4. Innate defence Flashcards

1
Q

what are the phagocytic cells?

A

Macrophages
Neutrophil
immature Dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the phagocytic precursor?

A

Monocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are tissue resident macrophages also known as?

A

Mononuclear phagocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What tissues do mononuclear phagocytes reside in?

A

Lymph node sinuses
small blood vessels
Endothelial cells of sinusoids of liver, spleen and bone marrow
alveoli
brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are neutrophils also known as?

A

Polymorphonuclear neutrophilic leukocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

which phagocytes are short lived?

A

Neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

when are dendritic cells phagocytic?

A

when immature and resident in the tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what do mature dendritic cells do?

A

migrate to the lymph nodes and act as APC to T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the 3 steps of phagocytosis?

A
  1. chemotaxis
  2. attachment and uptake
  3. microbicidal activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the bacterial protein N-terminus used in chemotaxis to recruit phagocytes?

A

f-Met-Leu-Phe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what attracts monocytes to the site of infection in chemotaxis?

A

complement fragment C3a and C5a
chemokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What chemokine is the macrophage inflammatory protein?

A

CCL3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What chemokine recruits neutrophils and T cells to the site of infection?

A

CXCL8 (IL-8)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What receptors do cells rely on to detect the chemotaxis gradient?

A

G-protein coupled receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what receptors do macrophages express?

A

PRRs that bind microbe components
complement receptors
lipid receptors
scavenger mannose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the phagocytic receptors on macrophages?

A

Dectin-1
mannose receptor
scavenger receptors
complement receptors - CR1, CR3, CR4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what does dectin-1 bind?

A

B-1,3-linked glucans on fungi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what does mannose binding receptor bind?

A

mannosylated ligands on bacteria, fungi and viruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what do scavenger receptors bind?

A

anionic polymers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what do complement receptors bind?

A

inactivated C3b on bacterial surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

when does a macrophage initiate inflammation?

A

once a pathogen is phagocytosed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what do PRRs recognise?

A

pathogen-associated molecular patterns (PAMPS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what PRR represent an evolutionary ancient host defence?

A

Toll- like receptors

24
Q

What TLR recognises diacyl lipopeptides?

A

TLR2 and TLR6

25
Q

What TLR recognises triacyl lipopeptides?

A

TLR1 and TLR2

26
Q

What TLR recognises flagella?

A

TLR5

27
Q

What TLR recognises lipopolysaccharides (LPS)?

A

TLR4

28
Q

What TLR recognises dsDNA?

A

TLR3

29
Q

What TLR recognises ssRNA?

A

TLR7 and TLR8

30
Q

What TLR recognises methylated CpG DNA?

A

TLR9

31
Q

What is the signalling cascade when TLR2 is bound?

A
  1. starts with MyD88
  2. MyD88 activates transcription factor NF-kB
  3. NF-kB moves to the nucleus and induces the expression of proinflammatory cytokines
32
Q

what is MyD88?

A

a viral adaptor protein

33
Q

give an example of a PRR in the cytoplasm

A

NOD2

34
Q

What does NOD stand for?

A

Nucleotide binding oligomerisation domain

35
Q

what does binding to NOD2 cause?

A

start of the NF-kB signalling cascade

36
Q

do cytokines work locally?

A

yes

37
Q

what cytokines trigger inflammation?

A

IL-1b and TNFa

38
Q

what does IL-6 do?

A

acts on the liver to produce acute proteins like mannose binding lectin and C reactive protein

39
Q

what is phagocyte oxygen independent killing?

A

using an acidic environment,
lysozymes,
antimicrobial peptides,
hydrolases

40
Q

What is phagocyte oxygen dependent killing?

A

Respiratory bursts (important in neutrophils)
Oxygen-derived products (ROS)
superoxide
hydrogen oxide
singlet oxygen
hydroxyl radical
hypophalite

41
Q

what is critical for oxygen dependent killing?

A

NADPH and O2 are oxidised by NADPH oxidase to form H2O2 and O radicals

42
Q

what happens if a person lacks NADPH oxidase?

A

cannot make ROS
develop chronic bacterial infections
develop skin and liver granulomas

43
Q

how does the superoxide ion contribute to oxygen dependent killing?

A

cause influx of K+ and H+ into phagocytic vesicles and lowers the pH.
causes a release of cathepsin G and elastase from granules which are activated by lysosomal proteases

44
Q

how is NADPH oxidase assembled in the respiratory burst?

A

GP91is on the membrane of the neutrophil
associated with the cytoplasmic components and becomes a complex in the phagolysosome membrane
the enzymes in the primary granule can be activated in the phagosome
then start production of ROS

45
Q

What are NETs?

A

Neutrophil extracellular traps
Include DNA histones, granules and proteins outside the cell to trap and kill bacteria

46
Q

What are the 2 main viral components that trigger PRRs?

A

dsRNA triggers TLR3
unmethylated CpG DNA triggers TLR9

47
Q

what type of signalling cascade does the viral components trigger?

A

To produce type 1 interferons

48
Q

What are type 1 interferons?

A

antiviral effector molecules that effect the cells around then

49
Q

what anti viral responses do type 1 interferons produce?

A

induce resistance to viral replication
increase MHC-1 expression and antigen presentation
activate dendritic cells and macrophages
activate NK cells

50
Q

what is the purpose of the type 1 interferon antiviral state?

A

creates a fire-break
the virus cannot replicate in neighbouring cells to keep the infection local

51
Q

what are natural killer cells?

A

large granular lymphocytes for early defence
derived from the common lymphoid progenitors
activated by type 1 interferons and cytokines

52
Q

what is NK cells role in early immunity?

A

start killing the virus during the lag phase of adaptive immunity

53
Q

How do NK cells scan healthy cells?

A

binds the activating receptor to the ligand
binds MHC1 to the inhibitory receptor
the inhibitory signal overrides the activation

53
Q

how do NK cells scan infected cells?

A

the MHC1 is not expressed or expressed incorrectly
no inhibitory signal
NK cells activated and kill by triggering apoptosis

53
Q

What do NK granules contain?

A

Perforin = helps deliver granule contents to the target cell
serglycin = a proteoglycan scaffold
Granzymes = granules associated enzymes like serine proteases that trigger host cell apoptosis

54
Q

How do granzymes trigger apoptosis?

A

Granzyme B cleaves procaspase 3 to activate it
caspase 3 cleaves the inhibitor of caspase-activated DNase (ICAD)
CAD then triggers DNA degradation