The aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low... Show moreThe aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low muscle strength, while high acute pro-inflammatory response is associated with high muscle strength. Show less
In a world where bacterial infections are becoming harder and harder to fight due to rising antibiotic resistance, disease models that allow high throughput screening are needed more than ever. An... Show moreIn a world where bacterial infections are becoming harder and harder to fight due to rising antibiotic resistance, disease models that allow high throughput screening are needed more than ever. An ideal model organism for high throughput screening is the zebrafish embryo. However, models for high throughput screening of infection are still wanted. In this thesis the fish pathogen Edwardsiella tarda was tested for use in high throughput studies of infectious disease in zebrafish. First the genome of Edwardsiella tarda was sequenced to determine the virulence factors of this bacterium. Next different types of exposure of zebrafish to Edwardsiella tarda were tested. This showed an absence of detectable infection after static immersion, but a reproducible infection on the level of single embryos after caudal vein injection. Finally, using the caudal vein injection method, the zebrafish knock-out mutant in the gene Myd88 was characterized. This is the first zebrafish knock-out mutant in a gene central in the innate immune system. Show less
The scope of the current thesis is to obtain insight in immunological aspects of transplantation and diabetes. This thesis underscores the current concept of collaboration between the innate and... Show moreThe scope of the current thesis is to obtain insight in immunological aspects of transplantation and diabetes. This thesis underscores the current concept of collaboration between the innate and adaptive immune system by showing close interactions between both immune systems. Mannose binding lectin as a major recognition molecule of the lectin pathway and as a key protein of the immune system was studied in relation to its functional characteristics. Appreciating the Jekyll-and-Hyde character of MBL and the fact that MBL serum levels and functionality are under strict genetic control, MBL was studied under distinct pathological conditions. Chapter 2 describes molecular and biological aspects of mannose binding lectin and the interaction of MBL with the adaptive immune system. Chapter 3 focuses on the involvement of MBL in autoimmunity, by studying juvenile type 1 diabetic patients at disease onset. Chapter 4 addresses the role of the liver in production of serum MBL and evaluates the effect of MBL variant alleles on the susceptibility to infection after liver transplantation. Chapter 5 focuses on the effect of the adaptive immune system on islet transplantation, a novel treatment of type 1 diabetes. Show less
