Disertasi

Regulasi Respons Imun Subyek di Permukiman Kumuh: Studi Imunitas Seluler pada Kultur Sel Darah yang Distimulasi Malaria, BCG dan LDL. = Regulation of immune respons to people living in the slum area: a study of celluler immunity on Whole Blood Cultures stimulated malaria, BCG and LDL.

Pendahuluan: Pajanan mikroorganisme yang bervariasi dan terjadi terus menerus di lingkungan tempat tinggal berperan penting membentuk mekanisme repons imun individu yang dapat mempengaruhi kerentanan seseorang terhadap kejadian suatu penyakit. Penelitian ini bertujuan mengetahui mekanisme pajanan mikroorganisme di permukiman yang berbeda mampu memodulasi polarisasi perkembangan respons imun seluler individu terhadap antigen malaria, BCG dan oxLDL pada kultur sel darah dan mempelajari peranan sel T regulator sebagai mediator supresi proliferasi sel. Metode: Penelitian ini merupakan studi eksperimental in vitro yang dilakukan di Laboratorium Terpadu FKUI pada tahun 2013-2015. Malaria dan BCG digunakan sebagai antigen untuk memodulasi perkembangan repons imun terhadap penyakit infeksi dan LDL terhadap penyakit metabolik. Polarisasi respons imun diukur melalui ekspresi mediator proinflamati (TNF-α dan IFN-γ), dan antiinflamasi (IL- 10) pada kultur sel darah. Karakter makrofag dan fungsi sel T reg dipelajari dengan mengukur ekspresi Il-10 dan hitung sel PMBC dari kultur makrofag dan PBMC yang distimulasi dengan PHA, malaria, BCG dan LDL. Hasil: Respons imun dan aktivasi makrofag terhadap malaria dan BCG pada subyek di permukiman kumuh menunjukkan ekspresi rasio mediator pro/antiinflamasi (TNF-α/IL-10) yang lebih rendah dengan proporsi makrofag berisi malaria lebih tinggi secara bermakna (p < 0.01) dibandingkan subyek di permukiman nonkumuh. Respons imun dan aktivasi makrofag terhadap LDL pada subyek di permukiman nonkumuh menunjukkan ekspresi rasio mediator pro/antiinflamasi (TNF-α/IL-10) yang tinggi dengan derajat fagositosis terhadap LDL yang lebih tinggi secara bermakna (p < 0.01) dibandingkan subyek di permukiman kumuh. Karakter sel T regulator sebagai supresi proliferasi pada subyek di permukiman kumuh ditandai dengan kemampuan meningkatnya proliferasi sel yang lebih tinggi secara bermakna (p < 0.01) pada kultur PBMC yang dihilangkan sel T reg nya dibandingkan subyek di permukiman nonkumuh. Kesimpulan: Variasi pajanan mikroorganisme yang tinggi di permukiman kumuh mampu memodulasi perkembangan respons imun individu menjadi suseptibel terhadap malaria dan BCG dengan karakter sel T reg yang kuat. Respons imun individu di permukiman nonkumuh menunjukkan kecenderungan aktivasi makrofag terhadap LDL meningkat dengan karakter sel T reg lemah.
Kata kunci : makrofag, malaria, BCG, oxLDL, sel T reg, respons imun seluler.



Introduction: Constant exposure to a variety of microorganisms in domestic environment plays an important role in the shaping of individual immune response mechanism, which can affect one’s susceptibility to the diseases. The aim of the study to get an understanding how the exposure of microorganisms in the the different area where the people living might give a contribution to the profile and the regulation of the immune respons after stimulated to malaria, vaccine BCG and oxLDL antigents in PBMC and whole blood cultures, and to evaluate the character of T reg as a mediator to suppress the cell proliferation. Methode: It is an in vitro experimental study performed at Laboratorium Terpadu, Faculty of Medicine Univertas Indonesia, Jakarta in 2013-2014. As a model of infectious diseases is used pathogenic antigents such as Plasmodium falciparum infected red blood cells (malaria) and bacille calmette guѐrin (BCG) vaccine, and as a modell of inflammatory disease is used non a patonegic antigen, low-density lipoprotein (LDL). Whole blood cultures is done for 80 blood samples to know how the regulation of immune respons from people living a rural populatin. PBMC cultures is also done to explore macrophages after stimulated to malaria, BCG and LDL. PHA stimulated to the PBMC culture with and without T reg cells to evaluate the character of T reg. T regulatory cells perhaps play the important roles to suppress the immune respons to microorganisms was also done. Results: The profile of the immune respons of the people living in the unslum area is significantly more inflamatif than that in the slum area. The ratio of pro/anti inflammation cytokines (TNF-α/IL-10) of the people living in the unslum area is significantly higher than that in the slum area. This is marked by increasing of oxLDL accumulationis that is the important point of the low protection to oxLDL of the people living in the unslum area (p < 0.01). T regulatory cell may suppress the proliferation in the PBMC culture for the people living in the slum area marked by increasing not only the expression of IL-10 cytokines but also the sum of T regulatory sells (p < 0.01) significantly. Conclusion: The immune respons of the people living in the unslum area is more inflamatif and responsive to malaria, BCG vaccine and oxLDL. The character of macrophage of the people living in the slum area is marked by the low ratio of pro/anti inflammation cytokines (TNF-α/IL-10) to malaria, BCG vaccine and oxLDLstimulations. T regulatory cell may suppress the proliferation in the PBMC culture for the people living in the slum
Key word: macrophage, malaria, BCG, LDL, regulatory T cell, cellular.