Immunology of Fish


Innate immunity provides some form of defence against pathogens in all multicellular organisms but with cartilaginous and bony fish, although the lowest group of jawed vertebrates, the addition of a classic adaptive immune response becomes apparent. This provides the refinements of specificity for antigen recognition and memory. The T and B lymphocytes are the effector leucocytes, acquiring their antigen‐specific receptors (immunoglobulin for B cells and T‐cell receptor for T cells) in the anterior kidney (bone marrow being absent) and thymus. The B cells are responsible for the production of antibodies that function as different immunoglobulin classes, whereas subsets of T lymphocytes are capable of killing target cells or helping with B‐ and other T‐cell functions. Knowledge of these mechanisms is important for the use and design of vaccines, now so essential for the aquaculture industry, whereas studies of fish immunology contribute to the understanding of the evolution of adaptive immunity.

Key Concepts

  • Fish possess innate and adaptive immune responses, with classical adaptive immunity present only in jawed vertebrates.
  • Adaptive immunity allows memory of prior exposure to foreign molecules (antigens), so that on subsequent contact protective mechanisms are more rapidly mobilised: the basis of vaccination.
  • Lymphocytes mediate adaptive immunity and have surface receptors that recognise antigens, initiating the production of circulating antibodies and the activation of cell‐mediated responses.
  • The functions of the immune system are similar in fish and mammals although there are differences owing to the aquatic physiology and ectothermic nature of fish that provide evolutionary interest.
  • Leucocyte–antigen interactions take place in immune sites, such as the kidneys, spleen, gills and intestine. Bone marrow and lymph nodes are lacking.
  • Knowledge of fish immunology is proving essential for the development of vaccines for the expanding aquaculture industry.

Keywords: fish; haematopoiesis; immunology; inflammation; vaccines

Figure 1. Gene organisation of the IgM heavy chain seen in (a) cartilaginous fish and (b) bony fish.


Aas IB, Austbø L, König M, et al. (2014) Transcriptional characterization of the T cell population within the salmonid interbranchial lymphoid tissue. Journal of Immunology 193: 3463–3469.

Aggad D, Mazel M, Boudinot P, et al. (2009) The two groups of zebrafish virus‐induced interferons signal via distinct receptors with specific and shared chains. Journal of Immunology 183: 3924–3931.

Bajoghli B, Guo P, Aghaallaei N, et al. (2011) A thymus candidate in lampreys. Nature 470: 90–94.

Boehm T, McCurley N, Sutoh Y, et al. (2012) VLR‐based adaptive immunity. Annual Review of Immunology 30: 203–220.

Brudeseth BE, Wiulsrod R, Fredriksen BN, et al. (2013) Status and future perspectives of vaccines for industrialised fin‐fish farming. Fish and Shellfish Immunology 35: 1759–1768.

Castro R, Takizawa F, Chaara W, et al. (2013) Contrasted TCR beta diversity of CD8(+) and CD8(‐) T cells in rainbow trout. PLoS One 8: e60175.

Castro R, Bromage E, Abós B, et al. (2014) CCR7 is mainly expressed in teleost gills, where it defines an IgD+IgM− B lymphocyte subset. Journal of Immunology 192: 1257–1266.

Chang C‐I, Zhang Y‐A, Zou J, et al. (2006) Two cathelicidin genes are present in both rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). Antimicrobial Agents and Chemotherapy 50: 185–195.

Chang M‐X, Zou J, Nie P, et al. (2013) Intracellular interferons in fish: A unique means to combat viral infection. PLoS Pathogens 9: e1003736.

Chang C‐J, Sun B and Robertsen B (2015) Adjuvant activity of fish type I interferon shown in a virus DNA vaccination model. Vaccine 33: 2442–2448.

Chaves‐Pozo E, Pelegrín P, García‐Castillo J, et al. (2004) Acidophilic granulocytes of the marine fish gilthead seabream (Sparus aurata L.) produce interleukin‐1β following infection with Vibrio anguillarum. Cell and Tissue Research 316: 189–195.

Corripio‐Miyar Y, Zou J, Richmond H, et al. (2009) Identification of interleukin‐22 in gadoids and examination of its expression level in vaccinated fish. Molecular Immunology 46: 2098–2106.

Costa MM, Maehr T, Diaz‐Rosales P, et al. (2011) Bioactivity studies of rainbow trout (Oncorhynchus mykiss) interleukin‐6: Effects on macrophage growth and antimicrobial peptide gene expression. Molecular Immunology 48: 1903–1916.

Fillatreau S, Six A, Magadan S, et al. (2013) The astonishing diversity of Ig classes and B cell repertoires in teleost fish. Frontiers in Immunology 4 (1‐14): Article 28.

Fischer U, Koppang EO and Nakanishi T (2013) Teleost T and NK cell immunity. Fish and Shellfish Immunology 35: 197–206.

Gong Y‐F, Xiang L‐X and Shao J‐Z (2009) CD154‐CD40 interactions are essential for thymus‐dependent antibody production in zebrafish: insights into the origin of costimulatory pathway in helper T cell‐regulated adaptive immunity in early vertebrates. Journal of Immunology 182: 7749–7762.

Grayfer L, Hodgkinson JW and Belosevic M (2014) Antimicrobial responses of teleost phagocytes and innate immune evasion strategies of intracellular bacteria. Developmental and Comparative Immunology 43: 223–242.

Håstein T, Gudding R and Evensen Ø (2005) Bacterial vaccines for fish – an update of the current situation worldwide. Developments in Biologicals 121: 55–74.

Hedrick MS, Hillman SS, Drewes RC, et al. (2013) Lymphatic regulation in nonmammalian vertebrates. Journal of Applied Physiology 115: 297–308.

Hong S, Li R, Xu Q, Secombes CJ, et al. (2013) Two types of TNF‐α exist in teleost fish: Phylogeny, expression, and bioactivity analysis of type‐II TNF‐α3 in rainbow trout Oncorhynchus mykiss. Journal of Immunology 191: 5959–5972.

Husain M, Bird S, van Zwieten R, et al. (2012) Cloning of the IL‐1β3 gene and IL‐1β4 pseudogene in salmonids uncovers a second type of IL‐1β gene in teleost fish. Developmental and Comparative Immunology 38: 431–446.

Ma C, Ye J and Kaattari SL (2013) differential compartmentalization of memory B cells versus plasma cells in salmonid fish. European Journal of Immunology 43: 360–370.

Maier VH, Dorn KV, Gudmundsdottir BK, et al. (2008) Characterisation of cathelicidin gene family members in divergent fish species. Molecular Immunology 45: 3723–3730.

Martin SAM, Zou J, Houlihan DF, et al. (2007) Directional responses following recombinant cytokine stimulation of rainbow trout (Oncorhynchus mykiss) RTS‐11 macrophage cells as revealed by transcriptome profiling. BMC Genomics 8: 150.

Montgomery BC, Cortes HD, Mewes‐Ares J, et al. (2011) Teleost IgSF immunoregulatory receptors. Developmental and Comparative Immunology 35: 1223–1237.

Mulero I, Sepulcre MP, Meseguer J, et al. (2007) Histamine is stored in mast cells of most evolutionary advanced fish and regulates the fish inflammatory response. Proceedings of the National Academy of Sciences of the United States of America 104: 19434–19439.

Mulero I, Noga EJ, Meseguer J, et al. (2008) The antimicrobial peptides piscidins are stored in the granules of professional phagocytic granulocytes of fish and are delivered to the bacteria‐containing phagosome upon phagocytosis. Developmental and Comparative Immunology 32: 1531–1538.

Nomiyama H, Hieshima K, Osada N, et al. (2008) Extensive expansion and diversification of the chemokine gene family in zebrafish: identification of a novel chemokine subfamily CX. BMC Genomics 9: 222.

Østergaard AE, Martin SAM, Wang T, et al. (2009) Rainbow trout (Oncorhynchus mykiss) possess multiple novel immunoglobulin‐like transcripts containing either an ITAM or ITIMs. Developmental and Comparative Immunology 33: 525–532.

Page DM, Wittamer V, Bertrand JY, et al. (2013) An evolutionary conserved program of B‐cell development and activation in zebrafish. Blood 122: e1–e11.

Pijanowski L, Scheer M, Verburg‐van Kemenade BML, et al. (2015) Production of inflammatory mediators and extracellular traps by carp macrophages and neutrophils in response to lipopolysaccharide and/or interferon‐γ2. Fish and Shellfish Immunology 42: 473–482.

Sfacteria A, Brines M and Blank U (2015) The mast cell plays a central role in the immune system of teleost fish. Molecular Immunology 63: 3–8.

Shen L, Stuge TB, Zhou H, et al. (2002) Channel catfish cytotoxic cells: a mini‐review. Developmental and Comparative Immunology 26: 141–149.

Stachura DL, Svoboda O, Campbell CA, et al. (2013) The zebrafish granulocyte colony‐stimulating factors (Gcsfs): 2 paralogous cytokines and their roles in hematopoietic development and maintenance. Blood 122: 3918–3928.

Utke K, Bergmann S, Lorenzen N, et al. (2007) Cell‐mediated cytotoxicity in rainbow trout, Oncorhynchus mykiss, infected with viral haemorrhagic septicaemia virus. Fish and Shellfish Immunology 22: 182–196.

Utke K, Kock H, Schuetze H, et al. (2008) Cell‐mediated immune responses in rainbow trout after DNA immunization against viral hemorrhagic septicaemia virus. Developmental and Comparative Immunology 32: 239–252.

Xu J, Du L and Wen Z (2012) Myelopoiesis during zebrafish early development. Journal of Genetics and Genomics 39: 435–442.

Yoder JA and Litman GW (2011) The phylogenetic origins of natural killer receptors and recognition: relationships, possibilities, and realities. Immunogenetics 63: 123–141.

Yoon S, Mitra S, Wyse C, et al. (2015) First demonstration of antigen induced cytokine expression by CD4‐1+ lymphocytes in a poikilotherm: Studies in zebrafish (Danio rerio). PLoS One 10: e0126378.

Yu L‐P, Sun B‐G, Li J, et al. (2013) Characterization of a c‐type lysozyme of Scophthalmus maximus: expression, activity and antibacterial effect. Fish and Shellfish Immunology 34: 46–54.

Zhang Y‐A, Hikima J‐I, Li J, et al. (2009) Conservation of structural and functional features in a primordial CD80/86 molecule from rainbow trout (Oncorhynchus mykiss), a primitive teleost fish. Journal of Immunology 183: 83–96.

Zhang M, Long H and Sun L (2013) A NK‐lysin from Cynoglossus semilaevis enhances antimicrobial defense against bacterial and viral pathogens. Developmental and Comparative Immunology 40: 258–265.

Zhang H, Shen B, Wu H, et al. (2014) Th17‐like immune response in fish mucosal tissues after administration of live attenuated Vibrio anguillarum via different vaccination routes. Fish and Shellfish Immunology 37: 229–238.

Zhu C, Lee V, Finn A, et al. (2012) Origin of immunoglobulin isotype switching. Current Biology 22: 872–880.

Zhu L‐Y, Lin A‐F, Shao T, et al. (2014) B cells in teleost fish act as pivotal initiating APCs in priming adaptive immunity: an evolutionary perspective on the origin of the B‐1 cell subset and B7 molecules. Journal of Immunology 192: 2699–2714.

Zou J, Gorgoglione B, Taylor NGH, et al. (2014) Salmonids have an extraordinary complex type I interferon system: Characterisation of the IFN locus in rainbow trout Oncorhynchus mykiss reveals two novel IFN subgroups. Journal of Immunology 193: 2273–2286.

Zou J, Redmond AK, Qi Z, et al. (2015) The CXC chemokine receptors of fish: insights into CXCR evolution in the vertebrates. General and Comparative Endocrinology 215: 117–131.

Zwollo P, Cole S, Bromage E, et al. (2005) B cell heterogeneity in the teleost kidney: evidence for a maturation gradient from anterior to posterior kidney. Journal of Immunology 174: 6608–6616.

Zwollo P (2011) Dissecting teleost B cell differentiation using transcription factors. Developmental and Comparative Immunology 35: 898–905.

Further Reading

Belosevic M and Wiegertjes GF (2014) Special issue on Immunity to infectious diseases of fish. Developmental and Comparative Immunology 43: 129–312.

Flajnik MF and Kasahara M (2010) Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nature Reviews Genetics 11: 47–59.

Flajnik MF (2014) Re‐evaluation of the immunological Big Bang. Current Biology 24: R1060–R1065.

Gudding R, Lillehaug A and Evensen O (eds) (2014) Fish Vaccination, 404 pp. Wiley‐Blackwell: Chichester.

Rakers S, Niklasson L, Steinhagen D, et al. (2013) Antimicrobial peptides (AMPS) from fish epidermis: perspectives for investigative dermatology. Journal of Investigative Dermatology 133: 1140–1149.

Secombes CJ and Ellis AE (2012) The immunology of teleosts. In: Roberts RJ (ed.) Fish Pathology, 4th edn, pp. 144–166. Wiley‐Blackwell: Chichester.

Smith SL, Sim RB and Flajnik MF (eds) (2015) Immunobiology of the Shark, 307 pp. Boca Raton, FL: CRC Press.

Sunyer JO (2011) Special issue on Teleost fish immunology. Developmental and Comparative Immunology 35: 1193–1399.

Wang T and Secombes CJ (2013) The cytokine networks of adaptive immunity in fish. Fish and Shellfish Immunology 35: 1703–1718.

Zhu L, Nie L, Zhu G, et al. (2013) Advances in research of fish immune‐relevant genes: a comparative overview of innate and adaptive immunity in teleosts. Developmental and Comparative Immunology 39: 39–62.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Fletcher, Thelma C, and Secombes, Christopher J(Nov 2015) Immunology of Fish. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000520.pub3]