Models for investigation of immune defense mechanism in aquatic animals.
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Biomedical subjects
Publications and source records attributed to R T Smith.
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Actively induced resistance to Eimeria ferrisi was studied clinically and histologically in Mus musculus. Results indicated that a partial resistance to challenge was obtained. Initially infected animals had severe symptoms of coccidiosis but the symptoms diminished as the infections progressed. Previously infected mice had only slight symptoms of infection when challenged. Challenge doses produced severe coccidiosis in the non-immune controls although none died. Six mice died at peak patency during the immunizing inoculations. Histologic examination indicated that parasite numbers were reduced in resistant animals. The reduction appeared greatest during late sexual development. Tissues from resistant animals showed little evidence of damage and appeared to contain an increased amount of lymphoid tissue. Tissues from non-immunized mice killed after challenge were heavily infected and contained extruded blood, mucous, and cellular debris in the gut lumen. Considerable destruction of host epithelial cells occurred. The observations are discussed and compared to other coccidial immunity studies.
This study examines the role of formal and informal intervention systems utilized by the chronically disabled in the process of rehabilitation and recovery. In addition to formal community resources (agents and agencies), the disabled tend to rely on informal social networks (family and peers) as sources of support in the recovery process. The findings presented in this paper focus on the extent to which formal interventions and informal resources are supportive for the disabled and the effect of these support systems on outcome. The analysis is based on empirical data derived from a survey of 950 chronically disabled adults interviewed in a metropolitan community in the U.S.A. Among other findings, the evidence suggests that informal social networks play an important role in the rehabilitation of the disabled. Reliance on informal resources is enhanced in the absence of formal rehabilitation intervention, suggesting alternative modes of social support are actively sought and utilized by the disabled. Furthermore, lay-initiative may constitute another effective resource in the process of recovery. These findings suggest that informal resources are effectively utilized by the disabled, but are not usually identified as part of the formal intervention system in the community.
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Chemically induced tumors of mice exhibit apparently unique antigenicity upon syngeneic transplantation into appropriately immunized hosts. An in vitro counterpart of this pattern in terms of specificity has not been reported. Data are presented that demonstrate that immune peritoneal exudates contain cells cytotoxic for the specific immunogen tumor but with rare exceptions, not toward other syngeneic methylcholanthrene-induced fibrosarcomas. Only tumors highly immunogenic by transplantation criteria induce cytotoxic PEC regularly; nonimmunogenic tumors consistently fail to do so. The effector cell responsible is eliminated by pretreatment with anti-Thy.1 but not anti-Ig plus complement. In concomitant experiments, PEC populations cytotoxic in vitro also conveyed adoptive protection against the specific tumor in syngeneic hosts. This in vitro assay appears to provide a tool for studying T cell-mediated cytotoxicity toward a set of unique surface antigens present on chemically induced tumors.
The studies reported here explore the relationship between tumor-specific transplantation antigens (TSTA) and (1) the expression of serologically defined specificities, and (2) the immunogenicity of H-2K- or H-2D-determined alloantigens on methylcholanthrene (MCA)-induced murine fibrosarcomas. Expression of H-2K and H-2D serologically-detected private specificities on groups of tumors raised in B10.A, B10.BR or B10.D2 strains varied greatly among tumors. No regular reciprocal or direct relationship to tumor TSTA strength was found. Each tumor, however, expressed H-2K or H-2D alloantigens stably as determined by direct cytotoxicity or absorption techniques. Even those tumors expressing little or no detectable alloantigen by serologic analysis were immunogenic in H-2K or H-2D incompatible congeneic hosts. This was assayed in terms of capacity to evoke primary or secondary tumor resistance, and to induce allo-antibody toward private H-2K or H-2D end specificities. An exception was that B10.BR tumors failed to induce anti-H-2Dk antibody despite strong surface alloantigen expression. While TSTA strength did not correlate with serologically detected alloantigen expression, TSTA strength did tend to correlate inversely with capacity to resist primary growth in the H-2K different host, and directly with resistance in the H-2D different host.
Asymmetry in the relationship between the H-2K mutant strain C57Bl/6.CH-2ba (H-2ba) and the wild-type congenic C57Bl/6 has been demonstrated both in MLR and serologically by haemagglutination. MLR between these strains, when B6 was the responder, was as strong as that toward allogeneic stimulator cells: H-2ba was regularly less responsive toward B6. Responses in both directions were increased, in terms of augmented proliferative responses, by prior immunization. In this context the MLR resembles that towards minor H-locus antigens rather than those controlled by the H-2 locus. Immunization of (H-2ba X BALB/c)F1 hybridgs with B6 lymphoid cells induced the production of a haemagglutinating antibody not directed toward any known H-2 specificity. The B6 haemagglutinogen, termed He, was present on B6 lymphoid as well as red blood cells. Segregation studies of F2 and back-cross progeny of (H-2ba X BALB/c)F1 hybrids suggest that the response to He is controlled by two Ir genes, one of which is linked to H-2.
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The effect of serum from mice bearing methylcholanthrene-induced fibrosarcomas on the lympho-proliferative responses of their spleen and lymph-node cells to 3 M KCl-solubilized tumor antigens has been investigated. Low concentrations of serum (less than or equal to 2.5%) collected throughout the course of tumor growth were inhibitory. Normal sera collected from age-matched control mice were often slightly inhibitory, but to a significantly lesser extent at identical serum concentrations. The inhibitory effect of tumor-bearing serum was not limited to homologous tumors, but was also observed when cross-reacting syngeneic tumor antigens or serum from animals bearing other syngeneic tumors were added to the assay mixture. At the low concentrations used, tumor-bearing sera inhibited only tumor-antigen-induced proliferation, and not proliferation induced by T cell mitogens. The inhibitory effects of tumor-bearing sera on lympho-proliferative responses to soluble tumor antigens appear to be similar to the inhibition seen as "serum blocking" in other assays of tumor immunity.
Immunocompetent mouse thymus cell subsets (TH-2) cultured with allogeneic TH-2 cells, required a peripheral lymphoid cell in order to generate specifically cytotoxic T cells (CTL) in vitro. The helper cell is identified as a B cell, and can be supplied either in the mixture of target or responding peripheral cells, or in optimal ratios of 10:1 to 20:1 as nonproliferating cells syngeneic to the responder, when both responder and target are TH-2. Allogeneic helper cells are much less effective. Kinetic studies indicate that helper cell activity involves initial interaction with stimulator cell and is then required throughout the period of generation of cytotoxic lymphocytes. Addition of critical levels of certain IgG preparations, particularly IgG2A appears to support generation of CTL in TH-2/TH-2 cultures but is considerably less effective than intact B cells. Cytotoxicity generated under these conditions has the same genetic requirements for I-region histoincompatibility between stimulator and responder, and for K or D identity of stimulator and target cell, as has been reported for peripheral cell CTL.
When thymus cells which are unresponsive to LPS are combined with numbers of peripheral lymphoid cells giving minimal responses to LPS, synergistic incorporation of [3H]thymidine occurs. Synergy requires that both components proliferate, but most of the augmented response is the result of peripheral cell proliferation. The thymus cell is a T cell of variable density, low in thy-1.2 antigen, not concanavalin A responsive, present in the major thymus subpopulation, and may be from lipopolysaccharide (LPS)-unresponsive strains. The peripheral cell is sensitive to anti-IgG or IgM plus complement (C'), resistant to anti-Thy-1.2 and C', exhibits adherence properties of B lymphocytes, and must be from LPS-responsive strains. Synergistic responses depend on critical thymus/peripheral cell ratios, inhibition occurring at high peripheral cell numbers. The data provide evidence that B-cell proliferative responses to LPS may be regulated by a subclass of thymus T cells.
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A lymphocyte proliferation assay (LPA) for cellular immune responses to osteosarcoma antigens is described and applied to an examination of peripheral blood lymphocytes (PBL) taken from osteosarcoma patients. The antigen preparations were derived from 3 M KC1 solubilized osteosarcoma, taken from a limited number of patients. Lymphocytes from most tumor-bearing patients were stimulated to significant proliferation when cultured in normal human serum. Such stimulation was observed whether or not the lymphoid cells were preincubated 24 hours at 37 degrees C prior to addition of antigen. Patients whose lesion had been resected and who were without evidence of disease for 5-70 months had diminished proliferative responses. Lymphocytes from normal subjects, from patients having other types of sarcoma, and patients having carcinomas rarely responded to the soluble osteosarcoma antigens. When responsive PBL taken from tumor-bearing patients were cultured in autologous serum, the proliferative responses were abrogated or blocked. Serial assays made in the course of bearing this tumor under a variety of therapeutic regimens, including an immunotherapy protocol, suggest that the LPA may be useful in monitoring clinical progress of the disease and possibly in other immunotherapy protocols for osteosarcoma.
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