BIOL 435 Ch. 4 Part Two (Innate Immunity) Flashcards
C-type lectin receptors (CLRs)
- activate innate and inflammatory responses
- generally recognize CHO componenents of fungi, viruses, mycobacteria, parasites and allergens
CLRs trigger pathways
-leading to TFs that induce expression of proinflammatory cytokines >INF alpha/beta >IL-1beta >TNF >IL-23
NOD-like receptors
- nucleotide oligomerization domains-receptors
- cytosolic PRRs activated by intracellular PAMPs and DAMPs
- induce expression of genes encoding antimicrobial proteins and peptides
- initate autophagy
initiate autophagy (NOD-receptors)
-by forming autophagosomes that fuse with lysosomes to then kill bacteria
NOD1 and NOD2
- bind PAMPs of intracellular microbial components
ex. bacterial cell wall fragments
RIG-1-like receptors (RLRs)
- recognize viral dsRNAs
- function as cytosolic PRRs
- trigger signalling pathways that activate IRFs and NF-kappa beta TFs
IRFs
- interferon regulatory factors
- lead to increased expression of interferons (IFN-alpha and IFN-beta)
- potent antiviral cytokines
dsRNA
-only with viruses
PRR signalling pathways
-activate expression of a large variety of genes >antimicrobial peptides >type 1 interferons >cytokines >chemokines >enzymes (iNOS an COX2)
COX2
- Arachidonate to prostaglandins: pain sensations
2. Promote inflammation
Type 1 interferons
- IFN-alpha and IFN-beta
- potent antiviral effects
- inhibit viral replication, transcription and translation
- activate NK cells
- regulate macrophages and T-cells
signalling through TNF receptors
- binding of TNF activates cytoplasmic death domain (DD)
- response depends on cell and its environment
1. Cell survival and immune response
2. Apoptosis: cut in a clean way (doesn’t lead to inflammation)
innate immune response steps
- Leukocytes in blood respond to chemical attractants released by pathogens and signals from nearby injuried cells
- Leukocytes squeeze between cells of the capillary wall
- Within damaged tissue, neutrophils release chemicals to break apart pathogens
>monocytes differentiate into macrophages
>phagocytosis
>take some bacteria to a lymph cell to start an adaptive response
phagocytosis
-engulfment and internalization of materials for their clearance and destruction
-microbes are recognized by receptors on phagocytes
>may recognize soluble opsonin protein bound to microbes
phagocytes
- macrophages, neutrophils, dendritic cells
- may recognize PAMPs directly through PRR binding
- may be induced indirectly through opsonization
opsonins
- soluble pattern recognition proteins
- mannose binding lectin (MBL)
- complement proteins
- C-reactive protein
- Antibodies
opsonization
- ‘to make tasty’
- the process of chemical modification that enhance binding to a phagocytoic cell=enhances phagocytosis
phagosomes
-fuse with lysosomes or granules
destruction occurs through
- enzyme degradation
- antimicrobial proteins
- toxic effects of ROS and RNS
respiratory burst
-intracellular killing
-bleach fireball
-ROS lead to cell death
>neutrophils sometimes commit suicide for the greater good
cell death induced by receptor activated signal pathways
- apoptosis
- NETs
- pyroptosis
apoptosis
- cell death induced by TNF binding to TNFR, NK cells and T cytotoxic cells
- clean, tidy, controlled
NETs
- neutrophil extracellular traps
- activation requires NADPH oxidase and generation of ROS
pyroptosis
- induced by inflammasome activation eliminates infected macrophages allowing release of IL-1beta and IL-18
- messy
IL-1beta and IL-18
- made in cytosol, not in a vesicle
- need to be cleaved to be activated
- then cells commit suicide to release them
apoptosis steps
- Cell shrinks, chromatin condenses
- Membrane starts blebbing, organelles disintegrate
- Nucleus and organelles collapse, membrane continues to bleb
- Apoptotic bodies form
- Macrophages phagocytose apoptotic bodies
* no inflammation
NETs steps
- Signals from PRR activate neutrophils
- Phagosome NADPH oxidase (PHOX) is induced and intracellular membrane begin to break down
- Granule enzymes neutrophils elastase (NE) and myeloperoxidase (MPPO) enter the nucleus and modify histones
>chromatin decondenses - PM ruptures and cytoplasm and nucleoplasm are expelled forming NETs
- Cells die form NEToses
inflammasome formation
- may be due to signalling of TLR, NOD-like receptor and others
- allows cleavage of procaspase 1 to caspase-1
caspase-1
-cleaves pro-IL-1beta and pro-IL-18 into IL-1beta and IIL-18
>may lead to cell death to release them (pyropotosis)
IL-1beta
-potent inflammatory cytokine (and IL-18)
proinflammatory cytokines and chemokines triggered by
-innate responses to infection, damage or harmful substances
early components of inflammation include
- increase vascular permeability
- recuritment of neutrophils and other leukocytes from the blood to the side of damage/infection
5 inflammatory signs
- Heat: vasodilation, increased blood flow
- Redness: increased blood flow
- Swelling: plasma through gaps
- Pain: pressure on nocireceptors
- Loss of function
inflammatory response steps
- Tissue damage
- release chemoattracts and vasoactive factors
- these trigger a local increase in blood flow and capillary permeability - Influx of fluid and cells
- Neutrophils and other phagocytes migrate to site of inflammation
- Phagocytes and antibacterial substances destroy bacteria
later stages of inflammation
- acute phase responses (APRs)
- induced by acute inflammaoty triad
- incrased synthesis/secretion of antimicrobial proteins by liver
antimicrobial liver proteins examples
- MBL: mannose binding lectin
- CRP: C-reactive protein
- complement components
- activate other processes that help eliminate pathogens
acute inflammatory triad
- IL-1
- TNF-alpha
- IL-6
innate lymphoid cells (ILC)
- derived from common lymphoid progenitor cells
- include NK cells and 6 other ILC populations
NK cells found in
-lymphoid tissue and recirculate
other ILC found
-in epithelium
ILC group based on
-cytokines produced
ILCs lack PRRs
-are not activated directly by pathogens
NK cells
- lymphocytes with innate immune functions
- express a limited set of receptors for self-proteins
- activated and perform 1 of 2 functions
NK receptors induced by
- infections
- malignant transformations (ex. cancer)
- other stresses
activated NK cell functions
- Kill altered self-cell by releaseing perforin and gronzymes inducing apoptosis
- Produce cytokines that induce adaptive responses against the altered self-cell
