Immune responses and tolerance

Chickens are generally good antibody producers, and their evolutionary distance from us enables them to respond to some proteins (e.g. cytoskeletal elements) whose sequences are highly conserved in mammals. Immune responses develop early in chickens. They can respond to some protein antigens injected on the day of hatching, and in some cases to viruses or allogeneic or xenogeneic cells introduced into the egg. Responses to individual protein antigens develop at different times after hatching. As in mammals, IgM responses precede IgG; however, in some (but not all) antihapten responses, only poor affinity maturation is observed, consistent with the idea that there is not extensive generation of antibody variability in peripheral tissues (see below). Because of the difficulty of preparing monoclonal antibodies from chickens, their idiotypes and antibody repertoire have not been extensively studied.

Avian T cell-dependent responses (mixed lymphocyte reaction (MLR), skin graft rejection, delayed-type hypersensitivity given by cells injected into the wattle, responses to T cell mitogens) can be assayed essentially as for mammalian cells, while graft-ver-sus-host reactions can be quantitated by the embryonic splenomegaly assay or by pock formation on the chorioallantoic membrane. T cell-dependent cytotoxic assays are established, and spleen cells from chickens infected with leukosis or reticuloendo-theliosis viruses can kill infected target cells in an MHC-restricted, antigen-specific manner. Cytotoxic CD8+ cells play an important role in regression of some virally induced tumors.

Depending on the antigen and mode of injection, tolerance can be induced in chick embryos or newly hatched birds. Several interesting tolerance models have been studied. The antigens used include mammalian serum albumins (large doses given to newly hatched chicks lead to B cell tolerance, which is not suppressor cell dependent); quail embryo wing buds grafted into chick embryos (tolerance is induced only if a quail thymus is also grafted with the wing bud, and may be suppressor cell dependent); parabiosed allogeneic chick embryos (leads to tolerance in early embryos, but to development of leukemias and other abnormalities in later embryos); and allogeneic bursa cells injected into cyclophosphamide-treated 4-day-old chicks, leading to long-lasting and specific B cell chimerism. This model has been useful in studies of B cell development, requirements for T-B cell collaboration and antigen presentation by B cells.

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