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Infection and immunity > 4. Innate defence > Flashcards

4. Innate defence Flashcards

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1
Q

what are the phagocytic cells?

A

Macrophages
Neutrophil
immature Dendritic cells

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2
Q

what is the phagocytic precursor?

A

Monocytes

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3
Q

what are tissue resident macrophages also known as?

A

Mononuclear phagocytes

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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

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5
Q

What are neutrophils also known as?

A

Polymorphonuclear neutrophilic leukocytes

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6
Q

which phagocytes are short lived?

A

Neutrophils

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7
Q

when are dendritic cells phagocytic?

A

when immature and resident in the tissue

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8
Q

what do mature dendritic cells do?

A

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

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9
Q

What are the 3 steps of phagocytosis?

A
  1. chemotaxis
  2. attachment and uptake
  3. microbicidal activity
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10
Q

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

A

f-Met-Leu-Phe

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11
Q

what attracts monocytes to the site of infection in chemotaxis?

A

complement fragment C3a and C5a
chemokines

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12
Q

What chemokine is the macrophage inflammatory protein?

A

CCL3

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13
Q

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

A

CXCL8 (IL-8)

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14
Q

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

A

G-protein coupled receptors

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15
Q

what receptors do macrophages express?

A

PRRs that bind microbe components
complement receptors
lipid receptors
scavenger mannose

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16
Q

what are the phagocytic receptors on macrophages?

A

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

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17
Q

what does dectin-1 bind?

A

B-1,3-linked glucans on fungi

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18
Q

what does mannose binding receptor bind?

A

mannosylated ligands on bacteria, fungi and viruses

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19
Q

what do scavenger receptors bind?

A

anionic polymers

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20
Q

what do complement receptors bind?

A

inactivated C3b on bacterial surface

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21
Q

when does a macrophage initiate inflammation?

A

once a pathogen is phagocytosed

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22
Q

what do PRRs recognise?

A

pathogen-associated molecular patterns (PAMPS)

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23
Q

what PRR represent an evolutionary ancient host defence?

Study These Flashcards
A

Toll- like receptors

24
Q

What TLR recognises diacyl lipopeptides?

Study These Flashcards
A

TLR2 and TLR6

25
What TLR recognises triacyl lipopeptides?
TLR1 and TLR2
26
What TLR recognises flagella?
TLR5
27
What TLR recognises lipopolysaccharides (LPS)?
TLR4
28
What TLR recognises dsDNA?
TLR3
29
What TLR recognises ssRNA?
TLR7 and TLR8
30
What TLR recognises methylated CpG DNA?
TLR9
31
What is the signalling cascade when TLR2 is bound?
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
what is MyD88?
a viral adaptor protein
33
give an example of a PRR in the cytoplasm
NOD2
34
What does NOD stand for?
Nucleotide binding oligomerisation domain
35
what does binding to NOD2 cause?
start of the NF-kB signalling cascade
36
do cytokines work locally?
yes
37
what cytokines trigger inflammation?
IL-1b and TNFa
38
what does IL-6 do?
acts on the liver to produce acute proteins like mannose binding lectin and C reactive protein
39
what is phagocyte oxygen independent killing?
using an acidic environment, lysozymes, antimicrobial peptides, hydrolases
40
What is phagocyte oxygen dependent killing?
Respiratory bursts (important in neutrophils) Oxygen-derived products (ROS) superoxide hydrogen oxide singlet oxygen hydroxyl radical hypophalite
41
what is critical for oxygen dependent killing?
NADPH and O2 are oxidised by NADPH oxidase to form H2O2 and O radicals
42
what happens if a person lacks NADPH oxidase?
cannot make ROS develop chronic bacterial infections develop skin and liver granulomas
43
how does the superoxide ion contribute to oxygen dependent killing?
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
how is NADPH oxidase assembled in the respiratory burst?
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
What are NETs?
Neutrophil extracellular traps Include DNA histones, granules and proteins outside the cell to trap and kill bacteria
46
What are the 2 main viral components that trigger PRRs?
dsRNA triggers TLR3 unmethylated CpG DNA triggers TLR9
47
what type of signalling cascade does the viral components trigger?
To produce type 1 interferons
48
What are type 1 interferons?
antiviral effector molecules that effect the cells around then
49
what anti viral responses do type 1 interferons produce?
induce resistance to viral replication increase MHC-1 expression and antigen presentation activate dendritic cells and macrophages activate NK cells
50
what is the purpose of the type 1 interferon antiviral state?
creates a fire-break the virus cannot replicate in neighbouring cells to keep the infection local
51
what are natural killer cells?
large granular lymphocytes for early defence derived from the common lymphoid progenitors activated by type 1 interferons and cytokines
52
what is NK cells role in early immunity?
start killing the virus during the lag phase of adaptive immunity
53
How do NK cells scan healthy cells?
binds the activating receptor to the ligand binds MHC1 to the inhibitory receptor the inhibitory signal overrides the activation
53
how do NK cells scan infected cells?
the MHC1 is not expressed or expressed incorrectly no inhibitory signal NK cells activated and kill by triggering apoptosis
53
What do NK granules contain?
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
How do granzymes trigger apoptosis?
Granzyme B cleaves procaspase 3 to activate it caspase 3 cleaves the inhibitor of caspase-activated DNase (ICAD) CAD then triggers DNA degradation

Infection and immunity (22 decks)

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