Multipla skleroza: temeljne značajke i mehanizam nastanka

undergraduate thesis

• Title (english): Multiple sclerosis: basic features and underlying disease mechanism
• Author: Petra Nižić
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2011, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Multipla skleroza je upalna demijelinizacijska bolest središnjeg živčanog sustava (CNS-a) čija je glavna manifestacija nastanak lezija koje su rezultat gubitka mijelinske ovojnice oko aksona neurona, ali i oštećenja samih demijeliniziranih aksona. Lezije koje nastaju posljedica su djelovanja autoreaktivnih imunosnih stanica koje se infiltriraju u mozak prelazeći krvno moždanu barijeru, zbog čega se multipla skleroza smatra autoimunosnom bolešću. Uzrok bolesti je nepoznat, no prevladava mišljenje da je uzrokovana s više međusobno neisključivih čimbenika, kao što su okolišni i infektivni čimbenici u genetski predisponiranim pojedincima u kojih dolazi do aktivacije postojećih autoreaktivnih pomagačkih limfocita T i njihovog posljedičnog patogenog djelovanja. Mnoga saznanja o mehanizmu nastanka oštećenja CNS-a u multiploj sklerozi dolaze iz istraživanja na animalnom modelu izazvane autoimunosti - eksperimentalnog autoimunog encefalomijelitisa - koji ima brojne kliničke, neuropatološke i imunološke značajke multiple skleroze. Tako je pomoću tog modela pokazano da nakon ekspanzije autoreaktivnih TH1 i / ili TH17 limfocita u sekundarnim limfnim organima dolazi do njihovog probijanja krvno-moždane barijere izlučenjem proupalnih citokina i drugih topljivih čimbenika poput matriks metaloproteaza i reaktivnih radikala kisika. Također, stanice mozga aktivirane upalnim proizvodima infiltrirajućih leukocita također otpuštaju citokine koji dodatno pridonose novačenju leukocita iz krvi i probijanju barijere. Veliki broj aktiviranih TH stanica i drugih proupalnih stanica migrira dublje u bijelu tvar mozga što rezultira nastankom upalne lezije, odnosno dolazi do demijelinizacije, ali i oštećenja aksona i oligodendrocita. Smatra se da najveću ulogu u ozljedi aksona, s posljedičnim trajnim kliničkim deficitom, imaju aktivirani makrofagi i mikroglija stanice koje izlučuju kisikove i dušikove radikale koji su odgovorni za intenzivnu oksidativnu štetu u lezijama oboljelih. Još uvijek ne postoji zadovoljavajuća terapija oboljelih, a meta liječenja bi svakako trebala biti neka točka u slijedu događaja od skretanja autoreaktivnih stanica na patogeni put što naglašava važnost znanja o mehanizmu tijeka bolesti.

Abstract (english)

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system (CNS) whose main manifestation is the formation of lesions that result from the loss of myelin sheath around the axons of neurons and damage of axons themselves. Lesions arise as a result of action of autoreactive immune cells that infiltrate the brain crossing the blood brain barrier, which is why multiple sclerosis is considered an autoimmune disease. The cause of the disease is unknown but the prevailing opinion is that it is caused by a number of mutually non-exclusive factors, such as environmental and infectious factors in genetically predisposed individuals in whom an activation of existing autoreactive helper T lymphocytes happens with their subsequent pathogenic actions. Many insights about the mechanism of CNS damage in multiple sclerosis come from an animal model of induced autoimmunity - experimental autoimmune encephalomyelitis - which has many clinical, neuropathological and immunological features of multiple sclerosis. This model demonstrated that the activation and expansion of autoreactive TH1 and / or TH17 lymphocytes in secondary lymphoid organs leads to breaking of the blood-brain barrier by secretion of proinflammatory cytokines and other soluble factors such as matrix metalloproteinases and reactive oxygen species. Also, the brain cells activated by inflammatory products of the infiltrating white blood cells release cytokines that further contribute to the recruitment of leukocytes from the blood and breaking of the blood-brain barrier. A large number of activated TH cells and other proinflammatory cells migrate deeper into the white matter of the brain, resulting in the appearance of inflammatory lesions in which demyelination and damage to axons and oligodendrocytes occur. It is believed that activated macrophages and microglia cells which secrete oxygen and nitrogen radicals have the greatest role in axonal injury, which results with permanent clinical deficit. There is still no satisfactory treatment of multiple sclerosis; the target for treatment should be a point in the sequence of events from the turn of autoreactive cells in the pathogenic way and that comprehension highlights the importance of knowledge about the underlying disease mechanism.

• Keywords: multipla skleroza
• Keywords (english): multiple sclerosis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:545802
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-04-09 10:38:28