Journal of Microbiology and Genetics (ISSN: 2574-7371)

Article / mini review

"Cytokines as Effective Elements of the Avian Immune System"

Hanan Al-Khalaifah*, A. Al-Nasser

Environment and Life sciences Research Center, Kuwait Institute for Scientific Research, Safat, Kuwait

*Corresponding author: Hanan Al-Khalifa, Environment and Life sciences Research Center, Kuwait Institute for Scientific Research, P.O. Box 24885, 13109 Safat, Kuwait. Email: hkhalifa@sr.edu.kwu

Received date: 18 September 2018; Accepted Date: 05October 2018; Published Date: 12 October 2018

1.      Abstract

The immune system is generally divided into two main branches: the adaptive (specific) and the innate (non-specific) immune responses. Components of the immune system (i.e. adaptive and innate) include T-lymphocytes, B-lymphocytes, macrophages, Natural Killer (NK) cells, heterophils, basophils, diverse humoral communication factors such as eicosanoids and cytokines (e.g., interleukins, interferons, tumour necrosis factor) and effector molecules (e.g. immunoglobulins, complement, lysozymes, nitric oxide). Additionally, some tissues in the body are dedicated to support the immune system such as dendritic, reticular and stromal cells. Regulation, interaction, and communication between various elements of the specific and the innate immune responses result into birds possessing a highly sophisticated immune system, capable of protecting against invading pathogens.

In addition to the various types of cells that are involved in the innate immunity, there are soluble physiological elements that play a role in defending the host from invading foreign substances and pathogens. Cellular and soluble elements coordinate in a sophisticated network of interactions to mount an effective innate and adaptive immune responses capable of eliminating foreign antigens. These soluble physiological elements include: complement proteins, lysozyme, acute phase proteins, and cytokines. The current paper sheds light on cytokines as effective elements of the avian immune system.

2.      Keywords: Avian; Cytokines; Immune System; Lysozymes

1.      Introduction

The innate immunity reflects the inherent non-specific response that provides the first line of defence, just after the exposure to a pathogen. It is characterised by broad specificity where cells and other components of the immune system identify classes of molecules and pathogens, rather than specific antigens. Anatomic barriers, phagocytic cells, physiological components, and inflammation are the main elements of the innate immune response.In common with other animals, birds have evolved an immune system that can respond to and protecting against pathogens such as Escherichia coli, Salmonellasp. Pasteurellamultocida, coronavirus, and avian Influenza A virus [1-3].

There are several white blood cells that play a role in the non-specific avian immune response. Most of these cells are capable of engulfing extracellular particles by phagocytosis, endocytosis or receptor- mediated endocytosis. Others can produce substances that play a role in the inflammation response and allergic reaction. For example, activated eosinophils can produce lipids and proteins that have antiviral activity and induce degranulation of other cells such as mast cells and basophils[4,5].

The complement system is an important element of the innate immune system that also triggers the adaptive immunity. It was reported by Pandit et al. [6] and Skeeles, et al. [7] that the complement system can provide protection against viruses in the early innate defence in birds. Similar haemolytic complement activity was also reported against parasites and bacteria in birds[8-10].

2.      Complement System

Complement components are proteins and glycoproteins that are mainly synthesized in the liver. Other cells such as the tissue macrophages and the blood monocytes are involved in the complement production. These proteins are circulating in the blood in an inactive form. Once activated upon exposure to an antigen, they enter an enzymatic biochemical cascade that helps in the elimination of antigens by lysis of cells, opsonisation, binding to specific complement receptors on cells of the immune system, and/or immune clearance of immune complexes [5,11,12].

There are three different pathways by which the complement cascade is activated, namely the classical pathway, the alternative pathway and the mannan-binding lectin pathway. The classical pathway is antibody-dependent, so it is more related to the adaptive immunity. It is initiated by antigen-antibody binding to form immune complexes or when an antibody binds to an antigen on the surface of a pathogen. Activation of complement component 1, often simply called C1 (a protein of the immune system) then occurs when it binds to such antibodies of type IgM and some classes of type IgG. On the other hand, the alternative and the mannan-binding lectin pathways are more related to the innate immunity because they are antibody-independent. The former is initiated by complement component 3 (C3 complement), activation upon exposure of foreign substances on the cell wall of pathogens like bacteria, while mannan-binding lectin pathway is activated when a lectin binds to a mannose residue on the cell wall of pathogens such as Salmonella. This lectin is a serum acute phase protein that is produced because of the inflammatory response in the site of inflammation. The Membrane Attack Complex (MAC) is produced upon activation of the complement system in the three pathways. This complex mediates lysis of the cell wall of bacterial pathogens. There are serum proteins as well as proteins on the surface of self-cells that control the activity of the complement system to ensure that host cells are not attacked [5-8,10,13-19].

In addition to playing a role in the innate immune response, the complement system plays a role in activation and regulation of the adaptive immune response[11,13,14]. Studying the different avian haplotypes that are related to immunocompetence has shown that the complement levels are genetically inherited, and that lower disease resistance is associated with lower levels of complement components [11,13,20,21].

2.1.  Lysozyme

Lysozyme is a hydrolytic protein that destroys the bacterial cell wall by digesting the sugar mucopeptides, causing lysis of the pathogen. It is present in mucosal secretions such as saliva and tears [22-27]. Burns [28] reported the presence of lysozyme activity against Micrococcus lysodeikticusin the poultry serum, saliva, gut contents, faecal washes, urine and in tears. In the same study, lysozyme was also found to be present in the mucus-producing cells of the alimentary tract as well as the secretions of the Harderian gland and the lacrymal gland. Moreover, the secretory cells in the lumen of the tympanic cavity of the middle ear epithelium in the chicken Gallus galluswas shown to secret lysozymes[29,30]. Interestingly, Immunoglobulin A (IgA) was noticed in several tissues that contained lysozyme. This would suggest a role of IgA in the lysozyme activity against bacteria [22,25,27,28,30,31].

2.2.  Acute Phase Proteins

Acute Phase Proteins (APPs) are a group of serum proteins, the concentrations of which are significantly affected by infection and inflammatory status[32-34]. The production of APPs is influenced by the pro-inflammatory cytokines, infectious agents and injury. Accordingly, these proteins can be used as biomarkers for infectious diseases and inflammation [33,35-38].

2.3.  Cytokines

These are low molecular weight proteins secreted by a wide range of cells, including leukocytes, and are known to regulate and control type and intensity of the immune response as well as other biological functions. These proteins are produced immediately after infection or vaccination and act by binding with high affinity to specific receptors on the cell membrane of the host or foreign body and inducing an intracellular signalling pathway which results in either stimulation or inhibition of a physiological response. Cytokines are considered to be important elements in both the innate and the adaptive immunity that act by stimulating an interactive network of biological responses, including effects on other cells and on cytokines themselves [5,39-44].

The progress in detection and discovery of the avian cytokine genes repertoire gave a great opportunity to categorise and determine the function of avian cytokines[45]. Classifying cytokines is really a debating issue as they could be classified according to their biological effect, the cells producing them or the cells that they affect. Most often, classification of cytokines is based upon the effect or activity they drive. Accordingly, they can be classified into: pro-inflammatory cytokines, interferons, and colony stimulating factors[46-48].

Pro-inflammatory cytokines are cytokines that are produced by both phagocytic and non-immune cells at the site of inflammation or acute phase response due to disease, infection or tissue trauma.The acute inflammatory reaction initiates the production of cytokines that include: interleukin-1 (IL-1β), IL-6, IL-12 and Tumour Necrosis Factor-alpha (TNF-α). These cytokines act on the site of inflammation by increasing permeability of the vessels and by inducing the production of another cytokine called IL-8. This is a chemokine that stimulates chemotaxis [39,46,49-51].IL-1β is known to be an active pro-inflammatory cytokine that induces an acute inflammatory response by activating cells like macrophages and T-lymphocytes to produce other kinds of cytokines and chemokines[52]. Laurent, et al. [53]have reported that expression ofIL-1βmRNA in the gut of chickens was increased 80-fold seven days after infection with Eimeriatenella. IL-6 is known to be a multifunctional cytokine that activates B- and T- lymphocytes and induces macrophage haematopoiesis[50,54-58]. In addition, IL-6 has a role in regulating B-cell differentiation to the effector antibody producing plasma cells [59]. In vitroIL-1β and IL-6activity was increased in macrophage supernatants from birds infected with poultry enteritis and mortality syndrome[60], indicating their role in a bird’s infection. IL-8 is a chemokine that attracts and induces the accumulation of neutrophils in the site of inflammation. The term chemokine refers to a specific class of cytokines that mediates chemoattraction (i.e. chemotaxis between cells). This accumulation usually causes damage to the tissues. Also, IL-8 attracts peripheral blood monocytes and fibroblasts[40,41,47,61,62]. In addition, there is evidence of the presence of an avian homologue of the mammalian TNF-α which is secreted by macrophages, T-lymophocytes and NK cells. TNF-α plays an important role in the systemic inflammation, cytotoxicity to tumour cells, and apoptosis. Fever and septic shock are usually associated with TNF-α activity [62-64].

Other chicken cytokines that are believed to be involved in the inflammatory reactions are IL-15 and IL-16. IL-15 has a role in the cell-mediated immune response by activating T- and B- lymphocytes as well as NK cells. Also, IL-15 is known to play a role in heterophil activation[39,46,55,65]. Kaiser [59] has proposed the role of IL-15 in inducing autoimmune disease in chickens as a result of increased immunity that results in inflammation and damage. IL-16 was also cloned in chickens, this cytokine is known to play a role in attracting TH-lymphocytes, monocytes and eosinophils. Interestingly, Concanavalin A (conA)-stimulated splenic TH cells in adult chickens, immunized with Salmonella enteritidis, can produce a lymphokine called SalmonellaImmune Lymphokine (SILK). Prophylactic treatment with this lymphokine can provide protection against Salmonella enteritidisin one day old chicks[66,67].Crippen et al. [66] also reported that the rP33 domain of SILK is an active part that is capable of inducingin vitroantimicrobial effects of heterophils against Salmonella enteritidisby triggering degranulation of these lymphocytes.

Interferons (IFN) are a group of cytokines that are produced by leukocytes and viral-infected cells because of stimulation of the immune system by viral infection and inflammation reactions.Knowledge about avian interferons was lacking molecular analysis of these proteins. Recently, purification, functional characterisation, cloning and sequencing of genes that encode chicken interferons from the cDNA library has proved the presence of two types of interferons in chickens[68-76]. These are: IFN-α/β (type I) that is produced by mononuclear cells and fibroblasts upon viral infection and IFN- γ (type II) that is produced by T-cells (TH1) and NK cells upon stimulation by an immunogenic factor. IFN-α/β increase level of class I -MHC molecules on the surface of viral infected cells so that these cells are identified for cytotoxic T-cells (Tc). Also, these interferons have a role in affecting tumour cells by slowing down the cell cycle[41,55,59,62,77]. On the other hand,IFN-γ is more known in modulation of the immune response and more involved in the inflammatory response of chickens, it is also known to play a role in macrophage activation[41,45,55,62,78-89]. Neutralization of the immunological effects of IFN- γ has been accomplished by Monoclonal Antibody (mAb) techniques[90]. In addition to IFN-γ, T-cells (TH1) produce IL-2. This is a well identified cytokine in chickens and turkeys by cloning of genes encoding this interleukin from the cDNA library. IL-2 is known to have a role in the cell-mediated immune response as well as in macrophage activation[40,91]. Furthermore, cDNA was cloned for chickens and turkeys IL-18. Like IL-2 and IFN-γ, IL-18 develops a cell-mediated immune response (TH1-type response) and activates macrophages. It also stimulates the production of IFN-γ. It is reported that IL-18 is produced by Kupffer cells (liver macrophages)[59,62,92,93].

In addition, Growth Factors are a family of cytokines that have been shown to play a role in the development of immune cells. In birds, these include granulocyte colony stimulating factor (G-CSF), macrophage colony stimulating factor (M-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), transforming growth factor- β (TGF-β) and chicken myelomonocytic growth factor (cMGF). McGruder et al. [94] has reported thatin vitroobservations ofchicken cytokine cultures indicated the biological activities of G-CSF and M-CSF in supporting the proliferation and differentiation of macrophages and granulocytes and the activity of GM-CSF in supporting differentiation of myeloid precursors to granulocytes and macrophages. On the other hand, TGF-β is a growth factor that regulates the development of T-lymphocytes and has a role in the anti-inflammatory response[94,95,96]. The anti-inflammatory activity of TGF-βwas reported by Choi, et al. [97] when he showed that m-RNA expression of this cytokine was increased in caecal tonsil, spleen and duodenum after microbial infection in chickens. cMGF stimulates avian myeloid cells differentiation into mononuclear cells. Moreover, there are other growth factors that are described in chickens. Among these are: Fibroblasts Growth Factors (FGF), Platelet-Derived Growth Factor (PDGF) and Stem Cell Factor (SCF). PDGF and SCF have a role in healing from injury and in differentiation of stem cells, respectively[98,99].

Interestingly, modulation of the immune system could be achieved using purely cloned cytokines or cytokine adjuvants. This has many applications in the field of experimental and clinical research in poultry. For example, cytokines are used in neonatal poultry to support and accelerate the onset of the immune system.In vivoinjection of recombinantcMGF avian cytokine has shown that this cytokine can increase the number of bone marrow progenitor cells that will be differentiated to immune cells in newly hatched chicks[100].Lowenthal et al. [101] have reported that IFN- γ is an effective vaccine adjuvant in birds injected withsheep red blood cells. This cytokine considerably elevates the immune response and triggers more IgG response, compared with the control birds. Also, IL-18 as an adjuvant in case of Salmonellainfection of birds was observed to considerably increase TH1-type response, IFN- γ and macrophage activation.Taken together, cytokines, along with other component of the immune system, play critical role in the immune response.



1.                   Leitner G, Uni Z, Cahaner A, Gutman M, Heller ED (1992) Replicated Divergent Selection of Broiler Chickens for High or Low Early Antibody Response To Escherichia Coli Vaccination. Poult Sci 71: 27-37.

2.                   Yunis R, Ben-David A, Heller ED, Cahaner A (2002) Antibody Responses and Morbidity Following Infection with Infectious Bronchitis Virus and Challenge with Escherichia Coli, In Lines Divergently Selected On Antibody Response. Poultry Science 81: 149-159.

3.                   Kramer J, Visscher AH, Wagenaar JA, Cornelissen JBJW, Jeurissen SHM (2003) Comparison of natural resistance in seven genetic groups of meat-type chicken. British Poultry Science 44: 577-585.

4.                   Koenen ME, Boonstra-Blom AG, Jeurissen SHM (2002) Immunological differences between layer- and broiler-type chickens. Veterinary Immunology and Immunopathology 89: 47-56.

5.                   Goldsby RA, Kindt T, OsborneB,Kuby J (2003) Immunology, 5th edition, New York, W.H. Freeman.

6.                   Pandit F, Mishra SC, Jaiswal TN (1997) Effect of Glucosaminyl Muramyl Dipeptide in Haemolytic Complement Activity Against Fowl Box. Indian Veterinary Medicine Journal 21: 265-268.

7.                   Skeeles JK, Lukert PD, De Buyssher EV, Fletcher OJ, Brown J (1979) Infectious Bursal Viral Infections. Ii. The Relationship of Age, Complement Levels, Virus-Neutralizing Antibody, Clotting and Lesions. Avian Diseases 23: 107-117.

8.                   Touray MG, Seeley DC, Jr, Miller LH (1994) Plasmodium Gallinaceum: Differential Lysis of Two Developmental Stages of Malaria Sporozoites by The Alternative Pathway of Complement. Experimental Parasitology 78: 294-301.

9.                   Saxena VK, Nath M, Singh H, Roy AKD (2000) Immunocompetence Based Genetic Divergence Among Guinea Fowl Varieties, Desi Fowl and Commercial Broilers. Indian Journal of Poultry Science 35: 236-239.

10.                Nolan LK, Giddings CW, Horne SM, Doetkott C, Gibbs PS, et al. (2002) Complement Resistance, As Determined by Viable Count and Flow Cytometric Methods, And Its Association with The Presence of Iss and The Virulence of Avian Escherichia Coli. Avian Diseases 46: 386-392.

11.                Bacon LD, Witter RL (1993) Influence of B-haplotype on the relative efficacy of Marek's disease vaccines of different serotypes. Avian Diseases 37: 53-59.

12.                Powell PC (1983) Fundamental Concepts of Avian Immunology. [French]. Point Veterinaire 14: 57-66.

13.                Dorny P, Baelmans R, Parmentier HK, Nieuwland MGB, Demey F, et al. (2005) Serum haemolytic complement levels in German Dahlem Red chickens are affected by three major genes (naked neck, dwarf, frizzled) of tropical interest. Tropical Animal Health and Production 37: 1-9.

14.                Baelmans R, Parmentier HK, Udo HMJ, Dorny P, Demey F (2004) Different serum haemolytic complement levels in indigenous chickens from Benin, Bolivia, Cameroon, India and Tanzania. Tropical Animal Health and Production 36: 731-742.

15.                Toivanen A, Toivanen P (1987) Avian Immunology: Basis and Practice. Volume I. Volume Ii, Avian Immunology: Basis and Practice. Volume I. Volume Ii. Crc Press Inc Boca Raton Fl 33431.

16.                Dietert RR, Lamont SJ (1994) Avian immunology: From fundamental immune mechanisms to the integrative management of poultry. Poultry Science 73: 975-978.

17.                Lydyard PM, Whelan A, Fanger MW (2000) Instant Notes in Immunology, Oxford, Bios.

18.                Male DK (1996) Advanced Immunology, London, Mosby.

19.                Frank SA (2002) Immunology and evolution of infectious disease. Princeton University Press. New Jersey, USA.

20.                Bacon LD, Witter RL (1991) Influence of B-haplotype on Marek's disease (MD) depends on the strain of MD herpesvirus and HVT vaccination in 15.B congenic chickens.  Poultry Science 70: 1-9.

21.                Bacon LD, Witter RL (1992) Influence of turkey herpesvirus vaccination on the B-haplotype effect on Marek's disease resistance in 15.B-congenic chickens. Avian Diseases 36: 378-385.

22.                Zheng Q, Ye X, Bai J, Wu R, Lao H, et al. (2005) Expression of Penaeus Monodon Lysozyme Gene in Prokaryocyte System and Evaluation of Its Lytic Activity. Journal of Fisheries of China 29: 20-24.

23.                Jarosz J (1998) Active resistance of entomophagous rhabditid Heterorhabditisbacteriophora to insect immunity. Parasitology 117: 201-208.

24.                Smith-Gill SJ, Sercarz EE, National Cancer Institute (1989) The Immune Response to Structurally Defined Proteins: The Lysozyme Model: Proceedings of A Workshop Sponsored by The National Cancer Institute of Nih, Held at The Mary Woodard Lasker Center for Health Research and Education, Bethesda, Md, June 13-15. Schenectady, Ny, Adenine Press.

25.                Fernie-King BA, Seilly DJ, Davies A, Lachmann PJ (2002) Streptococcal Inhibitor of Complement Inhibits Two Additional Components of the Mucosal Innate Immune System: Secretory Leukocyte Proteinase Inhibitor and Lysozyme Infect Immun 70: 4908-4916.

26.                Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, et al. (1996) Antibacterial activity of antileukoprotease. Infect Immun 64: 4520-4524.

27.                Imoto T, N JL, T NAC, C PD, A RJ (1972) Vertebrate lysozymes, New York, N Y, Academic Press 1972.

28.                Burns RB (1979) Lysozyme in chicken secretions and tissues. Journal of Anatomy 129: 194.

29.                Lim, D. 1976. Functional Morphology of The Mucosa of The Middle Ear And Eustachian Tube. Annals of Otology 25: 36-43.

30.                Giannessi F, Ruffoli R (1993) Fine structure of the middle ear epithelium in the chicken (Gallus gallus). J Anat 183: 103-111.

31.                Hikima JI, Minagawa S, Hirono I, Aoki T (2001) Molecular cloning, expression and evolution of the Japanese flounder goose-type lysozyme gene, and the lytic activity of its recombinant protein. Biochimica et Biophysica Acta, Gene Structure and Expression 1520: 35-44.

32.                Gabay C, Kushner I (1999) Acute phase proteins and other systemic response to inflammation. New Engl J Med 340: 448-454.

33.                Kushner I, Mackiewicz A, Baumann H (1993) The acute phase response: an overview. In: Mackiewicz A, Kushner I, Baumann H, (ed.). Acute phase proteins: molecular biology, biochemistry, and clinical applications. Boca Raton. CRC Press, Florida, USA. 704.

34.                Petersen HH, Nielsen JP, Heegaard PMH (2004) Application of Acute Phase Protein Measurements in Veterinary Clinical Chemistry. Veterinary Research 35: 163-187.

35.                Eckersall PD (2004) The time is right for acute phase protein assays. Veterinary Journal. London: Bailliere Tindall Ltd 2004.

36.                Murata H, Shimada N, Yoshioka M (2004) Current Research On Acute Phase Proteins in Veterinary Diagnosis: An Overview. The Veterinary Journal 168: 28-40.

37.                Xie H, Newberry L, Clark FD, Huff WE, Huff GR, et al. (2002) Changes in Serum Ovotransferrin Levels in Chickens with Experimentally-Induced Inflammation and Diseases. Avian Dis 46: 122-131.

38.                Reid M, Badaloo A, Forrester T, Morlese JF, Heird WC, et al. (2002) The Acute-Phase Protein Response to Infection in Edematous and Nonedematous Protein-Energy Malnutrition. American Journal of Clinical Nutrition 76: 1409-1415.

39.                Klasing KC (1994) Avian leukocytic cytokines. Poultry Science 73: 1035-1043..

40.                Ahmed JS (2002) The role of cytokines in immunity and immunopathogenesis of piroplasmosis. Parasitology Research 88: 48-50.

41.                Lowenthal JW, Lambrecht B, Berg TPVD, Andrew ME, Strom ADG, et al. (2000) Avian Cytokines - The Natural Approach to Therapeutics. Developmental and Comparative Immunology 24: 355-365.

42.                Wood P (2001) Understanding Immunology, Harlow, Pearson 2001.

43.                Abbas AK, Lichtman AH (2003) Cellular and molecular immunology, Philadelphia, Saunders 2003.

44.                Roitt IM, Jonathan B, Male DK (2001) Immunology, Edinburgh, Mosby 2001.

45.                Zhou H, Buitenhuis AJ, Weigend S, Lamont SJ (2001) Candidate Gene Promoter Polymorphisms and Antibody Response Kinetics in Chickens: Interferon- Gamma, Interleukin-2, And Immunoglobulin Light Chain. Poultry Science 80: 1679-1689.

46.                Kogut MH (2000. Cytokines and prevention of infectious diseases in poultry: a review. Avian Pathology 29: 395-404.

47.                Kaiser P (1996) Avian Cytokines. In: Davison TF, TRM, Payne LN (ed.). Poultry immunology. Carfax Publishing Co., Abingdon, UK 1996: 83-114.

48.                Hilton LS, Bean AGD, Lowenthal JW (2002) The emerging role of avian cytokines as immunotherapeutics and vaccine adjuvants. Veterinary Immunology and Immunopathology 85: 119-128.

49.                Johnson MA, Pooley C, Lowenthal JW (2000) Delivery of avian cytokines by adenovirus vectors. Developmental and Comparative Immunology 24: 343-354.

50.                Allison AC, Eugui EM (1995) Induction of cytokine formation by bacteria and thier products, Washingto, Dc, ASM Press 1995.

51.                Junk HC, Eckmann L, Yang SK, Panja A, Firrer J, et al. (1995) A distinct array of poinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. Journal of Clinical Investigation 95: 55-65.

52.                Weining KC, Sick C, Kaspers B, Staeheli P (1998) A Chicken Homologue of Mammalian Interleukin-1b: Cdna Cloning and Purification of Active Recombinant Protein. European Journal of Biochemistry 258: 994-1000.

53.                Laurent F, Mancassola R, Lacroix S, Menezes R, Naciri M (2001) Analysis of Chicken Mucosal Immune Response to EimeriaTenella And Eimeria Maxima Infection by Quantitative Reverse Transcription-Pcr. Infection and Immunity 69: 2527-2534.

54.                Hirano T (1998) Interleukin 6, San Diego, Academic Press 1998.

55.                Schat, K. A. & Kaiser, P. 1997. Avian Cytokines. Cytokines in Veterinary Medicine. Cab International Wallingford Uk: 1997: 289-300.

56.                Schoolmeester MLD, Little MC, Rollins BJ, Else KJ (2003) Absence of Cc Chemokine Ligand 2 Results in an Altered Th1/Th2 Cytokine Balance and Failure to Expel TrichurisMuris Infection. Journal of Immunology 170: 4693-4700.

57.                Yang Z, Petitte JN (1994) Use of Avian Cytokines in Mammalian Embryonic Stem Cell Culture. Poultry Science 73: 965-974.

58.                Kaiser P, Bumstead N, Goodchild M, Atkinson D, Rothwell L (2001) Characterizing chicken cytokine genes - IL-1b, IL-6, IL-15 and IL-18. In: Schat KA (ed.). 7th Avian Immunology Research Group. American Association of Avian Pathologists. Pennsylvania 2001: 27-32.

59.                Kaiser P, Rothwell L, Galyov EE, Barrow PA, Burnside J, et al. (2000) Differential cytokine expression in avian cells in response to invasion by Salmonella typhimurium, Salmonella enteritidis and Salmonella gallinarum. Microbiology (Reading) 146: 3217-3226.

60.                Heggen CL, Qureshi M, Edens FW, Barnes HJ (2000) Alterations in macrophage-produced cytokines and nitrite associated with poult enteritis and mortality syndrome. Avian Dis 44: 59-65.

61.                Barker KA, Hampe A, Stoeckle MY, Hanafusa H (1993) Transformation-associated cytokine 9E3/CEF4 is chemotactic for chicken peripheral blood mononuclear cells. Journal of Virology 67: 3528-3533.

62.                Wigley P, Kaiser P (2003) Avian Cytokines in Health and Disease. RevistaBrasileira De CienciaAvicola 5: 1-14.

63.                Gulcubuk A, Altunatmaz K, Sonmez K, Haktanir-Yatkin D, Uzun H, et al. (2006) Effects of curcumin on tumour necrosis factor-alpha and interleukin-6 in the late phase of experimental acute pancreatitis. J Vet Med APhysiolPatholClin Med 53: 49-54.

64.                Qureshi MA (2003) Avian Macrophage and Immune Response: An Overview. Poultry Science 82: 691-698.

65.                Poli G, Zanella A, Dall'ara P, Bonizzi L (2000) Avian Immunology: The Old and The New. [Italian]. SelezioneVeterinaria 8: 535-560.

66.                Crippen TL, Bischoff KM, Lowry VK, Kogut MH (2003) rP33 activates bacterial killing by chicken peripheral blood heterophils. Journal of Food Protection 66: 787-792.

67.                Mcgruder E, Ray P, Tellez G, Kogut MH, Corrier DE, et al. (1993) Salmonella Enteriditis (Se) Immune Cytokines: Effect On Increased Resistance to See Organ Invasion in Day-Old Leghorn Chicks. Poult Sci 72: 2264-2271.

68.                Puehler F, Schwarz H, Waidner B, Kalinowski J, Kaspers B, et al. (2003) An Interferon- Gamma -Binding Protein of Novel Structure Encoded by The Fowlpox Virus. Journal of Biological Chemistry 278: 6905-6911.

69.                Orringer DA, Staeheli P, Marsh JA (2002) The Effects of Thymulin On Macrophage Responsiveness to Interferon- Gamma. Developmental and Comparative Immunology 26: 95-102.

70.                Liu S, Chen H, Kong X, Zhang B, Ma Y, et al. (2000) Cloning and Sequencing of Chicken Interferon- Gamma. [Chinese]. Chinese Journal of Veterinary Science 20: 228-230.

71.                Ellis MN, Eidson CS, Brown J, Kleven SH (1983) Studies on interferon induction and interferon sensitivity of avian reoviruses. Avian Diseases, 27, 927-936.

72.                Holmes HC, Darbyshire JH (1978) Induction of chicken interferon by avian infectious bronchitis virus. Research in Veterinary Science 25: 178-181.

73.                Lillehoj HS, Kaspers B, Jenkins MC, Lillehoj EP (1992) Avian Interferon and Interleukin-2. A Review by Comparison with Mammalian Homologues. Poultry Science Reviews 4: 67-85.

74.                Sekellick MJ, Ferrandino AF, Hopkins Da, Marcus PI (1994) Chicken Interferon Gene: Cloning, Expression, And Analysis. J Interferon Res 14: 71-79.

75.                Digby MR, Lowenthal JW (1995) Cloning and expression of the chicken interferon-gamma gene. J. Interferon Cytokine Res 15: 939-945.

76.                Weining KC, Schultz U, Munster U, Kaspers B, Staeheli P (1996) Biological Properties of Recombinant Chicken Interferon-Γ. Eur. J. Immunol 26: 2440-2447.

77.                Xia C, Liu J, Wu ZG, Lin CY, Wang M (2004) The Interferon- Alpha Genes from Three Chicken Lines and Its Effects On H9n2 Influenza Viruses. Animal Biotechnology 15: 77-88.

78.                Merlino PG, Marsh JA (2002) The Enhancement of Avian Nk Cell Cytotoxicity by Thymulin Is Not Mediated by The Regulation of Ifn-[Gamma] Production. Developmental & Comparative Immunology 26: 103-110.

79.                Dalloul RA, Lillehoj HS, Tamim NM, Shellem TA, Doerr JA (2005) Induction of local protective immunity to Eimeriaacervulina by a Lactobacillus-based probiotic. Comparative Immunology, Microbiology & Infectious Diseases 28: 351-361.

80.                Alcaide P, Jones TG, Lord GM, Glimcher LH, Hallgren J, et al. (2007) Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue. Journal of Experimental Medicine 204: 431-439.

81.                Babu US, Gaines DW, Lillehoj H, Raybourne RB (2006) Differential reactive oxygen and nitrogen production and clearance of Salmonella serovars by chicken and mouse macrophages. Developmental and Comparative Immunology 30: 942-953.

82.                Kogut MH, Pishko EJ, Kaspers B, Weining KC (2001) Modulation of functional activities of chicken heterophils by recombinant chicken IFN- gamma. Journal of Interferon & Cytokine Research 21: 85-92.

83.                Lowenthal JW, York JJ, O'neil TE, Rhodes S, Prowse SJ, et al. (1997) In Vivo Effects of Chicken Interferon- Gamma During Infection with Eimeria. Journal of Interferon & Cytokine Research 17: 551-558.

84.                Mo CW, Cao YC, Lim BL (2001) The in Vivo and in Vitro Effects of Chicken Interferon Alpha On Infectious Bursal Disease Virus and Newcastle Disease Virus Infection. Avian Diseases 45: 389-399.

85.                Schito ML, Chobotar B, Barta JR (1998) Cellular Dynamics and Cytokine Responses in Balb/C Mice Infected with EimeriaPapillata During Primary and Secondary Infections. Journal of Parasitology 84: 328-337.

86.                Ao Y, Ren T, Kong L (2006) Cloning and sequencing of interferon- gamma from chicken spleen cells. [Chinese]. Journal of South China Agricultural University 27: 86-89.

87.                Roh H, Sung H, Kwon H (2006) Effects of Dda, Cpg-Odn, And Plasmid-Encoded Chicken Ifn- Gamma On Protective Immunity by A Dna Vaccine Against Ibdv in Chickens. Journal of Veterinary Science 7: 361-368.

88.                Ye X, Cai J, Wu Z, Wang M (2005) The Histological Effects of Recombinant Chicken Interferon- Gamma on the Intestinal Mucosa of Broilers Immunized with EimeriaTenella Oocysts. [Chinese]. Chinese Journal of Veterinary Science 25: 484-486.

89.                Lambrecht B, Gonze M, Meulemans G, Berg TPVD (2004) Assessment of the Cell-Mediated Immune Response in Chickens By Detection Of Chicken Interferon- Gamma In Response to Mitogen And Recall Newcastle Disease Viral Antigen Stimulation. Avian Pathology 33: 343-350.

90.                Lawson S, Rothwell L, Lambrecht B, Howes K, Venugopal K, et al. (2001) Turkey and Chicken Interferon-G, Which Share High Sequence Identity, are Biologically Cross-Reactive. Developmental and Comparative Immunology, Microbiology & Infectious Diseases 25: 69-82.

91.                Sundick RS, Gill-Dixon CA (1997) Cloned Chicken Lymphokine Homologousto Both Mammalian Il-2 And Il-15. Journal Of Immunology 159: 720-725.

92.                ERF GF (2004) Cell-mediated immunity in poultry. Poultry Science 83: 580-590.

93.                Schneider K, Puehler F, Baeuerle D, Elvers S, Staeheli P, et al. (2000) cDNA Cloning of Biologically Active Chicken Interleukin- 18. Journal of Interferon Cytokine Research 20: 879-883.

94.                Mcgruder ED, Kogut MH, Corrier DE, Deloach JR, Hargis BM (1996) Characterization of Colonoy- Stimulating Activity in The Avian T Cell-Derived Factor, Salmonella Enteritidis- Immune Lymphokine. Research in Veterinary Science 60: 222-227.

95.                Jakowlew SB, Dillard PJ, Sporn MB, Roberts AB (1990) Complementary deoxyribonucleic acid cloning of an mRNA encoding transforming growth factor-b2 from chicken embryo chondrocytes. Growth Factors 2: 123-133.

96.                Burt DW, Jakowlew SB (1992) A new interpretation of a chicken transforming growth factor-b4 complementary DNA. Molecular Endocrinology 6: 989-992.

97.                Choi KD, Lillehoj HS, Zalenga DS (1999) Changes in local IFN-gamma and TGF-beta4 mRNA expression and intraepithelial lymphocytes following Eimeriaacervulina infection. Veterinary Immunolology and Immunopathology 71: 263-275.

98.                Horiuchi H, Inoue T, Furusawa S, Matsuda H (2001) Characterisation and expression of three forms of cDNA encoding chicken platelet-derived growth factor-A chain. Gene 272: 181-190.

99.                Metz T, Graf T, Leutz A (1991) Activation of Cmgf Expression Is a Critical Step in Avian Myeloid Leukemogenesis. Embo Journal 10: 837-844.

100.            Johnston PA, Liu H, O'connel T, Phelps P, Bland M, et al. (1995) Application in in ovo technology. Poultry Science 76: 165-178.

101.            Lowenthal JW, O’neil TE, Broadway M, Strom ADG, Digby M, et al. (1998) Co administration of Ifn-G Enhances Antibody Responses in Chickens. Journal of Interferon Cytokine Research 18: 617-622.

102

Citation: Al-Khalaifah H, Al-Nasser A (2018) Cytokines as Effective Elements of the Avian Immune System.J Microbiol Genet: JMGE-119. DOI: 10.29011/2574-7371.00019

free instagram followers instagram takipçi hilesi