The role of bacterial LPS is to trigger a good enough innate immune system in mammalian hosts. The lipid moiety, lipid A, is regarded to be endotoxic and is important to the endotoxin activity of LPS. Additionally, it is a bioactive element of LPS and is recognised by the innate immune system even when it is minimally present. Immune detection of lipid A is highly sensitive and potent that even a bloodstream infection can cause endotoxic shock. LPS stimulates an immune response by interacting with some of the active receptors – cluster of differentiation 14 (CD14) and lymphocyte antigen 96 (MD2) receptor complex, all of which have been found to trigger the production of pro-inflammatory cytokines such as tumour necrosis factor-? (TNF), interleukin-6 (IL-6) and interleukin-1 (IL-1). LPS can also bind to Toll receptors, which are intracellular signalling domain, and LPS signalling has also been specifically linked to Toll-like receptor 4 (TLR4). LPS activates proximal signalling pathways in a similar way to those used by IL-1, IL-1 receptor-associated kinase (IRAK) and TNFR-associated factor 6 (TRAF 6). Moreover, LPS exposure has been associated with the activation of a number of signalling cascades, hence stimulating the secretion of inflammatory mediators. LPS are recognised by their host cells because TLR4 and myeloid differentiation factor 2 (MD-2) form a heterodimer, and are able to pick out certain common characteristics in structurally diverse LPS molecules. Determining the crystal structure of the TLR4-MD-2-LPS complex helps to simplify their ligand specificity and receptor activation mechanism. Two copies of the TLR4-MD-2-LPS complex are arranged symmetrically and this comes about from the formation of an m-shaped receptor multimer resulting from LPS binding. LPS interacts with a large hydrophobic pocket in MD-2, with one of the six lipid chains of LPS forming a hydrophobic interaction with the conserved phenylalanines of TLR4.