Jelátviteli kompartmentek és proteolózis az immunválasz, valamint az immun- és idegrendszer közötti kommunikáció szabályozásában  részletek

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Projekt adatai

  
azonosító
44711
típus NI
Vezető kutató Gergely János
magyar cím Jelátviteli kompartmentek és proteolózis az immunválasz, valamint az immun- és idegrendszer közötti kommunikáció szabályozásában
Angol cím Signaling compartments and proteolysis in regulation of immune responses and the communikation between the immune- and nervous systems
zsűri Immun-, Tumor- és Mikrobiológia
Kutatóhely Immunológiai Tanszék (Eötvös Loránd Tudományegyetem)
résztvevők Ábrahám István
Erdei Anna
Gráf László
Hegyi György
Juhász Gábor
László Glória
Matkó János
Nyitray László
Prechl József
Sármay Gabriella
Sass Miklós
Szilágyi László
projekt kezdete 2003-01-01
projekt vége 2005-12-31
aktuális összeg (MFt) 82.800
FTE (kutatóév egyenérték) 0.00
állapot lezárult projekt





 

Zárójelentés

  
kutatási eredmények (magyarul)
Több új immunreceptor-kölcsönhatást (FcR/CR/BCR; sejthalál-R/TCR), és több szabályozó mechanizmust azonosítottunk a lipid raftok és más membrán mikro-kompartmentek, valamint limfocita adaptor fehérjék részéről, melyek fontosak a limfociták effektor funkcióiban ill. a sejthalál folyamatában. Leírtuk az utóbbi folyamatokban kritikus miozin motorfehérje izotípusok néhány molekuláris kapcsolatának szerkezeti hátterét és szabályozási lehetőségét. Kimutattuk egyes komplement (C) faktorok és receptorok sokrétű szerepét az immunválasz szabályozásában és, hogy a belőlük származtatott peptidekkel az allergiás hízósejtválasz gátolható. Leírtuk a C-rendszer szabályozó szerepét a Sclerosis Multiplex (SM) állatmodelljében is. Kimutattuk a tripszin-szerű proteáz aktivitás szabályozó szerepét a B-sejt válaszban, és valószínűsítettük szerepüket a mielin bázikus fehérje specifikus hasításában, mely fontos eleme lehet az SM kialakulásának. Eredményeink alapját képezik szelektív immunmodulánsok kifejlesztésének autoimmun ill. allergiás kórképekben. Kimutattunk egyes immunrendszeri effektor- és idegrendszeri funkciók között fellépő, a citokin hálózat ill. steroid hormonok (ösztrogének, glukortikoidok) útján megvalósuló kommunikációs útvonalakat. Új módszereket is kifejlesztettünk (pl. antigén-targetingre alkalmas egyláncú ellenanyag konstrukciók) és a projekt támogatásával beszereztünk egy konfokális mikroszkópot, melyen több új metodikát optimalizáltunk a celluláris kommunikáció vizsgálatára.
kutatási eredmények (angolul)
We identified several novel immunoreceptor cross-talk elements (FcR/CR/BCR; cell death-R/TCR) and regulatory mechanisms by lipid rafts, other membrane-compartments, as well as adaptor proteins, which are essential in the lymphocytes’ effector functions and cell death. Structural and regulatory aspects of some important molecular interactions of myosin motor protein isotypes, essential players in the above processes, were also described. Multiple regulatory functions of the complement system in the immune response and the inhibitory potential of C3a-derived peptides in the allergic mast cell response were identified. The regulatory potential of the complement system was also shown in an animal model of Sclerosis Multiplex (SM). We have shown that trypsin-like protease activities are involved the B cell response through formation of soluble receptors and that trypsin-4, specifically cleaving MBP, may be a critical element in development of SM. Our results form a basis for development of selective immunomodulators for autoimmune- and allergic diseases. We explored several novel communication pathways between effector mechanisms of the immune system and certain nervous system functions, through the inflammatory cytokine network and steroid hormones. New methods and molecular constructs (e.g. antigen-targeting by engineered single-chain antibodies) and several modern confocal imaging techniques for studying cellular communication were also developed with the support of the grant.
a zárójelentés teljes szövege http://real.mtak.hu/1232/
döntés eredménye
igen





 

Közleményjegyzék

  
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