Pathogen Recognition and Innate Immunity

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

▪ Abstract The innate immune system is a universal and ancient form of host defense against infection. Innate immune recognition relies on a limited number of germline-encoded receptors. These receptors evolved to recognize conserved products of microbial metabolism produced by microbial pathogens, but not by the host. Recognition of these molecular structures allows the immune system to distinguish infectious nonself from noninfectious self. Toll-like receptors play a major role in pathogen recognition and initiation of inflammatory and immune responses. Stimulation of Toll-like receptors by microbial products leads to the activation of signaling pathways that result in the induction of antimicrobial genes and inflammatory cytokines. In addition, stimulation of Toll-like receptors triggers dendritic cell maturation and results in the induction of costimulatory molecules and increased antigen-presenting capacity. Thus, microbial recognition by Toll-like receptors helps to direct adaptive immune responses ...

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Innate Immune Recognition

One of the mechanisms by which the innate immune system senses the invasion of pathogenic microorganisms is through the Toll-like receptors (TLRs), which recognize specific molecular patterns that are present in microbial components. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also instructs the development of antigen-specific acquired immunity. Here, we review the rapid progress that has recently improved our understanding of the molecular mechanisms that mediate TLR signalling.

Toll-like receptor signalling

ObjectiveTo determine the incidence, cost, and outcome of severe sepsis in the United States.DesignObservational cohort study.SettingAll nonfederal hospitals (n = 847) in seven U.S. states.PatientsAll patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification

Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

This invention provides hybridoma cell lines producing monoclonal antibodies which inhibit CD14 mediated cell activation. Monoclonal antibodies produced by these cell lines also are provided. The antibodies are useful for the detection of the presence of cell surface and soluble CD14 in a sample. Chimeric and CDR grafted antibodies generated from the above monoclonal antibodies are further provided. Pharmaceutical compositions containing the above biological compositions are provided. These are useful to treat and prevent disorders associated with CD14 mediated cell activation, such as spesis.

Methods for inhibiting cd14 mediated cell activation

RadolfGangloff, Sanna M. Goyert, Michael V. Norgard and Justin D.Richard P. Darveau, Jerome Pugin, Richard J. Ulevitch, Sophie C. Timothy J. Sellati, Deborah A. Bouis, Richard L. Kitchens,http://www.jimmunol.org/content/160/11/5455J Immunol€1998; 160:5455-5464; ;Referenceshttp://www.jimmunol.org/content/160/11/5455.full#ref-list-1This article cites 72 articles, 54 of which you can access for free at: Subscriptionshttp://jimmunol.org/subscriptionsInformation about subscribing to The Journal of Immunology is online at: Permissionshttp://www.aai.org/ji/copyright.htmlSubmit copyright permission requests at: Email Alertshttp://jimmunol.org/cgi/alerts/etocReceive free email-alerts when new articles cite this article. Sign up at:

This information is current as Distinct from That Used by Lipopolysaccharide Monocytic Cells via a CD14-Dependent Pathway Lipoproteins and Synthetic Lipopeptides Activate Borrelia burgdorferi and Treponema pallidum

Macrophages and dendritic cells are in the front line of host defense. When they sense host invasion, they produce cytokines that alert other innate immune cells and also abet the development of an adaptive immune response. Although lipoly- saccharide (LPS), peptidoglycan, unmethylated DNA, and other microbial products were long known to be the primary targets of innate immune recognition, there was puzzlement as to how each molecule triggered a response. It is now known that the Toll-like receptors (TLRs) are the principal signaling molecules through which mammals sense infection. Each TLR recognizes a restricted subset of molecules produced by microbes, and in some circumstances, only a single type of molecule is sensed (e.g., only LPS is sensed by TLR4). TLRs direct the activation of immune cells near to and far from the site of infection, mobilizing the com- paratively vast immune resources of the host to confine and defeat an invasive organism before it has become widespread. The biochemical details of TLR signaling have been analyzed through forward and reverse genetic methods, and full elucidation of the molecular interactions that transpire within the first minutes following contact between host and pathogen will soon be at hand. J. Leukoc. Biol. 74: 479-485; 2003. inferences may accumulate so that every requirement for proper function of a complex system is understood, much as every enzyme in the tricarboxylic acid cycle is now known. In no field has reductionism played a greater role than it has in the science of genetics. Mutations have fueled progress in genetics, and genetic tools have transformed every area of biology. The present review concerns innate immunity: the inherited resistance to infection, shared to some extent by all normal metazoans. We would like to understand innate immunity at a fine molecular level. We would like to catalog each of the biochemical events that innate immunity entails so that every protein participant in the innate immune response is known. We would like to understand the temporal sequence of molec- ular interactions that occur and the importance of this temporal sequence to the outcome that is observed. In the long run, we might wish to modify innate immune responses, damping them when they cause harm (as they do in the course of inflammatory diseases) and augmenting them when they are required (as they are during focal infections that need to be checked before they become generalized).

Richard J. Ulevitch

Papers

Methods for inhibiting cd14 mediated cell activation

This information is current as Distinct from That Used by Lipopolysaccharide Monocytic Cells via a CD14-Dependent Pathway Lipoproteins and Synthetic Lipopeptides Activate Borrelia burgdorferi and Treponema pallidum

receptors and their transducers

Reducing bacterial endotoxin contamination in solutions of macromolecules

Méthode pour réduire la contamination bactérielle d'endotoxines dans des solutions de macromolécules