Organ-specific immunity: LIVER - Adaptive Immunity Flashcards
How do you obtain tissue from patients? (2)
- Tissue biopsies
- Fine-Needle Aspiration Biopsy (FNAB)
How does the intrahepatic T cell population differ from peripheral blood?
Blood: CD4+ > CD8+
Liver: CD8+ > CD4+
Which other cells are more abundant in the liver than in the peripheral blood?
NK and NKT cells
What are the disadvantages of tissue biopsies?
- Patient discomfort
- Complications
Why do we prefer FNAB?
- Reflects intrahepatic T cell population
- Less invasive and safe
When do lymphocytes become activated in context of the liver? What is their activation marker?
- As soon as they enter the liver
- HLA-DR
What are intrahepatic lymphocytes enriched for? Why?
Activated memory T cells. They immediately become this when entering the liver
Which cells interact most intimately in the liver?
LSEC and Kupffer
Where does interaction between lymphocytes and hepatocytes occur?
Parenchyma
When do you see activation of T cells by hepatocytes?
Hepatocyte + a lot of stimulation
In the absence of inflammation, which cells express MHC-II?
- KC
- LSEC
- DC
What do resting/activated hepatocytes express?
Resting: MHC-I, CD1 and ICAM1
Activated: MHC-II, CD40L and costim
Name examples of immune cell-mediated liver diseases (4)
- Chronic alcohol use-induced hepatitis
- Hepatocellular carcinoma
- Liver graft immunology
- HBV/HCV infection
What kind of immune cells drive immune cell-mediated liver diseases?
Very strong T cell component (but also B cell)
What should you see on a biopsy specimen from a patient with chronic HBV?
Dense inflammation around portal tract area
What is the most striking clinical feature during viral hepatitis?
Jaundice
Which hepatitis viruses are self-resolving?
A and E
What is the disease pathogenesis pathway of HBV and HCV? (4)
- Fibrosis
- Cirrhosis
- Liver failure
- HCC
True or False: “HBV infection is often asymptomatic.”
False. Often symptomatic
Which hepatitis infection is often asymptomatic?
HCV
Which category of people is most likely to develop a chronic HBV infection?
Newborns
What are the treatments of HBV? (2)
- Immune modulation: PEG-IFNa
- Viral replication inhibitors: tenofovir, entecavir
Which category of people is most likely to develop a chronic HCV infection?
Adults
What are the treatments of HCV? (2)
- PEG-IFNa + Ribavirin
- Sofosbuvir + simeprevir
What is considered a chronic HCV infection?
If you still have the virus detectable in the blood after six months
What scenario is the most ideal to study an acute HCV infection? Why?
Needle stick infection in the hospital. Known exposure
When does the adaptive immune response really take of in acute HCV infection?
6-10 weeks post infection
Why can you use ALT as a tool to measure liver damage?
Death of hepatocyte –> release of ALT enzyme
What happens to the T cell response in chronic HBV infection?
- Weak or absent
- Arise initially, but are lost when the infection becomes chronic
Describe the correlation between HBV-specific T cells in the liver and the HBV DNA load
Lot of virus, low level of HBV specific T cells
In what kind of hepatitis infections do you see large amounts of liver damage?
Acute infections
Why don’t you see large amount of liver damage in chronic hepatitis infections?
Lot of activities in the immune system that makes that T cells and NK cells are dampened
What are host mechanisms that promote persistence of HBV? (7)
- 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
How does a high viral load lead to persistence of HBV in the liver?
CD8+ T cell exhaustion
How does CD8+ T cell exhaustion work?
Exposure of T cell to very high level of antigen for longer period of time causes negative signaling and gradual loss of function
Which marker is often found on exhausted CD8+T cells?
PD-1
What happens with the T cell response if you treat patients with HBV infection with nucleoside analogues?
Restoration of T cell response
What are the different options to restore T cell responses in patients with HBV infection? (4)
- Reduce antigen load
- Blockade of inhibitory receptors
- Blockade of other inhibitory pathways
- Immunotherapeutic boosting of T cells
What are other inhibitory pathways you can block to restore T cell responses in patients with HBV infection? (3)
- IL-10
- TGF-B
- NK cells
Describe the balance between protective immunity and pathology in chronic HBV infection
Lot of virus, very weak immune response, AND mild pathology
Even though there is lots of virus, the pathology is mild
Which T cells are abundantly present in HCV infected livers, while absent from healthy livers?
CD4+CD5+FoxP3+ Treg
