Organ-specific immunity: LIVER - Adaptive Immunity

Question 1

How do you obtain tissue from patients? (2)

Answer 1

• Tissue biopsies
• Fine-Needle Aspiration Biopsy (FNAB)

Question 2

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

Answer 2

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

Question 3

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

Answer 3

NK and NKT cells

Question 4

What are the disadvantages of tissue biopsies?

Answer 4

• Patient discomfort
• Complications

Question 5

Why do we prefer FNAB?

Answer 5

• Reflects intrahepatic T cell population
• Less invasive and safe

Question 6

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

Answer 6

• As soon as they enter the liver
• HLA-DR

Question 7

What are intrahepatic lymphocytes enriched for? Why?

Answer 7

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

Question 8

Which cells interact most intimately in the liver?

Answer 8

LSEC and Kupffer

Question 9

Where does interaction between lymphocytes and hepatocytes occur?

Answer 9

Parenchyma

Question 10

When do you see activation of T cells by hepatocytes?

Answer 10

Hepatocyte + a lot of stimulation

Question 11

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

Answer 11

• KC
• LSEC
• DC

Question 12

What do resting/activated hepatocytes express?

Answer 12

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

Question 13

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

Answer 13

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

Question 14

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

Answer 14

Very strong T cell component (but also B cell)

Question 15

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

Answer 15

Dense inflammation around portal tract area

Question 16

What is the most striking clinical feature during viral hepatitis?

Answer 16

Jaundice

Question 17

Which hepatitis viruses are self-resolving?

Answer 17

A and E

Question 18

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

Answer 18

• Fibrosis
• Cirrhosis
• Liver failure
• HCC

Question 19

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

Answer 19

False. Often symptomatic

Question 20

Which hepatitis infection is often asymptomatic?

Answer 20

HCV

Question 21

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

Answer 21

Newborns

Question 22

What are the treatments of HBV? (2)

Answer 22

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

Question 23

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

Answer 23

Adults

Question 24

What are the treatments of HCV? (2)

Answer 24

• PEG-IFNa + Ribavirin
• Sofosbuvir + simeprevir

Question 25

What is considered a chronic HCV infection?

Answer 25

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

Question 26

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

Answer 26

Needle stick infection in the hospital. Known exposure

Question 27

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

Answer 27

6-10 weeks post infection

Question 28

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

Answer 28

Death of hepatocyte --> release of ALT enzyme

Question 29

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

Answer 29

- Weak or absent - Arise initially, but are lost when the infection becomes chronic

Question 30

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

Answer 30

Lot of virus, low level of HBV specific T cells

Question 31

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

Answer 31

Acute infections

Question 32

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

Answer 32

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

Question 33

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

Answer 33

- 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

Question 34

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

Answer 34

CD8+ T cell exhaustion

Question 35

How does CD8+ T cell exhaustion work?

Answer 35

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

Question 36

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

Answer 36

PD-1

Question 37

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

Answer 37

Restoration of T cell response

Question 38

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

Answer 38

- Reduce antigen load - Blockade of inhibitory receptors - Blockade of other inhibitory pathways - Immunotherapeutic boosting of T cells

Question 39

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

Answer 39

- IL-10 - TGF-B - NK cells

Question 40

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

Answer 40

Lot of virus, very weak immune response, AND mild pathology | Even though there is lots of virus, the pathology is mild

Question 41

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

Answer 41

CD4+CD5+FoxP3+ Treg