Induced immunity effector functions
phagocytosis targeted killing antimicrobial peptides cytokine release inflammation cellular recruitment B and T cell activation
What is the timeline for induced innate repsonse
hours to days
usually 4 hours to 4 days
What are the cells of the innate immune system
monocyte which leads to Macs and Dendritic mast cells eosinophils NK cell Neutrophil Basophil
what cells are already in the tissues
Specialized T cells
what are 4 ways the induced immune response can be initiated
- tissue resident immune cells
- pro-inflammatory signaling
- interferon response and altered MHC expression
what are the four pro inflammatory signaling systems
acute phase response
what are the four different tissue resident Macs
liver: kupffer cells
skin: langerhans cells
what are the four effector mechanisms of macrophages
phagocytosis cytokine release degranulation antigen presentation *activate the adaptive immune system
innate immune cells recognize what?
patterns on the surface of cells
macrophage receptors recognize the cell-surface carbohydrates of bacterial cells but not those of?
what cells recognize human cells that are infected?
what is the purpose of Toll Like Receptors?
induce the release of cytokines
what is the purpose of mannose, complement, dectin, scavenger receptors A and B, and Lipopolysaccharaide receptors?
the induce phagocytosis
what are the 3 innate phagocytic cells
what is the process of phagocytosis
- bacterium becomes attached to membrane envaginations called pseudopodia
- bacterium ingested forming phagosome
- phagosome fuses with lysosome
- bacterium is killed
- digestion products are released(PMNs) and Macs and dendritic cells present
agents in phagolysosomes and granules that kill pathogens
acidification toxic oxygen products toxic nitrogen oxides antimicrobial peptides enzymes competitiors
what are the external TLRs?
what are the internal TLRs?
what must TLRs do the send signal?
what does TLR 9 recognize
CpG DNA bacteria
what does TLR 7 recognize
what does TLR 8 recognize
what does TLR 3 recognize
what does TLR 5 recognize
*also only external to recognize a protein not a lipid
what does TLR 4 recognize
what does TLR 1-2 recognize
what does TLR 2-6 recognize
what are the two heterodimer TLRs
TLR signals cytokine production through what?
NF-kB which is a transcription factor
what is the process of cytokine production through NFkB?
IRAK4->TRAF6->IKK phosphorylates inhibitor of kB which releases the inhibition of NFkB and allows cytokine production which are made in the cytoplasm and secreted via the ER
what do nucleotide-binding oligomerization domain NOD receptors detect?
what is the process of activating NFkB via NOD receptors
intracellular toxins, viruses, cell stress proteins are detected to phosphorlyate inhibitor of kB to allow NFkB to be released and to make cytokines
- also forms and inflammasome
- cooperate with TLRs
what is an inflammasome?
activates and promotes cytokine release by proteolytic activity (caspase 1), enhancing other pro-inflammatory signals and is a CHECKPOINT FUNCTION
what are cytokines
signaling molecules of the immune system
- paracrine and autocrine
- other names interleukins, chemokines
what are the six families of cytokines based on?
- class I
- class II
- interleukin 1
- interleukin 17
what are the common intracellular signaling pathways
what are the five pro-inflammatory cytokines released by macrophages
IL-1B TNF-alpha IL-6 CXCL 8 (chemokine) IL-12
which of the pro-inflammatory cytokines produce fever?
IL-lB, TNF-alpha, IL-6
this decreases the replication of viruses and bacteria
what does IL-6 do?
induces the liver to produce acute-phase proteins
what are acute phase proteins?
- c reactive proteins
- mannose binding lectin
- LPS binding protein
- complement components
- coagulation factors
- inflammatory response factors
what else do cytokines do?
initiate leukocyte recruitment and increased permeability of blood vessels
what three things does extravasation depend on?
chemokines, adhesion molecules and proteases(MMPs and elastase)
chemokines grandients recruitment of cells to tissue
immune targeting mechanisms
chemokines released by target (CXCL)
receptors present on immune cells (CXCR)
cells respond to specific chemokines
leukocytes extravasate to sites of inflammation how?
chemokine receptor(CXCL8) activates LFA-1 and s-Lex on PMN to bind to endothelial cells eg: LFA-1 to ICAM-1 and s-Lex to selectin
what does binding of the PMN trigger?
MMPs and elastase which breaks down basement membrane and cell enters the tissue
what are the four steps for leukocytes to get into tissues?
excessive plasma TNF-alpha causes what?
Septic shock syndrome
what leads to septic shock syndrome
blood borne infection systemic extravasation systemic PMN infiltration vascular collapse rapid multi-organ failure
what is the primary cell of the induced response?
- mostly found in the blood and most numerous portion of leukocytes
what are the effector mechanisms of neutrophils?
phagocytosis degranulation extracellular traps cytokine release *die after they are done
what are the four types of granuels
what is the dual purpose of granules in neutrophils?
the neutrophil oxidative burst kills what two things?
pathogen and the PMN
what is the non-lytic trap of PMNs
chromatin that moves through vasculature
what is the lytic trap of PMN
cell turns inside out and chews up pathogen
dendritic cells are loaded with what receptors? and what do they do?
PRR and TLRs
- process pathogens into antigens
- present antigens to lymphocytes
- cytokine regulation
- basically a big vaccum
large cytotoxic lymphocytes
- target and kill diseased self cells
- respond to interferons, MHC I and stress ligands
- regulate shift from induced innate to adaptive immune system
- selected for self and non self cells (educated) based on MHC I
what type of infections causes the interferon response?
what do interferon alpha and beta do?
- activate NK cells
- induce resistance to viral replication
- increase NK cell ligand expression on infected cell
NFkB causes the release of
interferons and cytokines
what TLRs induce interferons
TLR 3 and 7
interferons do what?
reduce viral replication
prevent cell division
activate NK cells, Mac, and T cells
interferons signal in what type of fashion?
autocrine and paracrine
interferons activate what type of cells?
mostly NK cells and then macs and T cells
what is the relationship between macs and NK cells in terms of mac phagocytosis?
sometimes macs need extra signaling to complete phagocytosis
- macs release CXCL8 and IL-12 which brings the NK cell to form a synapse.
- NK cells proliferate and secrete IFN-gamma
- IFN gamma binds to mac and activates the mac to increase phagocytosis and secretion of cytokines
if there is a large NK response what happens to the dendritic cell?
the presentation of antigen is inhibited thus regulating the adaptive immune response
if there is a small NK response what happens to the dendritic cells?
they are activated and they go and activate the adaptive immune response
granulocytes protect local tissues how?
express PRRs and degranulate when activated
- cell-type specific granule components
- respond to parasitic organisms
- responsible for type I hypersensitivity
what are the effector mechanisms that innate immune cells employ?
traps (PMNs only)
what do dendritic cells and macs do that PMNs don’t?
what do NK cells do that macs and PMNs don’t do?
directly target self cells