Proper immune function is indispensable, as failure to mount an immune
response against a pathogen can lead to serious complications or even death. T
cells act by enhancing the activation of phagocytic cells as well as the activation of
B cells. Their widespread influence on an immune response makes optimal T cell
activation vital. Maximal T cell proliferation and survival is accomplished by
stimulation with antigen, a costimulatory signal, and an adjuvant. However,
excessive T cell activation can lead to chronic B cell activation and the production
of autoantibodies, a hallmark of autoimmune disease.
In this thesis, optimal T cell stimulation was studied using an in vivo
adoptive transfer model. Results showed that antigen stimulation of T cells along
with ligation of the costimulatory molecule OX40 led to an accumulation of
antigen-specific cells. OX40 ligation allowed the antigen specific cells to proceed
through more cell cycles than cells stimulated with antigen alone. The addition of
the adjuvant lipopolysaceharide (LPS) to this system allowed for increased cell
survival.
However, the continual presence of an adjuvant may also have injurious
effects. This was highlighted with the appearance of "Toxic Oil Syndrome" (TOS)
in which an adulterated rapeseed oil, an oil with known adjuvant activity, was sold
for human consumption. People developed an autoimmune condition characterized
by polyclonal B cell activation and autoantibody production. A genetic
predisposition was implicated with TOS and was further investigated in this thesis.
Although the A. SW mouse has the genetically susceptible genotype, these mice did
not develop TOS following exposure to "toxic oil" indicating that other factors may
be important in TOS susceptibility.
Extending the techniques used in these studies and applying them to the
canine immune system was the final topic investigated in this series of studies.
Understanding immune pathways of the mammalian immune system is particularly
important for comparative studies when dogs are used as models to investigate
human immune system disorders. These studies combined will allow for a better
understanding of the balance between an optimal immune response and an
imbalance leading to hypersensitivity or immunosuppression, as well as
interspecies relationships. / Graduation date: 2002
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/32371 |
| Date | 25 April 2002 |
| Creators | Weatherill, Amy R. |
| Contributors | Hall, Jean A. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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