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The UNESCO Interdisciplinary Chair in Biotechnology and Bioethics (2000-2009): An example of Responsible Research and Innovation between Europe and Africa,
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DEPRESSION OF CONTACT SENSITIVITY BY PSEUDOMONAS-AERUGINOSA INDUCED SUPPRESSOR CELLS WHICH AFFECT THE INDUCTION-PHASE OF IMMUNE-RESPONSE
No full textThe cellular basis of depression of contact sensitivity to oxazolone in mice injected with Pseudomonas aeruginosa was studied. Cells from draining lymph nodes of mice sensitized with oxazolone 18 h previously were able to induce contact sensitivity to normal mice when administered in their footpads. In contrast, cells from draining lymph nodes of P. aeruginosa-injected and oxazolone-sensitized donors failed to induce contact sensitivity when injected in the footpad of normal mice and were capable of actively blocking the immunizing process brought about by lymph node cells from sensitized mice when injected together in the footpad of normal recipients. The P. aeruginosa-induced suppressor cells required antigenic stimulation, had precursors sensitive to cyclophosphamide, and did not affect the effector mechanisms of contact sensitivity. Thus, the results suggest that P. aeurginosa depresses contact sensitivity to oxazolone by enhancing the activity of suppressor cells which normally arise during the sensitization process and which affect the afferent limb of the immune response, probably by inhibiting the normal recruitment of T lymphocytes in the draining lymph node
DEPRESSION OF CONTACT SENSITIVITY BY ENHANCEMENT OF SUPPRESSOR CELL ACTIVITY IN PSEUDOMONAS-AERUGINOSA-INJECTED MICE
No full textHeat-killed Pseudomonas aeruginosa depresses contact sensitivity to oxazolone in C56BL/6 mice. The draining lymph nodes and spleens of mice exhibiting an impaired reactivity to oxazolone contain a cell population capable of depressing the response to oxazolone of recipients sensitized immediately before cell transfer. The suppressive activity of these cells appears to be antigen specific, since they do not affect the response to picryl chloride and because they do not arise in P. aeruginosa-injected but not oxazolone-sensitized mice. These suppressor cells occur in the draining lymph nodes and spleen at 3 and 4 days after sensitization, respectively, and have precursors sensitive to cyclophosphamide. It is concluded that P. aeruginosa depresses contact sensitivity to oxazolone by enhancing the suppressor cell activity of the regulatory cells which arise during conventional sensitizatio
AUTO-ANTI-IDIOTYPIC ANTIBODIES INHIBIT T-CELL-MEDIATED HYPERSENSITIVITY IN BCG-INFECTED MICE
No full textt is shown that serum from mice heavily infected with BCG contains antibodies which block the cell transfer of delayed-type hypersensitivity (DTH) to purified protein derivative (PPD) when BCG-immune cells were preincubated in it. This suppressive activity is antigen specific in that the serum does not block the cell transfer of contact sensitivity to oxazolone. However, the suppressive activity is not antigen directed in that it is absorbed neither by PPD-coupled Sepharose beads nor by PPD-pulsed normal peritoneal exudate cells. On the other hand, the activity can be absorbed to BCG-immune T cells and eluted from a Sepharose column conjugated with affinity-purified mouse anti-PPD antibodies. The possibility that antireceptor antibodies arise during the BCG infection and regulate DTH reaction is discussed
DEPRESSION OF THE ANTIBODY-RESPONSE IN PSEUDOMONAS-AERUGINOSA-INJECTED MICE
No full textHeat-killed Pseudomonas aeruginosa inhibit antibody response in C57BL/6 mice. The depression of this response is dependent on the dose of bacteria injected, on the time interval between microorganism injection and antigen administration, and on the nature of the antigen used. Cell transfer experiments provide evidence that suppressor cells are not operative in this model. Furthermore, the results show that P. aeruginosa induces a marked dose-dependent proliferation of spleen cells in vivo, and the in vitro targets of this proliferative effect are B lymphocytes. It is suggested that whole, heat-killed P. aeruginosa in vivo also behave as cell mitogens on B lymphocytes which, when strongly stimulated to proliferate, temporarily lose their capacity to mount a normal antibody respons
EVIDENCE FOR AUTOANTIBODY PRODUCTION ASSOCIATED WITH POLYCLONAL B-CELL ACTIVATION BY PSEUDOMONAS-AERUGINOSA
No full textExperimental infection of mice with Pseudomonas aeruginosa resulted in the polyclonal activation of B lymphocytes, as assessed by the spontaneous plaque-forming cell (PFC) response to trinitrophenyl and sheep erythrocytes. Additionally, a PFC response to bromelain-treated syngeneic erythrocytes (Br-MRBC) could be detected in infected mice, suggesting that P. aeruginosa infection might also induce activation of self-reactive B-cell clones and consequently lead to autoantibody production. Furthermore, in cultures of mouse peritoneal cells, heat-killed P. aeruginosa enhanced the development of anti-Br-MRBC PFC, even under conditions where cell division was blocked, suggesting that the in vitro P. aeruginosa-induced enhancement of anti-Br-MRBC PFC was essentially related to cell differentiation, cell division playing only a minor role. The mechanism of the in vivo and in vitro P. aeruginosa-induced activation of anti-Br-MRBC PFC are discusse
M. tuberculosis H37Rv comparative gene-expression analysis in synthetic medium and human macrophage.
No full textMycobacteria are intracellular pathogens that survive and grow in host macrophages. Following phagocytosis, sustained intracellular bacterial growth depends on its ability to avoid destruction by macrophage-mediated host defences such as lysosomal enzymes, reactive oxygen and the reactive nitrogen intermediates.This suggests that the interaction between host cell and microbe is delicately balanced, and can be tipped in favour of either organism. The identification of Mycobacterium tuberculosis H37Rv (MTB) genes expressed within host cells would contribute greatly to the development of new strategies to fight tuberculosis. In the present study, we compared MTB gene expression in the course of intra- (human macrophages) and extracellular growth (Sauton's medium) to ascertain whether differences might occur between gene-expression patterns in the two habitats of replication. Using reverse-transcriptase polymerase chain reaction (RT-PCR) on a group of 14 MTB-Complex-specific genes, we found that MT10Sa (a small stable RNA), 35 kDa (unknown), ahpC (alkyl hydroperoxide reductase, AhpC), sigF (alternative RNA Polymerase sigma factor), and katG (catalase-peroxidase, HPI) genes are expressed in both the environments, while Ag85B, Ag85C (members of the Antigen 85 Complex), rpoV (RNA Polymerase sigma factor) and ESAT6 (early secretory antigen, 6 kDa) are expressed only in the in vitro culture; on the other hand, Ag85A (Antigen 85 Complex), rpoB (RNA Polymerase beta sub-unit), pab (Protein antigen b), invA and invB genes (encoding proteins that show homologies with p60 of Listeria monocytogenes) are expressed only inside the macrophage. Positive RT-PCR products on cDNAs for these genomic regions were not obtained from approximately 1000-fold more bacteria grown in Laboratory Broth. Identification of M. tuberculosis genes expressed in response to phagocytosis by human macrophages increases our basic understanding of the host-pathogen interaction, and helps to identify bacterial factors necessary for in vivo survival and growth
PSEUDOMONAS-AERUGINOSA INFECTION DEPRESSES CONTACT SENSITIVITY TO OXAZOLONE BY ENHANCING SUPPRESSOR CELL-ACTIVITY
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