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Kar, Satwik
Languages: English
Types: Doctoral thesis
Subjects: QR180, R1
The innate immune system has a variety of ways of recognizing infection from pathogens such as viruses and bacteria. One of its first lines of defence is to detect Pattern Associated Molecular Patterns (PAMPs) using Pattern Recognition Receptors (PRRs) such as the Toll-Like Receptors (TLRs), the RIG-Like Helicases (RLHs) and the Nod-Like Receptors (NLRs). These receptors recognize certain molecular structures from the pathogens and lead to first line of defence which includes increased cytokines and IFNs.\ud This study delineate the human body’s innate immune responses to human respiratory viruses such as HRV (Human Rhinovirus), RSV (Respiratory Syncytial Virus) and IAV (Influenza A virus). In Vitro experiments carried out on various kinds of lung tissues suggest that respiratory disease pathogenesis is related to inflammatory mediators including interleukins and cytokines produced by the host’s innate immune system.\ud Virus induced respiratory tract infection are known to trigger bronchiolitis, wheezing and acute asthma exacerbations, as a result of inflammation of lung tissues and excessive release of pro- inflammatory cytokines such as IL-1β. This study identifies that intracellular macromolecular complexes called inflammasomes assemble as a result of viral trigger. Inflammasomes convert the inactive forms of the pro-inflammatory cytokines to their active forms. Although the exact mechanism of activations of these complexes was unknown. This study identified that Virus encoded proteins such as the 2B protein of HRV, the SH protein from RSV and the Influenza M2 which are also termed viroporins can activate the inflammasome by causing ion imbalance (across cells membranes and organelles). Thus providing a trigger for inflammasome assemblage.\ud v\ud Drugs which act as Ion channel blockers have been shown to block viroporin activity and hence reduce IL-1β production. Therefore in the future the use of ion inhibitors could be a possible therapeutic intervention in order to reduce lung inflammation and prevent associated respiratory disease such as COPD and Asthma.

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