Inflammation 1 Flashcards
initial interaction is b/w
PAMP and PRRs
one of consequences of PAMP by PRR is
assembly of inflammasome
inflammasome
important for production and section and activation of some cytokines important in inflammation
three tiered approach to defense
physical and chemical barriers
innate immunity
adaptive immunity
non-specific barriers
skin, microflora, tight junctions
what is an important barrier in skin
epithelial cells are joined by tight junctions
what are in lungs that provide first line of defense
mucus
cilia
what is in tears that helps against infection
lysosyme
chemical on skin to defend
fatty acid
antimicrobial peptides
chemical in gut to defend
low pH
antimicrobial enzymes
chemical defense in lungs
pulmonary surfactant
antimicrobial peptides
lysozyme
enzyme in tears, saliva, milk, mucus, etc.
lysozyme digests
peptidoglycan
where is peptidoglycan
cell wall of bacteria
cathelicidins
broad antimicrobial substances
alpha defensins
produced by PMNs (granulocytes, especially neutrophils) and Paneth cells (gut)
two kins of defensins
alpha and beta
antimicrobial peptides - defensins include
a-defensins
b-defensins
what bacteria are not sensitive to lysozyme
gram neg.
fat are contained in lamellar bodies and they form water tight layer in epidermis - what else do lamellar bodies make
antimicrobial peptides
main producers of mucous in the respiratory epithelial and gut epithelial
goblet cells
mucous functions
libricant
trap for pathogens
goblet cells secrete
anti-microbial peptides
and of course mucous
richest source of antimicrobial peptides in GI track
paneth cells @ base of crypt of leiberkuhn
anythig that gets past initial barrier have to be detected, mainaly based on
Pattern recognition receptors on PAMP
to discriminate b/w harmful and harmless
job of patern recognition receptors
many pathogens have conserved structures
PAMPSs
PAMPs stands for
Pathogen Associated Molecular Patterns (PAMPs).
where are pattern recognition receptors found
floating around in immune system neutrophils macrophages epithelial cells mast cells well equipped
LPS
outer membrane of gram neg bacteria
LPS is an example of a
PAMP
flagellin is ex. of a
PAMP
glucans chitin manna
fungal cell wall
ex. of PAMP
what are soluble PRR
- Mannose-Binding Lectin (MBL)
- Ficolins
- C1q
- C-reactive protein (CRP)
PRR stand for
pattern recognition receptor
soluble PRR’s activate
activating complement pathway
cell membrane associated pathogen associated receptors
membrane bound
toll like receptors are associated with
plasma membrane and also intracellular receptors
ex of intracellular PRR
Nod-like Receptors (NLRs)
- RNA helicases (RIG-I, MDA-5)
Toll-like receptors
immediate consequence of PAMP binding to PRR
more antimicrobial peptides
inducing production of cytokines, important in combating viral, bacterial, fungal infection
soluble PRR activate
complement pathway
TLR2 recognizes
gram pos and fungi
TLR4 recognizes
LPS (lipopolysaccharide) therefore gram neg.
TLR9 recognize
DNA
T3, 7, 8 reocngize
RNA
all toll like reeptors are on plasma membrane except
plasma membrane
3 7 8 9 - these are intracellular toll like receptors
following recognition of PAMP TLR4 with CD14 recognize what
LPS (lippopolysaccharide)
TLR4 couples with what to recognize LPS
CD14
recognition of the ligand by TLR4 and CD14 couples to activation of
NFkB
NFkB is important transcription factor b/c it’s involved in
regulation fo transcription of a wide variety of pro-inflammatory cytokines
intracellular cytoplasmic toll like receptors recognize
bacterial products
NOD1 & NOD2 (these are nod-like PRR ) recognize
intracellular bacteria or degradative products of bacteria (like those being taken up into macrophages or neutrophils)
NOD1 and NOD2 and couple to activation of
NFkB and ultimately production of pro-inflammatory cytokines
TLR3 and 7 detect
viral RNA
detection of viral genomes by
get production of what
TLR3 & TLR7
type I interferon
production of type I interferon important during viral infect. b/c main mech to
limit spread of virus - makes neighboring cells less susceptible to produce virus progeny particles
detection of PAMPs by PRR leads to assembly of multimolecular complex in cells (esp macrophages) and the complex is called
inflammasome
type I interferon acts on neighboring cells to do what
how does it act on infected cell
make them less susceptible to support virus replication
acts on infected cell to lead to production of components of inflammasome
detection of bacteria PAMPs by PRR leads to assembly of
inflammasome
inflammasome important b/c
it’s necessary for maturation of cytokines that are important in inflammatory response (esp. interleukin family like interleukin I)
assembly of inflammasome leads to death of
infected cell which limits spread of infection
type I interferon produced following detection of
viral PAMP
Type I interferon binds to
receptors on neighboring cells
what does tpe I interforon do when bind to neibhoring cells
reduces express of genes that encode three enzyme complexes
2’ 5’ OAS
induces RNase L
PKR
the enzymes prime cells to resopnd if they become infected with virus.
oligoadenylate made if
cell is affected with virus
once RNase L made it will
degrade mRNA
stops viral mRNA from being made, so viral can’t reproduce
PKR does what
phosphorylates initiaton factor needed for translation - when it’s phosphorylated it’s inactive so it inhibits protein syntehsis
PKR does what
phosphorylates initiaton factor needed for translation - when it’s phosphorylated it’s inactive so it inhibits protein syntehsis
early in infection dendritic cells migrate
to site of infection
dendritic cells do what
sample material and carry to the regional lymph node
once dendritic cell gets to lymph node
primed to activate t cells
cell that infiltrates to pick up the antigen (dendritic cell) is not capable of
activating t cell
once dendritic cell picks up antigen and exposed to cytokines in inflamed site
it changes so it cant pick up any more antigen and it can present it and activate t cells
NFkB is key regulator of transcription of
cytokines
cytokines are
soluble polypeptides
secreted by immune system and most cells in the body
(every cell needs to be able to communicate w/ immune system)
cytokines regulate
magnitude and duration of immune response
families of cytokines
interleukins
chemokines
interferons
interleukins
designated by IL-#
chemokines
small molecular weigh cytokines
interferons
interfere w/ virus replication
type I interferons
alpha and beta
type II interferons
interferon gamma
how do cytokines act
autocrin
paracrine
endocrine
autocrine in regards to cytokines
cell producing the cytokine is responsive to cytokine
paracrine in regards to cytokines
cell that is responding to cytokin is adj. to cell producing the cytokine
endocrine in regards to cytokines
not as common for cytokines
pleiotropy in regards to cytokines
one cytoken different responses from different cells
redundancy in regards to cytokines
more than one cytokine same response from cell
synergy in regards to cytokines
response to cell to two cytokines is much greater than you would expect if those two were added individually
antagonism in regards to cytokines
effects of one cytokine opposes another
interleukin receptor naming
IL followed by R
ex: IL-2R
most interleuken receptors signal via what pathway
jak stat pathway
jak state pathway
receptor that consists of two chains so the two chains come together when by bind ligand.
two of the chains have jak kinases associated withtails. one ligand binds dimerization of reeptor, brings jak close enough that they can autophosphorylate and phosphorylate the tails. the phosphotyrosine form docking site for state and then state echo 11:01
draw interleukin jak-stat pathway
pg 34
IL2R superfamily share what chain
IL2R gamma chain
in presence if IL3 the progenitor cell is biased to differentiate
along the lymphoid lineage
If there is IL3 and GM-CSF then bised to differentaite
along myeloid lineage
myeloid lineage gives rise to
neutrophils eosinophils mast cells basophils monocytes → macrophages
prominent barrier to infection in epidermis
include fatty layer that’s secreted by keratinocytes in stratum granulocum - note the fat is contained in lamellar bodies
interferon alpha and interferon beta are both
type I interferon
detection of viral genomes by intracellular RIG-1 & MDA5 couples to the production of what
type I interferon
