The avian immune system refers to the system of biological structures and cellular processes that protects birds from disease.The avian immune system resembles that of mammals since both evolved from a common reptilian ancestor and have inherited many commonalities. They have also developed a number of different strategies that are unique to birds. Most avian immunology research has been carried out on the domestic chicken, Gallus gallus domesticus. Birds have lymphoid tissues, B cells, T cells, cytokines and chemokines like many other animals. In addition, they can also have tumours, immune deficiency and autoimmune diseases.
Various bird organs function to differentiate avian immune cells: the thymus, Bursa of Fabricius and bone marrow are primary avian lymphoid organs whereas the spleen, mucosal associated lymphoid tissues (MALT), lymph nodes, germinal centers, and diffuse lymphoid tissues are secondary lymphoid organs. The thymus, where T cells develop, is located in the neck of birds. The Bursa of Fabricius is an organ that is unique to birds and is the only site for B cell differentiation and maturation. Located in the rump of birds, this organ is full of stem cells and very active in young birds but atrophies after six months. Bronchial associated lymphoid tissue (BALT) and gut associated lymphoid tissue (GALT) are found along the bronchus and intestines, respectively. In the avian respiratory system, there are heterophils, which are an important part of bird immunity. Within the head, there is head associated lymphoid tissues (HALT) that contain the Harderian gland, lacrimal gland and other structures in the larynx or nasopharynx. The Harderian gland is located behind the eyeballs and is the major component of HALT. It contains a large number of plasma cells and is the main secretory body of antibodies. Alongside these primary and secondary lymphoid organs, there is also the lymphatic circulatory system of vessels and capillaries that communicate with the blood supply and transport the lymph fluid throughout the bird’s body.
The antigen recognition by T cells is a remarkable process dependent on the T cell receptor (TCR). The TCR is randomly generated and thus has extensive diversity in the peptides-MHC complexes it can recognize. Using monoclonal antibodies that are specific for chicken T cell surface antigens, the development of T cells in birds is studied. The differentiation pathways, functional processes and molecules of T cells are highly conserved in birds. However, there are some novel features of T cells that are unique to birds. These include a new lineage of cytoplasmic CD3+ lymphoid cells (TCR0 cells) and a T cell sublineage that expresses a different receptor isotypes (TCR3) generated exclusively in the thymus. Homologues of the mammalian gamma, delta and alpha beta TCR (TCR1 and TCR2) are found in birds. However, a third TCR, called TCR3, has been found in avian T cell populations that lack both TCR1 and TCR2. These were found on all CD3+ T cells and were either CD4+ or CD8+. This subset of T cells, as others, develops in the thymus and gets seeded throughout the body with the exception of the intestines. The pattern of accessory molecules expressed by avian T cells resembles mammalian α/β T cells. High CD8 expression precedes the dual expression of CD4 and CD8 but following clonal selection and expansion, avian T cells cease to express either CD4 or CD8.
The central organ for B cell development in birds is the Bursa of Fabricius. The function of the bursa was discovered when it was surgically removed from neonatal chicks and this lead to an impaired antibody response to Salmonella typhimurium. It is now clear that the bursa is the primary site of B cell lymphopoeisis and that avian B cell development has some unique properties compared to human or mouse models. Almost all the B cell progenitors in the bursa of 4-day-old chickens express IgM on their cell surface. Studies have shown that B cells of 4 – 8 week old birds are derived from 2 – 4 allotypically committed precursor cells in each follicle. Bursal follicles are colonized by 2-5 pre-bursal stem cells and these undergo extensive proliferation after they are committed to an allotype. Expression of IgM is controlled by a biological clock as opposed to the bursal microenvironment. Moreover, the source of all B cells in adult birds was determined to be a population of self-renewing sIg+ B cells.
In studying the development of the avian immune system, the embryo offers several advantages such as the availability of many embryos at precise stages of development and distinct B and T cell systems. Each population differentiates from a primary lymphoid organ: T cells in the thymus and B cells in the Bursa of Fabricius. Research has found that early feeding of hydrated nutritional supplements in chickens heavily affects the immune system development. This is often measured by weight of the Bursa of Fabricius, improved resistance to disease and earlier appearance of IgA. Unlike other animals, newly hatched chicks are born with an incomplete immune system. Here, the amniotic fluid and yolk of the egg contain the maternal immunity to be passed on to the hatchling. Swallowing of the amniotic fluid during hatching confers immunity to these chicks until their immune system develops fully. In the first six weeks of the bird’s life, continuous gene conversion in the bursa completes the immune system. Upon hatch, birds do not have a library of genetic information for B cells to use for antibody production. Instead, B cells mature in the bursa during the first six weeks and then go on to seed other organs of the immune system. As a result, birds are highly susceptible to pathogens in the first few weeks after hatching. Research found that T cells from mature chickens proliferated extensively and produced high levels of IL-2 and other cytokines. On the other hand, T cells from 24 hour-old chickens failed to proliferate and could not secrete cytokines. Gene conversion within the bursa leads to the development of antibodies that are diverse in their recognition ability. Mammalian V, D and J gene segments allow for many combinations and therefore, yield a vast repertoire of antibodies. However, birds have only a single functional copy of the VL and JL genes for the Ig light chain and a single functional copy of the VH and JH heavy chain genes. This results in a low diversity from gene rearrangements of Ig heavy and light chains. However, clusters of pseudogenes upstream of the heavy and light gene Ig loci take part in somatic gene conversion – a process where pseudogenes replace the VH and VL genes. This diversifies the repertoire of bird antibodies.
Avian innate immune system
Little is known about the innate immune system of birds. Most research has been focused on chickens due to the increased threat of viral diseases within the poultry population. The innate immune response is known to be essential for viral infection and as a result, the publication of the full chicken genome sequence is a source for identifying possible adjuvants and immunity genes.