Innate immunity 3

Question 1

dendritic cells

- main function

Answer 1

communication with adaptive immunity

presentation of antigens

NOT directly attack invading microbes

Question 2

dendritic cells

• where do they reside?
• what do they do here?
• how do they migrate?
• what do mature DCs do?

Answer 2

peripheral tissues

take up pathogens + their antigens

via lymphatic vessels to regional lymph nodes

activate naive T cells in lymphoid organs e.g. lymph nodes
- as DCs display antigens

Question 3

lymphatic system

• made up of?
• what do lymph nodes do?

Answer 3

lymphoid immune tissues/organs

trap interstitial fluids draining from tissues

Question 4

lymphatic system

- how does interstitial fluid travel through the system,?

Answer 4

system of ducts traveling from blood vessels via veins

• > creates pressure (due to valves)
• > moves slowly through tissues

Question 5

lymph node

• structure
• contain what cell type?
• what happens here?

Answer 5

small, kidney shaped
1.2cm long

lymphocytes
macrophages
other immune cells

exchange between innate and adaptive systems
- DCs displaying antigens interact with other immune cells

Question 6

dendritic cells

- what happens on infection?

Answer 6

DCs recognise pathogens via PRRs + MAMPs
-> take up pathogens via phagocytosis

take up viruses + extracellular material via macropinocytosis

DCs travel to lymph nodes
-> display antigens to adaptive immune cells

Question 7

what is the basic function of the lymph nodes?

Answer 7

used to sample infection

- higher conc of DCs = bigger infection

Question 8

antigen presentation

• APCs
• how are the antigens derived?
• how are the peptide antigens loaded onto the surface?

Answer 8

= antigen presenting cells
- macrophages + DCs

from destruction of pathogens in phagolysosome

loaded onto MHC
- major histone compatability complex

Question 9

antigen presentation

- 2 types of MHC

Answer 9

MHC 1
= all nucleated cells
- endogenous antigens
(generated inside cell)

MHC 2
= on APCs
- exogenous antigens
(sampled from outside cell)

Question 10

CD8 T cell

CD4 T cell

Answer 10

deals with virus-infected host cells
- CD8 on target cell binds the alpha3 domain of MHC class 1

deals with extracellular pathogens
- CD4 on APC binds the beta2 domain of MHC class 2

Question 11

DCs in mucosal surveillance and homeostasis

Answer 11

DCs residing in GALT (gut associated lymphoid tissues)

• monitor luminal contents (sensing antigens)
  + ensure appropriate response

Question 12

GALT

- Peyer’s patches

Answer 12

similar organisation to lymph nodes

sites where luminal contents continually sampled
-> antigens shown to resident immune cells

Question 13

GALT

• Microfold cells (M cells)
• DCs

Answer 13

deliver material from gut lumen to underlying immune cells
(include resident DCs)

DCs can directly sample luminal contents
- extend dendrites between epithelial cells

Question 14

intracellular pathogens

Answer 14

all viruses = obligate intracellular pathogens

many bacteria function as intracellular pathogens

Question 15

intracellular pathogens

- barriers against

Answer 15

innate physical barriers help exclude viral infection

some TLRs recognise viral MAMPs

RIG-1- Like receptors detect viral nucleic acids in infected cells

Question 16

RIG-1- Like receptors (RLRs)

Answer 16

= retinoid acid inducible gene 1

in cytoplasm

induces production of interferons

Question 17

interferons

Answer 17

type 1
- induce production of intracellular proteins that inhibit viral replication in host cells

type 2

• activate white blood cells that deal with infected host cells
• > kills host cells

Question 18

interferons

- signalling

Answer 18

host cell 1 infected by virus

• > makes interferon
• > BUT killed by virus

interferon enters host cell 2

• > induces changes to protect cell
  e. g. antiviral proteins

Question 19

TLR mediated interferon response

Answer 19

TLR7 and TLR3 found in endosomes

-> recognise ssRNA or dsRNA
(viral nucleic acids)

-> signalling
-> production of type 1 interferons (IFN-alpha and beta)
via cascade similar to other TLRs
+ interactions with interferon regulatory factors (IRF7 + IRF3)

Question 20

interferons

- detection of viral infection

Answer 20

triggers phosphorylation + translocation of IRF3 to nucleus
-> activates INF-B
-> INF-B secreted out of cell
-> autocrine effect = works on infected cell
OR
paracrine effect = works on nearby cells

• > stimulates production of other INF types + induce interferon response inhibitory to viral replication
  (e. g. increasing MHC 1 expression so viral antigens are presented)

Question 21

3 interferon responses

Answer 21

induce resistance to viral replication in all cells

increase expression of ligands for receptors on NK cells

activate NK cells to kill virus-infected cells

Question 22

natural killer (NK) cells 
- 2 main functions

Answer 22

kill infected host cells (self cells)

increase/maintain inflammation

Question 23

NK receptors

Answer 23

NK cells have cell-surface receptors that activate/inhibit cell killing
- use a combination of both to evaluate host cells

Question 24

NK recognition of healthy cells

Answer 24

healthy cells express range of surface features that act as ‘don’t kill me’ signals to NK cells

Question 25

NK cells recognition of infected cells

Answer 25

NK cells look for changes in cell surface features that indicate a cell is infected
= ‘dysregulated self’

activating receptors identify changes resulting from metabolic stress
= ‘stress-induced self’

inhibitory receptors recognise molecules always produced at high levels by most cells e.g. MHC1
- loss of these = ‘missing self’

Question 26

NK cell killing

Answer 26

NK cells perforate target cell membrane
 \+ also release Granzymes (proteases)
-> enter pores
-> activate other normally inactive caspases
-> induce apoptosis 
- avoids further spread of virus