Comparative Phylogeny of the Nasopharynx-Associated Lymphoid Tissue

  • Ryan D. Heimroth
  • Irene SalinasEmail author


Mucosal surfaces are the main points of contact between animal bodies and the external environment. The olfactory system of vertebrates is one of the most ancient and conserved sensory systems and is responsible for the rapid detection of chemical stimuli. Apart from chemosensory functions, olfactory systems have evolved to defend animal hosts from invading pathogens. Although we know very little about the biological principles that govern nasal immune responses in nonmammalian vertebrates, our knowledge has increased over the past few years. This chapter reviews the phylogeny of olfactory systems and their associated lymphoid tissue, the nasopharynx-associated lymphoid tissue, and highlights how nasal vaccination studies have illuminated some of the immunological aspects of nasal immune systems from teleost fish to mammals.


Phylogeny Mucosal immunity Nasal immunity NALT MALT Lymphocyte aggregates 


  1. Allison AC (1953) The morphology of the olfactory system in the vertebrates. Biol Rev 2:195–244CrossRefGoogle Scholar
  2. Amemiya CT et al (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature 496:311–316CrossRefGoogle Scholar
  3. Asanuma H et al (1997) Isolation and characterization of mouse nasal-associated lymphoid tissue. J Immunol Methods 202:123–131CrossRefGoogle Scholar
  4. Atta KI (2013) Morphological, anatomical and histological studies on the olfactory organs and eyes of teleost fish: Anguilla anguilla in relation to its feeding habits. J Basic Appl Zool 66:101–108CrossRefGoogle Scholar
  5. Brandtzaeg P, Kiyono H, Pabst R, Russel MW (2008) Terminology: nomenclature of mucosa-associated lymphoid tissue. Mucosal Immunol 1:31–37CrossRefGoogle Scholar
  6. Brykczynska U, Tzika AC, Rodriguez I, Milinkovitch MC (2013) Contrasted evolution of the vomeronasal receptor repertoires in mammals and squamate reptiles. Genome Biol Evol 5:389–401CrossRefGoogle Scholar
  7. Cesta MF (2006) Normal structure, function, and histology of mucosa-associated lymphoid tissue. Toxicol Pathol 34:599–608CrossRefGoogle Scholar
  8. Chang S et al (2013) The sea lamprey has a primordial accessory olfactory system. BMC Evol Biol 13:172CrossRefGoogle Scholar
  9. Davis SS (2001) Nasal vaccines. Adv Drug Deliv Rev 51:21–42CrossRefGoogle Scholar
  10. Debertin AS, Tschernig T, Tönjes H, Kleemann WJ, Tröger HD, Pabst R (2003) Nasal-associated lymphoid tissue (NALT): frequency and localization in young children. Clin Exp Immunol 134:503–507CrossRefGoogle Scholar
  11. Døving KB, Trotier D (1998) Structure and function of the vomeronasal organs. J Exp Biol 201:2913–2925PubMedGoogle Scholar
  12. Feng B, Bulchand S, Yaksi E, Friedrich RW, Jesuthasan S (2005) The recombination activation gene I (RagI) is expressed in a subset of zebrafish olfactory neurons but is not essential for axon targeting or amino acid detection. BMC Neurosci 6:46CrossRefGoogle Scholar
  13. Forero A et al (2017) Evaluation of the innate immune responses to influenza and live-attenuated influenza vaccine infection in primary differentiated human nasal epithelial cells. Vaccine 35:6112–6121CrossRefGoogle Scholar
  14. Galli SJ, Tsai M (2013) IgE and mast cells in allergic disease. Nat Med 18:693–704CrossRefGoogle Scholar
  15. Goldstine SN, Manickavel V, Choen N (1975) Phylogeny of gut-associated lymphoid tissue. Am Zool 15:107–118CrossRefGoogle Scholar
  16. Gomez G, Celii A (2008) The peripheral olfactory system of the domestic chicken: physiology and development. Brian Res Bull 76:208–216CrossRefGoogle Scholar
  17. González A, Morona R, López JM, Moreno N, Northcutt RG (2010) Lungfishes, like tetrapods, possess a vomeronasal system. Front Neuroanat 4:130PubMedPubMedCentralGoogle Scholar
  18. Guo P, Hirano M, Herrin BR, Li J, You C, Sadlonova A, Cooper MD (2009) Dual nature of the adaptive immune system in lampreys. Nature 459:796–801CrossRefGoogle Scholar
  19. Haley PJ (2003) Species differences in the structure and function of the immune system. Toxicology 188:49–71CrossRefGoogle Scholar
  20. Hamdani EH, Døving KB (2007) The functional organization of the fish olfactory system. Prog Neurobiol 82:80–86CrossRefGoogle Scholar
  21. Hathaway LJ, Kraehenbuhl JP (2000) The role of M cells in mucosal immunity. Cell Mol Life Sci 57:323–332CrossRefGoogle Scholar
  22. Heritage PL, Underdown BJ, Arsenault AL, Snider DP, McDermott MR (1997) Comparison of murine nasal-associated lymphoid tissue and Peyer’s patches. Am J Respir Crit Care Med 156:1256–1262CrossRefGoogle Scholar
  23. Jacobson ER et al (2014) Mycoplasmosis and upper respiratory tract disease of tortoises: a review and update. Vet J 201:257–264CrossRefGoogle Scholar
  24. Kang H, Wang H, Yu Q, Yang Q (2012) Effect of intranasal immunization with inactivated avian influenza virus on local and systemic immune responses in ducks. Poult Sci 91:1074–1080CrossRefGoogle Scholar
  25. Kang H, Yan M, Yu Q, Yang Q (2013) Characteristics of nasal-associated lymphoid tissue (NALT) and nasal absorption capacity in chicken. PLoS One 8:e84097CrossRefGoogle Scholar
  26. Kang H, Yan M, Yu Q, Yang Q (2014) Characterization of nasal cavity-associated lymphoid tissue in ducks. Anat Rec 297:916–924CrossRefGoogle Scholar
  27. Kermen F, Franco LM, Wyatt C, Yaksi E (2013) Neural circuits mediating olfactory-driven behavior in fish. Front Neural Circuits 7:62CrossRefGoogle Scholar
  28. Kiyono H, Fukuyama S (2004) NALT- versus Peyer’s-patch-mediated mucosal immunity. Nat Rev Immunol 4:699–710CrossRefGoogle Scholar
  29. Lacalli TC (2004) Sensory systems in amphioxus: a window on the ancestral chordate condition. Brain Behav Evol 64:148–162CrossRefGoogle Scholar
  30. Larragoite ET, Tacchi L, LaPatra SE, Salinas I (2016) An attenuated virus vaccine appears safe to the central nervous system of rainbow trout (Oncorhynchus mykiss) after intranasal delivery. Fish Shellfish Immunol 49:351–354CrossRefGoogle Scholar
  31. Malnic B, Godfrey PA, Buck LB (2003) The human olfactory receptor gene family. Proc Natl Acad Sci 101:2584–2589CrossRefGoogle Scholar
  32. Marschang RE (2011) Viruses infecting reptiles. Virus 3:2087–2126CrossRefGoogle Scholar
  33. Meredith TL, Kajiura SM (2010) Olfactory morphology and physiology of elasmobranchs. J Exp Biol 213:3449–3456CrossRefGoogle Scholar
  34. Nakamuta S, Nakamuta N, Taniguchi K, Taniguchi K (2012) Histological and ultrastructural characteristics of the primordial vomeronasal organ in lungfish. Anat Rec 295:481–491CrossRefGoogle Scholar
  35. Nei M, Niimura Y, Nozawa M (2008) The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity. Nat Rev Genet 9:951–963CrossRefGoogle Scholar
  36. Niimura Y (2009a) Evolutionary dynamics of olfactory receptor genes in chordates: interaction between environments and genomic contents. Hum Genomics 4:107–118CrossRefGoogle Scholar
  37. Niimura Y (2009b) On the origin and evolution of vertebrate olfactory receptor genes: comparative genome analysis among 23 chordate species. Genome Biol Evol 1:34–44CrossRefGoogle Scholar
  38. Niimura Y, Nei M (2003) Evolution of olfactory receptor genes in the human genome. Proc Natl Acad Sci 100:12235–12240CrossRefGoogle Scholar
  39. Ohshima K, Hiramatsu K (2000) Distribution of T-cell subsets and immunoglobulin-containing cells in nasal-associated lymphoid tissue (NALT) of chickens. Histol Histopathol 15:713–720PubMedGoogle Scholar
  40. Oikawa T, Suzuki K, Saito TR, Takahashi KW, Taniguchi K (1998) Fine structure of three types of olfactory organs in Xenopus laevis. Anat Rec 252:301–310CrossRefGoogle Scholar
  41. Olender T, Lancet D, Nebert DW (2008) Update on the olfactory receptor (OR) gene superfamily. Hum Genomics 3:87–97CrossRefGoogle Scholar
  42. Pancer Z, Amemiya CT, Ehrhardt GRA, Ceitlin J, Gartland GL, Cooper MD (2004) Somatic diversification of variable lymphocyte receptors in the agnathans sea lamprey. Nature 430:174–180CrossRefGoogle Scholar
  43. Perry M, Whyte A (1998) Immunology of the tonsils. Immunol Today 19:414–421CrossRefGoogle Scholar
  44. Saraiva LR, Ahuja G, Ivandic I, Syed AS, Marioni JC, Korsching SI, Logan DW (2015) Molecular and neuronal homology between the olfactory systems of zebrafish and mouse. Sci Rep 5:11487CrossRefGoogle Scholar
  45. Satoh G (2005) Characterization of novel GPCR gene coding locus in amphioxus genome: gene structure, expression, and phylogenetic analysis with implications for its involvement in chemoreception. Genesis 41:47–57CrossRefGoogle Scholar
  46. Schumacher J (2003) Reptile respiratory medicine. Vet Clin Exot Anim 6:213–231CrossRefGoogle Scholar
  47. Sepahi A, Salinas I (2016) The evolution of nasal immune systems in vertebrates. Mol Immunol 69:131–138CrossRefGoogle Scholar
  48. Sepahi A, Casadei E, Tacchi L, Muñoz P, LaPatra SE, Salinas I (2016) Tissue microenvironments in the nasal epithelium of rainbow trout (Oncorhynchus mykiss) define two distinct CD8α+ cell populations and establish regional immunity. J Immunol 197:4453–4463CrossRefGoogle Scholar
  49. Sepahi A, Tacchi L, Casadei E, Takizawa F, LaPatra SE, Salinas I (2017) CK12a, a CCL19-like chemokine that orchestrates both nasal and systemic antiviral immune responses in rainbow trout. J Immunol 199:3900–3913CrossRefGoogle Scholar
  50. Śmiałek M, Tykałowski B, Stenzel T, Koncicki A (2011) Local immunity of the respiratory mucosal system in chickens and turkeys. Pol J Vet Sci 14:291–297CrossRefGoogle Scholar
  51. Tacchi L, Musharrafieh R, Larragoite ET, Crossey K, Erhardt EB, Martion SAM, LaPatra SE, Salinas I (2014) Nasal immunity is an ancient arm of the mucosal immune system of vertebrates. Nat Commun 5:5205CrossRefGoogle Scholar
  52. Tacchi L, Larragoite ET, Muñoz P, Amemiya CT, Salinas I (2015) African lungfish reveal the evolutionary origins of organized mucosal lymphoid tissue in vertebrates. Curr Biol 25:2417–2424CrossRefGoogle Scholar
  53. Taniguchi K, Taniguchi K (2014) Phylogenic studies on the olfactory system in vertebrates. J Vet Med Sci 76:781–788CrossRefGoogle Scholar
  54. Taniguchi K, Saito S, Taniguchi K (2010) Phylogenic outline of the olfactory system in vertebrates. J Vet Med Sci 73:139–147CrossRefGoogle Scholar
  55. Volff JN (2005) Genome evolution and biodiversity in teleost fish. Heredity 94:280–294CrossRefGoogle Scholar
  56. Yoplak KE, Lisney TJ, Collin SP (2015) Not all sharks are “swimming noses”: variation in olfactory bulb size in cartilaginous fishes. Brain Struct Funct 2203:1127–1143CrossRefGoogle Scholar
  57. Zardoya R, Meyer A (1996) Evolutionary relationships of the coelacanth, lungfishes, and tetrapods based on the 28S ribosomal RNA gene. Proc Natl Acad Sci 93:5449–5454CrossRefGoogle Scholar
  58. Zhao K et al (2016) IgA response and protection following nasal vaccination of chickens with Newcastle disease virus DNA vaccine nanoencapsulated with Ag@SiO2 hollow nanoparticles. Sci Rep 6:25720CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Center for Evolutionary and Theoretical Immunology (CETI), Department of Biology, University of New MexicoAlbuquerqueUSA

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