Thursday, September 8, 2011

Humoral Immune Response to HCV

nullAfter HCV infection, there is expression of the hypervariable NS1/E2 region on the surface of the virus, which stimulates B cells to produce high antibody titers of antibodies with the objective of destroying the permanence of the virus (Taylor et al., 2000). The appearance of anti-HCV antibodies is significantly delayed, and these antibodies can first be detected from 7 to 31 weeks after infection (Pawlotsky, 2004). The host applies selective pressure on HCV, and this stimulates high nucleotide variation, as well as the appearance of mutations in the envelope proteins, from which the virus selects genomic variants in an attempt to eliminate the site of immune response recognition (Botarelli et al., 1993). The great quantity of HCV quasispecies formed allows the virus to evade the humoral immune response, and the effect of HCV neutralizing antibodies appears to be insufficient to control the infection (Pawlotsky, 2004), which therefore persists (Giannini and Brechot, 2003).
Similar to what occurs in auto-immune type 2 hepatitis, HCV can mimic the immune system, leading to viral escape or post infection immunity (Cerny and Chisari, 1999 and Cerny and Chisari, 2000). Anti-HCV antibodies have been implicated in tissue damage due to the formation of immunocomplexes such as antinuclear antibodies (Cacoub et al., 1999), auto-antibodies that act against cytochrome P450 and antibodies that act against the liver and kidney (Cerny and Chisari, 1999). The deposition of immunocomplexes has been related to the appearance of extrahepatic manifestations, such as arthritis, cryoglobulinemia (Agnello, 1995), vasculitis, glomerulonephritis, Sicca syndrome and itchiness, all of which cause considerable morbidity (Cacoub et al., 1999).
There is evidence that HCV infection can be resolved by the cell response with specific CD4+ and CD8+ T cells when there is no formation of antibodies against this virus (Takaki et al., 2000 and Lechner et al., 2000), showing that the humoral immune response is not always involved in the response to HCV infection.

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