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I&I WC1 > Organ-specific immunity: LIVER - Physiology & Innate Immunity > Flashcards

Organ-specific immunity: LIVER - Physiology & Innate Immunity Flashcards

1
Q

Anatomy: of what parts does the liver consist?

A

Major left and right lobes + smaller inferior lobes

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2
Q

What is special about the liver as opposed to any other organ?

A

Dual blood supply

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3
Q

What is meant with this dual blood supply?

A
  • Nutrient-rich, oxygen-poor blood via portal vein from intestines
  • Oxygen-rich blood via hepatic artery
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4
Q

What are the three immunity characteristics of the liver?

A
  • Protection against pathogens and food toxin from the intestine
  • Removal of translocated intestinal bacteria and bacterial toxins
  • Tolerance to food antigens and commensal bacteria
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5
Q

Why does the liver need a tightly controlled immunity?

A

Tolerate antigens, but generate immune response against potential threats

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6
Q

Anatomy: What can be said about the structuring of hepatocytes?

A

Sheets of hepatocytes, centered around a central vain.

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7
Q

How are hepatocytes grouped?

A

In portal triads

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8
Q

What does this grouping of hepatocytes in portal triads mean for the blood flow? (direction)

A

Blood flowing from the portal vain towards the central vain

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9
Q

Anatomy: What is collected in the bile duct?

A

Drainage of hepatocytes

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10
Q

What is important about the blood flow from the portal vain to the central vain? What does that allow for?

A

Flow of blood is quite slow. Allows for hepatocytes to really come in contact with whatever is in that blood.

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11
Q

Anatomy: What is between the hepatocytes and the blood? What do they form?

A

Liver sinusoids and T cells that form an impermeable barrier

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12
Q

What is the Space of Disse (perisinusoidal space) and what is its function?

A
  • Space between sinusoids and hepatocytes
  • Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the sinusoids to be absorbed by the hepatocytes.
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13
Q

Which cells/substances stay in the vessel and which cells/substances can be directly taken up by hepatocytes?

A
  • Vessel: most cells
  • Direct uptake: nutrients
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14
Q

Main functions of the liver (3)

A
  • Metabolism
  • Detoxification
  • Synthesis
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15
Q

For what kind of immunity is the liver important?

A

Systemic immunity

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16
Q

Name three examples of the metabolizing function of the liver

A
  • Nutrients
  • Amino acid metabolism
  • Collestral
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17
Q

What is an example of nutrient metabolism in the liver?

A

Storing of glucose in the form of glycogen

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18
Q

What is an example of amino acid metabolism in the liver?

A

Deamination to form urea, which is secreted by the kidneys

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19
Q

What is an example of collestral?

A

Synthesis of phospholipids

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20
Q

Why is the synthesis of biomolecules important?

A

Proper functioning immune system

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21
Q

What is an important immune function of the liver?

A

Synthesis of molecules that are involved in co-agulation and complement system (systemic immunity)

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22
Q

What is the difference between PRRs in the liver and on cell membranes?

A

The liver PRRs are soluble

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23
Q

What can be said about the secretion levels of PRRs and immunological proteins?

A

They are not always secreted at equally high levels, especially when a threat is being sensed

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24
Q

Which cytokines lead to an increase of immunologically relevant systemic proteins by the liver? In what kind of situations is this induced?

A
  • IL-6, IL-1, TNF-a
  • Inflammation
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25
Q

How are systemic proteins produced by the liver called?

A

Acute-phase proteins

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26
Q

What is C-reactive protein? How is it often used in the clinic?

A

Acute-phase protein –> PRR that binds to phosphocholine on bacterial surfaces. Used as a marker of inflammation

27
Q

Which cytokine triggers C-reactive protein?

A

IL-6

28
Q

What does C-reactive protein do?

A

Activates complement system via classical pathway

29
Q

C-reactive protein: How is it often used in the clinic?

A

Used as a marker of inflammation in the blood –> diagnostic molecule

30
Q

Complement system: How is the classical pathway activated?

A

Antigen::antibody complexes

31
Q

Complement system: What is an important function of C3b? How does it do that?

A

Opsonization of the pathogen. Binds to complement receptors on phagocytes.

32
Q

Complement system: How is the alternative pathway activated? What does it result in?

A
  • Pathogen surfaces
  • Continuous C3b deposition on the pathogen surface
33
Q

How are host cells shielded from this continuous C3b deposition?

A

They have anti-C3b binding proteins on their surface

34
Q

Complement system: How is the MB-lectin pathway activated?

A

Mannose-binding lectin binds mannose on pathogen surfaces

35
Q

Describe the two-step recognition by MBL

A
  • Recognizes mannose on pathogen cell surface
  • Recognizes spacing of the mannoses in the membrane
36
Q

Why do we need recognition of the spacing of the mannoses in the membrane?

A

To make a distinction between self- and non-self

37
Q

Which association can be made between transplantation of a liver with MBL/Ficolin-2/MASP-2 polymorphisms and incidence of bacterial infections?

A

INCREASED bacterial infections

38
Q

Which factors are required for LPS-signaling? (2)

A

Liver produced LBP and CD14

39
Q

Characteristics of LBP (lipopolysaccharide binding protein) (3)

A
  • Secreted by liver
  • Binds LPS in circulation
  • Transfers LPS to CD14
40
Q

Characteristics of soluble CD14 (2)

A
  • Supports binding of LPS to TLR-4 (in absence of membrane bound CD14)
  • Inhibits binding of LPS to membrane bound CD14
41
Q

To what antigens do we need liver tolerance? (2)

A
  • (Endo)toxins
  • Food antigens
42
Q

Unwanted tolerance in the liver is geared towards..? (3)

A
  • HBV/HCV
  • Malaria
  • Tumor metastases
43
Q

Against what antigens do we need liver immunity? (3)

A
  • Hepatitis A virus
  • Hepatitis B virus
  • Many bacterial species
44
Q

Why are auto-immune reactions often happening in the liver?

A
45
Q

Why do tumors often metastasize to the liver? (2)

A
  • Circulation: seef function
  • Tolerance in the liver –> base level of tolerance against food antigens and commensals is needed
46
Q

What is unique for liver transplants? Why?

A

No HLA match required of the donor/recipient –> liver is a very tolerogenic organ

47
Q

Liver transplantation confers protection against?

A

Rejection of other organ grafts from the same donor

48
Q

True or false: “Liver transplant have a higher incidence of chronic rejection.”

A

False. Liver transplants have a lower incidence of chronic rejection.

49
Q

What can be a problem when weening a patient off of their immunosuppressive medication in case of a liver transplantation?

A

It is hard to determine if and when a patient is suitable to ween off.

50
Q

What are examples of situations when you ween someone off their immunosuppressive medication? (2)

A
  • They need vaccination
  • CMV infection
51
Q

How is the balance between tolerance and activation maintained?

A

Liver contains numerous innate immune cells involved in local immunity

52
Q

Which innate immune cells are present in the liver? (6)

A
  • Kupffer cells
  • DCs
  • NK cells
  • NKT cells
  • Hepatic stellate cells
  • Liver sinusoidal endothelium (LSEC)
53
Q

What is the function of hepatic stellate cells?

A

Vitamin A storage

54
Q

What are the functions of LSECs? (2)

A
  • Removal of ‘waste products’ and pathogens from circulation
  • Antigen presenting
55
Q

How do LSECs remove waste products and pathogens from the circulation? (2)

A
  • Receptor-mediated endocytosis
  • Lysosomal degradation
56
Q

Which receptors are used by LSECs?

A
  • Scavenger receptors
  • Carbohydrate receptors
57
Q

What does the slow blood flow in the sinusoids facilitate?

A

Detection and capture of pathogens, proteins and toxins

58
Q

What are Kupffer cells and what is their function?

A

Resident liver macrophages. Phagocytosis and degradation of particulate materials from blood

59
Q

Name examples of ‘particulate materials from blood’ (3)

A
  • Dying cells
  • Aged erythrocytes
  • Pathogens
60
Q

What kind of receptors do KCs express? (5)

A
  • Scavenger
  • Fcy and Fca
  • Complement
  • TLR-4
  • TLR3,9
61
Q

Why are Kupffer cells antigen-presenting cells with tolerogenic properties? (4)

A
  • Direct contact with T cells entering liver
  • Modest T cell stimulatory capacity
  • Suppress T cell activation via IL-10
  • Induce expansion of CD4+FoxP3+ Tregs
62
Q

What is the default mechanism of antigen-presenting DCs when they migrate from the liver to the hepatic lymph nodes?

A

Tolerance, via IL-10 secretion & IDO upon TLR-stimulation

63
Q

Tolerogenic mechanisms in the liver act through…(4)

A
  • Secretion of IL-10, TGF-B
  • Non-productive activation of CD8+ T cells
  • Stimulation of CD4+FoxP3+ Treg differentiation
  • Expression of PD-L1
64
Q

What is the function of PD-L1?

A

Inhibiting T cell functions

I&I WC1 (25 decks)

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