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Reducing pneumococcal meningitis related brain damage by inhibition of the host innate immune response.

Karens, Y.E. (2012) Reducing pneumococcal meningitis related brain damage by inhibition of the host innate immune response. Bachelor's Thesis, Biology.

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Abstract

Pneumococcal meningitis is an infectious disease of the central nervous system (CNS) caused by the Gram positive bacterium Streptococcus pneumoniae. The immune response in the CNS against S. pneumoniae is thought to be a cause of the pneumococcal meningitis related brain damage that results in long-term sequelae including deafness and cognitive impairment. In normal situation there are, due to the blood-brain barrier (BBB), no immune modulators present in the CNS, with the exception of microglia, the macrophages of the CNS. Pattern-recognition receptors (PRRs) on and in microglia, including Toll-like receptors (TLR; mainly 2, 4 and 9), Nod-like receptors (NLR) and SIGN-R1 (a C-type lectin receptor) are thought to be responsible for the activation of microglia. These microglia are then able to secrete immune modulatory factors including cytokines, chemokines, matrix metalloproteinases (MMPs) and complement factors. Various and some contradictory effects of the secreted cytokines have been seen in pneumococcal meningitis. While chemokines appear to be primarily responsible for recruitment of leukocytes, MMPs (especially MMP-9) are mainly responsible for the breakdown of the BBB what makes it possible for leukocytes to enter the brain. Complement factors seem to have various functions in the immune response during pneumococcal meningitis, but one important function is to activate leukocytes. Microglia and some leukocytes are able to phagocytize pathogens and secrete reactive nitrogen (RNS) and oxygen (ROS) species, with the intention to eliminate S. pneumoniae out of the CNS. In summary, the host innate immune response during pneumococcal meningitis is very complex and is formed by many immune modulators which can both induce and prevent brain injury. In the future long-term sequelae as a result of pneumococcal meningitis could be reduced by inhibition of pro-inflammatory immune modulators or by stimulation of anti-inflammatory immune modulators.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:48
Last Modified: 15 Feb 2018 07:48
URI: https://fse.studenttheses.ub.rug.nl/id/eprint/10079

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