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Title: Developmental innate immunoinsufficiency : comparison of term neonatal neutrophil proteinases and complement component levels relative to adults
Author: Abdulla, Salima Abubaker
ISNI:       0000 0004 2733 7615
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2012
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Despite current improvement in newborn care, infection is still a common cause of neonatal morbidity and mortality. Innate immunity is the first line of defence against pathogens particularly in newborn infants. Quantitative and functional deficit in non-cellular (complement system) and cellular (neutrophils) arms of innate immune system is believed to contribute to neonatal susceptibility to infection. Neutrophil granule subsets contain a variety of proteases, including elastase, cathepsins, MMP-9 and proteinase 3 along with different granule markers and receptors. This thesis demonstrated that normal term neonatal neutrophils express more proteinase 3 and CD177 on their surface while no differences were found in expression of markers CD35, CD66b and CD63 (representing the secretory, secondary and primary granule subsets, respectively). Cord neutrophils contain more PR3 than adult cells but the proportion of PR3 released by cord and adult neutrophils was similar. In contrast, neonatal neutrophils contained only half of the cathepsin G and elastase functional activity of adult neutrophils. Bronchoalveolar lavage fluid studied from preterm infants ventilated for respiratory distress demonstrated higher proteinase 3 concentrations in lavage samples from infants who went on to develop chronic lung disease than in infants with resolved respiratory distress syndrome. Concentration of proteinase 3 in lavage samples was significantly higher than MMP-9 and elastase levels, suggesting that it may have an important role in disease pathogenesis. Complement is an equally important component of the innate immune system that plays a central role in recruiting and activating neutrophils, as well as being directly bactericidal through the terminal lytic pathway. Analysis of neonatal complement system revealed that Complement function and terminal components levels particularly C9 are deficient (except C7) in healthy term newborn infants compared to normal adults. Bactericidal capacity of a selection of neonatal sera was tested along with adult sera against four serovars of Ureaplasma parvum, a potentially important perinatal pathogen. Results showed impaired bactericidal capacity of neonatal serum compared to adult serum especially against SV1. Ureaplasma SV3 was the most serum sensitive serovar whereas killing of the resistant serovars SV6 and 14 could not be induced by supplementation of the deficient components C6, C8 and C9.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR180 Immunology ; RJ Pediatrics