Respon Imun Terhadap KankerD.H. Setya Palupi
DefinisiAda pengaturan keseimbangan antara pembaharuan sel dan kematian selTumor/ Neoplasma = perkembangan sel yang tidak terkontrolTumor yang berkembang dan menyebar kanker
JinakNon invasifGanasInvasif dan metastasis
Tumor ganastumor ber-metastase dan berkembangbiaktumor sekunderKlasifikasi tumor ganas/ kanker berdasar asal jaringan embrio asal, yi:Karsinoma (jar endodermal/ektodermal kulit dan lapisan epitel organ internal dan kelenjar)Kanker sel darah/ hematopoietic cells leukimia dan limfomaSarkoma (jar ikatjar mesodermal tulang, lemak dan tulang rawan)
How do cells become transformed into malignant cells?RadiationCarcinogensVirusesexpression of oncogenes (aberrant versions of proto-oncogenes)
Ada 2 fase :Inisiasiperubahan dalam genomPromosipembelahan sel >>
Mutasi
Tipe pengaturan genProto-onkogenik menginduksi proliferasi dalam beberapa cara.Tumor suppressors menekan proliferasi selRegulasi apoptosis
Defects in any of these can lead to uncontrolled cell growth
Mutasi gen yang terakumulasi dalam sel akan membuat secara bertahap di konversikan menjadi sel ganas.
Translokasi terjadi pada kanker yg spesifik
Sel tumor berbeda dari sel normal => dikenal sbg non-self / foreignimmune responses fail to prevent tumor growth external activation of the immune system
Ada 2 tipe :tumor-specific transplantation antigens (TSTAs) unik utk tumor, tidak terjadi pd sel normalhasil mutasi pd sel tumor yang menghasilkan perubahan protein selularMHC kelas Iinduksi respon imun dimediasi sel oleh CTL spesiifik tumor.tumor-associated transplantation antigens (TATAs). Tidak unik untuk sel tumorHasil ekspresi protein pd sel normal selama pembentukan janin (sistem imun msh belum matang dan tdk dapat merespon)
mutations abnormal expression oncogenic viruses oncofetal antigens altered surface modifications tissue specific differentiation antigens
innate immune responses NK cells macrophages adaptive immune responses T cells antibodies
Anti-tumor antibody can block T cell responses (enhance tumor growth)Tumors can modulate antigens Ag modulation (Abs bind to Ag on leukemic cells, induce capping, endocytosis of Ag, shedding of Ag-Ab complexes)Tumors can reduce MHC Class I expression (selection; escape CTL recognition)Tumors can reduce second signal expression (no B7 -> clonal anergy)
Strategi ImunoterapiMake cells more immunogenic better CTL activation vaccine made up of cells?Enhancement of APC activity can modulate tumor immunity BCG attenuated Mycobacterium bovis mouse dendritic cells incubated with GM-CSF and tumor fragments, then into animal, activate anti-tumor Th and CTLs
Immunotherapy stimulation of immune responsevaccination with tumor cellscostimulators and cytokinesblock inhibitory pathwaysnonspecific stimulation of the immune system
Tumor vaccines
Downloaded from: StudentConsult (on 4 April 2008 09:13 PM) 2005 Elsevier
Systemic cytokine therapy
Immunotherapy passive immunotherapy adoptive cellular therapy graft-versus-leukemia antibodies
Monoclonal antibodies
Figure 14-17
Peransistem imun tubuhthd pertumbuhan tumor chronic inflammation as risk factor for cancer Helicobacter pylori (gastric cancer) hepatitis B and C (hepatocellular carcinoma)
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