Innate Immunity Flashcards
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
what is the process of phagocytosis
chemotaxis and adherence
ingestion of microbe into phagosome
fusion of phagosome with a lysosome - phagolysosome
digestion of microbe by enzyme forming residual body
discharge of waste
what are the leukocytes to move to site of infection
neutrophils
what is the function of neutrophils
kill microbes by releasing granules of degrading enzymes and ROS
what disease results from impaired development of neutrophils
what is the result
severe congenital neutropenia
recurrent bacterial infections in various organs
where does production of reactive oxygen and nitrogen species
why does it result in a respiratory burst
in the phagosome
results in a transient increase in oxygen consumption
what is the effect of chronic granulomatous disease
mutation in NADPH causing granuloma formation due to inability to kill phagocytosed bacteria
presence of cytokines and increased susceptibility to infection
what causes maturation of dendritic cells
mature in response to cytokines (infection)
what is the role of dendritic cells
where are they located
antigen presentation triggering Ag-specific lymphocyte response
located at body surface and in the T-cell area of lymphoid organs
where are NK cells developed and from what
bone marrow
lymphoid progenitor
which cytokines activate NK cells
IFNα/β
IL-12/18
what features and role of NK cells
two types of surface receptor (activating and inhibitory)
pre-formed cytosolic granules
kill infected or malignantly transformed cells
