A role for type 111 interferons in the natural killer cell immune response to virus
Citation:
Maria H. Morrison, 'A role for type 111 interferons in the natural killer cell immune response to virus', [thesis], Trinity College (Dublin, Ireland). School of Biochemistry and Immunology, 2012, pp 226Download Item:
Morrison TCD THESIS 9630 A role.pdf (PDF) 92.83Mb
Abstract:
Natural Killer (NK) cells are fundamental effector cells of the innate immune system
that function to eliminate virally infected and transformed cells. One key way in
which they do this is through the production of cytokines, of which the interferons
(IFNs) are particularly important in carrying out anti-viral effects. Hepatitis C (HCV)
is a virus found worldwide and in the majority of cases, leads to chronic infection and
liver damage. Recent evidence supports a role for the innate immune system in HCV
clearance as innate immune genes, in particular the NK cell gene KIR2DS3 and the
recently reported IL28B (IFN-λ3) SNP, have been shown to contribute to disease
progression. Research carried out for this thesis investigated whether the novel family
of IFN-λs contributed to the established role for NK cells in immunity to viral
infection. We investigated the response of human sorted NK cells to poly I:C, a
known inducer of lFN-λ. We have demonstrated a direct effect of poly I:C on human
NK cells and, although changes in IFN-A. gene expression were detected, we suggest
that NK cells are not the main producers of IFN-λ. We also assessed the effect of type
III IFNs on human NK cells. None of the three 1FN-λ family members activated NK
cells. However IL28A and IL28B inhibited IFN-y production by NK cells of some
healthy and HCV infected donors. This therefore supports a functional link between
NK cells and type III IFN. In addition we have shown IFN-λ production is impaired in
PBMCs from HCV infected patients, an observation that is further supported by
decreased levels of IFN-λ in the serum of HCV infected patients. Our findings
contribute to recent evidence suggesting that lFN-λ plays a role in the immune
response to HCV and finds a functional link between NK cells and IFN-λ cytokines.
Author: Morrison, Maria H.
Advisor:
Gardiner, ClairQualification name:
Doctor of Philosophy (Ph.D.)Publisher:
Trinity College (Dublin, Ireland). School of Biochemistry and ImmunologyNote:
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Biochemistry, Ph.D., Ph.D. Trinity College Dublin.Licences: