الفهرس 
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Abstract
Hepatitis C virus (HCV) infection has become a global health problem with around 170–190 million infected people worldwide. Spontaneous viral clearance of HCV is observed in only 15–40% of patients with acute hepatitis whereas, persistent infection is established despite evidence of immune regulation and is associated with progression to cirrhosis and hepato-cellular carcinoma.
HCV is a small enveloped positive sense single strand ribonucleic acid (RNA) virus of the family Flaviviridae consisting of three structural proteins (core, envelope 1 and 2) and at least four nonstructural proteins (NS2, NS3, NS4, NS5). Most HCV proteins have a clearly defined role in the viral replication cycle and may also facilitate immune evasion by altering cell signaling pathways involved in host defense.
Strong and persistent cell-mediated immune responses have been reported in HCV sero-negative individuals with documented exposure to HCV in the absence of detectable viral RNA.
The outcome of HCV infection is determined within six months of exposure to the virus. Control of acute primary viral replication is associated with expansion of antiviral CD4+ (helper) and CD8+.
In this thesis detect the level of a panel of cytokines namely: IL2, IFN-γ, and TNF-α in cell culture supernatant from stimulated peripheral blood mononuclear cells (PBMCs) by HCV specific C100 peptide by a commercially available Fluorokine MAP cytokine multiplex kit which is designed for use with the Luminex 100™ Analyzer. These samples were previously taken from study of health care workers (HCWs) in Ain Shams University Clinical Pathology Department done by Abdelhady (2009).
- The personnel included in the study were divided into two groups:
Group (1):
HCV double negative HCWs: 37 HCWs who showed no evidence of previous exposure to HCV as demonstrated by negative HCV-RNA by PCR and negative HCV antibody by ELISA.
Group (2):
HCV double positive HCWs (control group): 6 HCWs who were previously exposed to HCV infection as evidenced by positive HCV-RNA by PCR and positive HCV antibody by ELISA.
Cell proliferation assay was done by (CFSE) staining technique and flow cytometry using anti CD3 and CD8 monoclonal antibodies (Abdelhady, 2009).
Subjects were classified after that into 3 groups:
1) Positive proliferation index (+ve P.I) HCWs: 27 samples.
2) Negative proliferation index (-ve P.I) HCWs: 10 samples
3) Chronic HCV HCWs (+ve P.I): 6 samples
Our study showed that +ve P.I HCWs respond to HCV C100 with a significantly higher level of IFN-γ and TNF-α more than chronic and -ve P.I groups. IFN-γ produced in +ve P.I HCWs is positively correlated with both CD3-/CD8+ and CD3-/CD8- cells which are probably NK cells. Also there is significant negative correlation between IFN-γ and TNF-α as regard CD3+/CD8- (T cells other than T cytotoxic cells). There is a positive correlation between IFN-γ and TNF-α.
As for the chronic HCV HCWs, their response via TNF-α and IFN-γ is significantly less than both healthy groups. TNF α is positively correlated with both CD3-/ CD 8+ and CD3-/CD8- cells which are probably NK cells. Also there is significant negative correlation between TNF-α as regard CD3+/CD8- (T cells other than T cytotoxic cells).
As for -ve P.I HCWS there is positive correlation between IL2 and IFN-γ, also there is no significant correlation between IFN-γ, IL2 and TNF-α versus all CD markers among –ve P.I HCWs.
Health care workers who have cleared the virus (+ve P.I HCWs) have a significantly higher IFN-γ response from healthy individuals never exposed to HCV and a significantly higher TNF α and IFN-γ response from the chronic cases who have not cleared the virus i.e., chronic cases have a diminished TNF α and IFN-γ response than P.I +ve healthy group who have cleared the virus.
In conclusion, we can say that there is an important role of C100 in immune response against HCV as IFN-γ and TNF levels were significantly higher in +ve P.I HCWs samples stimulated with C100 and this may lead to control of the viral infection. Moreover, there is a crucial role for innate immune response in HCV infection.