Page 608 - Veterinary Immunology, 10th Edition

VetBooks.ir Tolerance

Tolerance is the name given to the situation in which the immune
system will not respond to a specific antigen. Tolerance is primarily

directed against self-antigens from normal tissues. In 1948 two
Australian immunologists, Burnet and Fenner, recognized this need
for self-tolerance and suggested that immature lymphocytes would
become tolerant to an antigen if they first met it early in fetal life.
Support for this suggestion came from observations on chimeric

calves. In 1945 Owen noted that when cows are carrying twin
calves, blood vessels in the two placentas commonly fuse. As a
result, the blood of the twins intermingles freely, and bone marrow

stem cells from one animal colonize the other. Each calf is born with
a mixture of blood cells, some of its own and some originating from
its twin. In dizygotic (nonidentical) twins, this is called a chimera.
These “foreign” blood cells persist indefinitely because each
chimeric calf is fully tolerant to the presence of its twin's cells (Fig.

20.1). Burnet and Fenner suggested that this could only happen
because each calf was exposed to the foreign cells early in fetal life
at a time when lymphocytes become tolerant upon encountering

antigens. Cells from an unrelated calf would be rejected normally if
administered after birth. Thus immune tolerance is not innate. It is
established during fetal and postnatal development and relies on
mechanisms that control lymphocyte development.

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