L4 - innate defences

Question 1

what are most bacteria killed by

Answer 1

phagocytes:

macrophages

neutrophils

Question 2

stages of phagocytosis

Answer 2

1. chemotaxis
2. attachment and uptake
3. microbicidal activity

Question 3

what is f-met and how is it involved in chemotaxis

Answer 3

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

Question 4

name a chemokine

Answer 4

CCL3

Question 5

how do chemokines work for phagocytosis

Answer 5

chemokines = chemo-attractant proteins

act via G-coupled receptors to promote movement towards the higher concentration of chemokines/site of infection

Question 6

Name the complement receptors on phagocytes that can bind to C3b on bacterial surface

Answer 6

CR1,CR3 and CR4

Question 7

what are pattern recognition receptors (PRRs)

Answer 7

recognise pathogen-asociated moleular pattens (PAMPs)

= toll-like receptors

toll defciecient organims cannot recognise fifference between own and foreign cells = uncontrollable growth of pathogens

Question 8

what are Toll like receptors (TLRs)

Answer 8

leucin rich dimer receptors

2 sickle shaped monomers dimerise to form actuive receptor

Question 9

what does TLR-2 recognise (PAMPs)

Answer 9

gram positive wall of bacteria

= polyteichoic acid residues

Question 10

what happens when TL-2 is activated

Answer 10

1. recognises protea-glycan cell wall component (polytechoic acid)
2. receptors tail recruits MyD88
3. activates transcription factor NFkB
4. production of pro-inflammatory cytokines

= IL-1B
= TNFa - tumour necrosis factor

Question 11

effects of pro-inflammatory cytokines - IL-1B and TNF-a

Answer 11

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

Question 12

what do phagocytes send out when engulfing pathogen

Answer 12

pseuodopdia

temporay arm like projectioms

extensions of the membrane with cytoplasm

Question 13

oxygen dependant and independant killing

Answer 13

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

Question 14

between neutrophiols and macrophages which is more effective at oxygen dependant mechanisms for lysis of phagosome

Answer 14

neutrophils

higher respiratory rate

Question 15

inititation mechanism of respiratory burst

Answer 15

1. f-met peptides on pathogens bind to TLRs
2. activates Rac2
3. causes assembly of active NADPH oxidase in phagolysomsome membrane

= generates reactive oxygen species (ROS)

Question 16

action of NADPH oxidase to create reactive oxygen radicals

Answer 16

NADPH oxidase acts on NADPH + oxygen

proudces superoxide anions

= superoxide further acted on to prouce other ROS by superoxide dimutase = hydrogen peroxide

Question 17

what are NETs

Answer 17

Neutrophil Extracellular Traps

trap bacteria in sticky DNA and contents of granules

activated by chemokine CXCR2

Question 18

what chemokine receptor activates formation of NETs

Answer 18

CXCR2

Question 19

what pathogen ton interferons mainly respond to

Answer 19

viral

Question 20

what TLR within the cytoplasm responds to double stranded RNA in virally infected cells

Answer 20

TLR-3

dsRNA only present in infected cells

Question 21

what does acyivation of TLR-3 indicate and what does it cause

Answer 21

presence of dsRNA = viral infection

interferon regulatory factors produced - IRF3

promote transcription of type 1 interfon genes

Question 22

name a type 1 interfon and what all type 1 interfons share

Answer 22

IFN-a

all Type 1 interfons share same receptor and hace same effect

Question 23

effects of type 12 interfon - IFN-a

Answer 23

prevent FURTHER infection of neighboring cells

FIRE BREAK

1. IFN-a binds to cognate receptors on adjhjacent cells
2. interfon-inducible genes expressed

= antiviral state that makes it harder for these cells to be infected

Question 24

name a few of the features of the ‘antiviral state’ induced by type 1 interfons

Answer 24

increased MHC-1 expression and antigen presentation

activate NK cells to kill virally infected cells

Question 25

what are Natural killer cells

Answer 25

large granular pre-activated lymphocytes

derived from common lymphoid progenitor

activated by type 1 interfons and cytokines from macrophages

Question 26

how do NK cells know what to kill and what not to (hint: MHC-1 !!)

Answer 26

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

Question 27

what is the actiavtion of NK cells dependant on

Answer 27

balance of inhibitory and activator signal from receptors

Question 28

name the 3 key components of NK cells granules

Answer 28

1. Perforin - helps deliver granule contents inbto cytoplasm
2. serglycin - acts as a scaffold
3. granenzymes - serine proteases that trigger apototosis

Question 29

how is apoptosis caused by Granenyme B from NK cells granules

Answer 29

Graneznyme-b cleaves Procaspase-3

active caspase 3 cleaves ICAD the inhibitor of CAD

DNA is degraded by CAD = apoptosis

CAD (Caspase-activated-DNase)