The Role Of The Innate Immune System In Infl ammatory Bowel Disease: We have met the enemy and he is us

The human intestine contains about 1014 micro-organisms that critically contribute to tissue homeostasis, host metabolism and other benefi cial processes. Despite a continuous microbial exposure within in the intestine, the mucosal immune system is able to maintain a state of tolerance to the microbiota. An aberrant immune response of the intestinal immune system results in a defective tolerance in the intestine, which leads to a breakdown of intestinal homeostasis. This in turn, can lead to chronic intestinal infl ammation or inflammatory bowel disease (IBD). From an immunological perspective, exaggerated responses by mucosal T and B cells (the adaptive immune system) have traditionally been regarded as the key contributors to the pathogenesis of IBD. However, discoveries of innate defects that are associated with IBD have refocused the attention to this arm of the immune system. In this thesis we try to answer some of the open questions concerning the pathogenesis of IBD and defects in the innate immune system.