L4 - innate defences Flashcards
what are most bacteria killed by
phagocytes:
macrophages
neutrophils
stages of phagocytosis
- chemotaxis
- attachment and uptake
- microbicidal activity
what is f-met and how is it involved in chemotaxis
f-met = N-formylmethionine
a modified 3 amino acid present in prokaryotes for protein synthesus
binds to ceeptors on phagocytes recruiting them
= similar to C3b
= phagocytes bind and move toeards
name a chemokine
CCL3
how do chemokines work for phagocytosis
chemokines = chemo-attractant proteins
act via G-coupled receptors to promote movement towards the higher concentration of chemokines/site of infection
Name the complement receptors on phagocytes that can bind to C3b on bacterial surface
CR1,CR3 and CR4
what are pattern recognition receptors (PRRs)
recognise pathogen-asociated moleular pattens (PAMPs)
= toll-like receptors
toll defciecient organims cannot recognise fifference between own and foreign cells = uncontrollable growth of pathogens
what are Toll like receptors (TLRs)
leucin rich dimer receptors
2 sickle shaped monomers dimerise to form actuive receptor
what does TLR-2 recognise (PAMPs)
gram positive wall of bacteria
= polyteichoic acid residues
what happens when TL-2 is activated
- recognises protea-glycan cell wall component (polytechoic acid)
- receptors tail recruits MyD88
- activates transcription factor NFkB
- production of pro-inflammatory cytokines
= IL-1B
= TNFa - tumour necrosis factor
effects of pro-inflammatory cytokines - IL-1B and TNF-a
all cytokines have local effects and some have systemic effects
IL-1B:
causes local tissue destruction and leakiness of capillaries
= increase accsses of effector cells
causes fever
TNF-a:
vascular permeablility aswell - increased entry and increased fluid drainage
causes fever = less hapitable for most pathogens
what do phagocytes send out when engulfing pathogen
pseuodopdia
temporay arm like projectioms
extensions of the membrane with cytoplasm
oxygen dependant and independant killing
inside phagolysosome vesicle
independent:
-acidic pH of 3.5-4 by injecting H+ ions
- lysozymes digest cell wall of gram +
dependant:
respiratory burst gegnerates reactive oxygen species (ROS)
= hydrogen perxoide and superoxide
between neutrophiols and macrophages which is more effective at oxygen dependant mechanisms for lysis of phagosome
neutrophils
higher respiratory rate
inititation mechanism of respiratory burst
- f-met peptides on pathogens bind to TLRs
- activates Rac2
- causes assembly of active NADPH oxidase in phagolysomsome membrane
= generates reactive oxygen species (ROS)
action of NADPH oxidase to create reactive oxygen radicals
NADPH oxidase acts on NADPH + oxygen
proudces superoxide anions
= superoxide further acted on to prouce other ROS by superoxide dimutase = hydrogen peroxide
what are NETs
Neutrophil Extracellular Traps
trap bacteria in sticky DNA and contents of granules
activated by chemokine CXCR2
what chemokine receptor activates formation of NETs
CXCR2
what pathogen ton interferons mainly respond to
viral
what TLR within the cytoplasm responds to double stranded RNA in virally infected cells
TLR-3
dsRNA only present in infected cells
what does acyivation of TLR-3 indicate and what does it cause
presence of dsRNA = viral infection
interferon regulatory factors produced - IRF3
promote transcription of type 1 interfon genes
name a type 1 interfon and what all type 1 interfons share
IFN-a
all Type 1 interfons share same receptor and hace same effect
effects of type 12 interfon - IFN-a
prevent FURTHER infection of neighboring cells
FIRE BREAK
- IFN-a binds to cognate receptors on adjhjacent cells
- interfon-inducible genes expressed
= antiviral state that makes it harder for these cells to be infected
name a few of the features of the ‘antiviral state’ induced by type 1 interfons
increased MHC-1 expression and antigen presentation
activate NK cells to kill virally infected cells
what are Natural killer cells
large granular pre-activated lymphocytes
derived from common lymphoid progenitor
activated by type 1 interfons and cytokines from macrophages
how do NK cells know what to kill and what not to (hint: MHC-1 !!)
Nk cells have an inhibitory and an activating receptor
healthy cells and infected cells have ligand present for activating receptor
BUT infected cells do not have MHC class1 = inhibitory receptor cannot bind
= no inhibition to stop activatioon signal
= granules resleased onto surface of infected cell
what is the actiavtion of NK cells dependant on
balance of inhibitory and activator signal from receptors
name the 3 key components of NK cells granules
- Perforin - helps deliver granule contents inbto cytoplasm
- serglycin - acts as a scaffold
- granenzymes - serine proteases that trigger apototosis
how is apoptosis caused by Granenyme B from NK cells granules
Graneznyme-b cleaves Procaspase-3
active caspase 3 cleaves ICAD the inhibitor of CAD
DNA is degraded by CAD = apoptosis
CAD (Caspase-activated-DNase)
