Immunological tolerance is a state of specific immunologic
unresponsiveness to a particular antigen to which a person has been exposed
earlier. The immune tolerance prevents the body to mount immune response
against the self-antigen.
Suggested mechanism of tolerance includes (a) clonal deletion, (b)
clonal anergy, and (c) suppression.
Clonal deletion: Clones of B and T lymphocytes
thatrecognize self-antigens are selectively deleted in embryonic life, hence
are not available to respond on subsequent exposure to antigen. This is known
as clonal deletion.
Clonal anergy: Clonal anergy means a
condition in whichclones of B and T lymphocytes that recognize self-antigens
might be present but cannot be activated.
Suppression: In this mechanism, clones of
B and T lym-phocytes expressing receptors that recognize self-antigens arepreserved.
However, expression of immune responses following antigen recognition might be
inhibited by active suppression.
The immune tolerance may be of two types: natural or acquired.
Natural tolerance: Natural tolerance is nonresponsivenessto
self-antigens. It develops during the embryonic life, and any antigen that
comes in contact with the immune system during its embryonic life is recognized
as self-antigen. The self-antigen would not induce any immune response. Burnet
and Fenner (1949) also postulated that foreign antigens would not induce immune
response if they were administered during the embryonic life.
Acquired tolerance: Acquired tolerance develops
when apotential immunogen induces a state of unresponsiveness to itself. The
antigen needs to be repeatedly or persistently admin-istered to maintain the
acquired tolerance. This is probably necessary because of the continuous
production of new B and T cells that must be rendered tolerant. Induction of
immune tolerance depends on a number of factors. These include (a) species and immune competence of the
host and (b) physical nature, dose,
and route of administration of antigens
Species and immune competence of the host: Tolerance dependson the
immunological maturity of the host. Embryos and neonatal animals are
immunologically immature, hence are more susceptible for induction of
tolerance. Rabbits and mice can be made tolerant more rapidly than guinea pigs
Physical nature, dose, and route of
administration of antigens:Soluble antigens and haptens can induce more
immune tolerance than the aggregated antigens. For example, heat aggregated
human gamma globulin is more tolerogenic than deaggregated gamma globulin in
mice. It may possi-bly be due to enhanced phagocytosis of aggregated proteins
than soluble antigens by macrophages, in which they can be presented to
antibody-forming cells, thus inducing antibody synthesis. The induction of
tolerance is dose dependent also. For example, a very simple molecule induces
tolerance more readily than a complex one. Repeated minute doses as well as
high doses of antigen induce B-cell tolerance, whereas a moderate degree of
same antigen may be immunogenic. The route of administration is also important.
In guinea pigs, intravenous or oral administration of certain hap-tens causes
tolerance, whereas intradermal administration causes induction of immunity. T
cells become tolerant more readily than B cells and also remain tolerant longer
than B cells. Tolerance is overcome spontaneously or by injection of
cross-reacting antigens. For example, in rabbits, tolerance to bovine serum
albumin can be abolished by immunization with cross-reacting human serum
albumin. Tolerance can be enhanced by administration of immunosuppressive
drugs. For example, tolerance is enhanced in patients who have received organ