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

Organ-specific immunity: LIVER - Adaptive Immunity Flashcards

1
Q

How do you obtain tissue from patients? (2)

A
  • Tissue biopsies
  • Fine-Needle Aspiration Biopsy (FNAB)
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2
Q

How does the intrahepatic T cell population differ from peripheral blood?

A

Blood: CD4+ > CD8+
Liver: CD8+ > CD4+

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3
Q

Which other cells are more abundant in the liver than in the peripheral blood?

A

NK and NKT cells

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4
Q

What are the disadvantages of tissue biopsies?

A
  • Patient discomfort
  • Complications
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5
Q

Why do we prefer FNAB?

A
  • Reflects intrahepatic T cell population
  • Less invasive and safe
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6
Q

When do lymphocytes become activated in context of the liver? What is their activation marker?

A
  • As soon as they enter the liver
  • HLA-DR
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7
Q

What are intrahepatic lymphocytes enriched for? Why?

A

Activated memory T cells. They immediately become this when entering the liver

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8
Q

Which cells interact most intimately in the liver?

A

LSEC and Kupffer

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9
Q

Where does interaction between lymphocytes and hepatocytes occur?

A

Parenchyma

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10
Q

When do you see activation of T cells by hepatocytes?

A

Hepatocyte + a lot of stimulation

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11
Q

In the absence of inflammation, which cells express MHC-II?

A
  • KC
  • LSEC
  • DC
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12
Q

What do resting/activated hepatocytes express?

A

Resting: MHC-I, CD1 and ICAM1
Activated: MHC-II, CD40L and costim

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13
Q

Name examples of immune cell-mediated liver diseases (4)

A
  • Chronic alcohol use-induced hepatitis
  • Hepatocellular carcinoma
  • Liver graft immunology
  • HBV/HCV infection
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14
Q

What kind of immune cells drive immune cell-mediated liver diseases?

A

Very strong T cell component (but also B cell)

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15
Q

What should you see on a biopsy specimen from a patient with chronic HBV?

A

Dense inflammation around portal tract area

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16
Q

What is the most striking clinical feature during viral hepatitis?

A

Jaundice

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17
Q

Which hepatitis viruses are self-resolving?

A

A and E

18
Q

What is the disease pathogenesis pathway of HBV and HCV? (4)

A
  • Fibrosis
  • Cirrhosis
  • Liver failure
  • HCC
19
Q

True or False: “HBV infection is often asymptomatic.”

A

False. Often symptomatic

20
Q

Which hepatitis infection is often asymptomatic?

A

HCV

21
Q

Which category of people is most likely to develop a chronic HBV infection?

A

Newborns

22
Q

What are the treatments of HBV? (2)

A
  • Immune modulation: PEG-IFNa
  • Viral replication inhibitors: tenofovir, entecavir
23
Q

Which category of people is most likely to develop a chronic HCV infection?

A

Adults

24
Q

What are the treatments of HCV? (2)

A
  • PEG-IFNa + Ribavirin
  • Sofosbuvir + simeprevir
25
Q

What is considered a chronic HCV infection?

A

If you still have the virus detectable in the blood after six months

26
Q

What scenario is the most ideal to study an acute HCV infection? Why?

A

Needle stick infection in the hospital. Known exposure

27
Q

When does the adaptive immune response really take of in acute HCV infection?

A

6-10 weeks post infection

28
Q

Why can you use ALT as a tool to measure liver damage?

A

Death of hepatocyte –> release of ALT enzyme

29
Q

What happens to the T cell response in chronic HBV infection?

A
  • Weak or absent
  • Arise initially, but are lost when the infection becomes chronic
30
Q

Describe the correlation between HBV-specific T cells in the liver and the HBV DNA load

A

Lot of virus, low level of HBV specific T cells

31
Q

In what kind of hepatitis infections do you see large amounts of liver damage?

A

Acute infections

32
Q

Why don’t you see large amount of liver damage in chronic hepatitis infections?

A

Lot of activities in the immune system that makes that T cells and NK cells are dampened

33
Q

What are host mechanisms that promote persistence of HBV? (7)

A
  • Regulatory T/B cells
  • IL-10 and/or TGF-β
  • Active elimination of T cells
  • Impaired NK cells
  • Myeloid derived suppressor cells
  • Impaired dendritic cells
  • High viral load
34
Q

How does a high viral load lead to persistence of HBV in the liver?

A

CD8+ T cell exhaustion

35
Q

How does CD8+ T cell exhaustion work?

A

Exposure of T cell to very high level of antigen for longer period of time causes negative signaling and gradual loss of function

36
Q

Which marker is often found on exhausted CD8+T cells?

A

PD-1

37
Q

What happens with the T cell response if you treat patients with HBV infection with nucleoside analogues?

A

Restoration of T cell response

38
Q

What are the different options to restore T cell responses in patients with HBV infection? (4)

A
  • Reduce antigen load
  • Blockade of inhibitory receptors
  • Blockade of other inhibitory pathways
  • Immunotherapeutic boosting of T cells
39
Q

What are other inhibitory pathways you can block to restore T cell responses in patients with HBV infection? (3)

A
  • IL-10
  • TGF-B
  • NK cells
40
Q

Describe the balance between protective immunity and pathology in chronic HBV infection

A

Lot of virus, very weak immune response, AND mild pathology

Even though there is lots of virus, the pathology is mild

41
Q

Which T cells are abundantly present in HCV infected livers, while absent from healthy livers?

A

CD4+CD5+FoxP3+ Treg

42
Q
A

I&I WC1 (25 decks)

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