4. What is Immunologic Tolerance?
• Tolerance refers to the specific immunological nonreactivity to an antigen resulting from a previous
exposure to the same antigen. While the most
important form of tolerance is non-reactivity to self
antigens, it is possible to induce tolerance to nonself antigens. When an antigen induces tolerance, it
is termed tolerogen
7. • Central Tolerance - this occurs during lymphocyte
development.
• Peripheral Tolerance - occurs after lymphocytes leave the
primary organs.
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8. • Central Tolerance
• T cells
• As we have already seen, during T cell development in the
thymus the process of negative selection leads to the deletion
of thymocytes whose T cell receptors have 'high affinity' for
self.
• B cells
• During B cell development in the bone marrow when the
complete antigen receptor (IgM) is first expressed on
'immature' B cells if those cells encounter their target antigen
in a form which can cross-link their sIgM then such cells are
programmed to die (deleted from the repertoire).
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9. Story discovary
• This was discovered many years ago when it was shown that
injection of a polyclonal anti-IgM from birth prevented the
development of B cells, resulting in a 'B-less' mouse. The
requirement for crosslinking means that the antigen has to be
polyvalent, the most obvious example of this being cellsurface molecules. This has been directly demonstrated by
using transgenic mice expressing rearranged Immunoglobulin
genes specific for natural or artificial membrane bound
molecules. Presumably other multivalent self antigens to
which immature B cells are exposed also induce deletion of
self reactive cells.
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10. • Peripheral Tolerance
• after the immune system has matured there need to be some
mechanisms to prevent autoreactivity of lymphocytes after
they have emigrated from the thymus/bone marrow. In fact
there are several such mechanisms:
• Ignorance
• Suppression
• Anergy
• Split Tolerance
•
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11. Advantages & disadvantages of tolerance
•
Advantages
1. Self-tolerance is essential for the function of the immune
system
2. Tolerance to foreign tissue grafts
3. Gene therapy
4. Control of damaging immune responses such as:
i.
ii.
•
Hypersensitivity
Autoimmune diseases
Disadvantages
1. Tolerance to certain foreign antigens that cause disease
such as bacterial infections
2. Tolerance to some self-antigens associated with cancer
