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InV [[:en:Immunology|immunology]],imunologii anoznačuje pojem '''immunologicalimunologická synapse''' (ortaké '''immuneimunitní synapse''') isrozhraní thevznikající interfacepři betweenkontaktu anmezi [[:en:Antigen-presenting_cell prezentující buňka|antigen-presentingprezentující cellbuňkou]] or target cell and a [[:en:LymphocyteLymfocyt|lymphocytelymfocytem]], such as annapř. effectorefektorovou [[:en:T_cellT-lymfocyt|T cellbuňkou]] ornebo [[:en:Natural_Killer_cellNK buňka|NaturalNK Killer cellbuňkou]].<ref name="pmid10398592">{{cite journal|vauthors=Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML|title=The immunological synapse: a molecular machine controlling T cell activation|journal=Science|volume=285|issue=5425|pages=221–227|date=July 1999|pmid=10398592|doi=10.1126/science.285.5425.221|url=|issn=}}</ref> ItImunologická is thesynapse subjectje ofpředmětem muchmnoha ongoingaktuálních researchvýzkumů.<ref>{{cite web|url=http://www.med.nyu.edu/skirball-lab/dustinlab/pdfs/Davis_Dustin.pdf|title=What is the importance of the immunological synapse?}}</ref>
== StructureStruktura and Function ==
The immuneImunologická synapse isbyla alsopůvodně knownoznačována asjako thetzv. '''supramolecular"supramolekulární activationaktivační cluster''' orklastr, '''SMAC'''." <ref name="pmid9738502">{{cite journal|vauthors=Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A|title=Three-dimensional segregation of supramolecular activation clusters in T cells|journal=Nature|volume=395|issue=6697|pages=82–86|date=September 1998|pmid=9738502|doi=10.1038/25764|url=|issn=}}</ref> ThisTato structurestruktura isse composedskládá ofze concentricsoustředných ringskruhů (oftenpřipomínajících refferedterč, toz asnichž akaždý bull’sobsahuje eye model of the immunological synapse) each containing segregated clusters ofspecifické proteinsproteiny:
* '''c-SMAC''' (central-centrální SMAC) composedsložený ofz the [[:en:PRKCQ|θ isoform]]isoformy of [[:en:Protein_kinase_C|protein kinasekinázy C]],<ref name="pmid8985252">{{citea journal|vauthors=Monks CR, Kupfer H, Tamir I, Barlow A, Kupfer A|title=Selective modulation of protein kinase C-theta during T-cell activation|journal=Nature|volume=385|issue=6611|pages=83–86|date=January 1997|pmid=8985252|doi=10.1038/385083a0|url=|issn=}}</ref>molekul [[:en:CD2|CD2]], [[:en:CD4|CD4]], [[:en:CD8|CD8]], [[:en:CD28|CD28]], [[:en:Lck kináza|Lck]], anda [[:en:FYN|Fyn]].,<ref name="pmid11859198">{{cite journal|vauthors=Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS|title=T cell receptor signaling precedes immunological synapse formation|journal=Science|volume=295|issue=5559|pages=1539–1542|date=February 2002|pmid=11859198|doi=10.1126/science.1067710|url=|issn=}}</ref>
* '''p-SMAC''' (peripheral-periferní SMAC) withinve whichkterém thejsou lymphocyteuspořádány function-associatedproteiny antigen-1 ([[:en:Lymphocyte_function-associated_antigen_1|LFA-1]]) and the cytoskeletal proteina [[:en:Talin_protein|talin]] are clustered.,<ref name="pmid9738502" />
* '''d-SMAC''' (distal-distální SMAC) enrichedbohatý inna molekuly [[:en:CD43|CD43]] anda [[:en:PTPRC|CD45]] molecules.<ref name="pmid11728332">{{cite journal|vauthors=Delon J, Kaibuchi K, Germain RN|title=Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin|journal=Immunity|volume=15|issue=5|pages=691–701|date=November 2001|pmid=11728332|doi=10.1016/S1074-7613(01)00231-X|url=|issn=}}</ref><ref name="pmid12244310">{{cite journal|vauthors=Freiberg BA, Kupfer H, Maslanik W, Delli J, Kappler J, Zaller DM, Kupfer A|title=Staging and resetting T cell activation in SMACs|journal=Nat. Immunol.|volume=3|issue=10|pages=911–917|date=October 2002|pmid=12244310|doi=10.1038/ni836|url=|issn=}}</ref>
NewNové investigations,výzkumy ale howeverukazují, haveže showntypická thatterčovitá thestruktura originalnení bull’spřítomna eyeve modelvšech istypech notimunologických present in all immunological synapsessynapsí. ForJiná example,uspořádání differentbyla patternspopsána appear innapř. theu synapse betweenmezi [[:en:T_cellT-lymfocyt|T-cell buňkou]] anda [[:en:Dendritic_cellDendritická buňka|dendriticdendritickou cellbuňkou]]. <ref>{{Cite journal|last=Tseng|first=Su-Yi|last2=Waite|first2=Janelle C.|last3=Liu|first3=Mengling|last4=Vardhana|first4=Santosha|last5=Dustin|first5=Michael L.|date=2008-10-01|title=T Cell-Dendritic Cell Immunological Synapses Contain TCR-dependent CD28-CD80 Clusters That Recruit Protein Kinase Cθ|url=http://www.jimmunol.org/content/181/7/4852|journal=The Journal of Immunology|language=en|volume=181|issue=7|pages=4852–4863|doi=10.4049/jimmunol.181.7.4852|issn=0022-1767|pmid=18802089}}</ref><ref>{{Cite journal|last=Brossard|first=Cédric|last2=Feuillet|first2=Vincent|last3=Schmitt|first3=Alain|last4=Randriamampita|first4=Clotilde|last5=Romao|first5=Maryse|last6=Raposo|first6=Graça|last7=Trautmann|first7=Alain|date=2005-06-01|title=Multifocal structure of the T cell – dendritic cell synapse|url=http://onlinelibrary.wiley.com/doi/10.1002/eji.200425857/abstract|journal=European Journal of Immunology|language=en|volume=35|issue=6|pages=1741–1753|doi=10.1002/eji.200425857|issn=1521-4141}}</ref>
This complex as a whole is postulated to have several functions including but not limited to:
TheCelý initialproces interactionformace occurstrvá betweencca [[6 hodin.<ref name=": en:Lymphocyte_function-associated_antigen_1|0" /> Prvotní interakce probíhá mezi LFA-1 ]] present inpřítomným thev p- SMACSMACu ofT a [[:en:T_cell|T-cell]]buňky, anda non-specificnespecifickými adhesionadhezními moleculesmolekulami ( suchnapř. as [[:en:ICAM-1 |ICAM-1]] ornebo [[:en:ICAM2|ICAM-2 ]]) onna targetcílové cellbuňce. WhenKdyž binded to the target cell,se T -cell canbuňka extendnaváže pseudopodiana andcílovou scanbuňku, themůže surfacena ofjejím targetpovrchu cellpomocí topseudopodií findhledat a specificspecifický [[ :en:Major_histocompatibility_complexHlavní histokompatibilní komplex| peptidepeptid:MHC complexkomplex]].<ref name=":0">{{Cite journal|last=Xie|first=Jianming|last2=Tato|first2=Cristina M.|last3=Davis|first3=Mark M.|date=2013-01-01|title=How the immune system talks to itself: the varied role of synapses|url=http://onlinelibrary.wiley.com/doi/10.1111/imr.12017/abstract|journal=Immunological Reviews|language=en|volume=251|issue=1|pages=65–79|doi=10.1111/imr.12017|issn=1600-065X|pmc=3645447|pmid=23278741}}</ref> <ref>{{Cite book|url=https://books.google.cz/books?id=WDMmAgAAQBAJ&dq=janeway+immunobiology&hl=cs&sa=X&redir_esc=y|title=Janeway's Immunobiology|last=Murphy|first=Kenneth M.|date=2011-07-25|publisher=Taylor & Francis Group|isbn=9781136665219|language=en}}</ref> ▼* Regulation of lymphocyte activation<ref name="Immunological Synapse">{{cite journal|last=Davis|first=DM|author2=Dustin, ML|title=What is the importance of the immunological synapse?|journal=Trends in immunology|date=June 2004|volume=25|issue=6|pages=323–7|pmid=15145322|doi=10.1016/j.it.2004.03.007}}</ref>
* Transfer of peptide-MHC complexes from APCs to lymphocytes<ref name="Immunological Synapse" />
* Direct secretion of cytokines or lytic granules<ref name="Immunological Synapse" />
Proces formace imunologické synapse začíná vazbou T-buněčného receptoru na peptid:MHC komplex antigen-prezentující buňky. Specifické signalizační dráhy spouští orientaci centrosomu T buňky směrem k budoucí synapsi. Celá imunologická synapse a všechny v ní probíhající děje jsou od této chvíle silně polarizovány.
== Formation ==
▲The initial interaction occurs between [[:en:Lymphocyte_function-associated_antigen_1|LFA-1]] present in the p-SMAC of a [[:en:T_cell|T-cell]], and non-specific adhesion molecules (such as [[:en:ICAM-1|ICAM-1]] or [[:en:ICAM2|ICAM-2]]) on target cell. When binded to the target cell, T-cell can extend pseudopodia and scan the surface of target cell to find a specific [[:en:Major_histocompatibility_complex|peptide:MHC complex]].<ref name=":0">{{Cite journal|last=Xie|first=Jianming|last2=Tato|first2=Cristina M.|last3=Davis|first3=Mark M.|date=2013-01-01|title=How the immune system talks to itself: the varied role of synapses|url=http://onlinelibrary.wiley.com/doi/10.1111/imr.12017/abstract|journal=Immunological Reviews|language=en|volume=251|issue=1|pages=65–79|doi=10.1111/imr.12017|issn=1600-065X|pmc=3645447|pmid=23278741}}</ref> <ref>{{Cite book|url=https://books.google.cz/books?id=WDMmAgAAQBAJ&dq=janeway+immunobiology&hl=cs&sa=X&redir_esc=y|title=Janeway's Immunobiology|last=Murphy|first=Kenneth M.|date=2011-07-25|publisher=Taylor & Francis Group|isbn=9781136665219|language=en}}</ref>
TheNěkteré processčásti ofprocesu formationformace begins when T-cell receptor ([[:en:T-cell_receptor|TCR]]) binds to the peptide:MHC complex on the [[:en:Antigen-presenting_cell|APC]]. Specific signalization pathways lead to polarization of the T-cell by orientation of its [[:en:Centrosome|centrosome]] towards the site of the immunologicaliunologické synapse. These symmetricmohou centripetallišit actin flow lays at the basis of formation Some parts of this process may differ inu CD4+ anda CD8+ cellslymfocytů. <ref>{{Cite journal|title=Cell polarisation and the immunological synapse|url=http://www.sciencedirect.com/science/article/pii/S095506741200138X}}</ref>
== Reference ==
The whole process of the immunological synapse formation takes about 6 hours. <ref name=":0" />
It was first discovered by [[:en:Abraham_Kupfer|Abraham Kupfer]] at the [[:en:National_Jewish_Medical_and_Research_Center|National Jewish Medical and Research Center]] in Denver and the term was coined by [[:en:Michael_Dustin|Michael Dustin]] at NYU who studied it in further detail. Daniel Davis and Jack Strominger showed structured immune synapses for a different lymphocyte, the [[:en:Natural_Killer_cell|Natural Killer cell]], and published this around the same time.<ref name="pmid10611338">{{cite journal|vauthors=Davis DM, Chiu I, Fassett M, Cohen GB, Mandelboim O, Strominger JL|title=The human natural killer cell immune synapse|journal=Proc Natl Acad Sci U S A|volume=96|issue=26|pages=15062–7|date=Dec 1999|pmid=10611338|doi=10.1073/pnas.96.26.15062|url=|issn=|pmc=24773}}</ref> Abraham Kupfer first presented his findings during one of the [http://www.keystonesymposia.org/ Keystone symposia] in 1995, when he showed three-dimensional images of immune cells interacting with one another. Key molecules in the synapse are the [[:en:T_cell_receptor|T cell receptor]] and its counterpart the [[:en:Major_histocompatibility_complex|major histocompatibility complex]] (MHC). Also important are [[:en:LFA-1|LFA-1]], [[:en:ICAM-1|ICAM-1]], [[:en:CD28|CD28]], and [[:en:CD80|CD80]]/[[:en:CD86|CD86]].
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