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week 2 > Liver and innate immune system > Flashcards

Liver and innate immune system Flashcards

1
Q

What two blood supplies feed into liver? What does liver excrete?

A

hepatic portal vein brings blood in from the intestine (80% of blood in the liver).
hepatic artery brings oxygenated blood to the liver.
Liver excretes bile through bile ducts.
hepatic vein (which drains blood from liver). this contains lots of complement and acute-phase proteins.

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2
Q

what is contained in the blood of hepatic portal vein?

A

from gut, pathogens, debris of pathogens (LPS), food products, immune cells.

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3
Q

What shape is the hepatic lobule?

A

hexagonal shape.

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4
Q

What vessels make up the portal tract?

A

heaptic vein and hepatic artery and bile duct and lymphatics.

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5
Q

Where does the blood of portal tract mix and end up?

A

Mixes in the sinusoids travels towards the terminal hepatic venule.

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6
Q

Why are there zones around the hepatic artery and hepatic veins?

A

Do to gradient of things like oygen and nutrients + other molecules that can induce transcriptional changes within ‘zones of hepatocytes’. e.g. HIF1.

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7
Q

How many zones with the hepatic acinus?

A

thought to be 3, now 9.

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8
Q

What are the two major cell types of the hepatic sinusois?

A 
fenestrated LSECs (liver sinusoidal endothelial cells).
and Kupfer cells (macrophages that line the endotheilium.)
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9
Q

Describe the relationship between sinusoids and hepatocytes?

A

one cell plate of heaptyocytes surrounded by sinusoid vessels on either side.
Heapatocytes stick processes into the

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10
Q

What lies between the hepatocytes and the LSECs?

A

the space of disse, e.g. where DCs can go to drain into the lymphatics.

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11
Q

What activites are hepatocytes known for?

A

metabolic and detoxing activities.
Complement and acute protein production.
Do express TLRs (but low level).

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12
Q

Where are kupfer cells most dense?

A

At periportal region.

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13
Q

What can specialised LSECs do?

A

fenestrated morhoplogy-sieve plates.
Biofilter between sinuisoidal blood and space of Disse.
Can do antigen presentation to T cells, but tend to induce tolerance.

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14
Q

How fast is flow through sinusoids?

A

Very slow due to small diameter which can promote Ag presentation and extravasatino.

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15
Q

What immune cell types apart from kupfer cells predominate in liver?

A

T cells common, B cells low. NK cells are high, as are unconventional T cells like NKT and iNKT cells and yD T cells.

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16
Q

Are memory T cells higher in liver? marker?

A

Yes, express CD45RO.

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17
Q

What effects do LSECs haev on T cells?

A

Can induce them into a Treg phenotype or can induce CD8+ T cell apoptosis.

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18
Q

How do kupfer cells respond to LPS?

A

Do express TLR4, but lower expression of CD14, and require a greater LPS concentration for stimulation.
Also will make IL-10 in response to LPS.

19
Q

what downregualtes DC reponse to LPS?

A

DCs can respond to LPS with IL-10 production and decreasing IL-12 production.

IL-10 and IL-6 and TGF-B from hepatyoctyes also reduces the response to LPS.

20
Q

Can liver respond well to viral infections?

A

Generally yes, TLR3 signalling and RIG1 signalling functions well.

21
Q

How do hepatocytes and stellate cells induce tolerance to CD8+ T cells?

A

via expression of PD-L.

22
Q

How do viruses like hepatitis C and malaria impair liver response?

A

By impairing RIG1 and TLR signalling through e.g. cleaving TRIF.

23
Q

How does the environment of liver induce tolerance?

A

has arginase at high levels which reduces argnine available for T and DC activation.

24
Q

In liver, how can DCs be recruited from sinusoidal blood directly to the liver?

A

Iflammation causes kupfer cells to make CCL3, which recruits immature DCs expressing CCR1.
Mautre DCs lose CCR1 expression and upregulate CCR7 wich homes them to the lymph node (CCL19 and CCL21).

25
Q

What chemokine ligands overlap with receptors CCR5 and CCR1?

A

chemokines CCL3,4, and 5 and 8)

Immature DCs express CCR1. Mature express CCR7.

26
Q

What chemokines bind to CCR5?

A

CCR3,4 and 5 (and 8)

27
Q

What chemokines recruit macrophages/ monocytes?

A

MCP1-4. Receptors are CCR2/

MCP2=CCL8 which binds both CCR5 and CCR2.

28
Q

what cell type does lymphotactin recruit?

A

NK cells and lymphocytes.

29
Q

what 3 fundamental functions is iron important for?

A

Hb binding.
DNA replication.
ETC in ATP production.

30
Q

Can iron be synthesised?

A

no, and bioavailibiity is limited, but essential for all life forms.

31
Q

What orgna is imporant for hepcidin and iron homeostasis?

A

liver

32
Q

where is the iron absorbed?

A

at the intestine and is exported into blood by ferritin.

33
Q

What carries iron in blood? and what receptor is important for iron uptake into cells?

A

transferrin, and transferrin receptors.

34
Q

What cell types require lots of iron?

A

RBCs the most, also muscle brain and immune cells.

35
Q

How is most of iron recycled?

A

By phagocytosis of senescent RBCs by kupfer cells and in the spleen.
Exported out of macrophages by ferriportin.

36
Q

What transporter does hepcidin inhibit?

A

ferriportin. Can induce its endocytosis as well as biding and blocking Fe transport.

37
Q

What two ponits does hepcidin alter iron?

A

At absorption and recylcing of Fe.

38
Q

What cell types wil express the hormone hepcidin?

A

Mostly expressed by hepatocytes.

39
Q

What does high hepcidin do to Fe levels in serum, blood, macrophages and hepatocytes?

A

If hepcidin high: anemia

low serum and blood levels, high macrophage Fe levels and low hepatocyte levels.

40
Q

What does low hepcidin do to Fe levels in serum, blood, macrophages and hepatocytes?

A

If hepcidin low (haemochromatosis)
serum and blood levels of iron high.
Macorphage Fe levels low,
HIgh Fe levels in heaptyocytes.

41
Q

Why is hepcidin improthatn for infections? When might you be susceptible?

A

virulence genes are associted with scavenging for Fe.

If you have low hepcidin levels, hemochromatosis, you ware very sucspeitble to some infections.

42
Q

Why is hepcidin good in plasmodium liver stage?

A

high hepcidin, low levels of Fe change distribution away from hepatocytes to the macrophages.

43
Q

What factors can induce hepcidin production?

A

IL-6 and IL-22, as well as TLR agonists./

44
Q

Is hepcidin important for the aaptive immune system?

A

Yes because adaptive immune cells highly dependent on Fe uptake for clnoal expansion.

week 2 (4 decks)

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