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Inhibitory NK cell receptors and possibilities of manipulation of cytotoxic properties.
Švubová, Veronika ; Frič, Jan (advisor) ; Krulová, Magdaléna (referee)
Acute myeloid leukemia makes up for 18 % of all leukemias among pediatric and young adult patients. The complete remission rate (80-90 %) and the overall survival (70 %) of the patients is relatively high, nevertheless, the relapse rate is still almost at 50 % and the prognosis remains extremely bad. The relapse treatment is rather challenging because the persisting leukemic clones might in fact start to be refractory to chemotherapy. Lately, NK cells are being perceived as an attractive therapeutical tool for treatment of the relapses. NK cells are a subpopulation of innate lymphoid cells, possessing the ability to eliminate dysfunctional cells through cytotoxic activities and further perpetuate the immune response. One of the advantages of NK cells is their functional independency of specific antigens. In the light of growing evidence about the role of leukemic stem cells in context of acute myeloid leukemia, NK cells seem to offer a new perspective in therapeutical efforts to eliminate them via several cytotoxic mechanisms. Yet despite optimistic preliminary results, treating this disease has proved to be rather challenging and the NK cell-based immunotherapy is still facing several limitations. Transforming growth factor β is partially responsible for maintenance of leukemic stem cell...
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Specifics of the use of opioids as important immunomodulators in the treatment of pain
Švubová, Veronika ; Hejnová, Lucie (advisor) ; Vašek, Daniel (referee)
This work deals with the specifics associated with the use of opioid analgesics in pain relief. In terms of antinociceptive effects, opioids have not yet been surpassed by other available drugs. However the use of these analgesics is quite problematic in many respects. For over 30 years, studies have shown that opioids can adversely affect components of the immune system (IS) and thus the overall condition of the patient. To understand the relationship between opioids and IS, it is necessary to know the mechanisms leading to immunomodulatory processes. Contact with opioids occurs at the cellular interface through interactions with opioid receptors (ORs). Within IS, we encounter all three basic types of OR - μ (MOR), δ (DOR), κ (KOR) and non-classical nociceptin receptors (NOP). Stimulation of these receptors induces activation of signaling cascades in target cells which can lead to dysregulation of cellular processes, thus modulating the immune response. However, the effect of opioids on IS cells may not be exclusively direct. More complex regulatory pathways have been found, involving parts of the central nervous system (CNS), the sympathetic nervous system (SNS), and endocrine-active tissues. Activation of these pathways then affects the activity of whole lymphoid organs. Each cell type within an...
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