When a bird is vaccinated, or exposed to a viral or bacterial infection, a complex biological mechanism is set in motion which normally results in the elevation of the bird's specific defenses against the disease in question. Sometimes this process also raises non-specifically its defenses against other infections. The immune response is generated by a complex system of specialized cells, the lymphocytes. All vertebrates have such a system but those of birds and mammals are the most complex. The serological tests measure only one component of the immune response, the antibodies circulating in the blood. Antibodies are proteins with one or more binding sites which attach to a specific site on a pathogen. The other main components of the immune system, which are not measured by standard serological tests, are antibodies produced and secreted locally (in tears, tracheal mucus, on the intestinal mucosa etc.), and the cellular immune response or delayed hypersensitivity.

Hieronymus Fabricius described the location and structure of a diverticulum of the avian cloaca in the late 16th century. It took almost another four centuries before the fundamental significance of the bursa for the development of immunity in birds was recognized (Glick, 1956). It was found that cells developing in the bursa and those developing in the thymus had different functions in the immune response. Both thymus and bursa have a role in producing or controlling the production of the antibody which we measure in serological tests. The separation of the two central maturing organs which is present in the fowl has led to its use as a model for the investigation of many basic immunological phenomena (Toivanen et al., 1981). For a summary of the progress in our understanding of these phenomena achieved over a 20 year period the reader is referred to Glick (1979) and Tizard (1979). Appendix A provides some further notes on the current understanding of the anatomy and physiology of the avian immune system. Figure 1.1, summarizes the chain of events leading from exposure to an antigen (natural infection or vaccination) to the production of antibody.

The antibodies which are secreted at mucosae are designated IgA, while IgM and IgG circulate in blood and lymph. The classes of antibody have varying chemical structure and numbers of attachment sites per molecule. Serological tests also vary in their ability to detect the different classes. Once the initial challenge has been dealt with, a group of cells (so-called "memory" cells) which have the required genetic make-up to produce antibody against the specific antigen, remain. Five days or so are generally required for the immune system to respond to the initial challenge but these cells allow a much more rapid and vigorous response to the secondary stimulus. This is known as an "anamnestic" reaction (Janeway, 1993).

Fig 1.1 (Nossal, 1994).

How the Immune System Defends the Body

"The body is protected by a diverse army of cells and molecules that work in concert. The ultimate target of all immune responses is an antigen, which is usually a foreign molecule from a bacterium or other invader. Specialized antigen-presenting cells, such as macrophages, roam the body, ingesting the antigens and fragmenting them into antigenic peptides . Pieces of these peptides are joined to the major histocompatibility complex (MHC) molecules and are displayed on the surface of the cell. Other white blood cells, called T lymphocytes, have receptor molecules that enable each of them to recognize a different peptide-MHC combination. T cells activated by that recognition divide and secrete lymphokines, or chemical signals, that mobilize other components of the immune system. One set of cells that responds to those signals comprise the B lymphocytes which also have receptor molecules of a single specificity on their surface. Unlike the receptors on the T cells however, those on the B cells can recognize parts of antigens free in solution, without MHC molecules. When activated, the B cells divide and differentiate into plasma cells that secrete antibody proteins, which are soluble forms of their receptors. By binding to the antigens that they find, the antibodies can neutralize them or precipitate their destruction by complement enzymes or by scavenging cells. Some T and B cells become memory cells that persist in the circulation and boost the immune system's readiness to eliminate the same antigen if it presents itself in the future. Because the genes for antibodies in the B cells mutate frequently, the antibody response improves after repeated immunizations."