December 13, 2013

 

 

At the inaugural Merial Avian Forum Asia, Prof Bernd Kaspers, Professor of Animal Physiology from the Institutes for Animal Physiology of Ludwig-Maximilians-University in Munich, provided the audience with a better understanding of the avian immune system.

 

Prof Kaspers described the immune system as an integrated system with many 'players' closely interacting to function and develop a good and sustainable immune response. By illustrating the functions of the B-cells and T-cells and how the system relates to immunosuppression, he also shed light on the limitation of classic vaccines and implication for the future development of animal vaccine.

 

Firstly, looking into the anatomy of a chicken, in the absence of lymph nodes, the thymus, bursa of Fabricius, spleen and bone marrow are important components of the immune system. 

 

Cells derived from the primary lymphatic organs in the bird perform immune-related functions, such as the B-cells from the bursa, which produce antibodies. However, B-cells on their own are not able to produce good antibodies without T-cells. In fact, not only do T-cells help B-cells to produce antibodies, they are also overall regulators of the immune system; kill virus-infected cells; and activate other cells of the immune system such as macrophages to kill pathogens hiding inside the cell, such as in the occurrence of tuberculosis.

 

Prof Kaspers explained how the bursa's mechanism modulates and changes B-cells into a vast number of different antibodies that can respond to almost any antigen encountered by the bird. The first mature B-cells leave the bursa around hatch and colonise secondary lymphatic structures such as spleen, ceacal tonsils and other mucosal tissues where they eventually interact with T-cells and other accessory cells during antigen-specific immune response.

 

However, Prof Kaspers warned that the bird's immunity system is not well-developed at hatch. Cells deriving from early hematopoietic precursors in the embryonic spleen migrate to the bursa anlage between embryonic day 10 and 14 and colonise the bursal follicles, where they proliferate and generate the broad antibody repertoire.

 

The development of a fully functional adaptive immune system continues during the first week after hatch, a time-frame during which the innate immune system and maternal antibodies are critically important to prevent the sudden encounter of microorganisms after hatch.

 

Like B-cells, T-cells require time to develop. Precursor cells enter the thymus and leave as T-cells in three major waves to the peripheral organs. The first wave takes place at 18 - 20 days of embryonic development, with waves 2 and 3 well after hatch. Thus, the majority of T-cells have not left the thymus at hatch to populate the periphery to help B-cells perform their function.

 

In the absence of T-helper cells, which help B-cells to produce antibodies, the number and diversity of antibodies will be sharply reduced, preventing the B-cells system to respond to the broad variety of antigens.

 

Prof Kaspers proceeded to explain how the B-cells and T-cells work together to activate an immune response. He explained that from hatch, a bird's immune system has cells expressing specific receptors, which can identify so-called pathogen-associated molecular patterns. By binding to these molecules the cells become activated and can take up the pathogenic microorganisms. Cells known as dendritic cells (DC) take the antigen with them and migrating from the tissues to the lymphoid organs. Here, they interact with the T-lymphocytes, which become activated and start to proliferate, to make more T-cells to combat diseases more efficiently.

 

An important feature of the immune system is the generation of increasingly better antibodies during an immune response. This is achieved through close collaboration of B-cells, T-cells and DCs. These cells interact with each other by using cell surface receptors or soluble signalling molecules - cytokines. Some of these molecules have been identified in chickens recently. The knowledge gained may help to improve vaccines in the future.

 

Importantly, the activation of T-cells through vaccination leads to the development of memory cells - a hallmark of the adaptive immune system. Memory cells can recall the antigen and will expand and become effector cells when they encounter the antigen again.

 

These memory cells are long-lived, respond very quickly to secondary vaccination or infection, and generate new effector cells in response to the challenge, thereby helping the bird to respond quickly to a second encounter of the pathogen. Hence, this cell is very important to vaccine producers, although markers to identify these cells in birds are not available currently.

 

On vaccine development, Prof Kaspers also said that better understanding of the mechanism of how DCs take up and process antigen  to educate the B and T-cells could advance vaccine development. Specifically, with that knowledge, it will be possible to design vaccines which are picked up and identified more easily by dendritic cells and presented more efficiently to the immune system to induce a more efficient immune response.

 

Lastly, Prof Kaspers shared the important distinction of the different subtypes of the T-cells. CD8+ T-cells (cytotoxic T-cells) act to control viral infections through the secretion of effector molecules which lyse infected cells to stop virus replication and thereby prevent virus spread. He further broke down the CD4+ T-cell population  into subtype Th1, Th2, Th17 and Treg, which function to activate macrophages; activate B-cells; attract  heterophis to the site of infection (e.g. against salmonella or pathogenic E.coli); and to produce  cykotines to control other effector cells, respectively. The absence of any of these will ultimately result in immunosuppression.

 

Prof Kaspers conclude that while there is good development in terms of tools and techniques to better understand the system and measure important variables, there is room for development to better understand the functional characterisation of T-lymphocytes, characterisation of the functional importance of cytokines and antigen delivery and presentation.

 

Prof Bernd Kaspers spoke at the inaugural Merial Avian Forum Asia, held in Bangkok during 3-4 September. The forum organised by the animal health company brought together over 250 Merial partners, distributors, customers and staff from over 20 Asian countries.