Tolerance and Autoimmunity

TOLERANCE AND AUTOIMMUNITY
Immunological tolerance is the failure to mount an immune response to
an antigen. It can be:
? Natural or "self" tolerance. This is the failure to attack the body s
own proteins and other antigens. If the immune system should
respond to "self", an autoimmune disease may result.
? Induced tolerance. This is tolerance to external antigens that has
been created by deliberately manipulating the immune system. Its
importance:
o to protect us from unpleasant, even dangerous, allergic
reactions to such things as food (e.g. peanuts), insect
stings, grass pollen (hay fever).
o to enable transplanted organs (e.g., kidney, heart, liver) to
survive in their new host; that is, to avoid graft rejection.
o to reveal the mechanisms of autoimmunity in the hope of
designing treatments for such diseases as systemic lupus
erythematosus (SLE) and multiple sclerosis (MS).
Both B cells and T cells can be made tolerant, but it is more
important to tolerize T cells than B cells because B cells cannot make
antibodies to most antigens without the help of T cells.
The main process by which T lymphocytes acquire the ability to
distinguish self from non-self occurs in the fetal thymus. This process,
called clonal deletion involves the killing of T cells ("negative
selection") that react against antigens (primarily self MHC proteins)
present in the fetus at that time. (Note that exogenous substances injected
into the fetus early in development are treated as self.) The self-reactive
cells die by a process of programmed cell death called apoptosis.
Tolerance to self acquired within the thymus is called central tolerance,
whereas tolerance acquired outside the thymus is called peripheral
tolerance.