lect 11 Flashcards
what are the three phases of the innate imunity
physical and chemical barrieres
cellular responses to infection ( macrophages, dendritic celll, nK cell)- pathogen binds to cell and actiavtes it
activataion of adaptive immune responses
what do dendritic cells do in the innate immune response
release cytokines and chemokines and antimicrobial substances and lead to inflamation and aid in phagocytosis
what are the innate components of the blood
many antimicrobial peptides proteins and other emdiators including cytokines
for adaptie repsonse it is antibodies and cytokines
what are the epithelial barriers
skin and mucosal membranes
produce:
acidic pH
enzymes and binding proteins
antimicrobial peptides
what is cholesterol used for
membrane targetting of antimicrobial peptides (AMP) it has a negative charge and goes to extracellular membrane leaflet for strong binding of AMP
what are the innate immune cells
NK cells
Macrophages
dendritic cells
neutrophils
lysis of viral infected cells
interferon
macrophage activation
NK cells
phagocytosis
inflamatory mediators
antigen presentation
reactive oxygen and nitrogen species
cytokines
complement proteins
macrophages
antigen presentation
costimulatory signals
reactive oxygen species
interferon
cytokines
dendritic cells
phagocytosis
reactive oxygen and nitrogen species
antimicrobial peptides
neutrophisl
what innate cells can do phagocytosis
macrophages and neutrophils
where are neutrophils found
they circulate in the periphery and usually not found in healthy tissue
how do iLC recognize and respond to infection
use innate type molecules and lack Ag specific receptors
how are microbes recognized
directly by receotors on phagocytes that recognize PAMPs
how are PAMPS distinguished
by cellular location and range of effects caused by ligand binding
variety of things recognized by TLR
many types
what do TLR do
dont induce phagocytosis
dimerize (hetero to increase diversity of recognition) with extracellualr leucine rich LRR domains that BIND PAMPs and DAMPs
steps of TLRs plasma membrane
MYD88 adaptor proteins actiavte TAK1 which activates MAPK pathway and NFKB
what does NFKB do
induces innate and inflamatory gene transcription shared amongs TLR
steps of endosomal TLRs
mYD88 and TRIF adaptor proteins activate TAK1 which activates MAPK and NFKB pathway
IRF induce type I interferon expression
what are type i interferosn
IFN a/B
what are IRFs
interferon regulatory factors
what is the function of type I interferons
when TLR bind to PAMPs on viruses, it induces IFN A/B expression which feeds back to inhibit viral replication
what are CLRs
c type lectin receptors
what do CLRs function for
as phagocytic receptors
what do CLRs recognize
CHO components on funghi, mycobacteria, viruses, parasites, and some allergnets
and trigger NFKB and IFN a/B
what are NLRs
NOD like receptors
what are NLRs actiavted by
pAMPS and DAMPS
what do NLRs trigger
NFKB and IFN a/B
some activate the NLRP3 inflammasome
what is the NLRP3 inflamasome
when NLRs assemble with other proteins in a complex that activates proteomes necesary for converting inctive procytokines precurosrs of IL1 and IL18 into thier mature forms
what are DAMPs
danger assocated moleculae patterns
sterile activators like self derived things and enviromentally derived things
what are PAMPS
pathogen activators that are pathogen derived
what are the steps in activating the NLRP3 inflamasome
signal 1- TLR, CLR, NOD NLR
signal 2- act thorugh ROS bc of influx of ATP and ions and particulates to activate NEK7
what does the NLRP3 inflamasome lead to
pro inflamatory cell death called pyroptosis to kill infected cells and activates inflamation via IL1B and IL18
kineret anakinra
human IL-1RA
what is DIRA
deficiency of IL-1 receptor atagnist
auto inflamatory disease
what are RLRs
RIG i like receptors
RNA helicases that function as cytosolic PRRs which are soluble
what do RLRs recognize
viral ds RNA
what is RIG I
major PRR of HCV infection
what do RLRs trigger
signaling pathways to actiavte IRFs to trigger antiviral interferon responses and NFKB transcription factor
what does cGAS do
recognizes cytosolic DNA and synth cGMP from ATP and GTP
activates STING
what does sting do
binds c-di-GMP which is a bacterial metabolite
what do cGAS and STING do collectively
activate NFKB and IRF transrciption factors
cytokine storm
when SARS-COV2 infects lungs, innate immune cells release pro inflammatory cytokines
leads to panoptosis and cytokine storm loop
TNF and IFNy
systemic inflamaion and multiorgan failure
death
