[Legal aspects of the use of the computer in a hospital department].
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Biomedical subjects
Publications and source records attributed to L Polak.
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Dinitrophenyl-specific T-cell lines were established by culturing lymph node-derived lymphocytes from dinitrochlorobenzene-sensitized guinea-pigs with dinitrophenyl-modified macrophages. Cells from this line were all Ia-positive and formed E-rosettes with rabbit erythrocytes; no Ig-positive cells were present in this suspension. Expanded cells exhibited enhanced in vitro and in vivo activity as demonstrated by DNA synthesis and systemic adoptive transfer of contact sensitivity. In vitro DNA synthesis was elicited not only be specific hapten-modified macrophages but also by conjugates of the hapten with homologous (GPA) and even heterologous (BGG, HSA) proteins, thus demonstrating the loss of carrier specificity. Moreover, the proliferative response of expanded cells was elicited not only with hapten-modified syngeneic (strain 2) but also with allogeneic (strain 13) macrophages. Cells from hapten-modified T-cell lines, but not from lymph nodes from in vivo primed guinea-pigs, showed specific accumulation in contact sensitivity skin test sites. Attempts to establish hapten-specific T-cell clones were also at least partially successful.
The antigen-presenting capability of macrophage modified with a single hapten (dinitrofluorobenzene) is partially or totally abolished by an additional haptenation with a second related (picryl chloride) or unrelated (oxazolone) hapten. This effect, 'antigenic competition', is only partially mediated by suppressor cells. There also seems to be an inhibition of the association of the hapten with particular Ia antigens. The prerequisite for antigenic competition is that both hapten responses are controlled by the same immune response gene. Hapten responses which are controlled by different genes, e.g., dinitrofluorobenzene, picryl chloride, and oxazolone on the one hand and benzilidene acetone on the other, do not compete. The pattern of competition thus varies with the strain of guinea pig.
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1. Female guinea pigs made tolerant before pregnancy do not transfer tolerance to their offspring. This result favours the concept of cellular mechanism of tolerance. 2. Guinea pig fetuses become tolerant when exposed to the tolerogen in the last two weeks of pregnancy. This is due to active tolerization by the tolerogen passing the placental barrier. 3. Fetuses exposed to the antigen earlier did not develop tolerance. This is due to immunological immaturity rather than to insufficiently developed vascularization. No functional active depot of tolerogen is formed. 4. Guinea pigs become immunologically mature between the 54th and 61st day of fetal live.
Contact sensitivity to dinitrochlorobenzene (DNCB) in guinea pigs could be rapidly suppressed by intravenous injection of dinitrobenzene sulfonic acid sodium salt (DNBSO3). This suppression is transient and antigen-specific. Macrophages from desensitized animals are not inactivated as shown by their ability to react, both in vivo and in vitro to lymphokines produced in a separate system. Therefore, effector lymphocytes are considered the target for the desensitizing antigen. Using an adoptive transfer system it was demonstrated that effector lymphocytes are inactivated by a direct effect of the hapten. Since this inactivation can be reversed by trypsin treatment, a receptor blockade of effector lymphocytes is proposed as the mechanism of desensitization of DNCB-contact sensitive guinea pigs. This does not exclude the possibility that additional mechanisms such as suppressor cells, compartmentalization or endogenous proliferation of lymph node lymphocytes may play an additional role.
The article reviews the recent experimental data that influenced the present concept of contact sensitivity. Particular emphasis is on the mechanism of stimulation of antigen-inexperienced specific lymphocytes, the eliciting phase, and the role of suppressor cells in sensitization and tolerance.
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Tolerance to dinitrochlorobenzene contact sensitivity induced i.v. injection of dinitrobenzenesulfonic acid in guinea pigs is a long-lasting phenomenon (up to 1 year). The tolerogen, however, was traceable in the circulation only up to 3 months after its application. In spite of that, tolerance was adoptively transferred by parabiosis 6 months after being induced. Moreover, active suppressor cells eliminated by cyclophosphamide treatment are able to regenerate in those adoptively tolerized animals. These results indicate that the tolerogenic injection stimulates precursors of suppressor cells to generate active suppressor cells and memory cells of suppression. The further formation of active suppressor cells from memory cells seems to be tolerogen independent, but the existence of specific stimulator cells for suppression may be considered. These cells may bind undetectable small amounts of tolerogen. The recovery of suppression might, however, be also due to recovery of suppressor cells which were temporarily inactivated but not destroyed by cyclophosphamide treatment.
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The effect of suppressor cells on the formation of effector cells was studied by comparing the development of DNCB contact sensitivity in cyclophosphamide-treated (suppressor cells eliminated) and non-treated (suppressor cells present) guinea-pigs. From experiments in four different models of generation of effector cells the following conclusions are drawn: (1) impulses activating the formation of effector cells also activate suppressor cells; (2) under conditions of conventional immunization, suppressor cells are activated later than effector cells; (3) elimination of suppressor cells results in an increase in the intensity and duration of specific skin reactions.
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