Inflammatory Response. Cytokines. Cytokines are small proteins or ____________ secreted for the purpose of altering the function of target cells in an _____________, ____________, or ________ fashion.
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What cytokine predominantly drives TH1 differentiation?
What cytokine predominantly induces TH2 differentiation?
which occur early and are not antigen specific, depend largely on proper functioning of natural killer (NK) cells and phagocytic cells, such as monocytes, macrophages, and neutrophils.
which develop later after antigen processing and the clonal expansion of T- and B-cell subsets, are antigen specific.
A number of cytokines, including transforming growth factor-β (TGF-β), tumor necrosis factor (TNF), IL-1, IL-6, IL-10, IL-12, and IL-18, are synthesized by cells of the innate immune system and contribute to the ability of the host to mount an early, innate immune response to an infectious challenge. Another group of cytokines, the interferons, are also key components of the innate immune system
just another kinase
the two-faced Roman god.
IL-1 was first described as a lymphocyte-activating factor produced by stimulated macrophages.
IL-1 is not a single compound, but rather a family of three distinct proteins:
IL-1α, IL-1β, and IL-1 receptor antagonist (IL-RA) , which are products of different genes located close to one another on the long arm of human chromosome 2.
IL-1RA, the third member of the IL-1 family of proteins, is biologically inactive but competes with IL-1α and IL-1β for binding to IL-1 receptors on cells and thereby functions as a competitive inhibitor to limit IL-1–mediated effects.
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There are two distinct IL-1 receptors, IL-1RI and IL-1RII
The extracellular domains of IL-1RI and IL-1RII are shed by activated neutrophils and monocytes.
The shed receptors can act as a sink for secreted IL-1 and, thus, along with IL-1RA, represent an important counter-regulatory component of the inflammatory response.
(Understandably, bleeding complications can occur with the use of drotrecogin alfa (activated). Furthermore, this agent was not beneficial for septic patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score lower than 25, postoperative patients with single–organ system dysfunction,or pediatric patients with severe sepsis.)
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COX-2, however, is an inducible enzyme. Expression of COX-2 is induced by a number of stimuli, including various growth factors and proinflammatory cytokines.
COX-1 is expressed constitutively in a variety of tissues, and mediators produced by this isoform are thought to be important in various homeostatic processes, such as regulating renal perfusion and salt and water handling, maintaining hemostasis by modulating platelet aggregation, and preserving gastrointestinal mucosal integrity.
Many of the downstream actions of the proinflammatory cytokines occur as a result of increased expression of two key enzymes, iNOS and COX-2.