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Lecture 3 - Danger Signals & PRRs
danger signals & PRRs
51
Immunology
Undergraduate 4
02/06/2015

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Cards

Term
What are the effector immune cells?
Definition
granulocytes
monocyte-derived macrophages
humoral proteins
Term
Where are sentinel cells found?
Definition
in tissues (usually peripheral tissues)
Term
What do sentinel cells do?
Definition
recognize tissue damage/infection via PRRs & become activated, releasing a variety of molecules
Term
How do sentinel cells recognize tissue damage / infection?
Definition
PRRs recognize danger-associated molecular patterns such as PAMPs and alarmins
Term
What molecules are released by sentinel cells upon activated?
Definition
vasoactive compounds
pro-inflammatory cytokines
chemokines
antimicrobial peptides & proteins
Term
What is the bird version of a neutrophil?
Definition
heterophil
Term
Describe the initial influx of immune effector cells
Definition
granulocytes are immediately recruited, then replaced by monocyte-derived macrophages
Term
What is the Stranger hypothesis?
Definition
an innate level of non-self recognition occurs as PRRs on sentinel cells recognize PAMPS
Term
What PAMPS would be recognized by a PRR to identify a gram positive bacteria such as staphylococcus?
Definition
peptidoglycans & lipoteichoic acids
Term
What are granulocytes?
Definition
neutrophils / heterophils
Term
What PAMPS would be recognized by a PRR to identify a gram negative bacteria such as e coli?
Definition
peptidoglycans & lipopolysaccharides
Term
What PAMPS would be recognized by a PRR to identify an acid-fast bacteria such as mycobacteria?
Definition
glycolipids & lipoarabinomannan
Term
What PAMPS would be recognized by a PRR to identify a fungus?
Definition
mannoprotein
B glucan
chitin
Term
What PAMPS would be recognized by a PRR to identify a vrius?
Definition
DNA / RNA sequence
Term
What hypothesis explains the presence of inflammation in sterile invironments?
Definition
Danger Hypothesis

-damaged or dying cells activate sentinel cells by releasing alarmins
Term
Uric acid, fibrinogen, defensins, DNA histones etc are all examples of....
Definition
alarmins
Term
What compound is normally found in the nucleus, initiates cell death when in the cytoplasm and acts as an alarmin when extracellular?
Definition
HMGB1
Term
True or False

HMGB1 is very specific in what receptors it will bind to
Definition
false, it binds to a variety of receptors
Term
TLRs are a type of....
Definition
PRR
Term
What types of TLRs recognize PAMPS on extracellular pathogens?
Definition
membrane-bound TLRs

TLR 1,2,4,5,6,11
Term
What types of TLRS recognize PAMPS on intracellular pathogens?
Definition
TLR 3,7,8,9
Term
What TLRs bind to viral nucleic acids?
Definition
TLR 3, 7, 8
Term
What TLRs bind to bacterial CpG DNA?
Definition
TLR 9
Term
How do TLRs recognize intracellular pathogens?
Definition
the bind to DNA that is less methylated than the host DNA would be
Term
What TLR complex would recognize lipopeptides, lipoteichoic acid & zymosans?
Definition
TLR2/6
Term
What TLR complex would recognize mycobacterial peptides?
Definition
TLR1/2
Term
What does TLR4 recognize?
Definition
host alarmins such as fibrinogin, heparin sulfate, HMGB1
Term
What avian TLR is related to the mammal TLR 2?
Definition
TLR 15
Term
What TLR do birds not have? What do they have instead?
Definition
TLR 9

have TLR 21 instead
Term
What bird TLR is orthologous to TLR 21 in fish & amphibians?
Definition
avian TLR 21
Term
What is endotoxemia?
Definition
When LPS binds to TLR 4, instigating a potent inflammatory reaction leading to septic shock
Term
How are sentinel cells activated by LPS?
Definition
LPS aggregates & is transferred to CD14
CD14 binds to TLR 4
2 possible activation pathways can be followed
LPS will dissociate from CD14
Term
What signaling pathway activates lots of kinase-dependent pathways?
Definition
MyD88 dependent pathway
Term
What is activated via the MyD88 independent pathway?
Definition
IRF-3
Term
What mammal TLR does NOT use the MyD88 dependent pathway?
Definition
TLR 3
Term
What results from the MyD88 dependent pathway?
Definition
-NFkB translocated
-Caspase-1 is assembled in inflammosome, cleaving pro IL-1,6,8 & TNF-alpha into their bioactive forms
Term
What results from the MyD88 independent pathway?
Definition

-IRF-3 activated

-type 1 IFN expressed

-IFN-inducible genes are expressed

Term
Why are fish & amphibians resistant to LPS/endotoxemia?
Definition
don't have CD14
don't have TLR-4
don't have LPS-BP
Term
Which fish are susceptible to endotoxemia?
Definition
most are not, except for zebra fish as they have paralogues TLR4 alpha and TLR4 beta
Term
Why are birds less susceptible to mammals to endotoxemia?
Definition
don't have CD14
don't have IRF3 so the MyD88 independent pathway is not responsive
Term
What PAMPs do G-type lectin membrane receptors recognize?
Definition
polysaccharides
Term
What PAMPs does CDM recognize?
Definition
LPS
peptidoglycan
lipoarabinomannan
Term
What PRR is important for maintaining host tolerance to commensal bacteria?
Definition
PGRP
Term
What PRR recognizes viral RNA?
Definition
Rig-1
Term
What animals do not have RIG-1?
Definition
chickens
Term
True or False

Chickens do not have CD-1 genes
Definition
False

they have 2 types of CD-1 genes
Term
What is the only TLR with anti-inflammatory properties?
Definition
human TLR-10
Term
What PRR presents vitamin antigens to MAIT cells?
Definition
MR-1
Term
True or False

amphibians do not have MR-1
Definition
true
Term
What PRR evolved from duplication of the MHC-1 family?
Definition
CD-1
Term
What do CD-1 PRRs bind to?
Definition
lipid antigens
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