Avian Influenza and Selenium

What is the Relationship Between Se and Avian Influenza?


Scientists say the selenium revolution has stimulated new research and provided practical applications in medicine and agriculture

By Peter Surai




Among many minerals selenium has a special place being the most controversial trace element. Indeed a narrow gap between essentiality and toxicity and environmental issues from the one hand and global selenium deficiency from the other hand, fuel research in this field. There were several breakthroughs in selenium research. The first one was a discovery a Se essentially in early 1960th. The second was a discovery of gluthathione peroxidase being a selenoprotein in 1973. The third one came almost 30 years later with characterization of main selenoproteins in human and animal body and further understanding the role of selenium in nutrition and health. Indeed, this third breakthrough is really a selenium revolution creating many hypotheses, stimulating new research and providing practical applications in medicine and agriculture.

It is generally accepted that most human and animal diseases at various stages of their development are associated with overproduction of free radicals.  For the majority of organisms on Earth, life without oxygen is impossible. Animals, plants and many microorganisms rely on oxygen for the efficient production of energy. However, the high oxygen concentration in the atmosphere is potentially toxic for living organisms. For the last few years free radical research has generated valuable information for further understanding not only detrimental, but also beneficial role of free radicals in cell signaling and other physiological processes. The benefit or harm of free radicals ultimately depend on the level of their production  and efficiency of antioxidant defense and immunity and viral mutations are two most important areas for natural antioxidant.

Part 1. Selenium and immunity

Animal defense against various diseases depends on the efficacy of the immune system responsible for elimination of foreign substances (e.g. parasites, bacteria,  moulds, yeast, fungi, viruses and various macromolecules) or the creation of specific inhospitable conditions within the host for a wide range of pathogens. This protective capacity is based on the effective immune system which is considered to be an important determinant of animal health and well being. In that sense, a remarkable ability of components of the immune system to distinguish between self and non-self is a great achievement of animal evolution.

These are two major types of immune function: natural and acquired immunity. It is well appreciated that immune system is the most complex system in the body and until now scientists are straggling to understand molecular mechanisms of the immune system regulation. Indeed, the immune system is a big army of various types of cells including neutrophils, macrophages, B-lymphocytes and T-lymphocytes. It is interesting to mention that there are millions of phagocytes and billions lymphocytes dealing with pathogens. All immune cells are highly specialized to perform their job properly.

Natural immunity, called the innate immune system, includes

·         Physical barriers (e.g. skin, mucus coat of the GI tract)

·         Specific molecules (e.g. agglutinins, precipitins, acute-phase protein, lysozyme)

·         Phagocytic function of phagocytes (macrophages and heterophils)

·         Lysing activity of a class of lymphocytes called natural killer (NK) cells

Macrophages perform a range of functions, including phagocytosis of foreign particles, destruction of bacterial or tumor cells, secretion of prostaglandis and cytokines and a result regulating activity lymphocytes and other macrophages. In fact, phygocytosis is the major mechanism by which microbes are removed from the body and is especially important for defense against extracellular microbes. Indeed, phagocyte cells are able to produce specific toxic chemicals and use them to kill phatogen. These are so called reactive oxygen species (ROS) and reactive nitrogen species (RNS) representing by a various free radical molecules. This is nothing else but chemical weapon which phagocytes use to deal with various types of pathogens.

Macrophage activation and phagocytosis of foreign particles are regularly accompanied by a so-called “respiratoy burst”, an increase in the production of ROS and RNS (Figure 2). Therefore macrophages as well as other phagocyte leukocytes can synthesize a range of toxic oxygen metabolites during the respiratory burst. Because of this powerful weapon, macrophages bind, internalize, and degrade foreign antigens (e.g. bacteria) quite quickly. For example, it takes only 15 minutes for chicken microphages to skill more than 80% of the internalized Salmonella. Therefore natural immunity works rapidly and gives rise to the acute inflammatory response. Phagocytes contain various substances (including enzymes producing free radicals and small peptides with an antibiotic activity) involving in microbial killing. They have also receptors for chemo-attractive factors released from microbes. In addition to ROS, RNS and eicosanoids mentioned above, macrophages also synthesize and secret a great number of such communicational molecules as cytokines, including the pro-inflammatory cytokines called inter-leukin 1(IL-1), interleukin 6 (IL-6), and tumour necrosis factora (TNF). Therefore phagocytes are important amplifiers of the immune response, both by cytokine production and by serving to present parasite derived peptides to T-cells. Indeed, these are wireless communicating stations enebling to provide communication between different types of immune cells.

The purpose of immune cell product is to destroy invading organisms. However excessive or inappropriate production of these substances is associated with mortality and morbidity after infection and trauma, and in inflammatory diseases. Various stresses (temperature, toxins, etc) are associated with overproduction of free radicals and the radicals damage the mobile connections leading to decreased immunocompetence. In fact, chemical weapon is not specific and can destroy any biological materials. From one side this high toxicity is essential to deal with various types of pathogens. On the other hand, for example, in the case of disease challenge, the overproduction of ROS may occur and they can leak from fagolysosomes into the surrounding cytoplasm and intracellular space and hey easily can kill phagocyte cells. Therefore, phagocytes killing pathogens is a suicidal job. We know that for soldiers using chemical weapon, the most important thing to do is to protect themselves from their own weapon. In the case phafocytes, antioxidants are those protective ammunitions preventing possible damages by their own weapon. A number of Se-dependent antioxidant enzymes is expressed to protect the cells from the cyto-toxic effect of ROS directed against engulfed microorganisms. However, low efficiency of these antioxidant mechanisms, for example due to selenium deficiency, could damage cell’s microbicidal and metabolic functions. In phagocyte cells there are regulatory mechanisms which decrease free radical production in the case of low antioxidant defenses. For example, in the case of Se deficiency respiratory burst in the phagocytes decreased. Indeed, macrophage function is disturbed, if there is a lack in antioxidant enzyme activity.

During fighting in over-crowded army, where friends and enemies are very close to each other a precision of shooting is the most important part of success. This is especially important for those who are using chemical weapon. However, it is inevitably there are always some casualties due to war actions. Indeed, activated phagocytes can cause a series of harmful effects, including killing host cells, injuring cells and tissue directly via oxidative degradation of essential cellular components and damaging cells indirectly by altering the protease/ antiprotease balance that normally exists within the tissue interstitium. They also can cause cell mutations and sister chromatid exchanges. In this case, effective antioxidant defense is a key protective measure against aforementioned damages and Se as a chief- executive of antioxidant system is in the centre of that protection.

Acquired or specific immunity includes humoral immunity and cell-mediated immunity. There are two major types of lymphocytes, B-cells and T-cells.  Humoral immunity is mediated by antibodies that are released by B-lymphocytes into the bloodstream. This immunity is based on the production of immunoglobulins. They are responsible for specific recognition and elimination of various antigens: they bind and remove from the host invading organisms/substances. Cell-mediated immunity is based on specific antigen recognition by T-lymphocytes. Due to this immunity, cells infected with a foreign agent, for example virus, are destroyed via a direct contact between an activated T-cell and target (infected) cell. Cell-mediated immunity is responsible for delayed-type hypersensitivity reactions, foreign graft rejections, resistance to many pathogenic microorganisms and tumor immunosurveillance. Natural Killer (NK) cells were originally described as a population of granular lymphocytes with the ability to lyse tumour and virally-infected target cells. They differ from classical lymphocytes being larger in size, containing more cytoplasm and having electron dense granules. The mechanism of killing is mediated through release of its granule contents (performs and granzymes) onto the surface of the infected cell. For example, in human NK cells comprise about 10-15% of all circulating lymphocytes. They produce cytokines and chemokines and can lyse target cells without prior sensitization being crucial components of the innate immune system. They also exert cell cytotoxicity by recognizing and including lysis of antibody-coated target cells and can be activated non-specifically by several cytokines via various receptors.

In birds, both T cell and B cell precursors originate in the bone marrow. Actual development of T cells takes place in the thymus and B cells develop in the bursa Fabricius. Interactions between T and B cells, as well as antigens presenting cells, are responsible for the development of specific immunity. These defense mechanisms of specific immunity are induced or stimulated by exposure to foreign substances, are specific for distinct macromolecules and increase in magnitude with each successive exposure to a particular macromolecule. In comparison to natural immunity, specific immunity takes longer to develop, but is highly specific antigens and has memory.

These two parts of the immune system work together through direct cell contact and through interactions involving such chemical mediators as cytokines and chemokines.




Marid Agribusiness Digest

Vol.17 *no.11 *April 2007





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