The influence of neoliberal thought on contemporary politics: an examination of the interrelationships between ideological hegemony, neoliberal thought and contemporary politics

This thesis critically assesses the impact of neoliberal ideology on liberal thought and contemporary politics specifically examining the question, To what extent has neoliberalism, as elucidated originally by Hayek affected change in contemporary politics? This question is crucial to understanding the nature, role, influence and impact of neoliberal ideas. This investigation required a broad engagement with the literature, identifying and discussing the relationships within neoliberalism allowing a clearer understanding of the role of ideas in neoliberalism’s continuing hegemony. The methodological approach adopted a social constructivist character that encompassed an individual centric emphasis, acknowledging the breadth and complexity of Neoliberalization through the use of interpretive repertoires. The initial chapters examine the ideational process and the role of particular understanding in motivating political conduct. In this context of the transfer of ideas through their everyday resonance eventually becoming ‘stubborn social facts’ (Habermas 2006:413) is highlighted. Later chapters discuss the historical and economic context of Neoliberalization focussing on the role of the hegemon and its influence, outlining and evaluating the contribution of Hayek to liberal thought. The penultimate chapter deals with the contemporary situation and the irony associated with Hayek’s original ideas. Concluding, several findings emerged contributing by combining available knowledge in a uniquely fresh way and generating originality by linking old ideas, new ideas and new facts. The results are grouped as, - Pragmatic, recognising that political pragmatism trumps ideological aspiration where liberal democratic processes require politicians are held to account. - Realistic, recognising the contrast and irony between political action and ideological insight reflected in the operationalization of neoliberalism. - General, recognising Hayek’s on-going but increasingly indirect influence. The thesis finishes with a short aside on ideational change within the context of the current crisis and advocates an introspective approach that includes entrepreneurial spirit, good conscience and duty as part of future deliberations.

Identification of novel innate immune mechanisms regulating inflammation in the gastrointestinal tract

The Gastro-Intestinal (GI) tract is a unique region in the body. Our innate immune system retains a fine homeostatic balance between avoiding inappropriate inflammatory responses against the myriad commensal microbes residing in the gut while also remaining active enough to prevent invasive pathogenic attack. The intestinal epithelium represents the frontline of this interface. It has long been known to act as a physical barrier preventing the lumenal bacteria of the gastro-intestinal tract from activating an inflammatory immune response in the immune cells of the underlying mucosa. However, in recent years, an appreciation has grown surrounding the role played by the intestinal epithelium in regulating innate immune responses, both in the prevention of infection and in maintaining a homeostatic environment through modulation of innate immune signalling systems. The aim of this thesis was to identify novel innate immune mechanisms regulating inflammation in the GI tract. To achieve this aim, we chose several aspects of regulatory mechanisms utilised in this region by the innate immune system. We identified several commensal strains of bacteria expressing proteins containing signalling domains used by Pattern Recognition Receptors (PRRs) of the innate immune system. Three such bacterial proteins were studied for their potentially subversive roles in host innate immune signalling as a means of regulating homeostasis in the GI tract. We also examined differential responses to PRR activation depending on their sub-cellular localisation. This was investigated based on reports that apical Toll-Like Receptor (TLR) 9 activation resulted in abrogation of inflammatory responses mediated by other TLRs in Intestinal Epithelial Cells (IECs) such as basolateral TLR4 activation. Using the well-studied invasive intra-cellular pathogen Listeria monocytogenes as a model for infection, we also used a PRR siRNA library screening technique to identify novel PRRs used by IECs in both inhibition and activation of inflammatory responses. Many of the PRRs identified in this screen were previously believed not to be expressed in IECs. Furthermore, the same study has led to the identification of the previously uncharacterised TLR10 as a functional inflammatory receptor of IECs. Further analysis revealed a similar role in macrophages where it was shown to respond to intracellular and motile pathogens such as Gram-positive L.monocytogenes and Gram negative Salmonella typhimurium. TLR10 expression in IECs was predominantly intracellular. This is likely in order to avoid inappropriate inflammatory activation through the recognition of commensal microbial antigens on the apical cell surface of IECs. Moreover, these results have revealed a more complex network of innate immune signalling mechanisms involved in both activating and inhibiting inflammatory responses in IECs than was previously believed. This contribution to our understanding of innate immune regulation in this region has several direct and indirect benefits. The identification of several novel PRRs involved in activating and inhibiting inflammation in the GI tract may be used as novel therapeutic targets in the treatment of disease; both for inducing tolerance and reducing inflammation, or indeed, as targets for adjuvant activation in the development of oral vaccines against pathogenic attack.