2&3innateimmunity

2&3innateimmunity - Innate Immunity Lectures 2 and...

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Innate Immunity Lectures 2 and 3, Chapter 2 MMI 188 Human Immunology José V. Torres, Ph.D. Professor Medical Microbiology & Immunology School of Medicine University of California Davis, CA 95616 [email protected] 530 752-3157; 3134 Tupper Hall
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Damage by Pathogens: 1. Exotoxins via cell surface receptors 2. Endotoxin release causing secretion of cytokines by phagocytes 3. Direct killing of cell
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Different compartments of the body are exploited by pathogens Different innate immune system components used on defense
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Complement System of blood proteins Cascade that results in covalent bonding of protein fragments to the pathogen’s surface Phagocytes have receptors for these fragments Uptake and destruction of pathogens by macrophages and neutrophils Complement complex makes holes on the cell membranes of pathogens Three complement activation pathways: Alternative Triggered by changes caused by bacterial surface components Lectin • Binding of complement to peptidoglycans on microbes Classical Antibody bound to pathogen triggers complement activation
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Complement Complement components are plasma proteins – Made in the liver – More than 30 proteins – Some circulate as enzyme zymogens The 3 pathways are triggered in different ways – All converge in the same reaction C3 is the most abundant component in plasma • C3 cleavage into C3b and C3a Covalent binding of C3b to the surface of pathogens ( complement fixation ) – Tags pathogen for destruction by phagocytes – Starts the cascade that damages the pathogen’s membrane • Soluble C3a recruits inflammatory cells Inherited deficiency of each complement component has been described C3 deficiency is the most severe (bacterial infections)
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Complement Activation -Proteolytic cleavage of complement component C3 -Large C3b fragment becomes covalently attached to pathogen - C3b labels the pathogen as dangerous - C3a attracts phagocytic cells
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Reactive thioester bond; Covalent binding to hydroxyl and amino groups
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3 Pathways of Complement Activation
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Initiation of Alternative Pathway of Complement - C3 hydrolyses near microbe - Activated C3 binds Factor B - Factor D cleaves Factor B producing the soluble convertase, iC3Bb - This convertase cleaves C3 into C3b and C3a - C3b binds to microbe - C3a attracts phagocytes
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- C3b binds Factor B - Factor D cleaves Factor B to produce C3bBb, the surface bound convertase - C3bBb cleaves C3 - More C3b is produced and binds to microbe - C3a attracts phagocytes Amplification
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C3bBb Bb fragment of Factor B cleaves C3 C3b fragment of C3 holds the enzyme at the surface of the pathogen
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Pathogen surface: C3bBb stabilized by properdin Factor H binding induces conformational change of C3b Factor I cleaves C3b DAF and MCP block complement fixation on human cells Complement control proteins
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This note was uploaded on 04/02/2010 for the course MMI 188 taught by Professor Josetorres during the Winter '10 term at UC Davis.

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2&3innateimmunity - Innate Immunity Lectures 2 and...

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