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Lecture 3.docx - Lecture 3: Cellular and Humoral Mediators...

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Lecture 3: Cellular and Humoral Mediators of Innate DefenseSoluble Mediators of Innate ImmunityCytokinesoTells cells how to change their behaviourComplementoFound in the serumInterferonoSubclass of cytokines used in viral infectionsAfter a pathogen breaches a barrier…oReleases PAMPsoDetected by PRRoActivated signal transductionoActivates NFκBoControls the production of soluble mediators of innate immunity (among other things)What are Cytokines?Cytokine: a category of signaling molecules that are used in cellular communicationCytokines mediate “inflammation” and generally enhance the ability of our cells to get rid of an invadingpathogen and promote healing – bring our body back to homeostasisFeatures of CytokinesoA diverse collection of soluble proteins that modulate the behaviour of cells at extremely smallconcentrationsoAct both locally and systemicallyoHave many biological activities (pleiotropic effects)oA special class of cytokines are “chemokines” – these are small molecules made up of a few amino acidsthat mainly induce “chemotaxis”Help to recruit cells to the site of infection/injuryGeneral Properties of Cytokines and ChemokinesCytokines are soluble proteinsoReleased by one celloBind to receptors on another cell (or on the same cell – autocrine effect)oInduce biological effectsPAMP binds to the PRRActivation in the cellCytokine secretionChange in the behaviour of the cell – proliferate or apoptosisChemokines recruit cells of the innate immune systemCytokine’s role is defense and healingNeed a level of inflammation in order to induce the healing processPro-inflammatory cytokines include:oIL-1ß, IL-6, tumour necrosis factor (TNF), others –many of these are what makes you feel sick (inducinga fever)oThey are drivers of the defense responseAnti-inflammatory cytokines include:oIL-10, IL-4, transforming growth factor ß (TGFß)oThese are important in healing and bring the body back to homeostasis after the infection or injury hastaken placeBoth Pre-inflammatory and anti-inflammatory cytokines can be secreted depending on the stage of infection
Interferon Response to viral infectionsSeveral endosomal PRR’s (TLR3/7/8) recognize viral genetics material and trigger a signaling pathway leading tothe production of “type 1 interferons”, which are key in viral innate immune defenseType I interferonsoType I IFN’s are produced by virus-infected cellsoThey bind to the IFN receptor expressed by most celltypes and induce in them an antiviral stateoAutocrine effect – tells its own cell to degrade the viralDNAoParacrine effect – tells other cells to protect themselvesfrom virusesoInhibition of viral protein synthesisCells will be able to degrade the viral DNAComplement proteinsAnother soluble mediator in innate immune responses

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Term
Spring
Professor
JenGommerman,DanaPhilpott
Tags
cells, immune cells, PRR, innate effector cells

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