimulants in parallel PBMN cultures it was found that vesiculation more effectively removed antigens involved in the stimulation of PBMN. Broken vesicles were less stimulatory than intact ones. This suggests that the manner in which membrane antigens are presented to antigen processing cells is critical. Incubation of schistosomula at 37 degrees C, but not 4 degrees C in medium containing 10% fetal calf serum from 3 to 48 hr decreased the capacity of the membrane to produce vesicles when treated with high salt solution.

Antigens, Helminth↗
PubMed1987

Prevalence of trachoma in school children and ophthalmological outpatients in rural Egypt.

The prevalence of trachoma in school children and ophthalmological patients in rural villages of the Qalyub Governorate of Egypt was determined by clinical and laboratory diagnostic procedures and reported as mild, moderate, or severe according to the WHO classification scheme. Of 777 primary school students examined in 3 villages, 204 (26%) had clinically active trachoma. The overall prevalence of the disease in this population ranged from 16% to 35%. The prevalence of infection was higher in younger groups and decreased throughout primary school. Of 312 patients with ocular complaints examined at the village outpatient clinics, 100 (32%) had trachoma infections. Monoclonal FA staining showed higher sensitivity in detecting positive cases of trachoma than did Giemsa staining. This study has shown that trachoma is still prevalent in rural Egypt and that the monoclonal FA staining is a relatively sensitive and practical test for the laboratory diagnosis of trachoma in a field study, where reasonable facilities for culture diagnosis are not available.

Adolescent↗
PubMed1986

Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity.

Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy-1+, Lyt1+, Lyt2-, surface Ig- lymphocytes.

Animals↗
PubMed1986

Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. II. Autoimmunoregulation of cell-mediated cutaneous sensitivity and its reversal.

C57BL/6 mice sensitized by abdominal, dermal exposure to irradiated (50 kR) Schistosoma mansoni cercariae develop partial protection against subsequent exposure with unattenuated cercariae and express cell-mediated cutaneous sensitivity upon challenge with irradiated cercariae. Autoimmunoregulation occurs as a part of this sensitization, and can be demonstrated by augmentation of cutaneous sensitivity upon use of appropriate regimens of cyclophosphamide. Mice exposed to irradiated cercariae by either intraperitoneal or ear pinna routes developed a transient hyporesponsiveness to cercarial challenge. This unresponsiveness was also reversed by pretreatment with cyclophosphamide. Timed removal of the site of effective sensitization (abdominal skin) 7 days after exposure consistently led to reduced cutaneous responsiveness. This artificially induced hyporesponsiveness was reversed by either cyclophosphamide treatment or systemic administration of anti-I-Jb, but not anti-I-Jk sera. The data indicate the involvement of cyclophosphamide-sensitive, I-J-bearing T-suppressor cells or factors in the autoimmunoregulation that controls this cutaneous sensitivity. Parallel challenge infection studies in immunized mice treated with cyclophosphamide demonstrated that the resultant augmentation of cutaneous sensitivity did not lead to concomitantly elevated levels of resistance. Furthermore, successful adoptive cell transfer of cutaneous responsiveness also did not ensure protection against cercarial challenge. These observations indicate that dermal cell-mediated anti-cercarial responsiveness is not a sufficient mechanism to explain resistance in mice immunized with irradiated cercariae.

Animals↗
PubMed1986

Studies of tolerance in schistosomiasis.

We have studied the induction of immune tolerance by exogenous exposure to schistosomal egg antigen (SEA). We compared routes of administration, exposure to different forms of SEA (eggs, normal SEA, reultracentrifuged SEA), and treatment schedules. Tolerance was evaluated in comparison to SEA sensitization, after challenge with SEA or eggs. Anti-SEA responses were measured by ELISA assays, and cell-mediated responsiveness by 24-hr skin tests and pulmonary granuloma formation 8 and 16 days after intravenous egg injection. Oral administration of either SEA in PBS or NaHCO3, or eggs in PBS did not induce tolerance or sensitization. Reultracentrifuged SEA was similar to SEA in inducing cell-mediated immune response. Intrathymic exposure to SEA either had no effect or sensitized the animal for subsequent exposure to SEA. Two intraperitoneal injections of 0.5 to 1.0 mg of SEA lead to reduced cell-mediated responses, but resulted in high levels of anti-SEA antibody, suggesting a state of split tolerance or immune deviation. Our studies suggest that with complex, poorly defined antigens such as SEA, many of the classic methods of eliciting tolerance fail. The biologic significance of the form of tolerance inducible by high doses of SEA remains to be defined.

Animals↗
PubMed1986

Immune responses and immunoregulation in relation to human schistosomiasis in Egypt. III. Immunity and longitudinal studies of in vitro responsiveness after treatment.

Immune responsiveness of schistosomiasis patients was assayed longitudinally, before and for two years after chemotherapeutic treatment with praziquantel, by in vitro peripheral blood mononuclear cell (PBMN) proliferation upon exposure to phytohaemagglutinin (PHA), or soluble schistosomal antigenic preparations from eggs (SEA), adult worms (SWAP) or cercariae (CAP). Parallel faecal and urine examinations documented the infection status of the patients during this time. Treatment resulted in substantially increased responsiveness to the schistosome-derived materials but not to PHA or C. albicans extract. The responses to SEA, SWAP, and CAP often remained elevated for one to two years after treatment. However, those patients who became reinfected had significantly lower PBMN responses to SEA or CAP at the time of the last blastogenesis assay before the observation that they were again stool-positive for Schistosoma mansoni eggs. No other demonstrable differences (such as age, sex, household location, pre-treatment intensities of infection or occupation) were observed between those who remained uninfected for at least two years (resistant?) and those who became reinfected during this time (susceptible?).

Adolescent↗
PubMed1986

The molecular biology of schistosomes.

Investigators in various laboratories have been studying the molecular biology of schistosome genetics for several years. A recent meeting at the Marine Biological Laboratory in Woods Hole, Massachusetts, USA, sponsored by the Edna McConnell Clark Foundation, brought together 30 scientists from 16 laboratories to share what they have learned from their studies and debate strategies and techniques.

Journal Article↗
PubMed1986

Inhibition of human peripheral blood mononuclear cell proliferative responses by released materials from Schistosoma mansoni cercariae.

During in vitro transformation of Schistosoma mansoni cercariae into schistosomula, surface and glandular materials are released into the culture medium. Extracts of these materials, termed cercarial released extracts 1 and 2 (CRE-1 and CRE-2), were analysed and found to consist primarily of protein and carbohydrate at ratios of 5:1 (CRE-1) and 7:1 (CRE-2). It was observed that inclusion of either CRE-1 or CRE-2 in cultures of human peripheral blood mononuclear cells (PBMN) led to decreased cell proliferation. This was true whether the cells were resting, control cultures or were stimulated with either phytohaemagglutinin or an antigenic preparation from adult S. mansoni worms. The inhibition was equally effective with PBMN of patients with active schistosomal infection or PBMN from uninfected individuals. Since these materials are released spontaneously during cercarial-to-schistosomular transformation they may have a putative immunosuppressive effect in decreasing antischistosomular activities early after cercarial penetration.

Animals↗
PubMed1986

Immune responses during human schistosomiasis mansoni. XIII. Immunological status of spleen cells from hospital patients with hepatosplenic disease.

Splenocytes from 25 patients with severe hepatosplenic schistosomiasis mansoni were obtained after therapeutic splenectomy. Spleen cells were phenotyped and analysed for responsiveness to mitogens or heterogeneous schistosome-derived antigenic preparations (eggs, SEA; adult worms, SWAP; cercariae, CERC) in blastogenesis assays and lymphokine production systems, and were compared with peripheral blood mononuclear cells (PBMN). Splenic lymphocytes were 55% T lymphocytes (sheep erythrocyte rosette-positive) and 37% surface immunoglobulin-positive B lymphocytes. The mean T4+:T8+ ratio of these splenocytes was 1.0. Phytohaemagglutinin stimulated spleen cell production of the lymphokine mitogenic factor, but exposure to SEA or SWAP did not. Spleen cell and PBMN blastogenic responses to SEA and SWAP were sometimes, but not always in accord. Removal of plastic adherent cells allowed the non-adherent spleen cells of 30-40% of the patients to respond substantially more vigorously to SEA, SWAP and CERC. Spleen cells from a subgroup of 20-30% of the patients failed to respond to the schistosomal antigens regardless of removal of adherent cells. Spleen cell responses to gram-negative lipopolysaccharide peaked on day 5 or 6 of culture, and were augmented by adherent cell removal. Pokeweek mitogen-stimulated responses were optimal on day 5 of culture. Spleen cells from most severe, hepatosplenic schistosomiasis mansoni patients do not respond well to schistosomal antigens or B-cell mitogens. The splenic responses of many of these patients were elevated by the removal of adherent spleen cells.

Adolescent↗
PubMed1986

Ocular sensitization of mice by live (but not irradiated) Chlamydia trachomatis serovar A.

Ocular exposure of mice to live elementary bodies of Chlamydia trachomatis serovar A results in immunological sensitization of the mice. This reactivity is manifested by the development of early (5 h) and delayed-type (24 h) dermal reactivity and serovar-specific antibody formation against either live or irradiated (100 kilorads) elementary bodies. Parallel ocular exposure of mice to irradiated elementary bodies does not result in this sensitization. The early and late dermal immune responses induced by ocular exposure to live organisms can be transferred to unexposed mice by serum and lymphoid cell transfers, respectively. It appears that successful murine ocular sensitization by human C. trachomatis serovar A elementary bodies is an ability manifested by live organisms and not by inactivated but antigenic organisms.

Animals↗
PubMed1986

Immune responses during human Schistosomiasis mansoni. Evidence for antiidiotypic T lymphocyte responsiveness.

We present a method for the examination of antiidiotypic cell-mediated reactivity during chronic human infections. Pooled and individual sera from patients with schistosomiasis mansoni were purified on immunoaffinity columns of schistosomal egg antigens (SEA). The eluates contained anti-SEA antibodies, but not SEA. These antibody preparations, and their F(ab)2 fragments, stimulated dose-dependent proliferation of peripheral blood mononuclear cells (PBMN) and T lymphocytes from some, but not all active or former schistosomiasis mansoni patients, and could do so autologously. Stimulation required presentation by plastic-adherent cells. The eluates did not stimulate PBMN from persons who had never had schistosomiasis. Affinity-purified anti-SEA antibodies from former patients (cured for greater than 10 yr) did not stimulate PBMN from patients with active infections. Reabsorption on SEA columns removed stimulatory activity from the eluates. We propose that multiclonal, SEA-related idiotypes expressed by some anti-SEA antibodies stimulate proliferation of T lymphocytes that express antiidiotypic specificities.

Antibody Formation↗
PubMed1986

Effects of anti-schistosomal chemotherapy on immune responses, protection and immunity. I. Changes in cellular and humoral responses.

The cellular and humoral immune responses of CF1 and C57BL/6 mice with schistosomiasis mansoni were evaluated before and after chemotherapeutic cure of their infections by praziquantel. Mice were infected for either 10 or 20 weeks prior to treatment and followed until 10 weeks after treatment. Peripheral blood eosinophilia, without concomitant general leukocytosis, was observed within 3 days of treatment and persisted for up to 4 weeks. By 6 and 10 weeks after treatment schistosomal-associated hepatosplenomegaly had greatly decreased. Delayed-type hypersensitivity to a soluble adult worm extract (SWAP) was modulated over 20 weeks of infection, and in C57BL/6 mice this modulation was alleviated by cure. In parallel studies of pulmonary egg granuloma formation, granuloma modulation was not effectively reversed. Antibodies against egg (SEA), cercarial (CAP) and adult worm (SWAP) extracts generally decreased by 10 weeks after chemotherapy of mice that were previously infected for 10 weeks. Mice infected for 20 weeks and then treated, generated increased levels of antibodies to SWAP and CAP by 10 weeks after treatment. Immunoglobulin isotypic analyses largely reflected the results of total antibody studies. These data demonstrate that the duration of infection prior to treatment is a determining factor in subsequent expression of immune reactivity, and provide the immunological background for experiments on resistance following chemotherapy of experimental murine schistosomiasis mansoni.

Animals↗