Role of Immune Modulators
Role of Immune Modulators in Replacement of Antibiotic Growth Promoters (AGPs)
Avian Immune System4
There are two parts to the avian immune system: unspecific, or innate immunity, and specific, or acquired immunity.
Innate immunity involves existing non selective defence mechanisms that birds use to resist disease. Attention needs to be given to enhancing these existing defence mechanisms when designing health management systems. The innate immune system includes the following:
- Genetic factors. Generations of genetic selection by breeders has given way to high levels of resistance to certain disease causing organisms in modern chickens. For example, some strains of chickens are genetically resistant to Marek’s disease.
- Body temperature. Chickens naturally have a higher body temperature (40°C –42°C) than mammals (35°C – 39°C). Most pathogens that affect mammals will therefore not be able to infect poultry. For example, cattle disease like black quarter and anthrax do not affect poultry.
- Anatomic features. A chicken's skin is covered with feathers that assist in preventing external injuries. Intact skin and mucous membranes form a physical barrier which prevents disease causing organisms from penetrating the chicken's body, and thus traps the organisms in the mucous membranes.
- Commensal bacteria. The intestinal tract of a healthy chicken contains a stable microbial population (microflora). The stable intestinal microflora assists in preventing pathogenic bacteria from invading the intestine.
- Cilia in the respiratory tract. The trachea of a chicken is lined with cilia. The role of the cilia is to remove debris and pathogenic organisms from the trachea. High levels of ammonia and dust can damage and overwhelm these cilia rendering the cilia ineffective.
- Maternal immunity. Antibodies from the hen are passed to the chick via the egg. These maternally derived antibodies will assist in protecting the growing chick until it can develop its own immunity.
The maintenance of good biosecurity and good farm management is vital in ensuring optimal functioning of these natural defence mechanism to keep chickens healthy and productive.
This part of the bird’s immune system must be developed by the bird in response to a challenge from a pathogen. The acquired immune system involves two type of responses: cell mediated and humoral. Cell mediated immunity involves the destruction of cells infected with a pathogen by T lymphocytes. Humoral immunity is directed at pathogens that are free within the blood or within the intestine, and is mediated by antibodies that are produced by B Lymphocytes. Acquired immunity is specific to specific pathogens and has a type of "memory." Re exposure to a pathogen will elicit a more rapid and effective response than was elicited at the first exposure. B and T Lymphocytes are derived from the same stem cells; B lymphocytes mature in the Bursa of Fabricius and T lymphocytes mature in the Thymus.
Acquired immunity is developed by exposure to bacteria and viruses in the bird’s environment and by exposure to viruses and bacteria in vaccines.
Gastro Intestinal Tract Immunity
As a result of the large surface area, the Gastro Intestinal Tract (GIT) is a major route of access of pathogens to the chicken’s body. The GIT therefore plays a very important role in maintaining the health of poultry. The GIT has to perform conflicting functions. The GIT needs to absorb nutrients without reacting to the foreign protein within the nutrients. The GIT must not react to commensal bacteria that are an important defence mechanism within the GIT but the GIT also needs to prevent access to pathogens. The GIT mucosal barrier and the gut-associated lymphoid tissue (GALT) are essential for protection from invasion by pathogenic organisms. Failure of these protection mechanism can adversely affect the health of the bird 12.
GALT plays a major role in maintaining gut health. Compromising gut health can lead to inflammation which, if not tightly controlled, can result in serious injury to the intestine. Compromised gut health will have a detrimental effect on the health of poultry that can result in increased risk of infections and growth retardation in poultry. Compromised gut health can result in Clostridium perfringens overgrowth resulting in necrotic enteritis. Antibiotic growth promoters (AGPs) have been shown to improve GIT health via controlling overgrowth of bacteria and thus controlling GIT inflammation. The emergence of bacterial antibiotic resistance has resulted in producers looking for alternatives to AGPs.10 & 12
In animals, immunomodulation is defined as the ability to regulate an immune response to enhance the production efficiency in food-producing animals and the substances that put forth this control are called immunomodulators. Immunomodulation refers to the manipulation of immune system and all therapeutic interruptions targeted for modulating the immune system. An immunomodulator may be defined as any biological or synthetic substance that can stimulate/suppress either innate, adaptive or both arms of the immune system. A potent immunomodulator has many advantages over antimicrobials. Since immunomodulators do not directly affect microbes, they may avoid the problem of rapid emergence of resistance.6
Commonly used immune modulators in poultry
1. Direct Fed Microbials (DFMs)/ Probiotics
DFMs have been used as prophylactic agents against enteric pathogens, presumably either by balancing microbiota, or by modulating host immunity, or both. Dietary Bacillus subtilis when used in broiler diets as a potential growth promoter, can provide beneficial effects on broiler performance and modulate host humoral and cellular immune responses to enteric pathogens.7
The stimulation of GALT by probiotics can be measured via the increase in the production of antibodies in the intestinal lumen, via the stimulation of macrophages and lymphocytes and also by enhanced production of γ-interferon.1 Regular and judicious use of probiotics has a striking effect on the immune system viz. stimulation of both humoral and cell mediated immunity through enhanced production of natural interferons/cytokines, increased macrophage, lymphocyte and natural killer (NK) cell activity, up regulated oxidative burst in heterophils, and increased immunoglobulin (IgG, IgM and IgA). Probiotics produce a gut-stabilising effect; and immune regulation, particularly through balanced control of pro-inflammatory and anti-inflammatory cytokines. Feeding probiotics could improve antibody titres against viral diseases like Newcastle disease (ND) and Infectious bursal disease (IBD). The use of probiotics increases the amount of IgA found in the intestinal lumen, the levels of IgA, IgM and IgG producing cells as well as the number of T cells in the cecal tonsils.5
Kemin’s proprietary organism Bacillus subtilis PB6 (CLOSTATTM) is found to have immunomodulatory activities. The prophylactic use of this organism helped in alleviating the intestinal inflammation in mice.2
Butyrate has been shown to have beneficial effect on the GIT, including trophic and anti-inflammatory effects on enterocytes 11. Scientific studies have indicated that dietary butyrate supplementation can improve the growth performance of chickens. It was also noticed that butyrate supplementation in the diet of broilers was especially beneficial in the presence of immune stress. The improvement in growth performance observed in poultry supplemented with butyrate can in part be attributed to the immune modulatory effect of butyrate 12. Kemin markets ButiPEARLTM an encapsulated source of Calcium Butyrate.
3. Essential Oils
Essential oils (EO) have shown to have marked antibacterial effect which is the main reason for the use of essential oils in poultry nutrition. Secondary effects of EO on animal performance include the production and secretion of endogenous digestive enzymes and modulation of the immune system and EO also poses antifungal and antiviral activity3. Carvacrol a commonly used essential oil has anti-inflammatory properties. The anti-inflammatory properties of carvacrol include the reduction in the production of inflammatory mediators, such as IL-1b and prostanoids, possibly through the induction of IL-10 release.8 Kemin’s FormaXOL and RepaXOL is a combination of highly concentrated Carvacrol and Thymol.
Prebiotics are non-digestible feed ingredients that are metabolized by specific members of intestinal microbiota and provide health benefits for the host including selectively enhancing the growth of beneficial gut bacteria to the detriment of pathogenic enteric bacteria 9.
CLOSTAT:V20842 Act36 of 1947, ButiPEARL: V22483 Act36 of 1947, FormaXOL: V22487 Act36 of 1947, RepaXOL: V22484 Act36 of 1947
- Ajit Singh Yadav, Exploring alternatives to antibiotics as health promoting agents in poultry – A review, http://jebas.org/Jou.Exp.Bio.Agr.Sci/Spl.Issue.BPADDT/10.18006_2016.4(3S).368.383.pdf
- Foligné B, Spores from two distinct colony types of the strain Bacillus subtilis PB6 substantiate anti-inflammatory probiotic effects in mice. Clin Nutr. 2012 Dec;31(6):987-94
- G. Lorenzoni , Poultry Diseases Influenced by Gastrointestinal Health - Traditional Treatments and Innovative Solutions, Nottingham University Press
- Jacquie Jacob, Avian Immune System articles.extension.org/pages/65345/avian-immune-system
- K. Dhama, Applications of Probiotics in Poultry: Enhancing Immunity and Beneficial Effects on Production Performances and Health - A Review, Journal of Immunology and Immunopathology Vol.13, No.1, January-June 2011: 1-19
- Kuldeep Dhama, Effect of Immunomodulation and Immunomodulatory Agents on Health with Some Bioactive Principles, Modes of Action and Potent Biomedical Applications, International Journal of Pharmacology 11 (4): 253-290, 2015
- Kyung-Woo Lee, Immune modulation by Bacillus subtilis-based direct-fed microbials in commercial broiler chickens; Animal Feed Science and Technology 200 (2015) 76–85
- Milena da Silva Lima, Anti-inflammatory effects of carvacrol: Evidence for a key role of interleukin-10; European Journal of Pharmacology 699 (2013) 112–117
- Mohsen Pourabedin and Xin Zhao, Prebiotics and gut microbiota in chickens, FEMS Microbiology Letters, 362, 2015, fnv122
- Theo Niewold, Gut Health, Intestinal Innate Immunity and Performance, 25th Australian Poultry Science Symposium (APSS) 2014
- Yukihiro Furusawa, Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells, doi:10.1038/nature12721
- W.H. ZHANG, Sodium butyrate maintains growth performance by regulating the immune response in broiler chickens; British Poultry Science Volume 52, Number 3 (June 2011), pp. 292—301
- D. R. Korver, Overview of the Immune Dynamics of the Digestive System, 2006 J. Appl. Poult. Res. 15:123–135