Lecture 3- PRR

Lecture 3- PRR - PRR functions Stimulate phagocytosis...

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PRR functions: Stimulate phagocytosis Promote chemotaxis Induce the production of molecular mediators (such as cytokines and chemokines) that activate innate and adaptive immune responses
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Pathogen Associated Molecular Patterns (PAMPs) Microbial Associated Molecular Patterns (MAMPs) TLR ligands Invariant among microorganisms of a specific type e.g. LPS for Gram-negative bacteria, dsRNA for viruses, LTA for Gram-positive bacteria Molecules are unique to microorganisms and not to host i.e. Bacteria have cell walls with LPS and LTA PAMPs have essential functions that are required by microbe i.e. LPS and LTA are required for cell integrity, RNA is the genome for many viruses, flagella are required for bacterial motility. Thus, the microorganism can not easily evolve to mutate these molecules
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Germinating Hyphes of A. fumigatus on a Dead Drosophila. Scanning electron micrograph of a Drosophila adult that succumbed to infection by A. fumigatus and is covered with germinating hyphae Lemaitre et al ., Cell (1996) Discovery of Toll in anti-fungal responses
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NF- k B regulated genes
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TLR signaling pathway
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MyD88-dependent pathway MyD88 associates with TLRs through their TIR domains (Toll/IL-1 Receptor domain) Upon engagement with ligand, MyD88 recruits IRAK-4, and facilitates IRAK-1 phosphorylation by IRAK-4 P -IRAK-1 associates with TRAF6 and increases I k B kinase activity I k B kinase phosphorylates I k B a leading to its degradation NF- k B translocates to the nucleus to initiate transcription TIRAP is a MyD88 homolog involved in TLR2/4 signaling
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