3: Innate Immunity: recognition and mediators Flashcards
what is the function of a sentinel cell?
to recognize invading pathogens
where are sentinel cells found?
present in tissues, under epithelium, along vessels and within the epithelium of mucosal surfaces
how do sentinel cells recognize pathogens?
via PRRs (pattern-recognition receptors) which recognize signals from PAMPs (pathogen associated molecular patterns) and DAMPs (damage associated molecular patterns)
PAMPs come from?
invading microorganisms (exogenous signals)
DAMPs come from?
dead/dying host cells (endogenous signals)
what do exogenous signals consist of?
molecules produced by microbial invaders (essential components of microbial invaders)
what do endogenous signals consist of?
molecules released by damaged, dead, or dying host cells
DAMPs and PAMPs are recognized by what?
PRRs
where are PRRs located?
on sentinel cells
recognition of pathogens by sentinel cells leads to what?
activation of the innate immune system
what are examples of PAMPs
bacterial lipopolysaccharides (LPS)
bacterial peptidoglycans
bacterial DNA
viral nucleic acids
what kind of kill do PAMPs elicit?
narrowed kill
where is LPS found?
gram-negative bacteria
where are bacterial peptidoglycans found?
gram-positive bacteria
what are the molecules released by DAMPs called?
alarmins
what kind of kill do DAMPs elicit?
broad kill
what are examples of PRRs?
TLRs (toll-like receptors)
RIG-like receptors (retinoic acid inducible gene)
NLRs (nucleotide-binding oligomerization domain
what is the most important PRR?
TLRs
where are RIG and NLRs found>
in the cytoplasm
where are TLRs found?
in the cytoplasm and cell membrane (transmembrane glycoprotein receptors)
what is the function of TLRs in the cell membrane?
recognize bacteria, fungi
what is the function of TLRs in the cytoplasm?
recognize viruses
what range of TLRs do cattle and humans have?
TLR1 to TLR10
what are the most important TLRs?
TLR2 and TLR4
where is TLR2 found?
cell surface
where is TLR4 found?
cell surface
what binds to TLR2?
lipoproteins (gram + bacteria)
what binds to TLR4?
LPS (gram - bacteria)
what does TLR2 recognize?
bacteria, viruses, parasites
what does TLR4 recognize?
bacteria, viruses
what happens when a bacterial PAMP binds to a TLR?
binding of a bacterial PAMP to a TLR2,4 generates a signaling cascade that activates 2 transcription factors:
MAPK (mitogen-activating protein kinases)
NK-kB (nuclear factor kappa B)
these transcription factors activate transcription of genes that code for different cytokines:
IL-1(interleukin 1)
IL-6
TNK-a (tumor necrosis factor 6) which then will turn on the inflammatory response
what happens when a viral PAMP binds to a TLR?
the viral PAMP will bind to TLR3,7,8,9 and results in the activation of a transcription factor:
IRF-3 (interferon regulatory factor 3)
IRF-3 then activates the genes that code for Type 1 interferons (antiviral) such as IFN-B (interferon beta)
what are the most important sentinel cells?
macrophages, dendritic cells, and mast cells
