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T Hraba

Publications and source records attributed to T Hraba.

At least 37 records · Page 2Linked to original sources

Recovery from polyclonal tolerance: simulation analysis.

Mathematical model of immunological tolerance was applied to polyclonal B cell tolerance induced in mice by treatment with bacterial lipopolysaccharide (LPS) followed by the application of cyclophosphamide (CY). Satisfactory simulation results were obtained with the life-span of lymphocytes shorter than the experimentally observed one. It could be assumed that the massive decrease of lymphocyte population in polyclonal tolerance would elicit a compensatory reaction. Therefore it was postulated that some kind of feedback mechanism increased the influx of B lymphocytes. Having this factor included in the model, satisfactory agreement of the simulation results with experimental data was obtained for experimentally determined life-span of B cells.

Animals↗

Increase by bacterial lipopolysaccharide of antibody production in mice rendered hyporesponsive to lysozyme.

The effect of bacterial lipopolysaccharide (LPS) on the immune response of adult mice to hen egg lysozyme (HEL) was studied under conditions in which hyporesponsiveness to HEL was induced by: (i) the intravenous injection of syngeneic spleen cells incubated with HEL; (ii) the intravenous administration of soluble HEL, and (iii) the intraperitoneal injection of HEL in IFA. In all cases, mice were immunized by footpad injection of HEL, with or without LPS. The antibody response produced was measured by the number of indirect anti-HEL plaque forming cells (PFC) detected in popliteal lymph nodes. The incorporation of LPS in the immunizing dose of HEL had little effect on the response of controls; however, it resulted in an appreciable increase in the antibody response of all three groups of hyporesponsive mice. Although, after treatment with LPS, the number of PFC detected in mice made tolerant by spleen cell injection approached those of the controls, lower increases in the antibody response were noted for the remaining two groups of hyporesponsive mice.

Animals↗

Application of mathematical model of immunological tolerance to HIV infection.

Our experimental model of immunological tolerance to non-reproducing antigens is based on the assumption that tolerance is caused by elimination or irreversible inactivation of lymphocytes reacting specifically with the tolerance inducing antigen, and that recovery from tolerance is due to the spontaneous maturation from the stem cells of new lymphocytes reacting with the tolerated antigen. The recovery starts, when the antigen is eliminated from the organism and does not induce tolerance in newly arising lymphocytes any more. Here we report the application of this model to the depletion of CD4+ lymphocytes in persons infected with HIV. This depletion seems to be effected either directly or indirectly by HIV products. Therefore, the dynamics of this depletion can be described by the equations characterizing the dynamics of lymphocytes exposed to tolerance inducing antigen, when HIV products are substituted for antigen. In contrast to non-replicating antigens, the concentration of HIV products increases, as the infection progresses. In consequence, the CD4+ lymphocyte depletion increases with time and its dynamics are reciprocal to those of tolerance to non-reproducing antigens, which decrease with time.

Acquired Immunodeficiency Syndrome↗

A contribution to mathematical modelling of immunological tolerance.

The original simple mathematical model describing the kinetics of B cell tolerance was extended by the inclusion of Th cell tolerance. It anticipates the existence of two compartments of B and Th cells reactive to the antigen--the immature cells and the mature ones. It is assumed that tolerance is induced by irreversible inactivation of the antigen-reactive cells and the escape from tolerance is due to their differentiation from the precursors. There is also considered the situation, where two categories of Th cells cooperate with the same B cells. Besides that, suppressive activity on Th cells is included in the model. The simulated values are compared with experimental data.

Animals↗

Simulation analysis of the mechanism of escape from immunoglobulin suppression.

The mathematical model of B cell tolerance was applied to idiotype and isotype suppression of short duration induced in mice by neonatal application of monoclonal antibodies specific for the respective immunoglobulin determinants. Suppressor cells play an important role in chronic idiotype or isotype suppression, but these suppressions of short duration seem to be caused by direct elimination of B cells by the injected antibodies. The recovery from suppression of short duration starts, when the injected antibody is eliminated from the organism and is caused by differentiation from stem cells of new B lymphocytes possessing the respective immunoglobulin markers. This mechanism is analogous to that assumed for immunological tolerance in the mathematical model except that the injected monoclonal antibody plays the role of tolerance-inducing antigen. However, satisfactory agreement of simulated values with the experimental ones could not be obtained, if experimentally observed elimination rate of the injected antibody was used for calculations. A better fit was obtained with elimination rate values decreasing with age which do not correspond to the actual ones of the injected antibody. At present, we do not know which mechanism is described by these "virtual" elimination rates.

Animals↗

Implications of a mathematical model for the role of lymphocytes with different lifespans in the recovery from tolerance.

An extension of the mathematical model of immunological tolerance including two categories of B and T helper cells, each having a different lifespan, is presented. The simulated recovery from tolerance is compared with experimental data on B and T helper cell tolerance to human gamma globulin (HGG) induced in adult mice. The performed simulation runs suggest the conclusion that in this case it seems impossible to incorporate a high ratio of both, long-lived B cells and/or short-lived T helper cells, if good agreement with the available experimental data should be preserved.

Animals↗

The effect of bone marrow regulatory peptides on antibody production by hybridoma cells.

Peptides produced by bone marrow cells (myelopeptides) increase antibody production. Since antibody producing cells seemed to be their targets, we tested in these experiments the effect of myelopeptides on antibody production by 2B2 and 2C12 hybridoma cells. Both hybridomas produce anti-SRBC monoclonal antibodies of the IgM class. The 2B2 cells do not produce direct haemolytic plaques and less than 5% of them produce the indirect ones during the 90-min assay period. When they were cultivated with myelopeptides for 15 h, the number of indirect plaques increased two-fold. A slightly lower increase was observed after 24 h of incubation, while the 48-h incubation period did not increase the number of detected plaques. After 6 h of preincubation, only a slight increase in indirect plaque numbers was observed. About 25% of the 2C12 hybridoma cells produce both direct and indirect haemolytic plaques during the assay period. The effect of myelopeptides was studied only on the indirect ones and no clear effect was observed. Only after the 15-h incubation period a slight increase in plaque numbers was observed. Because the myelopeptides affect antibody production of hybridoma cells, antibody producing cells are evidently the targets of these substances. It remains to be established, whether they are the only target cells in the myelopeptide action on the immune response.

Animals↗

Effect of proline-rich polypeptide on experimental autoimmune response to erythrocytes.

PRP administration in parallel with RRBC injections increased the AEAP in mice, as did adult thymectomy carried out six weeks before the RRBC injections. On the other hand, PRP administration to thymectomized mice during immunization with RRBC decreased the intensity of AEAP to the level observed in intact, RRBC immunized controls. The number of ARFC among non-B lymphocytes in peripheral blood was increased in mice immunized with RRBC compared to those in non-immunized animals. PRP administration during immunization with RRBC or adult thymectomy lowered their number below the values in non-immune animals and non-B ARFC number comparable to those in control, immunized animals was observed in thymectomized mice injected with PRP in parallel with RRBC. The values of ARFC among the NAL were higher than among the non-B lymphocytes but their shifts in the individual experimental groups were in the same direction as among the non-B lymphocytes. However, their shifts after thymectomy and/or PRP treatment were in opposition to those of the intensity of AEAP in the respective experimental groups.

Animals↗

Two-chain disulphide-bonded structure of antigen-specific T-helper factor: both chains are necessary for activity and their interaction is I-A restricted.

The molecular structure of the antigen-specific T-helper factor (ThF) which augments contact sensitivity in mice was studied. ThF was split into two types of polypeptide chain by mild reduction and alkylation; one antigen binding (which determined the specificity), the other non-antigen binding. The two chains were, by themselves, inactive but complemented each other and reconstituted biological activity. In addition, a genetic restriction was observed in the complementation of the two chains which mapped to the I-A subregion of the H-2 complex.

Animals↗

The effect of thymectomy on immunological tolerance to human serum albumin in chickens.

The effect of thymectomy performed on the day of hatching has been studied in chickens rendered tolerant by 100 mg of HSA injected also on the day of hatching. After challenge at the age of 6 and 9 weeks, no significant difference was observed between the group of tolerant chickens, in which the thymectomy was complete or incomplete, and the non-operated tolerant one. The delayed recovery from tolerance observed in mammals was not seen even in chickens in which thymus was removed completely and no thymic residue remained. The anti-HSA antibodies were even slightly higher in thymectomized birds than in the non-operated ones but the difference was statistically non-significant.

Animals↗

Experimental allergic encephalomyelitis in the chicken. Class-specific antibody to myelin basic protein, the ability of T cells to cause GvH reaction, brain and spleen histology, and nonspecific biochemical indicators of inflammation.

Experimental allergic encephalomyelitis (EAE) was induced in chickens by injecting human myelin basic protein (MBP) in Freund's complete adjuvant (CFA). Antibodies of IgM, IgA and IgG class to MBP were measured by enzyme-linked immunosorbent assay (ELISA). The ability of the blood from the experimental chickens to induce graft-versus-host (GvH) reaction was tested in chick embryos. Serum concentrations of sialic acid and antitrypsin were monitored. Substantial inflammatory infiltrations were found in various parts of the central nervous system of the animals injected with MBP, but not in the controls receiving plain CFA. Enlargement of the white pulp and plasmocytosis were found in the spleens of the EAE animals. In the course of the disease, anti-MBP IgM and IgA antibody levels strongly increased, while IgG antibodies remained unchanged. The GvH caused by the blood from EAE animals did not differ from that of control birds. The EAE group showed significantly higher antitrypsin concentration than the controls. The increase in sialic acid concentration was of equal magnitude in the EAE animals and in the CFA controls.

Animals↗

T helper cell inclusion into the mathematical model of immunological tolerance.

The experimentally observed recovery from tolerance to HSA in chickens is much slower than the values calculated by means of the simple mathematical model of B cell tolerance. The model assumes that tolerance is due to elimination or irreversible inactivation of immunocompetent cells reactive to the tolerated antigen, and that the recovery from tolerance is caused by the differentiation of new immunocompetent cells. Even when two collaborating B cell populations reactive to HSA were considered, the calculated recovery from tolerance was much slower than the observed one. Therefore, T helper cell tolerance was suspected and included into the mathematical model. The experimental data agreed best with the calculated values of the recovery from tolerance to HSA obtained with a T cell lifespan of 200 days. On the other hand, when two T helper cell populations cooperated with B cells in anti-HSA antibody production, the curve best fitting the experimental data corresponded to the T cell lifespan of 60 days.

Animals↗

Antibody-producing cells in chickens tolerant to human serum albumin.

Cells forming antibodies to HSA were determined by the haemolytic plaque technique in the spleens of chickens in which tolerance to HSA was induced on the day of hatching. After immunization with HSA 2 weeks after hatching, no anti-HSA PFC or their very low numbers were observed in chickens rendered tolerant by the dose of 100 mg HSA. In a considerable proportion of the chickens, in which tolerance was induced by 1 mg or 0.1 mg of HSA, PFC were detected, though in statistically significantly lower numbers than in control birds. In tolerant chickens receiving 100 mg of HSA after hatching, the number of PFC after immunization at 4 weeks of age was statistically significantly and at 6 weeks non-significantly lower than in the controls. After immunization with BSA at 4 weeks of age, chickens injected with 100 mg HSA after hatching had the number of anti-HSA plaque-forming cells higher than the controls, but the difference was not statistically significant.

Animals↗

Induction of tolerance in chickens by low doses of human serum albumin administered after hatching.

The possibility was tested whether tolerance can be induced in newly hatched chickens by a single injection of HSA on the day of hatching in doses one or several orders lower than the dose employed in previous experiments (100 mg of HSA). Doses of 10 and 1 mg of HSA induced a statistically significant suppression of anti-HSA antibody formation after challenge at the age of 2 and 4 weeks. Injection of 0.1 mg of HSA into newly hatched chickens also produced a statistically significant decrease in antibody formation after challenge at 2 weeks of age.

Animals↗

Fröhlich electromagnetic radiation from human leukocytes: implications for leukocyte adherence inhibition test.

The Fröhlich coherent vibrations may be a source of an electromagnetic field generated by living cells in the frequency range from 0.1 to 10 THz. The electromagnetic field may cause the time dependent orientation (i.e. rotation or rocking) of the polar molecules of the ambient liquid medium and may attract them. The attracted molecules move together with the cell and the friction coefficient of the cellular motion, therefore, may depend on the field. The cell-generated electromagnetic field may interact with the surface charge of various solid-state materials causing attractive forces. These interaction attractive forces may be significant in the process of the leukocyte adherence to the surfaces of various materials. The hypothesis presented in this paper assumes that the exposition of leukocytes from immune individuals to antigen causes changes of the Fröhlich coherent vibrations resulting in decrease of the leukocyte adherence observed in the leukocyte adherence inhibition test.

Cell Movement↗