CD200 and its receptor were recognized as having the multiple immunoregulatory functions. Their immunoregulatory, suppressive, and tolerogenic potentials could be very effectively exploited in the treatment of many diseases, e.g. Alzheimer disease, rheumatoid arthritis, and allergy to name only some. Many research projects are aimed to develop clinically valuable methods being based on the structure and function of these paired molecules. In this review, we would like to introduce CD200/CD200R functions in a clinical context., Drahomíra Holmannová, Martina Koláčková, Kateřina Kondělková, Pavel Kuneš, Jan Krejsek, Ctirad Andrýs, and Literatura 51
CD200/CD200R are highly conserved type I paired membrane glycoproteins that belong to the Ig superfamily containing a two immunoglobulin‑like domain (V, C). CD200 is broadly distributed in a variety of cell types, whereas CD200R is primarily expressed in myeloid and lymphoid cells. They fulfill multiple functions in regulating inflammation. The interaction between CD200/CD200R results in activation of the intracellular inhibitory pathway with RasGAP recruitment and thus contributes to effector cell inhibition. It was confirmed that the CD200R activation stimulates the differentiation of T cells to the Treg subset, upregulates indoleamine 2,3‑dioxygenase activity, modulates cytokine environment from a Th1 to a Th2 pattern, and facilitates an antiinflammatory IL‑10 and TGF‑β synthesis. CD200/CD200R are required for maintaining self‑tolerance. Many studies have demonstrated the importance of CD200 in controlling autoimmunity, inflammation, the development and spread of cancer, hypersensitivity, and spontaneous fetal loss., Drahomíra Holmannová, Martina Koláčková, Kateřina Kondělková, Pavel Kuneš, Jan Krejsek, Ctirad Andrýs, and Literatura 46
Imunitní systém prodělává v průběhu života zásadní změny, které reflektují odlišné potřeby jedince v různých údobích života. Nejvýznamnější ontogenetickou dynamiku vykazuje specifická, buňkami zprostředkovaná, imunita. v časných fázích života dominuje aktivita subsetu Th2 pomocných T-lymfocytů. V dospělosti dochází k přesmyku vedoucí k převaze subsetu Thl T-lymfocytů. Pro stán je opět charakteristický návrat k převaze aktivit subsetu Th2 T-Iymfocytů. Až překvapivě efektivní je imunitní systém osob, které se dožily vysokého věku 90-100 let. Zatím nelze doložit, zda je tento fakt příčinou nebo důsledkem dlouhověkosti. Z experimentu na zvířecích modelech vyplývá, že modulací imunitního systému lze prodlužovat věk i zvyšovat kvahtu života. Pro fyziologické změny imunitlího systému, které lze identifikovat u starých hdí, se zavádí termín imunosenescence., The immune system is undergoing a lot of substantial changes during life which reflect different demands of every individual in different periods of life. The most important ontogenetical dynamies is typical for specific cell-mediated immunity. The activity of Th2 subset of helper inducer CD4+ T cells is upregulated during early period of life. There is the shift from Th2 subset reactivity to predominant Thl subset eactivity during early adulthood. The return back to the predominant Th2 reactivity is typical for the late period of life. The immune system of earderly people who are 90-100 years old is supprisingly well preserved. It is not possible to say now if this fact is either the cause or the consequence of successful senescence. The term immunosenescence is now coined to describe the physiological changes of the immune system in elderly people., Jan Krejsek, Manuela Kudlová, Martina Koláčková, and Lit. 39
The presence of a broad spectrum of autoantibodies in Sjögren's syndrome (SjS) patients is the result of abnormal B-cell regulation that can be at least partially explained by abnormal BAFF/BAFFR regulation. The objective of this study was to determine both membrane and intracellular expression of BAFF/BAFFR in monocytes and B-cells in peripheral blood of 19 primary Sjögren's syndrome patients and 20 healthy controls using flow cytometry. We also measured sBAFF in serum. Compared to healthy controls, both surface and intracellular expression of BAFF was significantly increased in monocytes and B-cells of SjS patients. Also serum sBAFF level was elevated. Expression of BAFFR on B-cells of SjS patients was surprisingly decreased, but there was no clear increase or decrease within monocytes. Our results indicate that activated monocytes communicate with B-cells via BAFF and BAFFR, so that B-cells are stimulated, but BAFF is also produced to stimulate cells in autocrine way. The decrease of BAFFR expression in SjS patients suggests that there is the mechanism that attempts to take over in order to balance the high level of BAFF. and J. Krejsek, M. Koláčková, I. Lindrová, R. Slezák, C. Andrýs
Cardiac surgery is inseparably linked to the activation of innate immunity cells recognizing danger signals of both endogenous and exogenous origin via pattern recognition receptors such as TLR receptors. Therefore, we followed by flow cytometry TLR2 and TLR4 expression on blood monocytes and granulocytes of patients who underwent coronary artery bypass grafting using beating heart surgery (off-pump, n = 34), with use of standard cardiopulmonary bypass (CPB), (on-pump, n = 30), and miniinvasive CPB (mini on-pump, n = 25), respectively, before, during surgery, and up to 7th postoperative day. TLR2 and TLR4 expression both on monocytes and granulocytes was significantly diminished already at the end of CPB being highly significantly decreased at the end of surgery in all patients' groups. TLR2 and TLR4 expression reached preoperative value at the 1st postoperative day being significantly higher at the 3rd postoperative day. Using intracellular staining we found the peak of TLR2 and TLR4 expression inside of monocytes and granulocytes at the first postoperative day in a subgroup of on-pump patients. In conclusion, TLR2 and TLR4 expression is significantly modulated in patients undergoing coronary artery bypass grafting as a part of adaptive homeostatic mechanisms induced by major surgery. The very surgical trauma is responsible for TLR2 and TLR4 modulation. Surprisingly, cardiopulmonary bypass itself was little contributing to the modulation of TLR2 and TLR4 expression. and J. Krejsek, M. Kolácková, J. Mand'ák, P. Kunes, Z. Holubcová, D. Holmannová, M. AbuAttieh, C. Andrýs