الفهرس 
CoverOnly 14 pages are availabe for public view
 |  | from | 171 |  |  |
| | | from | 171 | | |
Abstract
Hepatitis C virus (HCV) infection has become a global health problem with around 130–170 million infected people worldwide.
The majority of those infected enter a chronic disease state and further develop liver cirrhosis, hepatocellular carcinoma. Although combination therapy with pegylated interferon and ribavirin is available, only 55% of the infected patients show a favorable response.
This response greatly varies with the HCV genotype involved in the infection. Furthermore, the combination therapy is expensive and the associated side effects limit their usage.
HCV is a small, enveloped, positive sense single strand ribonucleic acid (RNA) virus of the family Flaviviridae consisting of the structural proteins (core, envelope 1 and 2) and the 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.
The NS3 is a multifunctional protein, with a serine protease which responsible for the polyprotein cleavage and RNA helicase/NTPase which is indispensable for RNA replication.
There is a strong correlation with a strong and multi-specific CD4+ and CD8+ T cell response and successful clearance of HCV. Chronic hepatitis C is characterized by weak or absent HCV-specific CD4+ and CD8+ T cell responses.
In this thesis detect the level of a panel of cytokines namely: IL2, IFNγ, and TNF-α in cell culture supernatant from stimulated peripheral blood mononuclear cells (PBMCs) by HCV specific C33 peptide by a commercially available Fluorokine MAP cytokine multiplex kit which is designed for use with the Luminex100™ 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 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 (+ve P.I) HCWs: 6 samples.
The +ve PI HCWs respond to C33 with significantly higher level of IFN γ and IL2 compared to -ve PI HCWs but their levels are higher than chronic group without significant difference. They also have a significantly higher TNFα response than chronic HCV HCWs. IFN γ produced in +ve PI HCWs is correlated with CD3-/ CD 8+ are probably NK cells and negatively correlated with CD3+/ CD8-ve cells which are probably CD4+ cells. In +ve PI HCWs there was a positive correlation between IFN γ and IL2, between IFN γ and TNF α.
As for the chronic HCV HCWs, their response via TNF α is significantly less than both healthy groups. While IL2 level is less than +ve PI HCWs and higher than -ve PI HCWs without significant difference. Both IL2 and IFN γ show a negative correlation in the chronic group.
As for -ve PI HCWs their response via IFN γ and IL2 is significantly less than +ve PI HCWs. and IL2 show positive correlation with CD3-/ CD 8+ within this group.
Health care workers who have cleared the virus (+ve PI HCWs) have a significantly higher IL2, IFN γ response from healthy individuals never exposed to HCV and a significantly higher TNF α and higher IFN γ (no significant difference) response from the chronic cases who have not cleared the virus i.e., chronic cases have a diminished TNF α and IFNγ response than PI +ve healthy group who have cleared the virus and a diminished response for TNF even from the health care workers never exposed.
In conclusion, we can say that there is an important role of NS3 in immune response against HCV as IFNγ , IL2 and TNF levels were significantly higher in +ve P.I HCWs samples stimulated with C33 and this may lead to control of the viral infection. Moreover, there is a crucial role for innate immune response in HCV infection.