Highlights of the article: Immunomodulation in birds have become as important as vaccination when it comes to prevention and fast recovery of birds from the diseased condition. Many times role of common nutrients like protein, energy, trace minerals, and vitamins are overlooked and different substances are used for immunomodulation. This article throws light on how modifying or reconsidering the nutrient requirements plays an important role in maintaining optimum immune response during the diseased condition. The major Phytobiotics and their mechanism of action in stimulating the immune system is also briefed in this article.
Immunomodulation
Manipulation of the immune system in any manner is defined as immunomodulation. Immunomodulation to accomplish an intended goal can be achieved by pharmacological means or by supplementing specific dietary nutrients or by supplementing herbs with specific phytochemicals or by a combination of any of these. It is also distinct that correcting nutritional deficiency also has a positive impact on immunomodulation. In this article role of different nutrients and herbs in building, modulating, and functioning of the immune system is briefed
Poultry Immune System & Function
Birds primarily prevent the entry of foreign organisms entering the body system by physical barriers like skin and mucosal membrane which consists lining of the digestive tract and respiratory tract. If these physical barriers fail to prevent the entry of foreign organisms, the immune system of birds recognizes these foreign organisms to initiate and manage the physiological response of the body to neutralize or eliminate them.
Poultry immune system primarily consists of two forms of immunity i.e. innate and acquired immunity. Innate immunity is a group of non-antigen-specific mechanisms meant to eliminate pathogens from the bird and is one of the earliest defence mechanisms against any infectious agent. If pathogens evade these barriers, pathogen-associated molecular patterns (PAMP) present on the organisms are recognized by the cells of the innate immune system through Toll-like receptors (TLR) and pattern recognition receptors. The localized activation of innate immunity can lead to inflammation, which involves the release of chemical signals that result in the recruitment of phagocytic cells like heterophils, dendritic cells, and macrophages which kill pathogens through the release of toxic chemicals such as reactive oxygen species and nitric oxide and through degranulation. The phagocytes also process and present antigen to cells of the acquired immune system. Other innate immune cells protect the host through activation of complement proteins, which targets pathogens for elimination by other cells, and the release of histamine and heparin from mast cells, which dilates blood vessels and further recruits phagocytic cells to the site of inflammation. Unlike the acquired immune response, the innate response recognizes generic patterns and non-self molecules and therefore does not exhibit immunologic memory. That is, a given pathogen will elicit a similar innate response each time it is encountered.
During an inflammatory response, the innate immune cells release signals that travel throughout the body both to recruit distant immune cells to the site of infection, and change the metabolism of them, an inflammatory response can be nutritionally costly. The body creates an inhospitable environment for the invading pathogen by increasing metabolic rate (fever), reducing feed intake, and initiating the preferential breakdown of skeletal muscle to support gluconeogenesis and synthesis of acute phase proteins in the liver.
Acquired immunity involves a specific, targeted response to the exposure and recognition of specific activators of immune function (antigens). The acquired immune response involves B cells that produce antibodies to antigen and cytotoxic T cells that actively kill specific invading pathogens. The acquired response results in immunologic memory with rapid response to the particular antigen every next time encountered. The acquired response typically has a minimal effect on the energy and nutrient requirements of the bird, because the nutrients used for antibody production and expansion of B cell populations is minimal, even then lesser nutrients reaching to birds will result in sub-optimal immunity status.
The Role of Nutrition
Nutrition is a critical determinant of immune responses and malnutrition is the most common cause of immunodeficiency worldwide (Kirk, 1997; Chandra, 1997). Optimum nutrition not just ensures the proper growth of the bird but it also ensures optimum immunity. Role of major nutrients in maintaining and building immunity is discussed below.
Role of Protein
Each and every cells in the bird’s body is majorly made of protein next to water, these cells combine together to form a tissue and tissues combine to form an organ. Similarly, all the enzymes, receptors, antibodies, chemical signals that recruit phagocytic cells, immunoglobulins are majorly made of proteins. The lower protein level in the feed not just effects the production of the birds but also weakens the immunity of the birds which predisposes the birds to many other diseases. Hence recommended protein level is needed to maintain the good performance of the birds and also to maintain optimum immunity and to reduce the incidence of diseases. Likewise increasing the protein percentage in feed in diseased condition increases the bird’s ability to fight against the infection by producing enough immune cells, antibodies, immunoglobulins and related substances.
Role of Energy
Energy is the currency used in the body for every reaction. Birds receiving all nutrients in optimum level, with sub-optimum level of energy will express less immune response compared to birds receiving optimal energy. Poultry confronted with disease or physiological stress, adapt to the situation by increasing the body temperature, producing the immune cells and related substances in order to survive. This process of adaptation is essential and requires energy. The energy for adaptation comes from the three energy-yielding nutrients: carbohydrates, lipids, and proteins. These nutrients are only available from the feed and the nutrient reserves in the animal. During the diseased condition, feed intake reduces, and also nutrients in the feed are not digested and absorbed efficiently, and the animal must rely on the nutrient reserves of the body. These reserves are very important and help to sustain the animal during the diseased condition. The muscle and liver carbohydrate stores (glycogen) are immediately called upon to furnish energy. Protein is broken down to yield the glucogenic and ketogenic amino acids which, following deamination, will supply the bird with energy. This energy from carbohydrates and protein allows the bird to maintain its health and survival. During stress, the vital functions of the brain, liver, heart, lungs, kidney, etc. cannot be compromised. Therefore, the less important functions such as egg production, reproduction, growth, and immunity are set aside to promote the vital functions of the body in stressful situations. Immediate survival is the number one priority in all animals when they are confronted with a severe stressor. The full genetic potential of the bird for growth and egg production is not expressed during stress.
The shift in metabolism during stress results in muscle protein and glycogen store depletion. During stress the consumption of water increases as a result of the necessity to clear the additional uric acid excretion arising from protein breakdown (Siegel and Van Kampen 1984). The increased water consumption is also probably necessary to maintain osmolality in the body fluids due to the increased sodium retention concurrent with the effects of corticosterone (Holmes and Phillips 1976).
Role of Micro Nutrients
The Micronutrients especially trace minerals and vitamins even though their requirement is very little in the feed,they play a major role in influencing the immune responses. Micronutrients’ role in oxidative stress management also protects birds from decreased performance, compromised immune function, and poor meat quality.
Trace Minerals
The major trace elements such as selenium, zinc, copper, manganese, etc. have immunomodulatory effects and thus influence susceptibility to variety of viral infections. Some trace elements inhibit viral replication in the host cells and therefore have antiviral activity. Many trace elements act as antioxidants, regulate the host immune response and also has ability to alter the viral genome.
Selenium is an essential mineral for organic function and antioxidant function in organism, it neutralizes the free radicals that are resultant from many factors but especially by immune response. Selenium is the cofactor for the enzyme glutathione peroxidase which catalyzes the removal of peroxides (oxidative reaction of free radicals) thus important in the prevention of oxidative stress. Diet is the major source of selenium. In poultry, the nutritional requirements for all nutrients and even selenium was normally calculated based on experimental trial using the healthy animal in very low challenge conditions. However, on practical way animals are continually exposed to different infection challenges, and intense vaccine programs increasing immune system activation. On this aspect, there are studies that show that immune activation response increases the necessity of nutrients, vitamins, and minerals.
Trace minerals especially selenium, zinc, copper, manganese, are required for proper immune development and function. Deficiencies can cause decreased antibody responses to vaccination. Multiple inorganic (sulfate and oxide) and organic sources (glycinates, methionine, and HMTBa-chelated) in poultry have demonstrated source differences in both immune development and response to antigenic challenge. Supplementation with the organic sources had clear advantage over inorganic sources in improved cellular or antibody responses to vaccination.
Vitamins
The most important vitamins that influence the immune system are Vitamin C and Vitamin E, their influence on the immune system is mainly due to the strong antioxidant effect. Vitamin C acts as pro-oxidant and reduces transition metals, such as cupric ions (Cu2+) to cuprous (Cu1+), and ferric ions (Fe3+) to ferrous (Fe2+) during the conversion of ascorbate to dehydro-ascorbate, which otherwise generate superoxide and other reactive oxygen species. Reduction of Fe3+ into Fe2+ improves iron assimilation by the intestine and thereby improves resistance to infections. A high concentration of Vitamin C is found in immune cells and is consumed readily during infections. It has been hypothesized Vitamin C to modulate the activities of phagocytes, the production of lymphocytes and cytokines, and the number of cell adhesion molecules in monocytes (Preedy et al., 2010).
Dietary vitamin E supplementation has an excellent immunomodulatory effect, The role of vitamin E for the functionality of the immune system has been extensively studied and it is based on the capability of vitamin E to prevent lipid peroxidation in membranes caused by lipid peroxyl radicals. Infectious diseases are an important factor in the production of free radicals for example as a consequence of macrophage function.
It was observed in several studies that 300 mg/kg vitamin E improved immune response and reduced mortality during the diseased conditions in poultry. Vitamin E also improved the immune response to vaccinations against Newcastle disease and promotes the phagocytic activity of macrophages, especially at the thymus level, and is involved in other immune mechanisms mediated by cells. Chicks from hens supplemented with vitamin E presented better humoral immunity and more active lymphocytes. Broilers infected with the virus causing malabsorption syndrome have suffered less damage and recovered sooner if the breeders had received a higher vitamin E supplementation.
Role of Phytobiotic or herbal extracts
Natural products and natural product derivatives has a traditional history as immunostimulants. Emerging evidence indicates that herbal plants exert their beneficial effects on the animal immune systems mostly by plant’s secondary metabolites. The immunostimulating activities of many of these components have been most widely studied in mouse, chicken, and human cell lines. These pharmacological effects are extensive ranging. For example, Ginsing with its steroidal saponine, has immune-stimulating properties including cytokine production (IL-2, IL6, TNF-a, and INF-y), macrophage activation, and lymphocyte activity (Tan and Vanitha, 2004). Conversely, flavonoids and terpenes from Ginkobilobacan mediate production and inflammatory cytokines (Li, 2000). Saponins have ability to stimulate the cell-mediated immune system, as well as to enhance antibody production and cytokines such as interleukins and interferons (Od a et.al., 2000).As against the stimulatory effects on specific immunity components, saponins have also been shown to be capable to put a stop to some non -specie immune reactions such as inflammation and monocyte proliferation (Delmaset al ., 2000; Yuietal .,2001).
Herbal plant polysaccharides also has been extensively studied for immunomodulatory effects, polysaccharides obtained from Chinese herbs, Astragalus root, Isatis root, Achyranthesrootand Chinese Yam improves antibody titer in vaccinated chicken. Phytosterol complex seems to target specific T -helper lymphocytes, the THl, and TH2 cells helping normalize their functioning, resulting in improved T-lymphocyte and natural killer cell activity. Furthermore, it has also been reported that Chinese herbs can stimulate the development of immune organs, such as the thymus and spleen as well as increase antibody production.
Conclusion:
Immune system cannot always rely on feed alone, but it is strongly supported by nutrients. Stressors like infectious challenges increase specific nutrient requirements, especially trace minerals like Selenium and Zinc and Vitamins like E and C which cannot be overlooked for better immune response. Herbal extracts with emerging evidence strongly indicate its major role in improving the immune response. Ensuring the crucial-nutrient requirement via supplementation along with the addition of specific herbal extracts ensures optimal immunity in birds.
Dr. Sathya Sooryan,
MVSc (Animal Nutrition), PGDOH
Product Manager, Vetogen Animal Health
