نگاهی به ایمونولوژی و واکسنهای تولید شده بر علیه تیلریوز گاوی
نویسنده = هاشمی فشارکی، دکتر سیدرضا
نویسنده = هاشمی فشارکی، رضا
تعداد مقالات: 1
1. نگاهی به ایمونولوژی و واکسنهای تولید شده بر علیه تیلریوز گاوی
دوره 27، شماره 2، تابستان 1393، صفحه 70-79
غلامرضا حبیبی؛ رضا هاشمی فشارکی
https://vj.areeo.ac.ir/article_100994.html
نگاهی به ایمونولوژی و واکسنهای تولید شده بر علیه تیلریوز گاوی
نویسندگان
1 استادیار موسسه تحقیقات واکسن و سرم سازی رازی،کرج
2 استاد موسسه تحقیقات واکسن و سرن سازی رازی،کرج
چکیده
تیلریوز گرمسیری بیماری انگلی ناشی از عفونت سلولهای میلوئیدی (متوسیت و ماکروفاژ ) و لمفوئیدی (لمفوسیت های B) به تک یاخته تیلریا آنولاتا بوده و در مرحله ای موجب آلودگی گلبول های قرمز خون نیز می شود. بیماری به وسیله کنه های جنس هیالوما منتقل شده و موجب عوارض گسترده ای از تب و کم خونی مختصر تا در گیری شدید اعضا لمفاوی بدن شده که می تواند در نژاد های حساس تلفاتینیز به همراه داشته باشد.با توجه به زندگی اجباری درون سلولی تک یاخته،سیستم ایمنی سلولی تنها بازوی موثر و محافظت کننده بدن در برابر تیلریا می باشدو ایمنی هومورال با تولید آنتی بادی های اختصاصی بر علیه اشکال اسپوروزوایت و مروزوایت های آزاد تنها قادر به کاهش قدرت عفونت زایی تیلریا می باشد.در مقابل،پاسخ ایمنی سلولی با فعالیت مجموعه ای از سلولهای T.NKC و ماکروفاژها و مشتقات آنها نظیر اینتر فرون گاما و TNF-a و بخصوص لمفوسیت های TCB8+ بخوبی در برابر شیزونت درون سلولی و سلول های آلوده به تیلریاپاسخ داده و موجب مرگ سلول های آلوده می شوند و با تولید خاطره ایمنی از بروز دوباره بیماری جلوگیری بعمل می آورند.البته نقش ایمنی طبیعی یا ذاتی همچون عوامل مکملو سلول های بیگانه خوار،به خصوص در مراحل اولیه عفونت از اهمیت خاصی برخوردار است.با توجه به حضور تیلریا و کنه ناقا بیماری در ایران و از طرفی وجود آلودگی در حیوانات اهلی و وحشی حامل تک یاخته که موجب بومی کردن بیماری شده اند تلاش هایی به منظور تولید واکسن در بسیاری از کشورها منجمله ایران صورت گرفته است.واکسن های نو ترکیب متنوعی بر علیه آنتی ژن های مربوط به مراحل مروزوایت و اسپوروزوایت بصورت آزمایشی تهیه شده است که در بررسی های صحرایی موفقیتهایی نسبی به همراه داشته اند.در حال حاضر واکسن زنده تخفیف حدت یافته تیلریا آنولاتا با فناوری کشت سلول های آلوده به شیزونت،قدرت محافظت کنندگیو پاسخ CTL قوی که دارد بر اساس تجربیات نزدیک به چهاردهه واکسیناسیون ملی در ایران و همچنین توصیه مراکز بین المللی نظیر OIEو FAO جهت ایمن سازی فعال گاوهای نژاد حساس و دو رگ بهترین گزینه می باشد.
عنوان مقاله [English]
A Glance at the Immunity and Vaccines against Tropical Theileriosis
نویسندگان [English]
- GR Habibi 1
- R Hashemi-Fesharki 2
1 Assistant Professor of Razi vaccine and serum research institute, Karaj
2 Professor of Razi vaccine and serum research institute, Karaj
چکیده [English]
Tropical Theileriosis is caused by infection of bovine myeloid mononuclear cells (Monocytes and macrophages) and lymphoid cells (B lymphocytes) as well as red blood cells by the protozoan parasite Theileria annulata. The disease is transmitted by ticks of the genus Hyalomma. The clinical signs of theileriosis in stages appear from mild symptoms to serious, including fever and anemia to severe involvement of lymphoid organs that can cause death. The cellular immunity is a main part of effective and protective against Theileria infection as an intracellular protozoan, but the humoral immunity with specific antibody had a neutralizing effect directed against extracellular sporozoites and merozoites. But the adaptive cell-mediated immunity is driven by activation of T cells, macrophages and natural killer cells (NKC) and their derivatives like as IFN-gamma and TNF-alpha can respond to schizont infected cells, particularly CD8+ T cells kill these infected cells and remain as memory T cells for the next parasite challenge. However, the innate immune response such as the complement system and phagocytic cells is believed to play an important role in protecting against bovine theileriosis especially during primary stage of Theileria infection. Iran as a sub-tropical region and the Hyalomma spp. vector for transmission of the Theileria annulata make the Theileriosis as an endemic disease. The circulating Theileria parasites in carrier domestic and wild ruminants, and tick infestation make Theileriosis more difficult to control, therefore many efforts have been performed for producing the efficient bovine theileriosis vaccine. The recombinant candidate vaccines have been produced based on the merozoite and sporozoite stages of the protozoa and examined experimentally with partially success in the field. However, live attenuated Theileria annulata with cell culture methodology induced a strong, antigen-specific CTL activity for recognition by schizont antigen-specific cytotoxic T lymphocytes. Based on nearly four decades of our practical experiences on vaccination in Iran and the World Organisation for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) recommendations, the live attenuated vaccine is recommended as evidence-based strategies to control T. annulata infection by active immunization of susceptible exotic cattle and their cross-breds.
مراجع
1. Abbas, A.K. and Lichtman, A.H. (2004). Basic immunology: functions and disorders of the immune system, 2nd edn. London: Elsevier Health Sciences.
2. Ahmed JS, Shayan P, Hugel FU, Biermann R, Ewald C, Schein E, Gerdes J. (1997). Macroschizonts of Theileria annulata as vaccine and diagnostic tools. Tropical Animal Health and Production. Vol, 29, 4 Suppl. pp: 128S-132S.
3. Ahmed, J.S. and Mehlhorn, H. (1999). Review: the cellular basis of the immunity to and immunopathogenesis of tropical theileriosis. Parasitology Research. Vol, 85, No, 7. pp: 539-49.
4. Ahmed, J.S., Diesing, L., Oechtering, H., Ouhelli, H. and Schein, E. (1988). The role of antibodies in immunity against Theileria annulata infection in cattle. Zentralblatt für Bakteriologie, Mikrobiologie und Hygiene.Vol, 267, No, 3. pp: 425-31.
5. Ahmed, J.S., Glass, E.J., Salih, D.A. and Seitzer, U. (2008). Innate immunity to tropical theileriosis. Innate Immunity. Vol, 14, No, 1. pp: 5-12.
6. Ahmed, J.S., Hartwig, H., Rothert, M., Steuber, S. and Schein, E. (1989). Cytotoxicity and production of interleukin-2 and gamma interferon by peripheral blood lymphocytes of T. annulata infected cattle. Immunobiology. Vol, 14, Suppl. P: 175.
7. Beniwal, R.K., Sharma, R.D. and Nichani, A.K. (2000) Determination of duration of immunity of calves vaccinated with the Theileria annulata schizont cell culture vaccine. Veterinary Parasitology. Vol, 90, No, 1-2. pp: 25-35.
8. Bishop, R., Nene, V., Staeyert, J., Rowlands, J., Nyanjui, J., Osaso, J., Morzaria, S. and Musoke, A. (2003). Immunity to East Coast fever in cattle induced by a polypeptide fragment of the major surface coat protein of Theileria parva sporozoites. Vaccine. Vol, 21, No, 11-12. pp: 1205-12.
9. Boulter, N., Knight, P.A., Hunt, P.D., Hennessey, E.S., Katzer, F., Tait, A. et al. (1994). Theileria annulata sporozoite surface antigen (SPAG-1) contains neutralizing determinants in the C terminus. Parasite Immunology. Vol, 16, No, 2. pp: 97-104.
10. Brown, C.G., Stagg, D.A., Purnell, R.E., Kanhai, G.K. and Payne, R.C. (1973). Letter: Infection and transformation of bovine lymphoid cells in vitro by infective particles of Theileria parva. Nature. Vol, 245, No, 5420. pp: 101-3.
11. Brown, W.C., Shaw, M.K., Conrad, P.A. and Dolan, T.T. (1989). Theileria parva: reappearance of schizonts in infected lymphoblastoid cells treated with parvaquone is dependent on interleukin 2-like growth factors. Experimental Parasitology. Vol, 68, No, 3. pp: 308-25.
12. Chaudhri, S.S. and Subramanian, G. (1992). Cell-mediated immune responses to sporozoites and macroschizonts of Theileria annulata. Veterinary Parasitology. Vol, 41, No, 1-2. pp: 23-34.
13. Cunningham, M.P., Brown, C.G., Burridge, M.J. and Purnell, R.E. (1973). Cryopreservation of infective particles of Theileria parva. International Journal for Parasitology. Vol, 3, No, 5. pp: 583-7.
14. Darghouth, M.A., Ben Miled, L., Bouattour, A., Melrose, T.R., Brown, C.G., Kilani, M. (1996). A preliminary study on the attenuation of Tunisian schizont-infected cell lines of Theileria annulata. Parasitology Research. Vol, 82, No, 7. pp: 647-55.
15. de la Fuente, J., Almazán, C., Canales, M., Pérez de la Lastra, J.M., Kocan, K.M. and Willadsen, P. (2007). A ten-year review of commercial vaccine performance for control of tick infestations on cattle. Animal Health Research Reviews. Vol, 8, No, 1. pp: 23-8.
16. Dobbelaere, D.A., Fernandez, P.C. and Heussler, V.T. (2000). Theileria parva: taking control of host cell proliferation and survival mechanisms. Cell Microbiol. Vol, 2, No, 2. pp: 91-9.
17. d'Oliveira, C., van der Weide, M., Habela, M.A., Jacquiet, P. and Jongejan, F. J. (1995). Detection of Theileria annulata in blood samples of carrier cattle by PCR. Clinical Microbiology. Vol, 33, No, 10. pp: 2665-9.
18. Emery, D.L. (1981). Adoptive transfer of immunity to infection with Theileria parva (East Coast fever) between cattle twins. Research in Veterinary Science. Vol, 30, No, 3. pp: 364-7.
19. Fawcett, D.W., Doxsey, S., Stagg, D.A. and Young, A.S. (1982). The entry of sporozoites of Theileria parva into bovine lymphocytes in vitro. Electron microscopic observations. European Journal of Cell Biology. Vol, 27, No, 1. pp: 10-21.
20. Forsyth, L.M., Jackson, L.A., Wilkie, G., Sanderson, A., Brown, C.G. and Preston, P.M. (1997). Bovine cells infected in vivo with Theileria annulata express CD11b, the C3bi complement receptor. Veterinary Research Communications. Vol, 21, No, 4. pp: 249-63.
21. Geysen, D., Bishop, R., Skilton, R., Dolan, T.T. and Morzaria, S. (1999). Molecular epidemiology of Theileria parva in the field. Tropical Medicine and International Health. Vol, 4, No, 9. pp: A21-7.
22. Habibi, G., Bozorgi, S., Esmaeil-Nia, K., Najjar, E. and Mohammadipour, A.R. (2008). Detection and Discrimination of Theileria annulata and Theileria lestoquardi by using a Single PCR. Archives of Razi Institute, Vol, 63, No, 1. pp: 47-52.
23. Habibi, G., Bozorgi, S., Hatami, A., Esmaei-Nia, K. and Afshari, A. (2012). Study on Cryo-preservation of Theileria annulata Schizont Infected Cell Line Vaccine Strain S15. Archives of Razi Institute. Vol, 67, No, 2. pp: 167-172.
24. Habibi, G.R., Esmaeil Nia, K., Bozorgi, S., Hashemi-Fesharki, R. and Bordbar, N. (2009). Semi-quantitative Analysis of Expression of Various Genes in relation to Possible Markers for Theileria annulata Attenuation. Archives of Razi Institute, Vol, 64, No, 1.pp: 9-17
25. Habibi, G.R., Esmaeil-Nia, K., Bozorgi, S., Najjar E., Hashemi-Fesharki, R. and Bordbar, N. (2007). PCR-based Detection of Theileria infection and molecular characterization of Tams1 T. annulata vaccine strain. Archives of Razi Institute. Vol, 62, No, 2. pp: 83-89.
26. Habibi, G.R., Khamesipour, A., McMaster, W.R. and Mahboudi, F., (2001). Cytokine Gene Expression in healing and Non-healing cases of cutaneous Leishmaniasis in response to in vitro stimulation with recombinant gp63 using sqRT-PCR Scandinavian journal of Immunology. Vol, 54, No, 4. pp: 414-20.
27. Habibi, G. (2012). Phylogenetic Analysis of Theileria annulata Infected Cell Line S15 Iran Vaccine Strain. Iranian Journal of Parasitology. Vol, 6, No, 2. pp: 73-81
28. Habibi, GR.; Esmaeil-Nia, K.; Izadi, H.; Afshari, A. and Bozorgi, S. (2012). Evaluation of Tumor Necrosis Factor Alpha (TNF-) Gene Expression in Immunized Cattle with Two Types of Bovine Theileriosis Vaccine Preparation. The 11th International Congress of Immunology and Allergy of Iran. Milad Tower, Tehran, Iran 26-29 April.
29. Haghparast, A., Heidari Kharaji, M., Malvandi, A.M. and Habibi, Gh.R. Differential Expression of Pattern Recognition Receptors(PRRs)in Theileria Annulata Schizont Infected Cell Lines. Proceedings of the 9th international veterinary immunology symposium; 2010 August 16. Tehran, Iran. 2010.
30. Hall, R., Ilhan, T., Kirvar, E., Wilkie, G., Preston, P.M., Darghouth, M. et al. (1999). Mechanism(s) of attenuation of Theileria annulata vaccine cell lines. Tropical Medicine and International Health. Vol, 4, No, 9. pp: A78-84.
31. Hashemi-Fesharki, R. (1998). Recent development in control of Theileria annulata in Iran. Parasite. Vol, 5, No, 2. pp: 193-6.
32. Hashemi-Fesharki R. (1991) Chemotherapeutic value of parvaquone and buparvaquone against Theileria annulata infection of cattle. Research in Veterinary Sciences. Vol, 50. pp: 204–207.
33. Hashemi-Fesharki, R. (1988). Control of Theileria annulata in Iran. Parasitology Today. Vol, 4, No, 2. pp: 36-40.
34. Hashemi-Fesharki R. and Shad-Del F. (1973a). Vaccination of calves and milking cows with different strains of Theileria annulata. American Journal of Veterinary Research. Vol, 34, No, 11. pp: 1465-7.
35. Hashemi-Fesharki, R. and Shad-Del, F. (1973b). Long term maintenance of Theileria annulata strains by freezing at -70 degrees C. The Veterinary Record. Vol, 92, No, 6. pp: 150-1.
36. Hashemi-Fesharki, R., Golchinfar, F., Madani, R. and Esmaeilnia, K. (2006). Comparative evaluation of antibody positive titer by ELISA and IFA in Theileria annulata vaccinated cattle in Iran. Parasite. Vol, 13, No, 1. pp: 71-4.
37. Hashemi-Fesharki, R., Habibi, G.R. and Ahourai, P. (1998). Delayed type hypersensitivity theilerin test in cattle vaccinated against Theileria annulata infection. Veterinary Parasitology. Vol, 75, No, 2-3. pp: 261-3.
38. Hooshmand-Rad, P. and Hashemi-Fesharki, R. (1971). Complement-fixing antibodies in cattle experimentally infected with Theileria annulata or vaccinated with tissue cultures. The British Veterinary Journal. Vol, 127, No, 5. pp: 244-50.
39. Huang, D.S., Wang, Y., Marchalonis, J.J. and Watson, R.R. (1993). The kinetics of cytokine secretion and proliferation by mesenteric lymph node cells during the progression to murine AIDS, caused by LP-BM5 murine leukemia virus infection. Regional Immunology. Vol, 5, No, 6. pp: 325-31.
40. Irvin, A.D. (1987). Characterization of species and strains of Theileria. Advanced Parasitology. Vol, 26. pp: 145-97.
41. Jensen, K., Paxton, E., Waddington, D., Talbot, R., Darghouth, M.A. and Glass, E.J. (2008) Differences in the transcriptional responses induced by Theileria annulata infection in bovine monocytes derived from resistant and susceptible cattle breeds. International Journal of Parasitology. Vol. 38 No. 3-4 pp:313-25.
42. Jeyabal, L., Kumar, B., Ray, D., Azahahianambi, P. and Ghosh, S. (2012). Vaccine potential of recombinant antigens of Theileria annulata and Hyalomma anatolicum anatolicum against vector and parasite.Veterinary Parasitology. Vol, 188, No, 3-4. pp: 231-8.
43. Kachani, M., Spooner, R.L., Rae, P., Bell-Sakyi, L. and Brown, C.G. (1992). Stage-specific responses following infection with Theileria annulata as evaluated using ELISA. Parasitology Research. Vol, 78, No, 1. pp: 43-7.
44. Katzer, F., Carrington, M., Knight, P., Williamson, S., Tait, A., Morrison, I.W. and Hall, R. (1994). Polymorphism of SPAG-1, a candidate antigen for inclusion in a sub-unit vaccine against Theileria annulata. Molecular and Biochemical Parasitology. Vol, 67, No, 1. pp: 1-10.
45. McHardy, N. and Morgan, D.W. (1985). Treatment of Theileria annulata infection in calves with parvaquone. Research in Veterinary Science. Vol, 39, No, 1. pp: 1-4.
46. McKeever, D.J. (2009). Bovine immunity - a driver for diversity in Theileria parasites? Trends in Parasitology. Vol, 25, No, 6. pp: 269-76.
47. McKeever, D.J., Nyanjui, J.K. and Ballingall, K.T. (1997). In vitro infection with Theileria parva is associated with IL10 expression in all bovine lymphocyte lineages. Parasite Immunology. Vol, 19, No, 7. pp: 319-24.
48. Mohammad Al-Saeed, A.T., Omer, L.T., Abdo, J., Habibi, G., Salih, D.A., Seitzer, U. and Ahmed, J. (2009). Epidemiological studies on tropical theileriosis (Theileria annulata infection of cattle) in Kurdistan Region, Iraq. Parasitology Research. Vol, 106, pp: 403-407.
49. Morrison, W.I. and McKeever, D.J. (2006). Current status of vaccine development against Theileria parasites. Parasitology. Vol, 133, Suppl: S169-87.
50. Muhammed, S.I., Lauerman, L.H. Jr. and Johnson, L.W. (1975). Effect of humoral antibodies on the course of Theileria parva infection (East Coast fever) of cattle. American Journal of Veterinary Research. Vol, 36, No, 4. Pt.1 pp: 399-402.
51. Nene, V., Iams, K.P., Gobright, E. and Musoke, A.J. (1992). Characterisation of the gene encoding a candidate vaccine antigen of Theileria parva sporozoites. Molecular and Biochemical Parasitology. Vol, 51, No, 1. pp: 17-27.
52. OIE (World Organization for Animal Health), Theileriosis (2008). http:/ /www.oie.int/ fileadmin/ Home/ eng/ Health_standards/ tahm/ 2.04.16_THEILIERIOSIS.pdf.
53. Pipano, E. and Tsur, I. (1966). Experimental immunization against Theileriosis due to Theileria annulata with a tissue culture vaccine. Refuah Veterinarith. Vol, 23. pp: 188-194.
54. Preston, P.M. and Brown, C.G. (1988). Macrophage-mediated cytostasis and lymphocyte cytotoxicity in cattle immunized with Theileria annulata sporozoites or macroschizont-infected cell lines. Parasite Immunology. Vol, 10, No, 6. pp: 631-47.
55. Preston, P.M., Brown, C.G. and Spooner, R.L. (1983). Cell-mediated cytotoxicity in Theileria annulata infection of cattle with evidence for BoLA restriction. Clinical and Experimental Immunology. Vol, 53. pp: 88–100.
56. Preston, P.M., Brown, C.G., Entrican, G., Richardson, W. and Boid, R. (1993). Synthesis of tumour necrosis factor-alpha and interferons by mononuclear cells from Theileria annulata-infected cattle. Parasite Immunology. Vol, 15, No, 9. pp: 525-34.
57. Preston, P.M., Hall, F.R., Glass, E.J., Campbell, J.D., Darghouth, M.A., Ahmed, J.S. et al. (1999). Innate and adaptive immune responses co-operate to protect cattle against Theileria annulata. Parasitology Today. Vol, 15, No, 7. pp: 268-74.
58. Rose, R.M., Fuglestad, J.M. and Remington, L. (1991). Growth inhibition of Mycobacterium avium complex in human alveolar macrophages by the combination of recombinant macrophage colony-stimulating factor and interferon-gamma. American Journal of Respiratory Cell and Molecular Biology. Vol, 4, No, 3. pp: 248-54.
59. Schnittger, L., Katzer, F., Biermann, R., Shayan, P., Boguslawski, K., McKellar, S. et al. (2002). Characterization of a polymorphic Theileria annulata surface protein (TaSP) closely related to PIM of Theileria parva: implications for use in diagnostic tests and subunit vaccines. Molecular and Biochemical Parasitology. Vol, 120, No, 2. pp: 247-56.
60. Sergent E., Donatien A., Parrot L. and Lestoquard F. (1935). Theilerioses bovines de 1'Afrique du Nord et du Proche-Orient. Archives de l'Institut Pasteur d'Algerie Vol. 13. P: 472.
61. Shayan P., and Sadegh Rahbari (2005). Simultaneous differentiation between Theileria spp. and Babesia spp. on stained blood smear using PCR. Parasitology Research.Vol, 97. pp: 281-286.
62. Shayan P., and Sadegh Rahbari (2007). Differentiation of Theileria spp. and Babesia spp. by polymerase chain reaction. Journal of veterinary Research. Vol, 62, No, 2. pp: 15-20.
63. Shiels, B.R., d'Oliveira, C., McKellar, S., Ben-Miled, L., Kawazu, S. and Hide, G. (1995). Selection of diversity at putative glycosylation sites in the immunodominant merozoite/piroplasm surface antigen of Theileria parasites. Molecular and Biochemical Parasitology. Vol, 72, No, 1-2 pp: 149-62.
64. Spooner, R.L., Innes, E.A., Glass, E.J. and Brown, C.G. (1989). Theileria annulata and T. parva infect and transform different bovine mononuclear cells. Immunology. Vol, 66, No, 2. pp: 284-8.
65. Steinaa, L., Saya, R., Awino, E. and Toye, P. (2012). Cytotoxic T lymphocytes from cattle immunized against Theileria parva exhibit pronounced cross-reactivity among different strain-specific epitopes of the Tp1 antigen.Veterinary Immunology and Immunopathology. Vol, 145, No, 3-4. pp: 571-81.
66. Swan, D.G., Phillips, K., Tait, A. and Shiels, B.R. (1999). Evidence for localisation of a Theileria parasite AT hook DNA-binding protein to the nucleus of immortalised bovine host cells. Molecular and Biochemical Parasitology. Vol, 101, No, 1-2. pp: 117-29.
67. Swan, D.G., Stern, R., McKellar, S., Phillips, K., Oura, C.A., Karagenc, T.I. et al. (2001). Characterisation of a cluster of genes encoding Theileria annulata AT hook DNA-binding proteins and evidence for localisation to the host cell nucleus. Journal of Cell Science. Vol, 114, Pt 15. pp: 2747-54.
68. Suzuki, Y., Orellana, M.A., Schreiber, R.D. and Remington, J.S. (1998). Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. Vol, 240, No, 4851. pp: 516-8.
69. Tait, A. and Hall, F.R. (1990). Theileria annulata: control measures, diagnosis and the potential use of subunit vaccines. Revue Scientifique et Technique. Vol, 9, No, 2. pp: 387-403.
70. Taracha, E.L., Awino, E. and McKeever, D.J. (1997). Distinct CD4+ T cell helper requirements in Theileria parva-immune and -naive bovine CTL precursors. Journal of Immunology. Vol, 159, No, 9. pp: 4539-45.
71. Tsur, I. and Adler, S. (1965). The cultivation of lymphoid cells and Theileria annulata schizonts from infected bovine blood. Refuah Veterinarith. Vol, 22. P: 62.
72. Uilenberg G, Hashemi-Fesharki R. (1984). Theileria orientalis in Iran. Vet Q. Vol, 6. No, 1. pp: 1-4.
73. Visser, A.E., Abraham, A., Sakyi, L.J., Brown, C.G. and Preston, P.M. (1995). Nitric oxide inhibits establishment of macroschizont-infected cell lines and is produced by macrophages of calves undergoing bovine tropical theileriosis or East Coast fever. Parasite Immunology. Vol, 17. pp: 91–102.
https://vj.areeo.ac.ir/article_100994.html