Innate Immunity Flashcards
(35 cards)
physical barriers
intact skin
internal epithelium is lined with mucous and cilia preventing microbe binding
why does cystic fibrosis lead to frequent
defective gene causes thick, sticky mucous which traps pathogens and is hard to remove from the lung
which antimicrobial enzymes act as a chemical barrier
what do they do
lysozyme - break down peptidoglycan
phospholipase A2 - break down cell membrane
what is the (immunological) effect of surfactants in the lung
important to maintain function
bind pathogens and make their removal by immune cells easier
antimicrobial peptides and their function
defensins - modulate inflammation
cathelicidins - damage microbial membrane, inhibit DNA and protein synthesis
histatins: antifungal activity
explain the microbiological barrier and give an example of what happens when its disrupted
competitive exclusion prevents colonisation of harmful bacteria
clostridium difficile infection
what are the type of pattern recognition receptors
how are they encoded in the genome
phagocytic receptors
toll-like receptors
NOD-like receptors
RIG-I-like receptors
germline encoded - do not require somatic recombination
ligands of these toll-like receptors:
TLR-3, -4, -5, -7, -8, -9
3: dsDNA
4: LPS
5: flagellin
7: ssRNA
8: ssRNA
9: CpG-ODN
structure of TLRs
horseshoe like leucine rich domain that recognises ligand
transmembrane signal transduction
cytoplasmic TIR domain
localisation of TLRs depending on target
localised on the cell membrane to recognise extracellular pathogens: bacteria
localised on the inside of the cell (on endosomes) to recognise intracellular pathogens: viruses
what happens upon TLR activation
two TLRs dimerise and TIR domains are brought together - activation of enzyme activity
adaptor proteins activate kinases which lead to activation of transcription factors
gene expression of IL-6, TNFα, INFβ
where are NOD-like receptors expressed and what do they recognise
expressed in the cytoplasm
sensors for intracellular bacteria
NOD-like receptor activation
dimerization leading to kinase activity leading to expression of inflammatory cytokines
diseases associated with NODs
Crohn’s disease
Blau syndrome
RIG–like receptors localisation and target ligand
expressed in cytoplasm
sensors for cytoplasmic viral RNAs
under the influence of cytokines, endothelial cells increase expression of what molecules into blood vessel lumens
selectins and ICAMs
what is the consequence of selectin expression
capture and tethering of neutrophils to the vessel wall
‘selection’ of passing neutrophils
what type of expressed molecules induce rolling
selectins
L-selectins on leukocyte
E-selectins on endothelium
what molecules mediate firm adhesion of leukocytes to blood vessel walls and stop rolling
ICAM - Integrin binding
ICAM on endothelium
integrin on leukocyte
what causes migration of adhered leukocytes through blood vessel wall during inflammation (after adhesion)
chemokines
what are the systemic protective effects of cytokines in inflammation
which cytokines cause them
brain induces fever: TNF, IL-1, and IL-6
liver produces acute phase proteins: IL-1, IL-6
bone marrow increases leukocyte production: TNF, IL-1, IL-6
what are the systemic pathological effects of cytokines in inflammation
what cytokine causes them
septic shock:
low cardiac output
thrombus formation and increased permeability in blood vessels
insulin resistance in multiple tissues
TNF
which immune cells are involved in innate immunity
macrophages
dendritic cells
neutrophils
NK cells
what are the key receptors used by macrophages
toll like receptors