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Innate Immunity.pdf

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Boston University
CAS BI 385
Trevor Siggers

Innate Immunity 3/25/14 12:05 PM Pathogen Mechanism • Exotoxin release- Vibrio cholerae • Endotoxin release- Y. pestis • Direct cytopathic effect.- influenza virus Site of infection • Extracellular- interstitial spaces, blood, lymph, epithelial surfaces • Intracellular- cytoplasmic Complement System- marks the bacteria; recognition system. • System of proteins made in the liver, present in blood, lymph, and extracellular fluids. o Coats the surface of bacteria and viruses and makes them more easy for phagocytosis. • Three componentns o C3 most important protein § Main goal- opsonization- process of enabling phagocytosis. § Tags bacteria for destruction § C3b ú High energy thioester bond to stick to the pathogen. • Three pathways o Alternative pathway- first one to act on a pathogen. § iC3àiC3Bb complexàC3a and C3b § C3 convertase- cleaves and inactivates C3. § Once C3b is attachedàanother Bb attachesàcontinuously cleavesà continues coating pathogen. § Positive feedback for amplification of coating. § Alternative C% convertase (C3b2bcBb) o Lectin pathway- second way to act – binds carbs. on pathogen surfaces o Classical pathway- Last to way- uses antibody to find pathogen. o They all cleave C3 to C3b to expose the thioester bond. • Complement Control proteins o 2 categories § Plasma control proteins ú Properdin (activator) stabilizes C3bBb complex • Factor P ú Factor H and Factor I (inhibit) together decrease C3b levels. § Human Cell, membrane control proteins ú Decay- accelerating factor (DAF) leads to Bb dissociation and inactivation ú Membrane co-factor (MCP) enhances cleave by factor I (Acts like Factor H) • Enhance Phagocytosis o Coats pathogen with Cb3 and macrophages have receptors for it. § Macrophages express complement receptor 1 (CR1)- arrays of Cr1 will recognize arrays of C3b Preventing attacks on human Cells • CD59 prevents recruitment of C9 to form pores. 3/25/14 12:05 PM Innate Immune Receptor: recognize biochemical differences between animal cells and microorganisms. • Present on many immune cells • Binds to diverse microbial ligands o Lectins- binds proteins and carbohydrates. § Ex. Mannose receptor, glucan receptor. o Scavenger receptor- bind charged ligands (ex nucleic acid) o Complement receptor 3 and CR4 • Can function as o Initiate receptor-mediated endocytosis. o Initiate immune signaling (eg. Cytokine production). Toll-like Receptors (TLRs) • Response to difference sets of pathogens and drive changes in gene expression •
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