Immunology: Animal Models

Animal models provided early proof that discrimination of self (that which the immune system identifies as belonging to the body) and nonself (that which the immune system identifies as foreign to the body) is determined not entirely at conception, but, to a large extent, during early fetal development by a process called immune adaptation. In 1945, Ray D. Owen reported that nonidentical cattle-twin embryos frequently share a common placenta, resulting in the exchange of blood between the fetuses. Owen discovered that this chimerism led to immune tolerance of skin grafts between the adult cattle. Their immune systems did not recognize allogeneic cells shared during the period of immune adaptation, when the immune system identifies cellular and molecular components of the body and memorizes them as self. Later, Milan Hasek connected the circulatory systems of chicken embryos and demonstrated tolerance of the adult birds to each other's tissues. In 1953, Peter B. Medawar and his colleagues demonstrated that the injection of foreign spleen cells into newborn mice resulted in adult tolerance of skin grafts from these foreign donors. These animal experiments confirmed the premise that immune adaptation is determined by the fetal or neonatal environment, rather than inherited.