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Dana Philpott

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LECTURE February 1, 2011
Different barriers prevent body from being infected by different microorganisms
What happens if the microorganisms break through barriers
Pathogens release MAMPs
These microbial products detected by TLR/Nod
Activates signal transduction response in cell
Signal downstream to activate these transcription factors NFkappaB
These transcriptioni factors produce mediators in inflammatory response to get
ride of infection
ALSO talked about DAMPS
oIndogenous -released from dead or dying cells
oDetected by NLRP
oOnce detected, also signal transduction response
oActivates protein complex called inflammasome
oActive inflammasome can process cytokines
oControls IL-1Beta
Different receptors
Innate immune mediators humoral secreted
Cells involved in killing bacteria and microorganisms
Secreted mediators of the innate system
oOr they kill or protect
General scheme of an innate immune response
Bacteria, fungus, viruses come into contact with gut cells
Break thorugh barrier changes cells
Epithelial cells thus activated change gene profile to activate things that will
kill bacteria
Cell secretes the mediators involved in getting rid of bacteria
Mediators called cytokines and chemokines
oThese call for reinforcements
oThus inflammation physiological feel
Inflammation includes local heat, swelling, redness, pain, loss of
function (in some cases, where the injury is)
Cytokines and Chemokines
Methods by which cells can talk to other celsl
In intercellular communication
Enhance cells ability to rid of microbial infections
oFamily of proteins
oProduced by infected cells
oV. small

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oAttract other cells recruit other cells to site of inflmaation to amplify
response to get rid of pathogen
Small amount of these molduels required to respond
Can be carried into systemic circulation can cause fever, anorexia
Many biological activities
EX. cytokines all the interleukins (all of them)
Ex. chemokines interleukin 8, MCP1
oAttract cells to site of inflammation
Real effect is to bring in effector cells to site of inflammation
Cytokines and chemokines must escape from blood vessels
Concentration gradient high at site of inflammation, lower in ________
Endotheiel cells make up blood vessel cells
oBarrier between endo cells break down, leakage results
oEndothelial layer leaks
oAlso vasodilation blod vessels get bigger
oPlasma leaked out of blood vessels cells call into site of inflammation, go
into submucuosal space follow the gradient up to site of inflammation
Brought to site of infection
White blood cells
Of innate system today’s focus
Leukocytes come to site of inflammation
Involve cell tethering to endotheial surface, rolling it along the surface, and
Endothelial cells line the blood vessels
When cytokines and chemokines produced, endo cells activated and express
adhesion molecules on their surface
oThese selectants thether leukocytes rolling along, holding them to the
oBinding of leukocytes to endothelial cell surface
oSo roll slowly along surface
Next step
oMicgration out of endothelial barrier
oActivated endo cells by mediators by infected epithelial cells
oExpress selectin molecule binds to leukocytes
oThen, leukocytes become firmly attached to endo cells, flattens
themselves, and ooze/poke through the barrier migrate to site of
oFollow gradient to low to high concentration of mediator
To find site of entry/infection in body
oMOVIE: live imaging of this occurring in animals
Neutrophils follow gradient get to site of infection to clean up
oMOVIE: labelled blood vessels to see capillaries surrounding site of injury
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