Modeliranje imunskega odziva na okužbo z organizmom Pneumocystis jirovecii : magistrsko delo

Lah, Darin

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Title:	Modeliranje imunskega odziva na okužbo z organizmom Pneumocystis jirovecii : magistrsko delo
Authors:	ID Lah, Darin (Author) ID Dobovišek, Andrej (Mentor) More about this mentor... ID Roškar, Zlatko (Comentor)
Files:	MAG_Lah_Darin_2022.pdf (2,04 MB) MD5: 6D92D31562519BD4715DEF4FE524D552
Language:	Slovenian
Work type:	Master's thesis/paper
Typology:	2.09 - Master's Thesis
Organization:	FNM - Faculty of Natural Sciences and Mathematics
Abstract:	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.
Keywords:	Pneumocystis jirovecii, imunski odziv, imunska pomanjkljivost, antibiotik, fizikalno-matematični model.
Place of publishing:	Maribor
Place of performance:	Maribor
Publisher:	[D. Lah]
Year of publishing:	2022
Number of pages:	40 str.
PID:	20.500.12556/DKUM-82555
UDC:	53:615.33(043.2)
COBISS.SI-ID:	121723395
Publication date in DKUM:	20.09.2022
Views:	2364
Downloads:	96
Metadata:
Categories:	FNM
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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	24.08.2022

Secondary language

Language:	English
Title:	Modelling of the immune response to Pneumocystis jirovecii infection
Abstract:	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.
Keywords:	Pneumocystis jirovecii, immune response, immunodeficiency, antibiotic, physical-mathematical model.

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