Immunity in the digestive system of birds

The immune system of the mucosa has evolved parallel to the systemic immune system. Consequently of this dichotomy, only the responses initiated in inductor places of the mucosa can become in an effective immune response. The secretor immune system provides an integrated net linked to organs of the mucosa which work independently of the systemic immunity.

This concept of “ common immune system of the mucosa” proposed by Bienenstock in 1974 has been supported by the migration of effector cells and the secretion of molecules of IgA which ensure that the antigenic experience in a mucosa can be reflected in the expression of the effector immune system in a distant surface. For example, the stimulation of the immune system in the intestine can provoke the production and detection of specific antibodies in the trachea, or the intraocular immunization can produce a stimulus at gastrointestinal tract level in birds, with the production of IgA and IgG at significant levels.

The mucous surfaces and associated lymphoid tissues have evolved with special characteristics, limiting the adherence of pathogens in epithelium and reducing the colonization. Many mechanisms in the development of the intestinal immunity in birds have been reviewed during last few years.

The development post birth of the lymphatic tissues associated to the mucosa in birds have been studied in eyes, lungs and intestines; having determined that in intestines, the lymphoid tissue develops specific areas for B cells and T cells. Three decades ago, studies were indicating that producer cells of immunoglobulin located in chick’s intestine were very small and they were increasing by response of the intestinal colonization, possibly the mithogenic activity of the bacterial lipopolisaccharides. However, three decades year, it has been confirmed that the lymphoid tissue associated to the intestine (GALT) is full of B cells at the fourth day of life and matures until the 2nd week; and the innate immunity is associated to two events:

• One independent of the exposition to aliments and bacteria regulated by a gen

• Dependent of the exposition to feed and flora which is being developed after birth.

Most agents invade animals through the mucosas. It has broadly been demonstrated that the presence of protector antibodies in the surface of mucosas protects the animals against the entry of microorganisms.

In the intestine of birds, the defensive mechanism associated to the intestinal mucosa is mediated by the secretor IgA and produced by the GALT. For this reason the use of agents capable of stimulating the local response is one of the alternatives for the prevention of the colonization of pathogenic microorganisms. In birds, the maternal antibodies are transferred to chick through the egg, and exists evidences that IgA, from unknown origin, can be found in the yolk one day before of the birth. However its function in the protection of bird during its first days of life has not been clarified. On the other hand the normal microflora is important for the early stimulation and the maturation of the cellular component in the intestinal immune system. These native bacteria modulate the immune response by increasing or reducing the secretor mediators for the immunocompetent cells associated to the intestine and for the stimulation of lymphoid Th and suppressors, and it is probably that changes during its growth, affect this micro environment.

Brandtzaeg and some collaborators of him described, more than one decade ago, that the immune system in the mucosa can act by using three basic mechanisms:

• The immune exclusion: It is a protection of non flammable surface that is carried out in collaboration with innate immunity factors and is mediated by the SIgA.

• The Immune regulation: It is a series of events in which participate cells presentors of antigens, where B and T lymphoids are activated and there exist liberation of specific cytokines.

• The immune elimination which involves the stimulation of mediators (cytokines and other substances), cells of innate defense, proliferation and differentiation of lymphoids, and the events related to the production of antibodies.

In birds, the limited studies carried out about the antigen binding by the GALT have not been conclusive. Despite of the existing differences among animal species, system works similarly in all cases. The generated immunity in mucosa, especially in the intestinal, is an important factor of the immune system, as it can reflect the immunity in other tissues or physiologic systems of the organism against infectious agents. The intestinal immune response involves a series of interactions and complex events that include mediators, cells and other factors presented in GALT, which induce and express the response of IgA in mucous surfaces.

Response against Salmonella infection

When an infection in a mucosa is initiated by an intracellular pathogen, despite of existing the activation of the innate immunity, the final result is the induction of the immunity mediated by cells, accompanied to the specific synthesis of SIgA, which provides an important first barrier of defense against the invasion of the deepest tissues. In case of Salmonella, this one arrives to the intestine and comes in through epithelial cells or M cells whose structure enhances the entry of enteric pathogens. As bacteria has three types of secretion systems, can enter in touch with plasmatic membrane easily and induce its own phagocytises. A second mechanism for the entry of the bacteria is mediated by dendritic cells which express some proteins that bind tightly and extend dendrites between epithelial cells to capture bacteria directly.

These mechanisms are associated to the type of host and the serotype of Salmonella which infects the host. Other factors which could influence on the immune response are the immunologic state of the host, the intestinal microenvironment and its balance. This has been demonstrated in several investigations, where it has been concluded that the invasion of Salmonella Enteritidis and Salmonella Typhimurium produce in birds’ cells an expression of citoquinas which induce an inflammatory response and limit the dissemination of the bacteria in intestine. On the contrary, Salmonella Gallinarum does not induce inflammatory response so it is not locally limited by the immune system by producing the systemic disease. It has been suggested that flagella and the SPI 1 are associated to the intestinal inflammation, and that the absence of flagella in specific salmonellas of birds can be a favourable tool to avoid being recognised by the TLR5 and develop the systemic infection through a “cautious” strategy of these bacteria.

Differences between the systemic infection host-specific and the infection by paratific salmonellas.

 1Chappell and collaborators 2009.

 It has been suggested that local immunity in intestine or lymphoid tissue associated (GALT) must play an important role in the protection acquired against salmonella. This has been confirmed by Salazar-Gonzales and collaborators that found a subpopulation of dendritic cells which expresses a receptor of quimiocina CCR6+, indispensable for activating T cells specific anti-Salmonella. Despite of the differences between mammals and birds, it is possible that mediators and populations, of similar cells with comparable functions, are surrounded in infections by Salmonella in birds. It is necessary to mention that activation of T cells by dendritic cells is a critical event in the initialization of the acquired immune response and the protection against enterpathogens. Apart from the component, there are many mediators involved in control of pathogenic strains of Salmonella, such as IFN- ɣ, TNF-α required among other functions for the activation of macrophages; IL-12 and IL-18 critical substances in activation of T cells, specially the subpopulation of Th1. Historically, cytokines derived from lymphocytes Th2 were considered essential for the response of antibodies. However, the response of antibodies SIgA can also be induced by responses dominated by lymphocytes Th1, as it can be observed specifically with some intracellular pathogens such as Salmonella in the intestinal tract. Please note, this permits to suggest the existence of an interaction in the intestinal microenvironment during the infection, which finally activates the immunity mediated by cells in order to eliminate the intracellular pathogen, and at the same time it activates the humoral immunity mediated by IgA secretor at intestinal mucosa level, providing a barrier against the colonization of the bacteria.