Astıma karşı oluşan immün yanıt

Hava yollarının kronik inflamasyonu ile karakterize astıma karşı hem doğal hem de edinsel immün yanıt gelişmektedir. Hayatın erken döneminde mikrobik ürünler ile karşılaşmanın yardımcı T hücre (Th) 2 yanıtını Th1 yanıtına değiştirdiği bilinmektedir. Doğal immünitede temel rol oynayan reseptörler toll-like reseptörler (TLR)’dir. Bronş epitel hücreleri ise inflamasyonda rol alan en önemli hücrelerdir, bu hücreler antijen sunan hücre (APC) özelliği taşırlar, salgıladıkları birçok büyüme faktörü ile hava yolu yeniden yapılanmasına katkıda bulunurlar. Doğal immünitede rol alan diğer hücreler; dendritik hücreler, bazofiller, mast hücreleri, eozinofiller, monositler, makrofajlar, trombositlerdir. Edinsel immün yanıt ise hücresel ve hümöral immün yanıt şeklinde ortaya çıkmaktadır. Uzun süredir astım patogenezinde temel rol oynayan hücrelerin Th2 hücreler olduğu bilinmektedir. Ancak son zamanlarda Th1, Th9, Th17, Th25, folliküler T hücre, regülatör T hücre, invariant natural killer T hücreler ve γδ T hücrelerin de patogene- ze katkıda bulundukları gösterilmiştir.

Immune response against to asthma

Both innate and adaptive immune responses develop against to asthma which is characterized by chronic inflammation of the airways. It is known that contacting the products of microorganisms in early period of life changes the T helper (Th) 2 cell response to Th1 response. Basic reseptors of innate immunity are toll-like receptors (TLR). Bronchial epitelial cells are the most important cells that take part in inflammation, these cells act as antigen presenting cells (APC), and they contribute to the airway remodelling by secreting some growth factors. The other cells in innate immunity are; dendritic cells, basophils, mast cells, eosinophils, monocytes, macrophages, platelets. Adaptive immune response occurs as cellular and humoral immunity. It is known for a long time that basic cells in asthma pathogenesis are Th2 cells. But recently it is shown that Th1, Th9, Th17, Th25, folli- cular T cell, regulator T cell, invariant natural killer T cell, and γδ T cell contribute to the pathogenesis.

PDF

___

1. Beutler B. Innate immunity: an overview. Mol Immunol 2004; 40: 845-59.
2. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4: 499-511.
3. Redecke V, Hacker H, Datta SK, et al. Cutting edge: activation of toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol 2004; 172: 2739-43.
4. Velasco G, Campo M, Manrique OJ, et al. Toll-like receptor 4 or 2 agonists decrease allergic inflammation. Am J Respir Cell Mol Biol 2005; 32: 218-24.
5. Rosenstiel P, Jacobs G, Till A, Schreiber S. NOD-like recep- 6. Bach JF. The effect of infections on susceptibility to autoim- tors: ancient sentinels of the innate immune system. Cell Mol mune and allergic diseases. N Engl J Med 2002; 347: 911–20. Life Sci 2008; 65: 1361-77.
6. Bach JF. The effect of infections on susceptibility to autoim- mune and allergic diseases. N Engl J Med 2002; 347: 911–20.
7. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 2008; 28: 454-67.
8. Vignola AM, Campbell AM, Chanez P, Bousquet J, Michel FB, Godard P. HLA-DR and ICAM-1 expression on bronchial epit- helial cells in asthma and chronic bronchitis. Am Rev Respir Dis 1993; 148: 689-94.
9. Tanaka H, Maeda K, Nakamura Y, Azuma M, Yanagawa H, Sone S. CD40 and IFN-gamma dependent T cell activation by human bronchial epithelial cells. J Med Invest 2001; 48: 109- 17.
10. Wenzel SE. The significance of the neutrophil in asthma. Clin Exp Allergy Rev 2001; 1: 89-92.
11. Holgate S. Pathogenesis of asthma. In: Kay AB, Kaplan AF, Bousquet J, Holt PG (eds). Allergy and Allergic Disease. 2nd Ed. Blackwell Publishing 2008; 1608-31.
12. Yorgancıoğlu A. Astım patogenezi. In: Özlü T, Metintaş M, Karadağ M, Kaya A (eds). Solunum Hastalıkları. İstanbul Medikal Yayıncılık ve Ticaret AŞ 2010; 617-24.
13. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004; 5: 987-95.
14. Akbari O, Freeman GJ, Meyer EH, et al. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 2002; 8: 1024-32.
15. Kaur D, Saunders R, Berger P, al. Airway smooth muscle and mast cell-derived CC chemokine ligand 19 mediate airway smooth muscle migration in asthma. Am J Respir Crit Care Med 2006; 174: 1179-88.
16. Barnes PJ, Djukanovic R, Holgate ST. Pathogenesis of asthma. Gibson GJ, Geddes GM, Costabel V, Sterk PJ, Corrin B (eds). Respiratory Medicine. WB Saunders, Edinburg 2003; 1212-64.
17. Yoshikawa S, Kayes SG, Parker JC. Eosinophils increase lung microvascular permeability via the peroxidase-hydrogen pe- roxide-halide system. Bronchoconstriction and vasoconstriction unaffected by eosinophil peroxidase inhibition. Am Rev Respir Dis 1993; 147: 914-20.
18. Kita H, Adalphson CR, Gleich GJ. Biology of eosinophils. In: Middleton E, Reed CE, Ellis EF, Adkinson NF, Yunginger JW, Busse WW (eds). Allergy. Mosby, St Louis 1998; 242-60.
19. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nature Reviews 2008; 8: 183-91.
20. Camcığolu Y. İnflamatuar hücreler. In: Gemicioğlu B (ed). Tanımdan Tedaviye Astım. Turgut Yayıncılık ve Ticaret AŞ 2005; 71-8.
21. Stites DP, Terr AI. Basic and Clinical Immunology. 7th Ed., Appleton&Lange, Connecticut 1991; 16-77.
22. Ying S, Humbert M, Barkans J, et al. Expression of IL-4 and IL-5 mRNA and protein product by CD41 and CD81 T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol 1997; 158: 3539-44.
23. Leggat JA, Gibbons DL, Haque SF, et al. Innate responsiveness of CD8 memory T-cell populations nonspecifically inhibits allergic sensitization. J Allergy Clin Immunol 2008; 122: 1014- 21.
24. Szabo SJ, Sullivan BM, Peng SL, Glimcher LH. Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 2003; 21: 713-58.
25. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature 1996; 383: 787-93.
26. Valerius T, Repp R, Kalden JR, Platzer E. Effects of IFN on human eosinophils in comparison with other cytokines. A novel class of eosinophil activators with delayed onset of action. J Immunol 1990; 145: 2950-8.
27. Look DC, Rapp SR, Keller BT, Holtzman MJ. Selective induction of intercellular adhesion molecule-1 by interferon-γ in human airway epithelial cells. Am J Physiol 1992; 263: 79-87.
28. Kumar RK, Webb DC, Herbert C, Foster PS. Interferon-γ as a possible target in chronic asthma. Inf Allergy 2006; 5: 253-6.
29. Bendelac A, Rivera MN, Park SH, Roark JH. Mouse CD1- specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 1997; 15: 535-62.
30. Messi M, Giacchetto I, Nagata K, Lanzavecchia A, Natoli G, Sallusto F. Memory and flexibility of cytokine gene expression as separable properties of human Th1 and Th2 lymphocytes. Nat Immunol 2003; 4: 78-86.
31. Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol 2007; 119: 1303- 10.
32. Wills-Karp M. Interleukin-13 in asthma pathogenesis. Immunol Rev 2004; 202: 175-90.
33. Veldhoen M, Uyttenhove C, van Snick J, et al. Transforming growth factor-β ’reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 2008; 9: 1341-6.
34. Renaud JC, Kermouni A, Vink A, Louahed J, Van Snick J. Interleukin-9 and its receptor: involvement in mast cell diffe- rentiation and T cell oncogenesis. J Leukoc Biol 1995; 57: 353- 60.
35. Louahed J, Kermouni A, Van Snick J, Renauld JC. IL-9 indu- ces expression of granzymes and high-affinity IgE receptor in murine T helper clones. J Immunol 1995; 154: 5061-70.
36. Van Snick J, Goethals A, Renauld JC, et al. Cloning and cha- racterization of a cDNA for a new mouse T cell growth factor [P40]. J Exp Medicine 1989; 169: 363-8.
37. Louahed J, Zhou Y, Maloy LW, et al. Interleukin 9 promotes influx and local maturation of eosinophils. Blood 2001; 97: 1035-42.
38. Louahed J, Toda M, Jen J, et al. Interleukin-9 upregulates mucus expression in the airways. Am J Respir Cell Mol Biol 2000; 22: 649-56.
39. Dong Q, Louahed J, Vink A, et al. IL-9 induces chemokine expression in lung epithelial cells and baseline airway eosinop- hilia in transgenic mice. Eur J Immunol 1999; 9: 2130-9.
40. Shimbara A, Christodoulopoulos P, Soussi-Gounni A, et al. IL- 9 and its receptor in allergic and nonallergic lung disease: inc- reased expression in asthma. J Allergy Clin Immunol 2000; 105: 108-15.
41. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector Th17 and regulatory T cells. Nature 2006; 441: 235-8.
42. Korn T, Bettelli E, Gao W, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 2007; 448: 484-7.
43. Stockinger B, Veldhoen M. Differentiation and function of Th17 T cells. Curr Opin Immunol 2007; 19: 281-6.
44. Zhao Y, Yang J, Gao Y, Guo W. Th17 immunity in patients with allergic asthma. Int Arch Allergy Immunol 2010; 151: 297-307.
45. Wong CK, Ho CY, Ko FW, et al. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol 2001; 125: 177-83.
46. Agache I, Ciobanu C, Agache C, Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respir Med 2010; 104: 1131-7.
47. Newcomb DC, Zhou W, Moore ML, et al. A functional IL-13 receptor is expressed on polarized murineCD41Th17 cells and IL-13 signaling attenuates Th17 cytokine production. J Immu- nol 2009; 182: 5317-21.
48. Tato CM, Laurence A, O’Shea JJ. Helper T cell differentiation enters a new era: le roi est mort; vive le roi! J Exp Med 2006; 203: 809-12.
49. Hurst SD, Muchamuel T, Gorman DM, et al. New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol 2002; 169: 443-53.
50. Ballantyne SJ, Barlow JL, Jolin HE, et al. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 2007; 120: 1324-31.
51. Ichii H, Sakamoto A, Hatano M, et al. Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells. Nat Immunol 2002; 3: 558-63.
52. Akiba H, Takeda K, Kojima Y. The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo. J Im- munol 2005; 175: 2340-8.
53. Bauquet AT, Jin H, Paterson AM, et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol 2009; 10: 167-75.
54. McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer- Williams L. Molecular programming of B cell memory. Nature reviews. Immunol 2011; 12: 24-34.
55. Ling EM, Smith T, Nguyen XD, et al. Relation of CD4+ CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 2004; 363: 608-15.
56. Hartl D, Koller B, Mehlhorn AT, et al. Quantitative and functional impairment of pulmonary CD41CD25hi regulatory T cells in pediatric asthma. J Allergy Clin Immunol 2007; 119: 1258- 66.
57. Hartl D, Koller B, Mehlhorn AT, et al. Quantitative and functi- onal impairment of pulmonary CD41CD25hi regulatory T cells in pediatric asthma. J Allergy Clin Immunol 2007; 119: 1258- 66.
58. Wilson MS, Pesce JT, Ramalingam TR, Thompson RW, Chee- ver A, Wynn TA. Suppression of murine allergic airway disea- se by IL-2: anti-IL-2 monoclonal antibody-induced regulatory T cells. J Immunol 2008; 181: 6942-54.
59. Capone M, Cantarella D, Schümann J, et al. Human invariant V α 24-J α Q TCR supports the development of CD1d-dependent NK1.1+ and NK1.1− T cells in transgenic mice. J Immunol 2003; 170: 2390-8.
60. Meyer EH, Goya S, Akbari O, et al. Glycolipid activation of invariant T cell receptor+ NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc Natl Acad Sci USA 2006; 103: 2782-7.
61. Akbari O, Faul JL, Hoyte EG, et al. CD4+ invariant T-cell- receptor+ natural killer T cells in bronchial asthma. N Engl J Med 2006; 354: 1117-29.
62. Vijayanand P, Seumois G, Pickard C, et al. Invariant natural killer T cells in asthma and chronic obstructive pulmonary di- sease. N Engl J Med 2007; 356: 1410-22.
63. Spinozzi F, Agea E, Bistoni O, et al. Increased allergen- specific, steroid-sensitive gamma delta T cells in bronchoalveo- lar lavage fluid from patients with asthma. Ann Intern Med 1996; 124: 223-7.
64. Zuany-Amorim C, Ruffie ́ C, Haile ́ S, Vargaftig BB, Pereira P, Pretolani M. Requirement for gammadelta T cells in allergic airway inflammation. Science 1998; 280: 1265-7.
65. Lahn M, Kanehiro A, Takeda K, et al. Negative regulation of airway responsiveness that is dependent on gammadelta T cells and independent of alphabeta T cells. Nat Med 1999; 5: 1150-6.
66. Xiong H, Dolpady J, Wabl M, Curotto de Lafaille MA, Lafaille JJ. Sequential class switching is required for the generation of high affinity IgE antibodies. J Exp Med 2012; 209: 353-64.
67. Acharya M, Borland G, Edkins AL, al. CD23/FcεRII: molecular multi-tasking. Clin Exp Immunol 2010; 162: 12-23.
68. Ying S, Humbert M, Meng Q, et al. Local expression of epsilon germline gene transcripts and RNA for the ε heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma. J Allergy Clin Immunol 2001; 107: 686-92.