Complexity in immunology, from molecule to herd

Journal title PNEI REVIEW
Author/s Paolo Bellavite
Publishing Year 2018 Issue 2018/1 Language Italian
Pages 23 P. 18-40 File size 1229 KB
DOI 10.3280/PNEI2018-001003
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Although the complexity of the immune system is out of the question, the practical applications of vaccinology are often based on simplistic strategies based on "linear" thinking. In this paper the basic mechanisms of infection defenses are highlighted, paying particular attention to the molecular mechanisms of influenza virus antigens recognition. By identifying some types of antibodies against hemagglutinin, the molecular basis of autoimmunity to these antigens has also begun to be understood. Autoimmunity, in general, can be induced by infections in particular predisposed subjects, but it can also be a rare consequence of vaccination, due to the interaction between specific antigens, nonspecific adjuvants, macrophages and immune system. The complexity in vaccinology derives from many factors, related to the actual vaccination intervention (vaccine efficacy, coverage, herd effect) or emerging from the very use of large-scale vaccines (appearance of resistant strains, vaccinated people as carriers, shift of disease onset at adult age, concerns for adverse events). Identifying the critical points that still hinder a unanimous opinion on the various vaccines is the premise to promote their more effective use and to direct research towards objectives useful for this purpose.

Keywords: Complex systems, Biological defenses, Influenza, Autoimmunity, Adjuvants, Vaccinations.

  1. Agmon-Levin N., Arango M.T., Kivity S., Katzav A., Gilburd B., Blank M., Tomer N., Volkov A., Barshack I., Chapman J. and Shoenfeld Y. (2014). Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model. J. Autoimmun., 54: 21-32.
  2. Andrighetto G. and Zoller M. (1987). Activation of help and contrasuppression as essential prerequisites for immune response. J. Mol. Cell. Immunol., 3(4): 214.
  3. Avitsur R., Hunzeker J. and Sheridan J.F. (2006). Role of early stress in the individual differences in host response to viral infection. Brain Behav. Immun., 20(4): 339-348.
  4. Bagavant H., Nandula S.R., Kaplonek P., Rybakowska P.D. and Deshmukh U.S. (2014). Alum, an aluminum-based adjuvant, induces Sjogren’s syndrome-like disorder in mice. Clin.Exp Rheumatol., 32(2): 251-255.
  5. Ball F., Pellis L. and Trapman P. (2016). Reproduction numbers for epidemic models with households and other social structures II: Comparisons and implications for vaccination. Math. Biosci., 274: 108-139.
  6. Barnett T.C., Lim J.Y., Soderholm A.T., Rivera-Hernandez T., West N.P. and Walker M.J. (2015). Host-pathogen interaction during bacterial vaccination. Curr. Opin. Immunol., 36: 1-7.
  7. Bellavite P. (2009). La complessità in medicina. Fondamenti di un approccio sistemico e dinamico alla salute, alla malattia e alle terapie integrate. Milano: Tecniche Nuove.
  8. Bellavite P., Andrighetto G.C. e Zatti M. (1995). Omeostasi, Complessità e Caos. Un’introduzione. Milano: Franco Angeli.
  9. Bolker B.M. and Grenfell B.T. (1993). Chaos and biological complexity in measles dynamics. Proc. Biol. Sci., 251(1330): 75-81.
  10. Bolotin S., Harvill E.T. and Crowcroft N.S. (2015). What to do about pertussis vaccines? Linking what we know about pertussis vaccine effectiveness, immunology and disease transmission to create a better vaccine. Pathog. Dis., 73(8): ftv057.
  11. Bottaccioli F. (2003). Psiconeuroimmunologia. Como: Edizioni Red.
  12. Caksen H., Ozkan M., Cemek M. and Cemek F. (2014). Oxidant and antioxidant status in children with subacute sclerosing panencephalitis. J. Child Neurol., 29(11): 1448-1452. DOI: 10.1177/088307381349447
  13. Camini F.C., da Silva Caetano C.C., Almeida LT. and de Brito Magalhaes C.L. (2017) Implications of oxidative stress on viral pathogenesis. Arch. Virol., 162(4): 907-917.
  14. Cappelletti F., Clementi N., Mancini N., Clementi M. and Burioni R (2015). Virusinduced preferential antibody gene-usage and its importance in humoral autoimmunity. Semin. Immunol., 27(2): 138-143.
  15. Cardinale F., Ciofi degli Atti M., Bartolozzi G., Martire B., Moschese V. and Rizzo C. (2012). Basi genetiche della risposta immune alle vaccinazoni. Riv. Immunol. Allergol. Pediatr., 4: 38-54.
  16. Chan M.C., Cheung C.Y., Chui W.H., Tsao S.W., Nicholls J.M., Chan Y.O., Chan R.W., Long H.T., Poon L.L., Guan Y. and Peiris J.S. (2005). Proinfl ammatory cytokine responses induced by infl uenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir. Res., 6: 135. DOI: 10.1186/1465-9921-6-13
  17. Chang C.Y., Choi D.K., Lee D.K., Hong Y.J. and Park E.J. (2013). Resveratrol confers protection against rotenone-induced neurotoxicity by modulating myeloperoxidase levels in glial cells. PLoS ONE, 8(4): e60654.
  18. Croucher N.J., Chewapreecha C., Hanage W.P., Harris S.R., McGee L., van der Linden M., Song J.H., Ko K.S., de Lencastre H., Turner C, Yang F., Sa-Leao R., Beall B., Klugman
  19. K.P., Parkhill J., Turner P. and Bentley S.D. (2014). Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape. Genome Biol. Evol., 6(7): 1589-1602.
  20. Cruz-Tapias P., Blank M., Anaya J.M. and Shoenfeld Y. (2012). Infections and vaccines in the etiology of antiphospholipid syndrome. Curr. Opin. Rheumatol., 24(4): 389-393.
  21. Dalziel B.D., Bjornstad O.N., van Panhuis W.G., Burke D.S., Metcalf C.J. and Grenfell B.T. (2016). Persistent Chaos of Measles Epidemics in the Prevaccination United States Caused by a Small Change in Seasonal Transmission Patterns. PLoS Comput. Biol., 12(2): e1004655.
  22. De Martino M., Chiappini E. and Galli L. (2013). Vaccines and autoimmunity. Int. J. Immunopathol. Pharmacol., 26(2): 283-290. DOI: 10.1177/03946320130260020
  23. Donzelli A. and Demicheli V. (2018). Varicella vaccination: scientifi c reasons for a different strategic approach. Epidemiol. Prev., 40. [In press]
  24. Favoino E., Favia E.I., Digiglio L., Racanelli V., Shoenfeld Y. and Perosa F. (2014). Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice. Clin. Exp. Immunol., 175(1): 32-40.
  25. Ferrari M.J., Bansal S., Meyers L.A. and Bjornstad O.N. (2006). Network frailty and the geometry of herd immunity. Proc. Biol. Sci., 273(1602): 2743-2748.
  26. Fine P.E. (1993). Herd immunity: history, theory, practice. Epidemiol. Rev., 15(2): 265-302.
  27. Gerlier D. and Valentin H. (2009). Measles virus interaction with host cells and impact on innate immunity. Curr. Top. Microbiol. Immunol., 329, 163-191. DOI: 10.1007/978-3-540-70523-9_
  28. Gois P.H.F., Ferreira D., Olenski S. and Seguro A.C. (2017). Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?. Nutrients, 9(7): E651.
  29. Goldstein E., Paur K., Fraser C., Kenah E., Wallinga J. and Lipsitch M. (2009). Reproductive numbers, epidemic spread and control in a community of households. Math. Biosci., 221(1): 11-25.
  30. Gu X.X., Plotkin S.A., Edwards K.M., Sette A., Mills K.H.G., Levy O., Sant A.J., Mo A., Alexander W., Lu K.T. and Taylor C.E. (2017). Waning Immunity and Microbial Vaccines-Workshop of the National Institute of Allergy and Infectious Diseases. Clin. Vaccine Immunol., 24(7): e00034-17. DOI: 10.1128/CVI.00034-1
  31. Hayashi M. (2009). Oxidative stress in developmental brain disorders. Neuropathology, 29(1): 1-8.
  32. He H., Chen E.F., Li Q., Wang Z., Yan R., Fu J. and Pan J. (2013). Waning immunity to measles in young adults and booster effects of revaccination in secondary school students. Vaccine, 31(3): 533-537.
  33. Hegerle N. and Guiso N. (2014). Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines. Expert. Rev. Vaccines, 13(9): 1135-1146. DOI: 10.1586/14760584.2014.93225
  34. Hickman C.J., Hyde T.B., Sowers S.B., Mercader S., McGrew M., Williams N.J., Beeler J.A, Audet S., Kiehl B., Nandy R., Tamin A. and Bellini W.J. (2011). Laboratory characterization of measles virus infection in previously vaccinated and unvaccinated individuals. J. Infect. Dis., 204 Suppl 1: S549-S558.
  35. Israeli E., Agmon-Levin N., Blank M., Chapman J. and Shoenfeld Y. (2012). Guillain-Barre syndrome--a classical autoimmune disease triggered by infection or vaccination. Clin. Rev. Allergy Immunol., 42(2): 121-130.
  36. Jara L.J., Izquierdo E. and Medina G. (2017). Is the immune neuroendocrine system the connection between epipharyngitis and chronic fatigue syndrome induced by HPV vaccine? : Editorial. Immunol. Res, 65(1): 5-7.
  37. Kanduc D. and Shoenfeld Y. (2016). From HBV to HPV: Designing vaccines for extensive and intensive vaccination campaigns worldwide. Autoimmun Rev., 15(11): 1054-1061.
  38. Kilgore P.E., Salim A.M., Zervos M.J. and Schmitt H.J. (2016). Pertussis: Microbiology, Disease, Treatment, and Prevention. Clin. Microbiol. Rev., 29(3): 449-486. DOI: 10.1128/CMR.00083-1
  39. Kinsey S.G., Bailey M.T., Sheridan J.F., Padgett D.A. and Avitsur R. (2007). Repeated social defeat causes increased anxiety-like behavior and alters splenocyte function in C57BL/6 and CD-1 mice. Brain Behav. Immun., 21(4): 458-466.
  40. Kleine B., Rapp W., Wiesmuller K.H., Edinger M., Beck W., Metzger J., Ataulakhanov R., Jung G. and Bessler W.G. (1994). Lipopeptide-polyoxyethylene conjugates as mitogens and adjuvants. Immunobiology, 190(1-2): 53-66. DOI: 10.1016/S0171-2985(11)80283-
  41. Krause J.C. and Crowe J.E.Jr. (2014). Committing the Oldest Sins in the Newest Kind of Ways-Antibodies Targeting the Infl uenza Virus Type A Hemagglutinin Globular Head. Microbiol. Spectr., 2(5).
  42. Lin Y., Wang X., Huang X., Zhang J., Xia N. and Zhao Q. (2017). Calcium phosphate nanoparticles as a new generation vaccine adjuvant. Expert. Rev. Vaccines, 16(9): 895-906. DOI: 10.1080/14760584.2017.135573
  43. Nahas R. and Balla A. (2011). Complementary and alternative medicine for prevention and treatment of the common cold. Can. Fam. Physician, 57(1): 31-36.
  44. Ovsyannikova I.G., Schaid D.J., Larrabee B.R., Haralambieva I.H., Kennedy R.B. and Poland G.A. (2017). A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses. PLoS.ONE, 12(2): e0171261.
  45. Perdan-Pirkmajer K., Thallinger G.G., Snoj N., Cucnik S., Zigon P., Kveder T., Logar D., Praprotnik S., Tomsic M., Sodin-Semrl S. and Ambrozic A. (2012). Autoimmune response following infl uenza vaccination in patients with autoimmune infl amatory rheumatic disease. Lupus, 21(2): 175-183. DOI: 10.1177/096120331142981
  46. Perricone C., Ceccarelli F., Nesher G., Borella E., Odeh Q., Conti F., Shoenfeld Y. and Valesini G. (2014). Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases. Immunol. Res., 60(2-3): 226-235.
  47. Philippe P. and Mansi O. (1998). Nonlinearity in the epidemiology of complex health and disease processes. Theor. Med. Bioeth., 19(6): 591-607. DOI: 10.1023/A:100997930634
  48. Plsek P.E. and Greenhalgh T. (2001). The challenge of complexity in health care. BMJ, 323(7313): 625-628.
  49. Polak M. and Lutynska A. (2017). The importance of Bordetella pertussis strains which do not produce virulence factors in the epidemiology of pertussis. Postepy Hig. Med Dosw. (Online), 71(0): 367-379. DOI: 10.5604/01.3001.0010.382
  50. Poland G.A., Kennedy R.B., McKinney B.A., Ovsyannikova I.G., Lambert N.D., Jacobson R.M. and Oberg A.L. (2013). Vaccinomics, adversomics, and the immune response network theory: Individualized vaccinology in the 21st century. Semin. Immunol., 25(2): 89-103.
  51. Poland G.A., Ovsyannikova I.G. and Jacobson R.M. (2009). Adversomics: The Emerging Field of Vaccine Adverse Event Immunogenetics. Pediatr. Infect. Dis. J., 28(5): 431-432.
  52. Quintas C., Pinho D., Pereira C., Saraiva L., Goncalves J. and Queiroz G. (2014). Microglia P2Y6 receptors mediate nitric oxide release and astrocyte apoptosis. J. Neuroinfl ammation., 11: 141.
  53. Ravel G., Christ M., Horand F. and Descotes J. (2004). Autoimmunity, environmental exposure and vaccination: is there a link?. Toxicology, 196(3): 211-216.
  54. Rea K., Dinan T.G. and Cryan J.F. (2016). The microbiome: A key regulator of stress and neuroinfl ammation. Neurobiol. Stress, 4, 23-33.
  55. Relyveld E.H., Bizzini B. and Gupta R.K. (1998). Rational approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids. Vaccine, 16(9-10): 1016-1023. DOI: 10.1016/S0264-410X(97)00288-
  56. Rhodes C.J. and Anderson R.M. (1996). Power laws governing epidemics in isolated populations. Nature, 381(6583): 600-602.
  57. Rinaldi M., Perricone C., Ortega-Hernandez O.D., Perricone R. and Shoenfeld Y. (2014). Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines. Lupus, 23(6): 554-567. DOI: 10.1177/096120331349995
  58. Ruiz J.T., Lujan L., Blank M. and Shoenfeld Y. (2016). Adjuvants- and vaccinesinduced autoimmunity: animal models. Immunol.Res., 65(1): 55-65.
  59. Saeedan A.S., Singh I., Ansari M.N., Singh M., Rawat J.K., Devi U., Gautam S., Yadav R.K. and Kaithwas G. (2018). Effect of early natal supplementation of paracetamol on attenuation of exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in albino rats. Infl ammopharmacology. [Epub ahead of print]
  60. Soriano A., Nesher G. and Shoenfeld Y. (2015). Predicting post-vaccination autoimmunity: who might be at risk?. Pharmacol Res., 92: 18-22.
  61. Szenborn L., Tischer A., Pejcz J., Rudkowski Z. and Wojcik M. (2003). Passive acquired immunity against measles in infants born to naturally infected and vaccinated mothers. Med. Sci. Monit., 9(12): CR541-CR546.
  62. Terhune T.D. and Deth R.C. (2013). How aluminum adjuvants could promote and enhance non-target IgE synthesis in a genetically-vulnerable sub-population. J. Immunotoxicol., 10(2): 210-222. DOI: 10.3109/1547691X.2012.70836
  63. Tipton C.M., Fucile C.F., Darce J., Chida A., Ichikawa T., Gregoretti I., Schieferl S., Hom J., Jenks S., Feldman R.J., Mehr R., Wei C., Lee F.E., Cheung W.C., Rosenberg A.F. and Sanz I. (2015). Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat. Immunol., 16(7): 755-765.
  64. Toussirot E. and Bereau M. (2015). Vaccination and Induction of Autoimmune Diseases. Inflamm. Allergy Drug Targets, 14(2): 94-98. DOI: 10.2174/187152811466616010511304
  65. Trentini F., Poletti P., Merler S. and Melegaro A. (2017). Measles immunity gaps and the progress towards elimination: a multi-country modelling analysis. Lancet Infect. Dis., 17(10): 1089-1097. DOI: 10.1016/S1473-3099(17)30421-
  66. Trottier H. and Philippe P. (2005). Scaling properties of childhood infectious disease epidemics before and after mass vaccination in Canada. J. Theor. Biol., 235(3): 326-337.
  67. Trottier H., Philippe P. and Roy R. (2006). Stochastic modeling of empirical time series of childhood infectious diseases data before and after mass vaccination. Emerg. Themes. Epidemiol. 3: 9. DOI: 10.1186/1742-7622-3-
  68. Valyi-Nagy T. and Dermody T.S. (2005). Role of oxidative damage in the pathogenesis of viral infections of the nervous system. Histol. Histopathol., 20(3): 957-967. DOI: 10.14670/HH-20.95
  69. Viana P.O., Ono E., Miyamoto M., Salomao R., Costa-Carvalho B.T., Weckx L.Y. and de Moraes-Pinto M.I. (2010). Humoral and cellular immune responses to measles and tetanus: the importance of elapsed time since last exposure and the nature of the antigen. J. Clin. Immunol., 30(4): 574-582.
  70. Vygen S., Fischer A., Meurice L., Mounchetrou Njoya I., Gregoris M., Ndiaye B., Ghenassia A., Poujol I., Stahl J.P., Antona D., Le Strat Y., Levy-Bruhl D. and Rolland P. (2016). Waning immunity against mumps in vaccinated young adults, France 2013. Euro Surveill, 21(10): 30156. DOI: 10.2807/1560-7917.ES.2016.21.10.3015
  71. Wang B., Shao X., Wang D., Xu D. and Zhang J.A. (2017). Vaccinations and risk of systemic lupus erythematosus and rheumatoid arthritis: A systematic review and metaanalysis. Autoimmun. Rev., 16(7): 756-765.
  72. Warfel J.M. and Edwards K.M. (2015). Pertussis vaccines and the challenge of inducing durable immunity. Curr. Opin. Immunol., 35: 48-54.
  73. Whitaker J.A., Ovsyannikova I.G. and Poland G.A. (2015). Adversomics: a new paradigm for vaccine safety and design. Expert. Rev. Vaccines, 14(7): 935-947. DOI: 10.1586/14760584.2015.103824
  74. Wong S.S. and Yuen K.Y. (2006). Avian infl uenza virus infections in humans. Chest, 129(1): 156-168.
  75. Yang Q., Fu C., Dong Z., Hu W. and Wang M. (2014). The effects of weather conditions on measles incidence in Guangzhou, Southern China. Hum. Vaccin. Immunother, 10(4): 1104-1110.

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Paolo Bellavite, La complessità in immunologia, dalla molecola al gregge in "PNEI REVIEW" 1/2018, pp 18-40, DOI: 10.3280/PNEI2018-001003