tumorska imunologija
DESCRIPTION
TUMORSKA IMUNOLOGIJA. Hanahan D. And Weinberg RA. The hallmarks of cancer. Cell 2000,100:57-70. Hanahan D. And Weinberg RA. The hallmarks of cancer. The next generation. Cell, 2011, 164:646-674. SADRŽAJ. IMUNSKI NADZOR TUMORSKI ANTIGENI EFEKTORSKI MEHANIZMI ANTITUMORSKE IMUNOSTI - PowerPoint PPT PresentationTRANSCRIPT
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TUMORSKA IMUNOLOGIJA
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Hanahan D. And Weinberg RA. The hallmarks of cancer. Cell 2000,100:57-70
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Hanahan D. And Weinberg RA. The hallmarks of cancer. The next generation. Cell, 2011, 164:646-674
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SADRŽAJ
• IMUNSKI NADZOR• TUMORSKI ANTIGENI• EFEKTORSKI MEHANIZMI
ANTITUMORSKE IMUNOSTI• MEHANIZMI IZBEGAVANJA IMUNSKOG
ODGOVORA• IMUNOTERAPIJA TUMORA
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Eliminacija ili supresija virusnih infekcija (prevencija virusom indukovanih tumora)
Efikasna eliminacija patogena i brzo okončavanje inflamacije (onemogućavanje tumorigeneze)
Identifikacija i eliminacija tumorskih ćelija kao rezultat prepoznavanja tumorskih antigena (imunski nadzor)
TRI ULOGE IMUNSKOG SISTEMA U PREVENCIJI
TUMORA
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IMUNSKI NADZOR
Fiziološka funkcija imunskog sistema da prepozna i uništi transformisane ćelije pre nego što nastane tumor i da ubija ćelije tumora kada se već razvio.
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Figure 14-12
Normalna ćelija
Tumorska ćelija
Mutacija
TUMORSKI ANTIGENI
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Figure 14-13
Tumorska ćelija
Normalna ćelija
Tumorska ćelija
Reaktivacija gena
Preterana ekspresija gena
TUMORSKI ANTIGENI
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TUMORSKI ANTIGENI
• Tumor-specifični antigeni (TSA)
• Tumor-asocirani antigeni (TAA)
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EFEKTORSKI MEHANIZMI ANTITUMORSKOG ODGOVORA
T limfocitiNK ćelijeAntitela
Makrofagi
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EFEKTORSKI MEHANIZMI ANTITUMORSKOG ODGOVORA
T limfocitiNK ćelijeAntitela
Makrofagi
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EFEKTORSKI MEHANIZMI ANTITUMORSKOG ODGOVORA
T limfocitiNK ćelijeAntitela
Makrofagi
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Figure 1-6
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Prepoznavanje zaraženih i tumorskih ćelija
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EFEKTORSKI MEHANIZMI ANTITUMORSKOG ODGOVORA
T limfocitiNK ćelijeAntitela
Makrofagi
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EFEKTORSKI MEHANIZMI ANTITUMORSKOG ODGOVORA
T limfocitiNK ćelijeAntitela
Makrofagi
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Ubijanje ćelija tumora
ROS, NO, lizozomalni enzimi, citokini (TNFα)
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Imunski odgovor na tumor je moguć
ALI
nije adekvatno pokrenut/aktivisan
suvuše je slab
ne traje dovoljno dugo da spreči rast tumora
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MEHANIZMI KOJIM TUMOR IZBEGAVA IMUNSKI ODGOVOR
Smanjena ekspresija MHC molekula Neadekvatna prezentacija tumorskih antigena Selekcija mutiranih tumorskih ćelija Antigenska modulacija Maskiranje antigena
Supresija imunskog odgovora– Produkcija imunosupresivnih proteina– Indukcija regulatornih ćelija
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IMUNOTERAPIJA TUMORA
Nespecifična
Specifična
Pasivnamonoklonska antitelaadoptivna (LAK, TIL)
AktivnaVakcinacija
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Monoklonska antitela
Uništavaju tumor aktivacijom komplementa ili posredstvom NK ćelija (ADCC)
Indukuju imunski odgovor na tumor (anti CTLA4, PD1)
Blokiraju receptorski protein uključen u nastanak ili progresiju tumora (EGFR, VEGF)
Vezani za izotop, toksin ili siRNA specifično ubijaju tumor
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Figure 14-17
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Adoptivna ćelijska imunoterapija
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VAŽNO ZA PRAVLJENJE VAKCINE PROTIV TUMORA
Identifikovati tumorske antigene
Stimulisati efikasan imunski odgovor protiv tumora
Izbeći autoimunsko oštećenje
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