| Themes > Science > Life Sciences > General Biology > Immunology > The Immune System & Disease > Tolerance > Timing |
Some 50 years ago Owen observed two types of non-identical twin cattle, those that had shared a haemopoietic system in utero were tolerant of blood cells from each other and those who had not, were not cross-tolerant. Burnet postulated that there was a temporal window of tolerance such that antigens encountered while the immune system was immature tolerised the relevant lymphocytes. Medewar subsequently investigated the effects of transferring haemopoietic cells from histoincompatible mice at different times after birth. He found that if the cells were transferred in the first few days of life (but not later) the recipient mouse acquired lifelong tolerance to the antigens of the donor. |
| We now understand a good deal
about the mechanism of this acquired tolerance. In essence bone marrow
stem cells establish chimaerism of the host. Some of these cells
differentiate into antigen presenting cells and migrate to the thymus
where they tolerise developing thymocytes by deletion (central
tolerance). Lifelong chimaerism is needed to maintain tolerance and
even a low level of chimaerism is sufficient. For the first few days of
the mouse's life there are too few post-thymic T cells to sustain a
response and these are tolerised either by peripheral deletion or some
other mechanism. If the transfer is done later the number and maturity of
the peripheral T cell pool is sufficient to destroy the donor stem cells
before they can engraft.
Even antigens which cannot establish chimaerism can establish a state of tolerance in neonatal mice, this is less permanent however. Timing is an important parameter on the tolerisability of the immune system. |
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