期刊论文详细信息
BMC Systems Biology
Autoimmunity and tumor immunology: two facets of a probabilistic immune system
Pablo Villoslada2  Jaime Iranzo1 
[1] Current address: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA;Institute of Biomedical Research August Pi Sunyer (IDIBAPS), Hospital Clinic of Barcelona, Casanova 145, Cellex Center 3A, Barcelona, 08036, Spain
关键词: Mathematical modeling;    Antigen presentation/processing;    Tumor immunity;    Autoimmunity;    Comparative immunology/evolution;   
Others  :  1091765
DOI  :  10.1186/s12918-014-0120-4
 received in 2014-08-11, accepted in 2014-10-13,  发布年份 2014
PDF
【 摘 要 】

Background

The immune system of vertebrates has evolved the ability to mount highly elaborate responses to a broad range of pathogen-driven threats. Accordingly, it is quite a challenge to understand how a primitive adaptive immune system that probably lacked much of its present complexity could provide its bearers with significant evolutionary advantage, and therefore, continue to be selected for.

Results

We have developed a very simple model of the immune system that captures the probabilistic communication between its innate and adaptive components. Probabilistic communication arises specifically from the fact that antigen presenting cells collect and present a range of antigens from which the adaptive immune system must (probabilistically) identify its target. Our results show that although some degree of self-reactivity in the immune repertoire is unavoidable, the system is generally able to correctly target pathogens rather than self-antigens. Particular circumstances that impair correct targeting and that may lead to infection-induced autoimmunity can be predicted within this framework. Notably, the probabilistic immune system exhibits the remarkable ability to detect sudden increases in the abundance of rare self-antigens, which represents a first step towards developing anti-tumoral responses.

Conclusion

A simple probabilistic model of the communication between the innate and adaptive immune system provides a robust immune response, including targeting tumors, but at the price of being at risk of developing autoimmunity.

【 授权许可】

   
2014 Iranzo and Villoslada; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150128174121809.pdf 727KB PDF download
Figure 4. 14KB Image download
Figure 4. 39KB Image download
Figure 2. 24KB Image download
Figure 1. 40KB Image download
Figure 4. 14KB Image download
Figure 3. 19KB Image download
Figure 2. 24KB Image download
Figure 1. 40KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 1.

Figure 2.

Figure 4.

Figure 4.

【 参考文献 】
  • [1]Dunn GP, Old LJ, Schreiber RD: The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004, 21(2):137-148.
  • [2]Litman GW, Cannon JP, Dishaw LJ: Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol 2005, 5(11):866-879.
  • [3]Cooper MD, Alder MN: The evolution of adaptive immune systems. Cell 2006, 124(4):815-822.
  • [4]Boehm T: Evolution of vertebrate immunity. Curr Biol 2012, 22(17):R722-732.
  • [5]Boehm T, Bleul CC: The evolutionary history of lymphoid organs. Nat Immunol 2007, 8(2):131-135.
  • [6]Hedrick SM: The acquired immune system: a vantage from beneath. Immunity 2004, 21(5):607-615.
  • [7]Pradeu T, Jaeger S, Vivier E: The speed of change: towards a discontinuity theory of immunity? Nat Rev Immunol 2013, 13(10):764-769.
  • [8]Rimer J, Cohen IR, Friedman N: Do all creatures possess an acquired immune system of some sort? Bioessays 2014, 36(3):273-281.
  • [9]Burnett FM: The clonal selection theory of acquired immunity. Cambridge University Press, Cambridge, England; 1959.
  • [10]Bretscher P, Cohn M: A theory of self-nonself discrimination. Science 1970, 169(3950):1042-1049.
  • [11]Matzinger P: Tolerance, danger, and the extended family. Annu Rev Immunol 1994, 12:991-1045.
  • [12]Grossman Z, Paul WE: Adaptive cellular interactions in the immune system: the tunable activation threshold and the significance of subthreshold responses. Proc Natl Acad Sci U S A 1992, 89(21):10365-10369.
  • [13]van den Berg HA, Rand DA: Quantitative theories of T-cell responsiveness. Immunol Rev 2007, 216:81-92.
  • [14]van den Berg HA, Rand DA: Dynamics of T cell activation threshold tuning. J Theor Biol 2004, 228(3):397-416.
  • [15]Atlan H, Cohen IR: Immune information, self-organization and meaning. Int Immunol 1998, 10(6):711-717.
  • [16]Smith HR, Steinberg AD: Autoimmunity–a perspective. Annu Rev Immunol 1983, 1:175-210.
  • [17]Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD: Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002, 3(11):991-998.
  • [18]Bailey M, Christoforidou Z, Lewis M: Evolution of immune systems: specificity and autoreactivity. Autoimmun Rev 2013, 12(6):643-647.
  • [19]Janeway CA Jr: Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989, 54(Pt 1):1-13.
  • [20]Medzhitov R, Janeway CA Jr: Innate immunity: the virtues of a nonclonal system of recognition. Cell 1997, 91(3):295-298.
  • [21]Wucherpfennig KW: Mechanisms for the induction of autoimmunity by infectious agents. J Clin Invest 2001, 108(8):1097-1104.
  • [22]Mueller DL: Mechanisms maintaining peripheral tolerance. Nat Immunol 2010, 11(1):21-27.
  • [23]Smith KA: The quantal theory of immunity. Cell Res 2006, 16(1):11-19.
  • [24]Carreno LJ, Riquelme EM, Gonzalez PA, Espagnolle N, Riedel CA, Valitutti S, Kalergis AM: T-cell antagonism by short half-life pMHC ligands can be mediated by an efficient trapping of T-cell polarization toward the APC. Proc Natl Acad Sci U S A 2010, 107(1):210-215.
  • [25]Huppa JB, Davis MM: T-cell-antigen recognition and the immunological synapse. Nat Rev Immunol 2003, 3(12):973-983.
  • [26]Vendetti S, Chai JG, Dyson J, Simpson E, Lombardi G, Lechler R: Anergic T cells inhibit the antigen-presenting function of dendritic cells. J Immunol 2000, 165(3):1175-1181.
  • [27]Carneiro J, Leon K, Caramalho I, van den Dool C, Gardner R, Oliveira V, Bergman ML, Sepúlveda N, Paixão T, Faro J, Demengeot J: When three is not a crowd: a crossregulation model of the dynamics and repertoire selection of regulatory CD4+ T cells. Immunol Rev 2007, 216:48-68.
  • [28]Irvine DJ, Purbhoo MA, Krogsgaard M, Davis MM: Direct observation of ligand recognition by T cells. Nature 2002, 419:845-849.
  • [29]Klein L, Kyewski B, Allen PM, Hogquist KA: Positive and negative selection of the T cell repertoire: waht thymocytes see (and don’t see). Nat Rev Immunol 2014, 14:377-391.
  • [30]Ramirez-Montagut T, Turk MJ, Wolchok JD, Guevara-Patino JA, Houghton AN: Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity. Oncogene 2003, 22(20):3180-3187.
  • [31]Tan EM, Zhang J: Autoantibodies to tumor-associated antigens: reporters from the immune system. Immunol Rev 2008, 222:328-340.
  • [32]Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T: Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 2014, 14:135-146.
  • [33]Lleo A, Invernizzi P, Gao B, Podda M, Gershwin ME: Definition of human autoimmunity–autoantibodies versus autoimmune disease. Autoimmun Rev 2010, 9(5):A259-266.
  • [34]Tan EM: Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis. J Clin Invest 2001, 108:1411-1415.
  • [35]Lacombe J, Mangé A, Solassol J: Use of autoantibodies to detect the onset of breast cancer.J Immunol Res 2014, ᅟ:ᅟ. in press.
  • [36]Tan EM, Shi FD: Relative paradigms between autoantibodies in lupus and autoantibodies in cancer. Clin Exp Immunol 2003, 134(2):169-177.
  • [37]Bei R, Masuelli L, Palumbo C, Modesti M, Modesti A: A common repertoire of autoantibodies is shared by cancer and autoimmune disease patients: inflammation in their induction and impact on tumor growth. Cancer Lett 2009, 281(1):8-23.
  • [38]Tonack S, Jenkinson C, Cox T, Elliott V, Jenkins RE, Kitteringham NR, Greenhalf W, Shaw V, Michalski CW, Friess H, Neoptolemos JP, Costello E: iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance. Br J Cancer 2013, 108(9):1846-1853.
  • [39]Barlow LJ, Badalato GM, McKiernan JM: Serum tumor markers in the evaluation of male germ cell tumors. Nat Rev Urol 2010, 7(11):610-617.
  • [40]Norgard O, Singh G, Solberg S, Jorgensen L, Halvorsen AR, Smaaland R, Brustugun OT, Helland A: Novel molecular tumor cell markers in regional lymph nodes and blood samples from patients undergoing surgery for non-small cell lung cancer. Plos One 2013, 8:e62153.
  • [41]Croft NP, Smith SA, Wong YC, Tan CT, Dudek NL, Flesch IE, Lin LC, Tscharke DC, Purcell AW: Kinetics of antigen expression and epitope presentation during virus infection. PLoS Pathog 2013, 9(1):e1003129.
  • [42]Hassan C, Kester MG, de Ru AH, Hombrink P, Drijfhout JW, Nijveen H, Leunissen JA, Heemskerk MH, Falkenburg JH, van Veelen PA: The human leukocyte antigen-presented ligandome of B lymphocytes. Mol Cell Proteomics 2013, 12(7):1829-1843.
  • [43]Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ: Natural innate and adaptive immunity to cancer. Annu Rev Immunol 2011, 29:235-271.
  • [44]Lettre G, Rioux JD: Autoimmune diseases: insights from genome-wide association studies. Hum Mol Genet 2008, 17(R2):R116-121.
  • [45]Zenewicz LA, Abraham C, Flavell RA, Cho JH: Unraveling the genetics of autoimmunity. Cell 2010, 140(6):791-797.
  • [46]Goodnow CC: Multistep pathogenesis of autoimmune disease. Cell 2007, 130(1):25-35.
  • [47]Baxter AG: The origin and application of experimental autoimmune encephalomyelitis. Nat Rev Immunol 2007, 7(11):904-912.
  • [48]Damico FM, Kiss S, Young LH: Sympathetic ophthalmia. Semin Ophthalmol 2005, 20(3):191-197.
  • [49]Bergstrom CT, Antia R: How do adaptive immune systems control pathogens while avoiding autoimmunity? Trends Ecol Evol 2006, 21(1):22-28.
  • [50]Dishaw LJ, Litman GW: Changing views of the evolution of immunity. Front Immunol 2013, 4:122.
  • [51]Kasamatsu J: Evolution of innate and adaptive immune systems in jawless vertebrates. Microbiol Immunol 2013, 57(1):1-12.
  文献评价指标  
  下载次数:17次 浏览次数:1次