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Need help with my writing homework on LPS. Write a 4250 word paper answering; The LPS of this group of bacteria can be divided into 3 components, 1) lipid A, 2) a core oligosaccharide, which can be fu
Need help with my writing homework on LPS. Write a 4250 word paper answering; The LPS of this group of bacteria can be divided into 3 components, 1) lipid A, 2) a core oligosaccharide, which can be further subdivided into an inner and outer core structure, and a glycosyl polymer of repeating units, called O-polysaccharide. The hydrophobic lipid A domain of the molecule contributes to the structural stability of LPS. The core oligosaccharide, on the other hand, maintain the semi-permeable barrier of the bacterial cell‘s membrane by cross-linking with divalent cations or polyamines (Frirdich and Whitfield, 2005). Because of its biological effects, it has been used in experimental research as a prototype endotoxin as well as an adjuvant. Through the elucidation that LPS’ lipid A component is a nontoxic immunostimulatory molecule, it was established that the lipid A domain modulates LPS’ biological activity (Harsoliya et al., 2011). According to Frirdich and Whitfield (2005), this domain of LPS is the most conserved, followed by the inner core oligosaccharide moiety attached to lipid A. 2. Modifications Just like other membrane proteins, LPS undergo structural changes to accommodate environmental changes such as availability of nutrients and balance of ions. In particular, lipid A modifications were found to enable the bacteria to adapt to an environment with low divalent cations, abundant cationic peptides and low temperature (Frirdich and Whitfield, 2005). The TLR4 pathway TLR4 is a membrane protein expressed by hematopoietic-derived, immune cells such as macrophages, neutrophils, lymphocytes and dendritic cells. It is the link of LPS to the innate immune pathway, which allows a faster recruitment of immune cells to the site of infection. It is able to do so by stimulating the transfer of nuclear factor-?? (NF-??) to the nucleus, thus initiating the expression of the genes coding for IL-6, IL-1 and TNF-? (Creely, 2007), whose importance will be discussed in detail later. Because many body surfaces and mucosa are susceptible to bacterial infection, many body parts may be exposed to LPS as well. As such, they are also expressed by non-hematopoietic cells such as epithelia and endothelia. In the respiratory tract, many studies have already recognized the role of TLR4 in inducing defensive mechanisms against pulmonary infection. Since the non-hematopoietic cells do not have immune functions, they release signals that allow the recruitment neutrophils to the site of infection. If uncontrolled, however, this response may lead to a decrease in lung function due to inflammation of the lungs, as well as exacerbation of allergic asthma. (Hollingsworth et al., 2005). However, it was determine by Hollingsworth et al. (2005) that, at least in the respiratory tract, immune response is different in magnitude when LPS is detected by hematopoietic cells than if it is by epithelial and endothelial cells of the airway. In their experiment, they used chimeric mice to limit expression of TLR4 in 1) hematopoietic cells only, or in 2) structural cells only. Number of neutrophils present, cytokine/chemokine production, and airway inflammation, through assessment of tracheal pressure.