Lipid A is the Toxic Part of LPS

Lipopolysaccharide (LPS, endotoxin) is a component of the membrane of Gram-negative bacteria that causes sepsis [20]. Bacterial toxins play a pivotal role in the pathophysiology of sepsis and mechanisms of multiple organ system dysfunction. However, the literature illustrates that no single mediator/system/pathway/pathogen drives the pathophysiology of sepsis [21]. Current knowledge on sepsis pathogenesis [1, 22-26] includes infection development and interaction with the host before bacteria enter the bloodstream. Actually, the mechanisms of host defense in extravasal compartment (local immunity) is different from the mechanisms of intravasal (bloodstream) defenense because extravasal defense is provided mainly by leukocytes whereas intravasal cellular defense is fulfilled by erythrocytes. The humoral immunity events of pre-septic stage affect bacteremic (septic) stage and interfere with the study of sepsis “per se.” As a result, the pathogenesis and pathophysiology of some pivotal aspects of sepsis remain

Reverend Dr. Lynda Marie Jordan is a native Bostonian, born in Roxbury Massachusetts. She is the third of less than fifteen women of African descent—to date— that has earned the Doctor of Philosophy (Ph.D.) degree in Chemistry, from the Massachusetts Institute of Technology (MIT). After receiving the Ph.D. degree, Dr. Jordan became a Postdoctoral Fellow at the Institut Pasteur in Paris France, where she made substantial contributions towards the purification and characterization of key proteins associated with human inflammatory processes. Her pioneering work of identifying both the calcium-dependent and calcium-independent high molecular weight Human Placental Phospholipase A2 (PLA2) isoforms contributed to the groundwork for the advancements

The lipids found in the membrane are known as phospholipids. Phospholipids are fat derivatives in which one fatty acid has been replaced by a phosphate group and one of several nitrogen-containing molecules. The phospholipids’ structure is such that it appears to have a ‘head’ attached to a ‘tail’. The head section of the lipid is made of a glycerol group which is then attached to an ionised

Overwhelming, deleterious host immune response to an infection due to release of chemicals to fight the infection 2• 1

Gram negative and gram positive bacteria differ from each other in many ways especially in the composition and size of their cell walls. Unlike Gram-positive bacteria, Gram-negative bacteria have a thin peptidoglycan layer surround by an outer membrane. This outer membrane contains many proteins one of them being lipopolysaccharides (LPS), which contributes to the bacteria’s negative charge. One part of this protein is a lipid, called Lipid A, which is considered an endotoxin because this lipid triggers an immune response stimulating fever

Because large doses of LPS cause severe liver injury, whereas small doses of LPS results in the absence of liver damage [6], there is a necessity to determine the optimal dosage of LPS. Therefore, we first carried out a pilot dose-finding study to explore the dose of LPS that can stimulate the production of cytokines without inducing massive cell death of PHH and KCs cells. Meanwhile, we also tested a few doses of APAP-LPS co-exposures to get an impression on the abilities of these combinations to induce the cytotoxicity and cytokine

Ever since I was younger I knew my voice was different. Growing up, I developed this constant fear that it would swallow me whole and tats all people would remember me as: that girl with the lisp. As stupid as it is, my mediocre fear would effect my daily life. I would be too afraid to talk in class, and meeting people for the first time would be like playing a game of Russian roulette. I either gave out a sigh of relief if they overlooked my lisp or gave out nervous laughter if they pointed it out. I’ve always seen my lisp as a burden. It was something that slowed me down, made me different, and caused attention. Always thought my opinion on that would stay the same, but lately I think I’ve matured enough to realize that it’s not a big deal. After all that worrying I’ve realized it has all shaped me to be the person I am today.

Cytokinines are the one of the primary mediators that signal other cells to release additional mediators such as tumour necrosis factor-a (TNF-a) interleukin (IL)-1, IL-6, IL-8, interferon, leukotrienes, histamine, bradykinin, prostaglandins, thromboxane A2, serotonin, nitric oxide, arachidonic acid, platelet-activating factor (PAF), oxygen free radicals and myocardial depressant factor (Munford, 2001:67). If the invading organism is a gram negative bacterium, endotoxins are also released, which further stimulate the production of these inflammatory mediators (Jones & Bucher, 1999:134).

Lipopolysaccharides (LPS) in their cell wall leads to the monocyte activation and production of RA-associated cytokines interleukin (IL)-1 and IL-33 through the TLR pathways. HLA-B27 has been shown to be a predisposing factor to increases the risk of developing arthritis that is more likely to be severe and prolonged[8]. However, there is strong evidence found between reactive arthritis and Human Leukocyte Antigen (HLA) B27 genotype (Major histocompatibility complex) in humans that are present on the surface of all body cells that contain a nucleus, and high concentrations were found in in leukocytes. HLA-B27 has been shown to be a predisposing factor in individuals with reactive arthritis and also affect the elimination of the infecting bacteria. Despite, HLA-B27 is not trigger the initial infection itself, but it increases the risk of developing arthritis. Overall, burden rates of Salmonella-associated arthritis to vary between 6% and 30% followed by the other enteric infection reported to be between 1 and 4% in adults with Campylobacter or Shigella

The endotoxins are released into the immediate surroundings when bacteria undergo rapid proliferation with production of unused sections of bacterial cell wall or when the bacterial cell wall breaks.The toxic principal of the lipopolysaccharide molecule is generally similar regardless of the bacterial source (Burrows,1981). Metabolic toxins may accumulate as a result of incomplete elimination of toxic materials normally or abnormaly produced by the metabolism. In a healthy animal toxic products produced in the

Numerous mediators of inflammation are present during the process of infection, comprising interleukin-1β (IL-1β) as well as tumor necrosis factor-α (TNF-α). Mucosal cells tissues infected by Chlamydia include the dendritic cells, the epithelial cells, fibroblast, as well as the macrophages. Toll-like receptors are expressed by these cells that identify the particular pathogen-connected molecular patterns, comprising, bacterial wall mechanisms, the bacterial DNA, the peptidoglycan, as well as double-stranded RNA. It is noted that the Toll-like receptors’ engagement by the products of microbial, result to the production of the biologically-dynamic mediators, comprising the chemokines and antimicrobial peptides that participate in the inflammatory reaction (Barber, 2013).

As mentioned before, CAD is caused by the unwanted build-up of plaque within the walls of the coronary arteries which leads to restriction of blood flow to the heart (Mayo Clinic, 2017). Risk factors that are associated with increasing one’s chance of developing CAD are high cholesterol, smoking, high blood pressure, diabetes/obesity, sedentary lifestyle, high stress, and family history (Mayo Clinic, 2017). There are two forms of cholesterol that travel within the blood: HDL (High-Density Lipoprotein) known as the good cholesterol and LDL (Low-Density Lipoprotein) known as the bad cholesterol. High cholesterol is correlated with high levels of LDL cholesterol and low levels of HDL cholesterol. The reason high cholesterol levels increase

A second toxin that is significant in human infection is the gamma- toxin (also called leukotoxin) which

Host defense antimicrobial peptides (AMPs) are important components for the innate immune function as they directly destroy pathogen or microbe that invaded body in the early stage. Antimicrobial peptides are be able to help in expanding the adaptive immune system in further handling the infection. Thus, the antimicrobial peptides may have two major role which are as a rapid microbes killer and also as a future immune regulation (Lai and Gallo, 2009). Most of the human AMPs which specifically 90 out of 103 can inhibit the growth of bacteria. They show a wide spectrum activity against various of gram-positive and gram-negative bacteria. However, there are three human AMPs that kill primarily gram-positive bacteria only which are RNase 5 that

Pathogenic L. monocytogenes go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. The bacterium is first phagocytosed by these cells and secretes a pore-forming toxin called listeriolysin, which allows the bacterium to escape from the phagosome. All virulent strains of L. monocytogenes synthesize and secrete listeriolysin. Phospholipase A and B are other virulence factors that facilitate escape of L. monocytogenes from the phagosome. Once out of the phagosome L. monocytogenes is capable of rapid division in the cytoplasm, evading the immune response and moving throughout the cytoplasm from cell to cell. L. monocytogenes is well known for its ability to propel itself like a rocket through the cell cytoplasm. This is the result of the bacterium’s ability to polymerize actin filaments at its tail end. Actin is arranged in subunits to form microfilaments that are capable of directing cell movement. L. monocytogenes accomplishes cell motility through a virulence factor called ActA that takes advantage of normal actin polymerization going on in the cell. The ActA protein shares sequence homology with a protein called WASP that is found in virtually all eukaryotic cells. WASP is responsible for recognizing and