how is the dual-blood supply regulated in the liver?
nutrient-rich and oxygen-poor blood via portal vein from intestines and oxygen-rich blood via hepatic artery
name 3 immune responses in the liver
- protection against pathogens and food toxins entering from intestines
- removal of translocated intestinal bacteria and bacterial toxins
- tolerance to food antigens and commensal bacteria
name the 3 functions of the liver
- metabolism
- detoxification
- synthesis (systemic immunity)
name the 2 immunological functions of the liver
- synthesis of complement factors and PRR molecules that are important for systemic immunity
- local defense against gut-derived pathogens, bacterial product (LPS) and food toxins
what are acute phase proteins?
only secreted by the liver during an infection, production is stimulated by IL-6
what is C-reactive protein?
- acute phase protein secreted by the liver in response to inflammation
- PRR binds to phosphocholine on bacterial surfaces
- activates complement system via classical pathway
- marker for inflammation
what is MBL?
- acute phase protein
- trigger complement activation via lectin pathway
- PRR recognizes PAMPs in micro-organisms
true or false? transplantation of liver with MBL/ficolin-2/MASP-2 polymorphisms is associated with increased incidence of bacterial infections
true, when SNPs were found in all three proteins there is an increase of infections
how are endotoxins recognized in the liver?
macrophages recognize LPS, secrete anti-microbial factors and phagocytose bacteria
LBP transfers LPS to CD14 on myeloid cells and binds LPS to TLR4
tolerance from the liver is needed for …
endotoxins and food antigens
hepatic immunity is needed for …
hepatitis A and B virus, bacteria
when is there unwanted tolerance?
hepatitis B and C virus, plasmodium sporozoite (malaria) and tumor metastases
name 4 reasons why the liver is less immunogenic
- HLA-matching not required
- low incidence of chronic rejection
- liver transplantation confers protection against rejection of other organ grafts from the same donor
- withdrawal of immunosuppressive medication is possible in part of stable LTx-patients without graft rejection
which immune cells are present in the liver (portal tracts and sinusoids)?
- Kupffer cell; phagocytic and APC
- dendritic cell
- NK cells
- T cells
- liver sinusoidal endothelium cells (LSEC); endocytic and APC
what is the function of liver sinusoidal endothelium cells (LSEC)?
- detection and capture of pathogens, proteins and toxins
- removes waste products and pathogens via receptor-mediated endocytosis and lysosomal degradation
- APCs with tolerogenic properties
what is the function of Kupffer cells?
- phagocytose and degrade pathogens and other components, this is done by expression of scavenger/complement/Fcy/a receptors, TLR4/3/9
Name 4 tolerogenic mechanisms of the liver by LSECs, Kupffer cells and DCs
- secretion of IL-10, TGFb
- non-productive activation of CD8+ T cells
- stimulation of CD4+Foxp3+ Treg differentiation
- expression of PD-L1 which inhibits T cell functions
what is the function of hepatocytes?
- rest; express MHCI, CD1 and ICAM1
- active; express MHCII, CD40-L and costim
- cytokine production induced by IL-6/1
- APC capacity
name the 9 host mechanisms that promote persistence of HBV in the liver
- regulatory T cells
- IL-10, TGFb
- regulatory B cells
- active elimination of T cells
- impaired NK cells
- myeloid derived suppressor cells
- impaired dendritic cells
- high viral load leading to T cell exhaustion
- mitochondrial dysfunction
what are the 2 characteristics of HBV and HCV?
- impaired virus-specific T cell responses
- both escape anti-viral immunity
name 4 methods to restore T cell responses in HBV
- reduce antigen load
- blockade of inhibitory receptors
- blockade of other inhibitory pathways
- immunotherapeutic boosting of T cells
name the 6 histological features of acute viral hepatitis
- predominantly lobular inflammation
- regeneration and disarray
- apoptotic bodies
- ballooning/hepatocyte proliferation
- hepatocyte dropout, necrosis
- cholestasis
name the 5 histological features of chronic viral hepatitis
- chronic inflammatory cells infiltration of portal tracts
- interface hepatitis
- intralobular necroinflammatory activity
- bridging necrosis
- fibrosis
name the 3 histological features of chronic HBV
- ground-glass hepatocytes
- sanded nuclei in hepatocytes
- spotty necrosis
