20.500.12556/DKUM-82555 Modeliranje imunskega odziva na okužbo z organizmom Pneumocystis jirovecii magistrsko delo Modelling of the immune response to Pneumocystis jirovecii infection Pneumocystis jirovecii ali krajše pnevmocista je mikroorganizem, uvrščen v kraljestvo gliv, ki pri imunokompromitiranih bolnikih ob oportunistični okužbi povzroči pnevmocistično pljučnico (PJP). Imunski odziv gostitelja ima ključno vlogo pri razvoju poteka bolezni. V magistrskem delu preučujemo imunski odziv na okužbo z organizmom Pneumocystis jirovecii in razvijemo fizikalno-matematični model, s katerim opišemo imunski odziv na okužbo pri imunokompetentnem in imunokompromitiranem gostitelju, okuženim s HIV. Pri razvoju modela upoštevamo naslednje celične populacije: okužene in neokužene celice pljučnega epitelija, alveolarne makrofage, limfocite B in CD4+T ter rekrutirane makrofage, ki se preobrazijo iz monocitov. Kot posrednike informacij med celicami in regulatorje celičnih interakcij upoštevamo dve vrsti citokinov. V modelu definiramo modelno stanje imunokompetentnega in tri različna modelna stanja imunokompromitiranega gostitelja. Model imunskega odziva sklopimo s standardnim dvoshrambnim farmakokinetičnim modelom peroralnega doziranja antibiotika sulfametoksazol/trimetoprim (SMX/TMP). Simuliramo različne klinično relevantne sheme doziranja SMX/TMP, s katerimi v klinični praksi preprečujejo ali zdravijo PJP. Osredotočimo se na simulacije časovnih potekov koncentracije pnevmociste v vseh definiranih modelnih stanjih z učinkovanjem ali brez učinkovanja antibiotika SMX/TMP. Rezultati modelnih simulacij kažejo, da v vseh modelnih stanjih koncentracija pnevmociste ob okužbi strmo naraste do maksimalne vrednosti in se nato ustali na nižji stacionarni vrednosti, ki se bistveno razlikuje med modelnimi stanji imunokompetentnega in imunokompromitiranega gostitelja. Na podlagi modelnih simulacij, v katere vključimo učinkovanje antibiotika, sklepamo, da s preventivnim načinom zdravljenja učinkovito preprečimo okužbo s pnevmocisto. Modelne simulacije zdravljenja PJP s pogostejšim doziranjem antibiotika kažejo, da pri zdravljenju populacijo pnevmociste hitro in uspešno zatremo v nekaj dneh. Pneumocystis jirovecii is an opportunistic fungal microorganism, which causes Pneumocystis pneumonia (PJP) in immunocompromised patients. The host's immune response plays a central role in determining the further course of the disease. In this work, we study the immune response to Pneumocystis jirovecii infection. A physical-mathematical model is developed to describe the immune response to infection in immunocompetent and immunocompromised HIV-infected hosts. The following cell populations are considered: uninfected and infected lung epithelial cells, resident alveolar macrophages, lymphocytes B, lymphocytes CD4+T and recruited monocyte-derived macrophages. Two groups of cytokines are included as crucial messengers and regulators of cell interactions. Within the model, we define one model state of an immunocompetent host and three different model states of an immunocompromised host. The immune response model is coupled with a standard two-compartment pharmacokinetic oral dosing model of the antibiotic sulfamethoxazole/trimethoprim (SMX/TMP). We simulate three different clinically relevant SMX/TMP dosing regimens used to prevent or treat PJP in clinical practice. The focus of this study is on model simulations of the Pneumocystis concentration as a function of time with or without antibiotic treatment. The results of model simulations show that during infection in the absence of SMX/TMP, the concentration of Pneumocystis initially increases and then decreases to its final steady-state value. We find that there are significant differences in this value between model states of an immunocompetent and an immunocompromised host. Simulations with antibiotic treatment included show that preventive antibiotic treatment successfully suppresses infection and thus prevents the development of PJP. Furthermore, we find that curative treatment of PJP with more frequent SMX/TMP dosing effectively suppresses the infection within a few days, as the Pneumocystis concentration drops sharply. Pneumocystis jirovecii imunski odziv imunska pomanjkljivost antibiotik fizikalno-matematični model. Pneumocystis jirovecii immune response immunodeficiency antibiotic physical-mathematical model. true true false [D. Lah] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2022-08-24 17:47:45 2022-09-20 08:53:56 2022-09-21 03:07:12 0000-00-00 00:00:00 2022 0 Maribor 0 Maribor 40 str. 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 53:615.33(043.2) 121723395 MAG_Lah_Darin_2022.pdf MAG_Lah_Darin_2022.pdf 1 6D92D31562519BD4715DEF4FE524D552 1008de8c1501e057d1978b7b005d6d72e36177ef858084c95d6824faac38b3fb 28e6a172-23c6-11ed-81ca-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=160725 Fakulteta za naravoslovje in matematiko 0 0 0