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Immune Defense

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Molecular Basis of Resilience
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Abstract

The world is full of life forms that threaten human health but they meet the most sophisticated immune defense system on Earth. The immune system continues to evolve shaped by changing pathogens. Pathogens counter with their own evolution probing for weak immune defenses. However, the ongoing emergence of new and re-emerging viral threats and drug resistant bacteria, fungi, and parasites mean immune defenses can rapidly adapt. This resilience is reflected in RNA transcripts that are part of the complex immune defense system.

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References

  • Agrawal A, Eastman QM, Schatz DG. Transposon mediated by RAG-1 and RAG-2 and its implications for the evolution of the immune system. Nature. 1998;394:744–51.

    Article  CAS  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.

    Article  CAS  Google Scholar 

  • Araki M, Chung D, Liu S, Rainbow DB, Chamberlain G, Garner V, et al. Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice. J Immunol. 2009;183(8):5146–57.

    Article  CAS  Google Scholar 

  • Arber W, Linn S. DNA modification and restriction. Annu Rev Biochem. 1969;38:467–500.

    Article  CAS  Google Scholar 

  • Ashman RF, Goeken JA, Latz E, Lenert P. Optimal oligonucleotide sequences for TLR9 inhibitory activity in human cells: lack of correlation with TLR9 binding. Int Immunol. 2011;23:203–14.

    Article  CAS  Google Scholar 

  • Baize S, Leroy EM, Georges AJ, Georges-Courbot MC, Capron M, Bedjabaga I, Lansoud-Soukate J, Mavoungou E. Inflammatory responses in Ebola virus-infected patients. Clin Exp Immunol. 2002;128:163–8.

    Article  CAS  Google Scholar 

  • Barti S, Baltimore D, Weissman IL. Molecular evolution of the vertebrate immune system. Proc Natl Acad Sci U S A. 1994;91:10769–70.

    Article  Google Scholar 

  • Beaulieu MJ, Li H, Bergeron J, Ross G, Auger FA, Rouabhia M. Involvement of male-specific minor histocompatibility antigen H-Y in epidermal equivalent allograft rejection. Cell Transplant. 1998;7:11–23.

    Article  CAS  Google Scholar 

  • Cai G, Anumanthan A, Brown JA, Greenfield EA, Zhu B, Freeman GJ. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat Immunol. 2008;9:176–85. https://doi.org/10.1038/ni1554.

    Article  CAS  PubMed  Google Scholar 

  • Chu JL, Brot N, Weissback H, Elkorn K. Lupus antiribosomal P antisera contain antibodies to a small fragment of 28S rRNA located in the proposed ribosomal GTPase center. J Exp Med. 1991;174:507–14.

    Article  CAS  Google Scholar 

  • Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180:5771–7.

    Article  CAS  Google Scholar 

  • De Sousa M. T lymphocytes and iron overload: novel correlations of possible significance to the biology of the immunological system. Mem Inst Oswaldo Cruz. 1992;87:23–9.

    Article  Google Scholar 

  • Ejrnaes M, Filippi CM, Martinic MM, Ling EM, Togher LM, Crotty S, von Herrath MG. Resolution of a chronic viral infection after interleukin-10 receptor blockade. J Exp Med. 2006;203:2461–72.

    Article  CAS  Google Scholar 

  • Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble CS, Kroeker AD, Iversen PL, Bavari S, Muhlberger K. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother. 2006;50(3):984–93.

    Article  CAS  Google Scholar 

  • Fabozzi G, Nabel CS, Ma D, Sullivan NJ. Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway. J Virol. 2011;85:2512–23. PubMed: 21228243

    Article  CAS  Google Scholar 

  • Field AK, Tyrell AA, Lampson GP, Hillman MR. Inducers of interferon and host resistance, II. Multiple synthetic polynucleotide complexes. Proc Natl Acad Sci U S A. 1967;58:1004–10.

    Article  CAS  Google Scholar 

  • Giltiay NV, Chappell CP, Sun X, Kolhatkar N, Teal TH, Wiedeman AE, Kim J, Tanaka L, Buechler MB, Hamerman JA, Imanishi-Kara T, Clark EA, Elkon KB. Overexpression of TLR7 promotes cell-intrinsic expansion and autoantibody production by transitional T1 B cells. J Exp Med. 2013;210:2773–89.

    Article  CAS  Google Scholar 

  • Giustiniani J, Bensussan A, Marie-Cardine A. Identification and characterization of a transmembrane isoform of CD160 (CD160-TM), a unique activating receptor selectively expressed upon human NK cell activation. J Immunol. 2009;182(1):63–71.

    Article  CAS  Google Scholar 

  • Good RA, Finstad J. The Gordon Wilson Lecture, “The development and involution of the lymphatic system and immunologic capacity.” Trans Am Clin Climatol Assoc. 1968;79:69–107.

    Google Scholar 

  • Grusel I, et al. Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. J Immunol. 2003;171:1393–400.

    Article  Google Scholar 

  • Hanawalt PC, Cooper PK, Ganesan AK, Smith CA. DNA repair in bacteria and mammalian cells. Annu Rev Biochem. 1979;48:783–836.

    Article  CAS  Google Scholar 

  • Hartmann G, Weeratna RD, Ballas ZK, Blackwell PS, Suparto I, Rasmusse WL, Waldschmidt M, Sajuthi D, Purcell RH, Davis HL, Krieg AM. Delineation of a CpG phophorothioate oligonucleotide for activating primate immune responses in vitro and in vivo. J Immunol. 2000;164:1617–24.

    Article  CAS  Google Scholar 

  • Hendrix CW, Margolik JB, Petty BG, Markham RB, Nerhood L, Farzadegan H, Tso POP, Lietman PS. Biologic effects after a single dose of poly(I):poly(C12U) in healthy volunteers. Antimicrob Agents Chemother. 1993;37(3):429–35.

    Article  CAS  Google Scholar 

  • Hwang SH, Lee H, Yamamoto M, Jones LA, Dayalan J, Hopkins R, Zhou XJ, Yarovinsky F, Connolly JE, Laffaille MAC, Wakeland EK, Fairhurst AM. B cell-TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in SLE-prone mice. J Immunol. 2012;189:5786–96.

    Article  CAS  Google Scholar 

  • Iversen PL. Chapter 26: In vivo studies with phosphorothioate oligonucleotides: rationale for systemic therapy. In: Crooke S, Lebleau B, editors. Antisense research and applications. Boca Raton: CRC Press; 1993.

    Google Scholar 

  • Iversen PL. Structure activity study of clinically observed adverse events and oligomer chemistry. J Drug Discov Develop Deliv. 2016;3(2):1022.

    Google Scholar 

  • Kahn LH. The growing number of immunocompromised. Bull At Sci. 2008;1:1–3.

    Google Scholar 

  • Kaiser S, Rimbach K, Eigenbrod T, Dalpke AH, Helm M. A modified dinucleotide motif specifies tRNA recognition by TLR7. RNA. 2014;20:1351–5.

    Article  CAS  Google Scholar 

  • Kandimalla ER, Agrawal S. Modulation of endosomal toll-like receptor-mediated immune responses by synthetic oligonucleotides. Adv Polym Sci. 2012;249:61–94.

    CAS  Google Scholar 

  • Kandimalla ER, Bhagat L, Wang D, Yu D, Sullivan T, La Monica N, Agrawal S. Design, synthesis and biological evaluation of novel antagonist compouinds of toll-like receptors 7, 8 and 9. Nucleic Acids Res. 2013;41(6):3947–61.

    Article  CAS  Google Scholar 

  • Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM. CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon γ. Proc Natl Acad Sci U S A. 1999;93:2879–83.

    Article  Google Scholar 

  • Krieg AM. CpG still rocks! update on an accidental drug. Nucleic Acid Ther. 2012;22(2):77–89.

    Article  CAS  Google Scholar 

  • Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182(2):459–65.

    Article  CAS  Google Scholar 

  • Krummel MF, Allison JP. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med. 1996;183(6):2533–40.

    Article  CAS  Google Scholar 

  • Kuhn JH. In: Calisher CH, editor. Filoviruses: a compendium of 40 years of epidemiological, clinical, and laboratory studies. New York: Springer-Verlag/Wein; 2008. p. 313.

    Google Scholar 

  • Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations. Lancet Infect Dis. 2009;9(8):493–504.

    Article  Google Scholar 

  • Litman GW, Cannon JP, Dishaw LJ. Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol. 2005;5(11):866–79.

    Article  CAS  Google Scholar 

  • Liu MF, Wang CR, Chen PC, Fung LL. Increased expression of soluble cytotoxic T-lymphocyte-associated antigen-4 molecule in patients with systemic lupus erythematosus. Scand J Immunol. 2003;57(6):568–72.

    Article  CAS  Google Scholar 

  • Luthra P, Ramanan P, Mire CE, Weisend C, Tsuda Y, Yen B, Liu G, Leung DW, Geisbert TW, Ebihara H, et al. Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome. Cell Host Microbe. 2013;14:74–84. PubMed: 23870315

    Article  CAS  Google Scholar 

  • Maiza H, Leca IG, Mansur IG, Schiavon V, Boumsell L, Bensussan A. A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity. J Exp Med. 1993;178:1121–6.

    Article  CAS  Google Scholar 

  • Market E, Papavasiliou FN. V(D)J recombination and the evolution of the adaptive immune system. PLoS Biol. 2003;1(1):024. https://doi.org/10.1371/journal.pbio.0000016.

    Article  CAS  Google Scholar 

  • Martin IV, NacNeill SA. ATP-dependent DNA ligases. Genome Biol. 2002;3(4). reviews3005.1–3005.7

    Article  Google Scholar 

  • Matsukura M, Zon G, Shiozuka K, Robert-Guroff M, Shimada T, Stein C, Mitsuya H, Wong-Staal F, Cohen JS, Broder S. Regulation of viral expression of human immunodeficiency virus in vitro by an antisense phosphorothioate oligodeoxyribonucleotide against rev (art/trs) in chronically infected cells. Proc Natl Acad Sci USA. 1989;86:4244.

    Article  CAS  Google Scholar 

  • Medzhitov R, Janeway CA. Innate immunity: the virtues of a nonclonal system of recognition. Cell. 1997;91:295–8.

    Article  CAS  Google Scholar 

  • Mourich DV, Jendrzejewski JL, Marshall NB, Hinrichs DJ, Iversen PL, Brand RM. Antisense targeting of cFLIP sensitizes activated T cells to undergo apoptosis and desensitizes responses to contact dermatitis. J Investig Dermatol. 2009;129(8):1945–53.

    Article  CAS  Google Scholar 

  • Mourich DV, Oda SK, Schnell FJ, Crumley SL, Hauck LL, Moentenich CA, Marshall NB, Hinrichs DJ, Iversen PL. Alternate splice forms of CTLA-4 induced by antisense mediated splice-switching, switching influences autoimmune diabetes susceptibility in NOD mice. Nucleic Acid Ther. 2014;24:114–26.

    Article  CAS  Google Scholar 

  • Peretz Y, He Z, Shi Y, Yassine-Diab B, Goulet JP, Bordi R, Filali-Mouhim A, Loubert JB, El-Far M, Dupuy FP, Boulassel MR, Tremblay C, Routy JP, Bernard N, Balderas R, Haddad EK, Sekaly RP. CD160 and PD-1 co-expression on HIV-specific CD8 T cells defines a subset with advanced dysfunction. PLoS Pathog. 2012a;8:e1002840.

    Article  CAS  Google Scholar 

  • Peretz Y, He Z, Shi Y, Yassine-Diab B, Goulet J-P, et al. CD160 and PD-1 co-expression on HIV-specific CD8 T cells defines a subset with advanced dysfunction. PLoS Pathog. 2012b;8(8):e1002840. https://doi.org/10.1371/journal.ppat.1002840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rinkevich B. Invertebrates versus vertebrate innate immunity: in the light of evolution. Scand J Immunol. 1999;50:456–60.

    Article  CAS  Google Scholar 

  • Simone R, Saverino D. The soluble CTLA-4 receptor and its emerging role in autoimmune diseases. Curr Immunol Rev. 2009;5(1):54–68.

    Article  CAS  Google Scholar 

  • Srahna M, Van Grunsven LA, Remacle JE, Vandenberghe P. CTLA-4 interacts with STAT5 and inhibits STAT5-mediated transcription. Immunology. 2006;117(3):396–401.

    Article  CAS  Google Scholar 

  • Stevenson M, Iversen PL. Inhibition of HIV mediated Cytopathicityby poly-L-lysine conjugated synthetic antisense Oligodeoxyribonucleotides. J Gen Virol. 1989;70:2673–82.

    Article  CAS  Google Scholar 

  • Strayer DR, et al. Activity of a synthetic dsRNA-Ampligen- in HIV disease. Clin Biotechnol. 1991;3:160–75.

    Google Scholar 

  • Strayer DR, Carter WA, Stouch BC, Stevens SR, Bateman L, et al. A double-blind, placebo-controlled, randomized, clinical trial of the TLR3 agonist Rintatolimod in severe cases of chronic fatigue syndrome. PLoS One. 2012;7(3):e31334.

    Article  CAS  Google Scholar 

  • Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal Os that spur autophagy and immunity. Immunol Rev. 2012;249:158–75.

    Article  CAS  Google Scholar 

  • Tu TC, Brown NK, Kim TJ, Wroblewska J, Yang X, Guo X, Lee SH, Kumar V, Lee KM, Fu YX. CD160 is essential for NK-mediated IFNγ production. J Exp Med. 2015;212(3):415–29.

    Article  CAS  Google Scholar 

  • Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003;423(6939):506–11.

    Article  CAS  Google Scholar 

  • Uhrberg M. The KIR gene family: life in the fast lane of evolution. Eur J Immunol. 2005;35:10–5.

    Article  CAS  Google Scholar 

  • Vijayakrishnan L, Slavik JM, Illes Z, Greenwald RJ, Rainbow D, Greve B, et al. An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity. 2004;20(5):563–75.

    Article  CAS  Google Scholar 

  • Villinger F, Rollin PE, Brar SS, Chikkala NF, Winter J, Sundstrom JB, Zaki SR, Swanepoel R, Ansari AA, Peters CJ. Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection. J Infect Dis. 1999;179(Suppl 1):S188–91.

    Article  CAS  Google Scholar 

  • Vollmer J, Krieg AM. Mechanisms and therapeutic applicatiions of immune modulatory oligodeoxynucleotide and oligoribonucleotide ligands for toll-like receptors. In: Crooke ST, editor. Antisense drug technology principles, strategies, and applications. Boca Raton: CRC Press; 2008. p. 747–72.

    Google Scholar 

  • Warfield KL, Swenson DL, Olinger GG, Nichols DK, Pratt WD, Blouch R, Stein DA, Aman MJ, Iversen PL, Bavari S. Gene-specific countermeasures against Ebola virus based on antisense Phosphorodiamidate Morpholino oligomers. PLoS Pathog. 2006;2(1):1–9.

    Article  Google Scholar 

  • Warren TK, Whitehouse CA, Wells J, Welch L, Charleston JS, Heald A, Nichols DK, Mattix ME, Palacios G, Kugleman JR, Iversen PL, Bavari S. Delayed time-to-treatment of an antisense morpholino oligomer is effective against lethal marburg Virus infection in Cynomolgus macaques. PLoS Negl Trop Dis. 2016;10(2):e0004456. PMID 26901785

    Article  Google Scholar 

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Iversen, P.L. (2018). Immune Defense. In: Molecular Basis of Resilience. Springer, Cham. https://doi.org/10.1007/978-3-319-98164-2_8

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