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Imm lecture 3 notes.docx - IMM250 Lecture 3 Innate...

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IMM250 Lecture 3Innate Immunity: the first line of defense to infectionPart IISOLUBLE MEDIATORS OF INNATE IMMUNITYWhen a pathogen breaches a barrier it then releases PAMPs, those are detected by PRRs, that activatesthe signal transduction which acticates NFkBcontrols the production of soluble mediators of innateimmunityCYTOKINESWhat are Cytokines?A category of signaling molecules that, like hormones and neurotransmitters, are used extensively incellular communication; cytokines generally enhance the ability of our cells to get rid of an invadingpathogen and promote healing (bring body back to homeotic state)Features of cytokines:diverse collection of soluble proteins (interleukins IL) that module the behaviour of cells at extremelysmall concentrationsAct both locally and systemicallyHave many biological activities (pleiotropic effects)Types of Cytokines:Pro-inflammatory cytokines:oIL-1β, IL-6, tumor necrosis factor (TNF)many of these are what make you feel sick (inducefever)Anti-inflammatory cytokines:oIL-10, IL-4, transforming growth factor β (TGFβ)ComplementA complex of network plasma and cell surface proteinsOperates in a manner similar to blood clotting cascade (pyramid effect)One active factor activates an inactive factor which then activates another inactive factor – “Zymogens”(inactive enzyme precursor that requires a biochemical change to become active)allows for hugeamplificationTriggers for activating the 1stfactor:Classical pathway: Antigen-antibody complexes on microbesAlternative pathway: Spontaneous activation on microbesLectin pathway: binding to microbes that express lectin carbohydrate on cell surface (mannose-bindinglectin)Complement effector mechanisms:1.Bacterial cell lysis MAC2.Opsonisation of bacteria3.Induction of acute inflammation1-The membrane attack complex aka MACComplement proteins (C5-C9) insert themselves into the membrane of pathogens, creating apore. C9 will form around the complex to form the pore
There is a high osmolarity gradient inside the cell compared to the outside so water will flowinto the pores and eventually lyse the cell (blow up)On human cells, we have CD59 which binds to the C5b,6,7,8 complex and prevents recruitmentof C9 to form the pore2-OpsonisationC3 cleaves into C3b and iC3bC3b and iC3b are “opsonins” – coats bacteria and signals (to complement receptors) them to bephagocytosed3-Enhance inflammationC3 cleaves into two fragments C3b and C3a; C3b opsonizes pathogensand C3a gets released(soluble fragment)C3a and C5a are anaphylatoxins; they bind to receptors on endothelial cells to increase vascular

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Term
Spring
Professor
JenGommerman,DanaPhilpott
Tags
nets, PAMPs, Pro inflammatory cytokines

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