Primary Biliary Cirrhosis (cont.)
In this Article
What causes destruction of the bile ducts in PBC?
AMA are tremendously important as a diagnostic marker in patients with PBC.
Despite that, no evidence exists that the AMA itself causes the destruction of
the biliary epithelial cells lining the small bile ducts. Neither the presence
nor the amount (titer) of AMA in the blood appears to be related to the
inflammatory destruction of the bile ducts. Indeed, immunization of animals with
PDC-E2 antigen results in production of AMA without any liver or bile duct
damage (pathology).
What, then, causes the destruction of the bile ducts in PBC? Inspection of
liver biopsies from patients with PBC indicates that T-lymphocytes surround and
invade the small bile ducts. Thus, T-lymphocytes appear to be responsible for
the death of the biliary epithelial cells lining the ducts and the destruction
of the bile ducts. T-lymphocytes capable of directly killing target-cells (for
example, biliary epithelial cells) are called cytotoxic T-lymphocytes, meaning
that these T-cells are toxic to the target cells. And, in fact, cytotoxic
T-lymphocytes have been observed in liver biopsies to invade the bile ducts and
to be present in areas where biliary epithelial cells are dying.
Other T-lymphocytes that surround the bile ducts are known to produce
chemicals that can also cause biliary epithelial cells to die. Some of these
chemicals actually stimulate the biliary epithelial cells themselves to secrete
small proteins that attract more T-lymphocytes. Paradoxically, then, this
response by the biliary epithelial cells might result in even greater injury to
the bile ducts, in sort of a vicious cycle.
Recent studies of T-lymphocytes isolated from the inflamed livers of patients with
PBC have shown that these T-lymphocytes can, in fact, kill biliary epithelial
cells. Moreover, many of the T-lymphocytes recognized the digested fragments
of PDC-E2. These observations suggest the possibility (hypothesis) that the
T-lymphocytes might attack the biliary epithelial cells because these cells
display PDC-E2 antigens in their HLA (Human Lymphocyte Antigen) molecules to
which the T lymphocytes react. No direct evidence, however, supports this
hypothesis. The fact is that the actual antigens on biliary epithelial cells
that are recognized by invading, destructive T-lymphocytes remain to be
determined. However, the biliary epithelial cells do contain molecules, such as
intercellular adhesion molecule-1, that are required for activated T lymphocytes
to adhere to the cells that they kill.
Next: What is the role of infection? »
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