|dc.contributor.author||Pattison, Mari Anne||
|dc.description.abstract||The immune system is a complex network of tissues, cells and proteins which protects
us against infections and invading pathogens we encounter every day.
Immunosenescence refers to age-related impairments in immune function which may
contribute to increased prevalence and severity of infectious disease in the elderly.
How and why ageing affects the immune system is not fully understood. Using a
naturally aged mouse model, work in this thesis shows that the abundance of a rare
type of lymphocyte, known as NKT cells, increased across multiple immune organs.
Additionally, macrophage abundance was also altered in the lymph nodes of aged
Invariant NKT (iNKT) cells express an invariant T cell receptor (TCR) which
recognises lipids presented on the CD1d molecule. iNKT cells can be activated and
respond to invading pathogens either by recognition of antigens through TCR-CD1d
interactions or cytokine-dependent means. Less is known about NKT-like cells, which
also express NK cell-associated surface markers, such as CD49b, but lack an invariant
Data within this thesis show that both iNKT and NKT-like cell populations are
abundant in the spleen and liver of aged mice. iNKT and NKT-like cells can be divided
into subpopulations based on their expression of surface markers or transcription
factors, and data suggests that not all subpopulations of these cells are affected by age
equally. For instance, flow cytometry showed that while spleen-derived iNKT cells
are significantly increased in aged mice, within the iNKT cell population the
percentage representation of CD4+ cells are significantly reduced with age.
Additionally, data indicates that both iNKT and NKT-like cells from aged mice show
compromised responses to in vitro stimulation compared to young controls. Using
bone marrow chimeras, where either young cells are reconstituted within an aged
mouse or old cells are reconstituted within a young mouse, provided the opportunity
to determine whether the aged environment contributes to this diminished response.
Data demonstrates that the aged environment plays at least a partial role in these age-related
changes to response to stimulation, however the young environment seems
unable to reverse these changes.
Macrophages are phagocytes which are found within all organs of the body. Studies in
this thesis show that CD169+ macrophages have diminished numbers in the lymph
nodes of aged mice, but this did not seem to affect the capture of the model antigen,
dextran. Further studies revealed ageing affects macrophage populations differently in
the different tissues within the body. For example, macrophage numbers remain
constant in the spleen with ageing, but appear to increase in density in the lungs.
To conclude, ageing can cause dramatic changes to the numbers and function of
different cells of the immune system across multiple organs. Furthering our
understanding of the ageing immune system and the underlying mechanisms which
cause age-related decline in immune function is important to design strategies to
improve the quality of the lives of the elderly.||en
|dc.contributor.sponsor||Biotechnology and Biological Sciences Research Council (BBSRC)||en
|dc.publisher||The University of Edinburgh||en
|dc.relation.hasversion||Mabbott, N. A., Kobayashi, A., Sehgal, A., Bradford, B. M., Pattison, M., & Donaldson, D. S. (2015). Aging and the mucosal immune system in the intestine. Biogerontology, 16(2), 133-145. doi: 10.1007/s10522-014- 9498-z||en
|dc.subject||T cell receptor||en
|dc.subject||ageing immune systems||en
|dc.title||Effects of ageing on murine NKT cell and macrophage populations||en
|dc.type||Thesis or Dissertation||en
|dc.type.qualificationname||PhD Doctor of Philosophy||en