Release of sequestered antigen
In the last lecture we mentioned that some
antigens are hidden away from the immune system in immunologically
privileged sites. When trauma or other events cause damage to the barriers
which protect such special sites this can lead to the release of novel
autoantigens and the production of autoantibodies. In the case of
autoimmune sympathetic opthalmia, damage to one eye leads to subsequent
autoimmune attack on the contralateral eye.
T cell bypass
This concept embodies the idea that
autoimmunity can arise as a result of T cell tolerance being bypassed.
This might occur in a number of ways
- modification. This can happen
when a small molecule (eg a drug) binds to a protein and alters an MHC-
binding peptide so that it becomes a neoantigen recognised by T cells.
This provides T cell help, through linked recognition, for antibody
production which need not be (and usually is not) directed against a
neodeterminant.
- inflammation. During an
inflammatory response an immunostimulatory environment is created by
the release of cytokines which recruit and activate professional
antigen presenting cells and provide support for T cell activation
rather than anergy. As a result autoreactive T cells which were
anergic or ignorant may become activated. This concept is central to
Matzinger's Danger Hypothesis (see lec 11).
- molecular mimicry is a rather
specialised version of the above in which an epitope of an invading
microorganism cross-reacts with a self protein. The T cell help
provided by the other microbial antigens permits the activation of B
cells which make an crossreactive antibody which either escaped
tolerance or which acquires sufficient self reactivity through somatic
mutation and selection driven by the cross-reactive antigen.
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