Innate Immunity and Host Defense

Öz

Innate immune system has an important role in the mammalian defense mechanism. Contrast to adaptive immune system, innate immune system provides occurrence of a rapid response against pathogens. It determines Pathogen Associated Molecular Pattern (P.A.M.P.), pathogenic structures of microorganisms, by Pattern Recognition Receptors (P.R.R.) and then induces intracellular signal mechanisms resulted with inflammation. Toll like receptors (T.L.R.s), an important component of the innate immune system, recognize pathogens.
P.R.R.s recognizes not only pathogens, but also these receptors response against physical factors such as radiation, heat, and trauma. Therapeutic studies targeting innate immune system are still continuing with extensive importance and a pace.

Anahtar Kelimeler

• Innate immunity
• Toll-Like Receptors
• Inflammation
• Pathogensis

İnnate İmmunite ve Konakçı Savunması

Öz

İnnate immun sistem memelilerin savunma sisteminde önemli bir role sahiptir. Adaptif immun sistemin aksine, patojenlerle karşılaşıldığı zaman ani olarak immun yanıtın şekillenmesini sağlar. İnnate immun sistem, mikroorganizmaların patojen olarak tanınmalarını sağlayan Patojen ilişkili moleküler yapıları (P.A.M.P.), bu yapıları tanımakla görevli yapı tanıyan reseptörler (P.R.R.) aracılığı ile tanıyarak, hücre içinde innate immun sistemin sinyal mekanizmalarını tetikler, sonuç olarak yangının şekillenmesi ile son bulan reaksiyonları başlatır. İnnate immun sistemin en önemli yapılarından olan Toll benzeri reseptörler (T.L.R.), patojenlerin tanınmasında rol oynarlar. P.R.R.’ler sadece patojen etkenleri tanımakla kalmayıp, radyasyon, yüksek sıcaklık, travma gibi fiziksel sebeplere karşı da yanıtın oluşmasını ve reaksiyonların başlatılmasını sağlarlar. İnnate immun sistemi hedef alan tedavi çalışmaları günümüzde büyük bir önem ve hızla devam etmektedir

Anahtar Kelimeler

• İnnate immunite
• Toll-Like Reseptör
• Yangı
• Patogenez

Kaynakça

1. Anand P.K., Tait S.W., Lamkanfi M., Amer A.O., Nunez G., Pagès G., Pouysségur J., Mcgar- gill M.A., Green D.R., Kanneganti T.D., 2011. TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal- regulated kinase (ERK) activation. The Journal of Biological Chemistry, 16;286(50):42981-42991.
2. Aono S, L.I. C, Zhang G., Kemppaınen R.J.,
3. Gard J., Lu W., Hu X., Schwartz D.D., Marrıson E.E., Dykstra C., Shi J., 2006. Molecular and functional characterization of bovine beta- defensin-1. Veterinary Immunology and Immu- nopathology; 113:181–190.
4. Boman H.G., 2003. Antibacterial peptides: Basic facts and emerging concepts. Journal of Internal Medicine, 254:197–215.
5. Caamaño J., Hunter C.A., 2002. NF-kappaB family of transcription factors: central regulators of innate and adaptive immune functions. Clini- cal Microbiology Reviews, 15(3):414-429.
6. Coffey T.J., Werlıng D., 2011. Therapeutic targe- ting of the innate immune system in domestic animals. Cell and Tissue Research, 343:251-261.
7. Colonna M., Facchettı F., 2003. TREM- 1 (triggering receptor expressed on myeloid cells): a new player in acute inflammatoryresponses. The Journal of Infection Disease, 15;187 2: 397- 401.
8. Covert M.W., Leung T.H., Gaston J.E., Baltımo- re D., 2005. Achieving stability of lipopoly- saccharide-induced NF-kappaB activation. Sci- ence, 16;309(5742):1854-1857.

9. Dıamond G., Russell J.P., Bevıns C.L., Inducible
10. expression of an antibiotic peptide gene in lipo- polysaccharide-challenged tracheal epithelial cells. Proceedings of the National Academy of Science of United States of America, 93:5156– 5160, 1996.
11. Diamond G., Zasloff M., Eck H., Brasseur M., Maloy W.L., Bevins C.L., 1991. Tracheal an- timicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: Peptide isolation and cloning of a cDNA. Proceedings of the Nati- onal Academy of Science of United States of America, 88:3952-3956.
12. Flynn R.J., Mulcahy G., Elsheikha H.M., 2010. Coordina- ting innate and adaptive immunity in Fasciola he patica infection: implications for control. Veteri- nary Parasitology, 11;169(3-4):235-240.
13. Goldammer T., Zerbe H., Molenaar A., Schu- berth H.J., Brunner R.M., Kata S.R., Seyfert H.M., 2004. Mastitis increases mammary mRNA abundance of beta-defensin 5, Toll-like receptor (TLR2), and TLR4 but not TLR9 in cattle. Clini- cal and Diagnostic Laboratory Immunology, 11:174–185.
14. Hans M., Hans V.M,. 2011. Toll-like recep- tors and their dual role in periodontitis: a review. Journal of Oral Science, 53(3):263-271.
15. He X.N., Su F., Lou Z.Z., Jia W.Z., Song Y.L., Chang H.Y., Wu Y.H., Lan J., He X.Y., Zhang Y., 2011. Ipr1 gene mediates RAW 264.7 mac- rophage cell line resistance to Mycobacterium bovis. Scandinavian Journal of Immunology, 74(5):438-444.
16. Hemmi H., Takeuchi O., Sato S., Yamamoto M., Kaisho T., Sanjo H., Kawai T., Hoshino K., Takeda K., Akira S., 2004. The roles of two IkappaB kinase-related kinases in lipopolysac- charide and double stranded RNA signaling and viral infection. The Journal of Experimental Medicine, 21;199(12):1641-1650.
17. Hua J., Liang S., Ma X., Webb T.J., Potter J.P., Li Z., 2011. The interaction between regula- tory T cells and NKT cells in the liver: a CD1d bridge links innate and adaptive immunity. PLoS One, 6(11):e27038.
18. Ignacio G., Nordone S., Howard K.E., Dean G.A., 2005. Toll-like receptor expression in feli- ne lymphoid tissues. Veterinary Immunology and Immunopathology, 106(3-4):229-237.
19. Kennedy-Crispin M., Billick E., Mitsui H., Gulati N., Fujita H., Gilleaudeau P., Sullivan-Whalen M., Johnson-Huang L.M., Suárez-Fariñas M., Krueger J.G., 2012. Human keratinocytes' res- ponse to injury upregulates CCL20 and other ge- nes linking innate and adaptive immunity. The Journal of Investtigative Dermatology, 132(1):105-113.
20. Kleinnijenhuis J., Oosting M., Joosten L.A., Netea M.G., Van Crevel R., 2011. Innate immune recognition of Mycobacterium tuberculosis. Cli- nicanl and Developmental Immunology, 2011:405310.
21. Krug A., Luker G.D., Barchet W., Leib D.A., Akira S., Colonna M., 2004. Herpes simplex vi- rus type 1 activates murine natural interferon- producing cells through toll-like receptor 9. Blood, 15;103(4):1433-1437.
22. Lauzon N.M., Mian F., Ashkar A.A., 2007. Toll- like receptors, natural killer cells and innate im- munity. Advances in Experimental Medicine and Biology, 598:1-11.
23. Lawyer C., Watabe M., Pai S., Bakir H., Eagle- ton L., Mashimo T., Watabe K., 1996. A synthe- tic form of tracheal antimicrobial peptide has both bactericidal and antifungal activities. Drug Design and Discovery, 14:171–178.
24. Le Negrate G., 2012. Viral interference with innate immunity by preventing NF-κB activity. Cellılar Microbiology, 14(2):168-181.
25. Lemaitre B., Nicolas E., Michaut L., Reichhart J.M., Hoffmann J.A., 1996. The dorsoventral re- gulatory gene cassette spätzle/Toll/cactus cont- rols the potent antifungal response in Drosophila adults. Cell, 20;86(6):973-983.
26. Li M., Carpio D.F., Zheng Y., Bruzzo P., Singh V., Ouaaz F., Medzhitov R.M., Beg A.A., 2001. An essential role of the NF-kappa B/Toll-like re- ceptor pathway in induction of inflamma- tory and tissue-repair gene expression by necrotic cells. Journal of Immunology, 15;166(12):7 128- 135.
27. Liang L., Zhao Y.L., Yue J., Liu J.F., Han M., Wang H., Xiao H., 2011. Association of SP110 gene polymorphisms with susceptibility to tuber- culosis in a Chinese population. Infection, Gene- tic and Evolution: Journal of Molecular Epidemi- ology and Evolutinary Genetics in Infectious Di- seases, 11(5):934-939.
28. Linde A., Ross Cr, Davis E.G., Dib L., Blecha F., Melgarejo T., and host defense peptides in veterinary medicine. Journal of Veterinary Internanl Medici- ne/American College of Veterinary Internal Me- dicine, 22(2):247-265.
29. Maxwell J.R., Yadav R., Rossi R.J., Ruby C.E., Weinberg A.D., Aguila H.L., Vella A.T., 2006. IL-18 bridges innate and adaptive immu- nity pathway. Journal of Immunology, 1;177(1):234- 245.
30. Medzhitov R., Preston-Hurlburt P., Janeway C.A. Jr., 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immu- nity. Nature, 24;388(6640):394-397.
31. Mitchell G.B., Al-Haddawi M.H., Clark M.E., Beveridge J.D., Caswell J.L., 2006. Effect of cor- ticosteroids and neuropeptides on the expression of defensins in bovine tracheal epithelial cells. Infection and Immunity; 75:1325–1334,
32. Mogensen T.H., 2009. Pathogen recognition and inflammatory signaling in innate immune defen- ses. Clinicanl Microbiology Reviews, 22(2):240- 273.
33. Mohamed M.R., McFadden G., 2009. NFkB inhibitors: strategies from poxviruses. The Cell Cycle, 1;8(19):3125-3132.
34. Netea M.G., Van Der Meer J.W., Kullberg B.J., 2004. Toll-like receptors as an escape mechanism from the host defense Trends in Microbio- logy, 12(11):484-488.
35. Raz E., 2007. Organ-specific regulation of innate immunity. National Immunology, 8:3–4.
36. Rijavec M., Volarevic S., Osolnik K., Kosnik M., Korosec P., 2011. Natural killer T cells in pulmonary disorders. Respiratory Medici- ne, 105 Suppl 1:20-25.
37. Roeder A., Kirschning C.J., Rupec R.A., Schaller M., Korting H.C., 2004. Toll-like receptors and innate antifungal responses. Trends Microbiolo- gy. (1):44-9.
38. Roosen S., Exner K., Paul S., Schroder J.M., Kalm E., Looft C., 2004. Bovine beta- defensins: Identification and characterization of novel bovine beta-defensin genes and their expression in mammary gland tissue. Mammalian Genome, 15:834–842.
39. Ruiz-Larrañaga O., Garrido J.M., Iriondo M., Manzano C., Molina E., Montes I., Vazquez P., Koets A.P., Rutten V.P., Juste R.A., Estonba A., 2010. SP110 as a novel susceptibility gene for Mycobacterium avium subspecies paratuberculo- sis infection in cattle. Journal of Dairy Science, 93(12):5950-5958.
40. Sang Y., Ortega M.T., Blecha F., Prakash O., Melgarejo T., 2005. Molecular cloning and cha- racterization of three beta-defensins from canine testes. Infection and Immunity, 73:2611-2620.
41. Sang Y., Teresa O.M., Rune K., Xiau W., Zhang G., Soulages J.L., Lushıngton G.H., Fang J., Wil- liams T.D., Blecha F., Melgarejo T., 2007. Cani- ne cathelicidin (K9CATH): Gene cloning, expression, and biochemical activity of a novel pro-myeloid antimicrobial peptide. Developmen- tal and Comparative Immunology, 31(12):1278- 1296.
42. Schontwetter B.S., Stolzenberg E.D., Zasloff M.A., 1995. Epithelial antibioticis induced at si- tes of inflammation. Science. 267:1645-1648.
43. Scott M.G., Hancock R.E., 2000. Cationic anti- microbial peptides and their multifunctional role in immune system. Critical Reviews in Immuno- logy, 20:407-431.
44. Slotwinski R., Slotwinska S., Kedziora S., Balan B.J., 2011. Innate immunity signaling pathways: Links between immunonutrition and responses to sepsis. Archivum Immunologiae et Therapiae Experinemtalis, 59:139-150.
45. Stolzenberg E.D., Anderson G.M., Ackermann M.R., Whitlock R.H., Zasloff M., 1997. Epithe- lial antibiotic induced in states of disease. Proce- edings of the National Academy of Science of United States of America, 94:8686–8690.
46. Summerfield A., Guzylack-Piriou L., Harwood L., McCullough K.C., 2009. Innate immune res- ponses against foot-and-mouth disease virus: cur- rent understanding and future directions. Veteri- nary Immunology and Immunopathology, 128(1- 3):205-210.
47. Swanson K., Gorodetsky S., Good L., Davis S, Musgrave D., Stelwagen K., Farr V., Molenaar A., 2004. Expression of a beta-defensin mRNA, lingual antimicrobial peptide, in bovine mam- mary epithelial tissue is induced by mastitis. Infection and Immunity, 72:7311–7314.
48. Swerdlow M.P., Kennedy D.R., Kennedy J.S., Washabau R.J., Henthorn P.S., Moore P.F., Car- ding S.R., Felsburg P.J., 2006. Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic epithelial cells. Veterinary Immu- nology Immunopathology, 15;114(3-4):313-319.
49. Takeda K., Akira S., 2005. Toll-like receptors in innate immunity. International Immunology, 17(1):1-14.
50. Tarver A.P., Clark D.P., Diamond G., Russell J.P., Erdjument-Bromage H., Tempst P., Cohen K.S., Jones D.E., Sweeney R.W., Wines M., Hwang S., Bevins C.L.. 1998. Enteric beta- defensin: Molecular cloning and characterization of a gene with inducible intestinal epithelial cell expression associated with Cryptosproidum par- vum 66(3):1045-1056.
51. Tydell C.C., Yount N, Tran D., Yuan J., Selsted M.E., 2002. Isolation, characterization and anti- microbial properties of bovine oligosaccharide- binding protein. A microbicidal granule protein of eosinophils and neutrophils. Journal of Biolo- gical Chemistery, 277:19658-19664.
52. Uematsu S, Akira S., 2008. Toll-Like receptors (TLRs) and their ligands. Handbook of Experi- mental Pharmacology, (183):1-20.
53. Vincent I.E., Zannetti C., Lucifora J., Norder H., Protzer U., Hainaut P., Zoulim F., Tommasino M., Trépo C., Hasan U., Chemin I., 2011. Hepati- tis B virüs impairs TLR9 expression and function in plasmacytoid dendritic cells. PLoS One 6(10):e 26313.
54. Yang W., Molenaar A., Kurts-Ebert B., Seyfert H.M., 2006. NF-kappaB factors are essential, but not the switch, for pathogen-related induction of the bovine beta-defensin 5-encoding gene in mammary epithelial cells. Molecular Immuno- logy, 43:210–225.
55. Zasloff M., 2002. Antimicrobial peptides of mul- ticellular organisms. Nature, 415:389–395.