Innate Immunology Flashcards
1-6
Innate immune cells in humans perform a similar function to
drosophila (& express homologous TLRs
Cytoplasm chocked full of
granules
what are granules?
vesicles containing various innate immune cell function proteins
7
Neutrophils are the most
abundant (50% to 70% of all
leukocytes)
what is the neutrophil life span?
7 to 10 hours in peripjhery - rapid turnover
neurtopjhil function?
Indiscriminately kill invading microbes (recognised as non-self) by a
process known as phagocytosis (ingest and kill)
Neutrophil passage through the blood is
slow
Neutrophil passage through the blood is slow due to
transient integrations with neutrophil cell surface receptors and blood vessel ligands – they roll through the vasculature
vascular damage cause
proinflammatory cytokine release by tissue
macrophages (TNFα, IL-1) causing neutrophil attraction
Once neutrophils have transmigrated
to the site of bacterial infection
(dermal region) they are
activated in numerous ways
A key mechanism for neutrophil
activation in the context involves
toll
like receptor-4 (TLR4)
TLR’s are
Pathogen Associated
Molecular Pattern (PAMP) receptors:
function as dimers
TLR4 recognises
bacteria endotoxin
lipopolysaccharide (gram -ve bacteria)
Engagement of TLR4 with LPS Initiates
a conformational change that is transmitted through the membrane to the cytoplasmic TIR domain
Downstream signalling involves
the activation of IL1-Receptor Associated Kinase (IRAK) and subsequent MAPkinase activation: TAK1 -> MKK4 -> JNK
13
toll like receptors function as
dimers
each monomer has
1) a leucine rich repeat extracellular
domain (and forms the characteristic
‘horseshoe’ shape)
2) an α-helical transmembrane domain
3) a cytoplasmic Toll/IL-1R (TIR)
signalling domain
there are
12 human TLRs which are expressed on a wide variety of innate
immune cells
The TLRs have the same
general topology
TLRs have
Leucine rich repeats in the extracellular domian
Conserved intracellular
TIR domain