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Biomedical subjects

T Hraba

Publications and source records attributed to T Hraba.

At least 55 records · Page 3Linked to original sources

The use of immunological tolerance to investigate B lymphocyte replacement kinetics in chickens.

A simple mathematical model has been derived, describing the irreversible inactivation of immature B cells by high doses of antigen during induction of tolerance, and the antigen-independent replacement of B cells by differentiation of their precursors. The latter leads to recovery from tolerance, the rate of which can be used to assess the rate of B cell replacement in experiments. The model has been compared with experimental tolerance to human albumin in newly hatched chickens. (1) It has been shown that this tolerance cannot be explained only by elimination of B cells but (2) the computed rate of B cell replacement agreed with the experimental rate assessed by immunization of tolerant chickens with a cross-reacting antigen. (3) In order to further verify the model, additional experiments to test the rate of B cell replacement were suggested by the model.

Animals↗

Oncostatic properties of the complex of bivalent copper with 3-mercapto-2-hydroxypropyl ether of dextran (C-79).

The oncostatic properties of C-79 preparation were examined on the mice with: sarcoma Sa-180, melanoma B-16, Ehrlich carcinoma and leukemia P-388. The preparation was observed to prolong the life of animals with sarcoma Sa-180 and to modulate the morphology of tumors in them. The preparation had no effect on three remaining investigation models. The investigations carried out on mice of AKR strain have revealed that C-79 significantly suppresses the occurrence of spontaneous leukemia, prolonging the mouse survival-time.

Animals↗

The influence of methylpropionic acid and pyridazinone-3 derivatives on some immunologic and hemopoietic functions.

There was studied the influence on the cell-mediated and humoral response in vivo manifested by selected methylpropionic acid and pyridazinone-3 derivatives which had been found to possess strong immunotropic effects in the in vitro screening previously. It was shown that the compounds were generally poorly tolerated by animals, and they exerted only weak suppressive effects on antibody production, the contact hypersensitivity and survival of skin grafts. This immunosuppressive activity was accompanied by a slight decrease in the number of spleen colony forming cells (CFU-s). Only limited correlation between the biological activity of the preparations and their chemical structure was found.

Animals↗

Specific unresponsiveness to sheep red blood cells visualized by levamisole in athymic nude mice.

The administration of levamisole at the time of and 2 days after challenge with 10(8) SRBC significantly increased the direct anti-SRBC PFC response of nude mice. Pretreatment of nude mice of BALB/c and C 57 B1/10Sn strains with 10(9) or 10(8) SRBC injected 14 and 7 days before challenge suppressed the increase of the immune response. Pretreatment with 10(7) SRBC did not induce this inhibition. Administration of levamisole at the time of pretreatment with SRBC did not prevent the induction of inhibition. It is suggested that B cell exhaustion is the cause of the observed unresponsiveness.

Animals↗

Immunological unresponsiveness to HSA in chickens.

HSA injected into chickens after hatching induces suppression of anti-HSA antibody formation. Unresponsive chickens react by producing the anti-HSA antibodies earlier and more intensively after BSA challenge than after challenge with HSA. This effect cannot be ascribed to T cells, because they were found to play no substantial role in the unresponsiveness to HSA. Neither was active suppression, which could account for the depressed antibody production, detected. B cell inactivation seems to be the major mechanism involved in this unresponsiveness. However, some additional mechanism must prevent B cells of unresponsive chickens from producing anti-HSA antibodies after HSA challenge, although they are able to form them after immunization with BSA. We suggest that cellular interactions, either between B cells of different specificities or between B cells and macrophages, are responsible for this differential reactivity.

Animals↗

Antibody production stimulating activity of bone marrow cells from tolerant rats.

The antibody production stimulating activity of BM cells from SRBC-tolerant and normal rats were studied. Tolerance was induced by repeated injections of SRBC which were begun within 24 h after birth. BM cells obtained from tolerant animals 14-24 days after the last SRBC injection or from normal rats of the same age were used. LN cells from mice immunized with SRBC or BRBC served for the detection of BM activity. Four days after the second injection of antigen, LN cells were removed and cultivated alone or with BM cells from tolerant or control rats for 16 h. After cultivation, immune reaction was estimated by enumeration of indirect PFC. BM cells from SRBC-tolerant rats increased the number of SRBC PFC in the culture more than BM cells from control rats. On the other hand, the stimulatory activity of the BM cells from SRBC-tolerant animals for the BRBC-PFC was lower than that of normal BM cells or it was completely absent. The implications of these findings for the mechanism of the stimulating BM activity are discussed.

Animals↗

Xenogeneic bone marrow stimulating effect in vitro on antibody-producing cells.

It was described earlier that in the tissue cultures of immune mouse LN cells the number of antibody producing cells was increased 2-3-fold when syngeneic of allogeneic nonimmune BM cells were included in the cultures. In these experiments, parallel mixed cultures were set up of mouse immune LN cells with non-immune BM cells of either syngeneic or xenogeneic origin (rat, pig and chicken). Xenogeneic BM also increased the number of PFC in the mixed cultures. The intensity of the stimulation effected by xenogeneic BM of all three species tested was comparable to that induced by syngeneic BM. The number of PFC in all types of the mixed cultures was significantly higher (P less than 0.005) than in the LN cell cultures alone. The differences between the effect of syngeneic and xenogeneic BM and between the xenogeneic BM cells of different origin were not statistically significant (P less than 0.05).

Animals↗

Persistence of immunological tolerance to HSA in chickens after cell transfer to immunosuppressed hosts.

The nature of immunological tolerance to HSA in chickens was analyzed by means of spleen cell transfers to 3-day-old, cyclophosphamide-treated, syngeneic recipients. The cell donors were 2-week-old tolerant or control chickens. The primary challenge with HSA was done 26 days after cell transfer. Spleen cells from both control and tolerant donors restored the immunoglobulin levels and the ability to produce antibodies to SRBC to normal. While cells from normal donors also reconstituted the ability to form antibodies to HSA, the recipients of cells from tolerant donors either did not form detectable amounts or formed only low titres of these antibodies. The ability of cells from normal donors to respond by anti-HSA antibody formation, when transferred together with cells from tolerant donors, was neither suppressed nor decreased. Thus, tolerance to HSA in chickens was not reversible and the existence of an active immune process, causing its duration, could not be demonstrated.

Animals↗

Termination of tolerance to HSA in chickens.

A major part of chickens made tolerant to HSA at hatching formed anti-HSA antibodies when immunized with cross-reacting antigen, the BSA, at 4 weeks of age, although tolerant birds immunized with HSA produced no detectable antibody levels. Immunization with HSA + BSA did not prevent anti-HSA antibody formation in tolerant chickens, but it seems that the escape from tolerance is more rapid in birds immunized with BSA only than in those immunized with HSA + BSA and/or HSA only.

Animals↗

Tolerance to alloantigens of the A and B systems in chickens.

Tolerance to alloantigens of the A and B systems in chickens has been induced by multiple injections of RBC and tested by the elimination of 51Cr-labelled RBC of the same specificity. Three doses consisting of at least 108 RBC each in the B system and 107 RBC in the A system were needed to induce tolerance in newly hatched chicks. Futhermore, it was found that large doses, 109 RBC, in both systems induced tolerance in 100% of week-old and 50% of 14-day-old chickens. With doses of 109 RBC, tolerance to the B antigen disappeared at 8 days in the absence of RBC, whereas in the case of the A antigen it disappeared after more than 50 days, and with the 107 cell doses after 35 days. The elimination of A-incompatible RBC was proportional to the amount of anti-A antibodies present in the recipient's circulation, whereas a minimal amount of antibodies was capable of considerably accelerating the elimination of B-incompatible RBC.

Aging↗

Activity of various immunosuppressive drugs on tuberculin hypersensitivity reaction in chickens.

Drug induced immunosuppression of chicken immune response was studied in F1 hybrids of the CB and IC inbred lines. In tuberculin reaction complete inhibition of wattle swelling was induced by the administration of methotrexate, colcemid (1 mg/KBW), and 6-mercaptopurine. The cellular infiltration was substantially reduced in these cases. Cyclophosphamide and colcemid (0.1 mg/KBW) reduced partially the wattle swelling but had no apparent effect on the cellular infiltration. Acetinomycin D did not affect in measurable degree the wattle swelling. The histologic picture was in this case the same as in the control animals. The same drug administration schedule had less pronounced effect on anti-HSA antibody production. No anti-HSA antibody was found after the 500 mg/animal doses of 6-mercaptopurine. Significant reduction of anti-HSA titres was found after 50 mg/animal doses of 6-mercaptopurine, colcemid (1 mg/KBW), 25 MG/KBW or cyclophosphamide and after the methotrexate treatment.

Animals↗

Cellular cooperation at the level of antibody-producing cells in chickens.

The effect of in vitro cocultivation of immune and non-immune syngeneic lymphoid cells on the antibody response was studied in chickens. Cocultivation of immune and non-immune spleen cells did not affect significantly the PFC numbers. Substantial increase in PFC was observed in mixed cultures of immune spleen cells with non-immune bone marrow cells. The existence of an enhancing effect of non-immune cells on the antibody-producing cells, which had been earlier described in mice, was observed in a phylogenetically distant species. Therefore it seems probable that it exists in most, if not all, homoiotherm animal species.

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