nach oben

Erschienen in:

2016 | OriginalPaper | Buchkapitel

11. Immunologische Toleranz und ihre Mechanismen

verfasst von : C. B. Schmidt-Weber, Prof. Dr. rer. nat.

Erschienen in: Allergologie

Verlag: Springer Berlin Heidelberg

Einloggen, um Zugang zu erhalten

Zusammenfassung

Die Ursache der Allergie ist immer noch verborgen unter den komplexen Verstrickungen der immunologischen Toleranz – sozusagen die »Blackbox« der Immunologie. Diese immunologische Toleranz ist so komplex, weil sie normalerweise in der Lage ist, harmlose von pathogenen Eindringlingen zu unterscheiden. In den letzten 5 Jahren ist deutlich geworden, dass das Immunsystem Signale aus der Umwelt mit verschiedenen, teilweise erst kürzlich entdeckten Zellen in Zusammenhänge setzt und diese Zellen in unterschiedlichen Differenzierungsschritten in bestimmte Muster einrasten lässt. Gerade das immunologische Gedächtnis ist ein Endprodukt dieser komplexen Verschachtelung und erlaubt dem Organismus schnell und dennoch ausgewogen auf Gefahren zu reagieren. Dieser Abschnitt versucht die wichtigsten Mechanismen, Zellen und Gene in ein gegenwärtiges Bild der Immuntoleranz zusammenzuführen.

Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Valenta R, Fiebig H, Kegel C, Disch R, Schmidt-Weber CB, Blaser K, Akdis CA (2004) Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 199(11): 1567–1575

Al-Alwan MM, Rowden G, Lee TD, West KA (2001) The dendritic cell cytoskeleton is critical for the formation of the immunological synapse. J Immunol 166(3): 1452–1456

Bacchetta R, Passerini L, Gambineri E, Dai M, Allan SE, Perroni L, Dagna-Bricarelli F, Sartirana C, Matthes-Martin S, Lawitschka A, Azzari C, Ziegler SF, Levings MK, Roncarolo MG (2006) Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest 116(6): 1713–1722

Balfour Sartor R (2007) Bacteria in Crohn’s disease: mechanisms of inflammation and therapeutic implications. J Clin Gastroenterol 41 Suppl 1: S37–43

Banchereau J, Pascual V, O’Garra A (2012) From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol 13(10): 925–931

Barlow JL, McKenzie AN (2014) Type-2 innate lymphoid cells in human allergic disease. Curr Opin Allergy Clin Immunol 14(5): 397–403

Bonito AJ, Aloman C, Fiel MI, Danzl NM, Cha S, Weinstein EG, Jeong S, Choi Y, Walsh MC, Alexandropoulos K (2013) Medullary thymic epithelial cell depletion leads to autoimmune hepatitis. J Clin Invest 123(8): 3510–3524

Bright JJ, Sriram S (1998) TGF-beta inhibits IL-12-induced activation of Jak-STAT pathway in T lymphocytes. J Immunol 161(4): 1772–1777

Bush RK, Wood RA, Eggleston PA (1998) Laboratory animal allergy. J Allergy Clin Immunol 102(1): 99–112

Carter NA, Rosser EC, Mauri C (2012) Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis. Arthritis Res Ther 14(1): R32

Castellani ML, Anogeianaki A, Felaco P, Toniato E, De Lutiis MA, Shaik B, Fulcheri M, Vecchiet J, Tete S, Salini V, Theoharides TC, Caraffa A, Antinolfi P, Frydas I, Conti P, Cuccurullo C, Ciampoli C, Cerulli G, Kempuraj D (2010) IL-35, an anti-inflammatory cytokine which expands CD4+CD25+ Treg Cells. J Biol Regul Homeost Agents 24(2): 131–135

Chen X, Wu X, Zhou Q, Howard OM, Netea MG, Oppenheim JJ (2013) TNFR2 is critical for the stabilization of the CD4+Foxp3+ regulatory T. cell phenotype in the inflammatory environment. J Immunol 190(3): 1076–1084

Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, Finkelstein D, Forbes K, Workman CJ, Brown SA, Rehg JE, Jones ML, Ni HT, Artis D, Turk MJ, Vignali DA (2010) IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 11(12): 1093–1101

Coutinho A, Carneiro-Sampaio M (2008) Primary immunodeficiencies unravel critical aspects of the pathophysiology of autoimmunity and of the genetics of autoimmune disease. J Clin Immunol 28 Suppl 1: S4–10

Dang VD, Hilgenberg E, Ries S, Shen P, Fillatreau S (2014) From the regulatory functions of B cells to the identification of cytokine-producing plasma cell subsets. Curr Opin Immunol 28: 77–83

De Benedetti F, Insalaco A, Diamanti A, Cortis E, Muratori F, Lamioni A, Carsetti R, Cusano R, De Vito R, Perroni L, Gambarara M, Castro M, Bottazzo GF, Ugazio AG (2006) Mechanistic associations of a mild phenotype of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome. Clin Gastroenterol Hepatol 4(5): 653–659

Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, Cianfarani F, Odorisio T, Traidl-Hoffmann C, Behrendt H, Durham SR, Schmidt-Weber CB, Cavani A (2009) Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 119(12): 3573–3585

Eyerich S, Onken AT, Weidinger S, Franke A, Nasorri F, Pennino D, Grosber M, Pfab F, Schmidt-Weber CB, Mempel M, Hein R, Ring J, Cavani A, Eyerich K (2011) Mutual antagonism of T cells causing psoriasis and atopic eczema. N Engl J Med 365(3): 231–238

Freitas do Rosario AP, Lamb T, Spence P, Stephens R, Lang A, Roers A, Muller W, O’Garra A, Langhorne J (2012) IL-27 promotes IL-10 production by effector Th1 CD4+ T cells: a critical mechanism for protection from severe immunopathology during malaria infection. J Immunol 188(3): 1178–1190

Geiser AG, Letterio JJ, Kulkarni AB, Karlsson S, Roberts AB, Sporn MB (1993) Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype. Proc Natl Acad Sci U S A 90(21): 9944–9948

Gomez G, Ramirez CD, Rivera J, Patel M, Norozian F, Wright HV, Kashyap MV, Barnstein BO, Fischer-Stenger K, Schwartz LB, Kepley CL, Ryan JJ (2005) TGF-beta 1 inhibits mast cell Fc epsilon RI expression. J Immunol 174(10): 5987–5993

Gorham JD, Guler ML, Fenoglio D, Gubler U, Murphy KM (1998) Low dose TGF-beta attenuates IL-12 responsiveness in murine Th cells. J Immunol 161(4): 1664–1670

Groux H, O’Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389(6652): 737–742

Guo Y, Wu W, Cen Z, Li X, Kong Q, Zhou Q (2014) IL-22-producing Th22 cells play a protective role in CVB3-induced chronic myocarditis and dilated cardiomyopathy by inhibiting myocardial fibrosis. Virol J 11(1): 2511

Hua F, Ji L, Zhan Y, Li F, Zou S, Chen L, Gao S, Li Y, Chen H, Cheng Y (2014) Aberrant frequency of IL-10-producing B cells and its association with Treg/Th17 in adult primary immune thrombocytopenia patients. Biomed Res Int 2014: 571302

Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY (1998) IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 160(7): 3555–3561

Johansson E, Harfast B, Johansson SG, van Hage-Hamsten M (1995) IgG1 and IgG4 antibody responses to the dust mite Lepidoglyphus destructor in a naturally exposed farming population. Allergy 50(6): 473–477

Karagiannidis C, Akdis M, Holopainen P, Woolley NJ, Hense G, Ruckert B, Mantel PY, Menz G, Akdis CA, Blaser K, Schmidt-Weber CB (2004) Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol 114(6): 1425–1433

Klein L, Klein T, Ruther U, Kyewski B (1998) CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is mediated by medullary thymic epithelium. J Exp Med 188(1): 5–16

Knodler A, Schmidt SM, Bringmann A, Weck MM, Brauer KM, Holderried TA, Heine AK, Grunebach F, Brossart P (2009) Post-transcriptional regulation of adapter molecules by IL-10 inhibits TLR-mediated activation of antigen-presenting cells. Leukemia 23(3): 535–544

Lepse N, Abdulahad WH, Rutgers A, Kallenberg CG, Stegeman CA, Heeringa P (2014) Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission. Rheumatol 53(9): 1683–1692

Levings MK, Roncarolo MG (2000) T-regulatory 1 cells: a novel subset of CD4 T cells with immunoregulatory properties. Journal Allergy Clin Immunol 106(1 Pt 2): S109–112

Levings MK, Gregori S, Tresoldi E, Cazzaniga S, Bonini C, Roncarolo MG (2005) Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 105(3): 1162–1169

Liu T, Peng L, Yu P, Zhao Y, Shi Y, Mao X, Chen W, Cheng P, Wang T, Chen N, Zhang J, Liu X, Li N, Guo G, Tong W, Zhuang Y, Zou Q (2012) Increased circulating Th22 and Th17 cells are associated with tumor progression and patient survival in human gastric cancer. J Clin Immunol 32(6): 1332–1339

Lombardi VC, Khaiboullina SF (2014) Plasmacytoid dendritic cells of the gut: relevance to immunity and pathology. Clin Immunol 153(1): 165–177

Lundgren M, Persson U, Larsson P, Magnusson C, Smith CI, Hammarstrom L, Severinson E (1989) Interleukin 4 induces synthesis of IgE and IgG4 in human B cells. Eur J Immunol 19(7): 1311–1315

Magnus T, Chan A, Grauer O, Toyka KV, Gold R (2001) Microglial phagocytosis of apoptotic inflammatory T cells leads to down-regulation of microglial immune activation. J Immunol 167(9): 5004–5010

Makrigiannakis A, Karamouti M, Drakakis P, Loutradis D, Antsaklis A (2008) Fetomaternal immunotolerance. Am J Reprod Immunol 60(6): 482–496

Mantel PY, Schmidt-Weber CB (2011) Transforming growth factor-beta: recent advances on its role in immune tolerance. Methods Mol Biol 677: 303–338

Mantel PY, Ouaked N, Ruckert B, Karagiannidis C, Welz R, Blaser K, Schmidt-Weber CB (2006) Molecular mechanisms underlying FOXP3 induction in human T cells. J Immunol 176(6): 3593–3602

Mantel PY, Kuipers H, Boyman O, Rhyner C, Ouaked N, Ruckert B, Karagiannidis C, Lambrecht BN, Hendriks RW, Crameri R, Akdis CA, Blaser K, Schmidt-Weber CB (2007) GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol 5(12): e329

Martinez-Gonzalez I, Roca O, Masclans JR, Moreno R, Salcedo MT, Baekelandt V, Cruz MJ, Rello J, Aran JM (2013) Human mesenchymal stem cells overexpressing the IL-33 antagonist soluble IL-1 receptor-like-1 attenuate endotoxin-induced acute lung injury. Am J Resp Cell Mol Biol 49(4): 552–562

McKenzie AN, Spits H, Eberl G (2014) Innate lymphoid cells in inflammation and immunity. Immunity 41(3): 366–374

Meiler F, Zumkehr J, Klunker S, Ruckert B, Akdis CA, Akdis M (2008) In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J Exp Med 205(12): 2887–2898

Merad M, Sathe P, Helft J, Miller J, Mortha A (2013) The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 31: 563–604

Nagato T, Kobayashi H, Yanai M, Sato K, Aoki N, Oikawa K, Kimura S, Abe Y, Celis E, Harabuchi Y, Tateno M (2007) Functional analysis of birch pollen allergen Bet v 1-specific regulatory T cells. J Immunol 178(2): 1189–1198

Noh J, Noh G, Kim HS, Kim AR, Choi WS (2012) Allergen-specific responses of CD19(+)CD5(+)Foxp3(+) regulatory B cells (Bregs) and CD4(+)Foxp3(+) regulatory T cell (Tregs) in immune tolerance of cow milk allergy of late eczematous reactions. Cell Immunol 274(1–2): 109–114

Ouaked N, Mantel PY, Bassin C, Burgler S, Siegmund K, Akdis CA, Schmidt-Weber CB (2009) Regulation of the foxp3 gene by the Th1 cytokines: the role of IL-27-induced STAT1. J Immunol 182(2): 1041–1049

Palucka K, Banchereau J (2013) Human dendritic cell subsets in vaccination. Curr Opin Immunol 25(3): 396–402

Park HS, Hong CS (1991) The significance of specific IgG and IgG4 antibodies to a reactive dye in exposed workers. Clin Exp Allergy 21(3): 357–362

Pennino D, Bhavsar PK, Effner R, Avitabile S, Venn P, Quaranta M, Marzaioli V, Cifuentes L, Durham SR, Cavani A, Eyerich K, Chung KF, Schmidt-Weber CB, Eyerich S (2013) IL-22 suppresses IFN-gamma-mediated lung inflammation in asthmatic patients. J Allergy Clin Immunol 131(2): 562–570

Pot C, Jin H, Awasthi A, Liu SM, Lai CY, Madan R, Sharpe AH, Karp CL, Miaw SC, Ho IC, Kuchroo VK (2009) Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J Immunol 183(2): 797–801

Qin S, Ma S, Huang X, Lu D, Zhou Y, Jiang H (2014) Th22 cells are associated with hepatocellular carcinoma development and progression. Chin J Cancer Res 26(2): 135–141

Riol-Blanco L, Delgado-Martin C, Sanchez-Sanchez N, Alonso CL, Gutierrez-Lopez MD, Del Hoyo GM, Navarro J, Sanchez-Madrid F, Cabanas C, Sanchez-Mateos P, Rodriguez-Fernandez JL (2009) Immunological synapse formation inhibits, via NF-kappaB and FOXO1, the apoptosis of dendritic cells. Nat Immunol 10(7): 753–760

Rutella S, Danese S, Leone G (2006) Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108(5): 1435–1440

Schmidt-Weber CB (2008) Th17 and treg cells innovate the TH1/TH2 concept and allergy research. Chem Immunol Allergy 94: 1–7

Sen P, Wallet MA, Yi Z, Huang Y, Henderson M, Mathews CE, Earp HS, Matsushima G, Baldwin AS, Jr., Tisch RM (2007) Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood 109(2): 653–660

Spiegelberg HL, O’Connor RD, Falkoff RJ, Beck L (1991) Interleukin-4 induced IgE and IgG4 secretion by B cells from atopic dermatitis patients. Int Arch Allergy Appl Immunol 94(1–4): 181–183

Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Ann Rev Immunol 21: 685–711

Strauss L, Czystowska M, Szajnik M, Mandapathil M, Whiteside TL (2009) Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin. PloS One 4(6): e5994

Thomson AW, Robbins PD (2008) Tolerogenic dendritic cells for autoimmune disease and transplantation. Ann Rheum Dis 67 Suppl 3: iii90–96

Torgerson TR, Ochs HD (2007) Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T cells. J Allergy Clin Immunol 120(4): 744–750; quiz 751–742

Trifari S, Spits H (2010) IL-22-producing CD4+ T cells: middle-men between the immune system and its environment. Eur J Immunol 40(9): 2369–2371

Wei X, Gong J, Zhu J, Wang P, Li N, Zhu W, Li J (2008) The suppressive effect of triptolide on chronic colitis and TNF-alpha/TNFR2 signal pathway in interleukin-10 deficient mice. Clin Immunol 129(2): 211–218

Yan T, Burkhardt H, Ritter T, Broker B, Mann KH, Bertling WM, von der Mark K, Emmrich F (1992) Specificity and T cell receptor beta chain usage of a human collagen type II-reactive T cell clone derived from a healthy individual. Eur J Immunol 22(1): 51–56

Yang XY, Wang HY, Zhao XY, Wang LJ, Lv QH, Wang QQ (2013) Th22, but not Th17 might be a good index to predict the tissue involvement of systemic lupus erythematosus. J Clin Immunol 33(4): 767–774

Yazdi AS, Ghoreschi K, Rocken M (2007) Inflammasome activation in delayed-type hypersensitivity reactions. J Invest Dermatol 127(8): 1853–1855

Akdis M, Akdis CA (2014) Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol 133(3): 621–631

Burks AW, Land MH (2014) Long-term follow-up of IgE-mediated food allergy: determining persistence versus clinical tolerance. Ann Allergy Asthma Immunol 112(3): 200–206

Casale TB, Stokes JR (2014) Immunotherapy: what lies beyond. J Allergy Clin Immunol 133(3): 612–619: quiz 620

Duan W, Croft M (2014) Control of regulatory T cells and airway tolerance by lung macrophages and dendritic cells. Ann Am Thorac Soc 11 Suppl 5: S306–313

Lynch JP, Mazzone SB, Rogers MJ, Arikkatt JJ, Loh Z, Pritchard AL, Upham JW, Phipps S (2014) The plasmacytoid dendritic cell: at the cross-roads in asthma. Eur Respir J 43(1): 264–275

Shevach EM, Thornton AM (2014) tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev 259(1): 88–102

Titel: Immunologische Toleranz und ihre Mechanismen
verfasst von: C. B. Schmidt-Weber, Prof. Dr. rer. nat.
Verlag: Springer Berlin Heidelberg
Buch: Allergologie
Print ISBN: 978-3-642-37202-5

Electronic ISBN: 978-3-642-37203-2

Copyright-Jahr: 2016
DOI: https://doi.org/10.1007/978-3-642-37203-2_11

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

11. Immunologische Toleranz und ihre Mechanismen

Zusammenfassung

Neu im Fachgebiet HNO

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

HNO-Op. auch mit über 90?

Intrakapsuläre Tonsillektomie gewinnt an Boden

Bilateraler Hörsturz hat eine schlechte Prognose

Update HNO

Springer Medizin

Zusammenfassung

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Neu im Fachgebiet HNO

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

HNO-Op. auch mit über 90?

Intrakapsuläre Tonsillektomie gewinnt an Boden

Bilateraler Hörsturz hat eine schlechte Prognose

Update HNO