sign in sign up
<<
Home , Fish, Teleost

Review Article Veterinarni Medicina, 56, 2011 (10): 486–503

Innate and adaptive immunity in : a review

C. Uribe1, H. Folch2, R. Enriquez1, G. Moran1

1Faculty of Veterinary Science, Universidad Austral de , , Chile 2Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile

ABSTRACT: The immune system of fish is very similar to , although there are some important dif- ferences. Fish are free-living organisms from the embryonic stage of life in their aquatic environment. They have mechanisms to protect themselves from a wide variety of . Consequently, fish rely on their for an extended period of time, beginning at the early stages of embryogenesis. The components of the innate are divided into physical, cellular and humoral factors and include humoral and cellular receptor molecules that are soluble in plasma and other body fluids. The lymphoid organs found in fish include the , and . Immunoglobulins are the principal components of the immune response against pathogenic organisms. Immunomodulatory products, including nucleotides, glucans and probiotics, are increasingly used in production. The use of these products reduces the need for therapeutic treatments, enhances the effects of and, in turn, improves the indicators of production. The aim of this review is to provide a review of the immune system in fish, including the ontogeny, mechanisms of unspecific and acquired immunity and the action of some immunomodulators.

Keywords: fish; immune response; immunomodulators CRP = C-reactive ; ICM = intermediate cell mass; IHNV = infectious hematopoietic necrosis virus; IL = interleukin; INF = interferon; IPNV = infectious pancreatic necrosis virus; ISAV = infectious anaemia virus; LPS = ; MHC = Major histocompatibility complex; MMCs = melanomacrophage centers; SAA = serum amyloid protein; TCR = receptor; TLR = toll-like receptor; TNF = tumour necrosis factor; VHSV = viral haemorrhage septicaemia virus

Contents 5.10. Protease inhibitors 1. Introduction 5.11. Lysozyme 2. Ontogeny of the immune system 5.12. Natural 3. Lymphoid organs 5.13. Pentraxins 3.1. Thymus 5.14. Transferrin 3.2. Kidney 6. Specific immunity 3.3. Spleen 6.1. Antibodies 4. Cells involved in immune response 6.2. Immunological memory 5. Nonspecific immunity 6.3. Cellular cytotoxicity 5.1. Physical barriers 6.4. Cytokines involved in adaptive immunity 5.2. Nonspecific cellular cytotoxicity 7. Environmental effect on immune response 5.3. Antimicrobial peptides 8. Compounds that modulate the immune system 5.4. Phagocytosis in fish 5.5. Complement 8.1. Nucleotides 5.6. Tumor necrosis factor (TNF) 8.2. Glucans 5.7. Interferon (INF) 8.3. Probiotics 5.8. Interleukins (IL) 9. Concluding remarks 5.9. Others cytokines and chemokines 10. References

486 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article

1. Introduction response, the anterior kidney and thymus are con- sidered to be complete before hatching occurs in The immune system of fish is physiologically rainbow and Atlantic salmon ( salar) similar to that of higher vertebrates, despite cer- (Razquin et al., 1990); this has not been clarified at tain differences. In contrast to higher vertebrates, the end of incubation in many marine , in- fish are free-living organisms from early embry- cluding bream (Sparus aurata), and turbot onic stages of life and depend on their innate im- ( maximus). Despite these differences, mune system for survival (Rombout et al., 2005). the sequence of lymphomyeloid development Nonspecific immunity is a fundamental defence in marine is as follows: kidney, spleen and mechanism in fish. In addition, it plays an key role thymus (Mulero et al., 2007), but larval spleen has a in the acquired immune response and greater erythropoietic function than lymphopoetic through a system of receptor . These recep- function (Nakanishi, 1986; Schroder et al., 1998). tor proteins identify molecular patterns that are Cells of myeloid lineage can be found around the typical of pathogenic microorganisms, including sac from 24 hours post fertilization (hpf) but are polysaccharides, lipopolysaccharide (LPS), pep- not seen in the ICM. Myeloblasts and neutrophilic tidoglycan bacterial DNA, viral RNA and other myelocytes are observed between 34 and 48 hpf. molecules that are not normally on the surface of On the other hand, numerous erythrocytes circulate multicellular organisms. This response is divided in the blood vessels, and mature are into physical barriers and cellular and humoral im- found in the blood system in the connective tissue mune response. These inmunological parameters that surrounds the at 34 hpf and adjacent to include growth inhibitors, lytic , the classic the first renal tubules at 48 hpf. In addition, young complement pathways, the alternative and lectin myelocytes and neutrophils migrate through blood pathway, agglutinins and precipitins (opsonins and vessel walls during the same period. Mature neu- primary lectins), antibodies, cytokines, chemok- trophils are described in various tissues at 72 hpf ines and antibacterial peptides. Various internal (Willett et al., 1999). and external factors can influence innate immune On the other hand, the first appearance of IgM in response parameters. Temperature changes, stress varies considerably among fish species management and density may have suppressive ef- (Magnadottir et al., 2005). However, the first appear- fects on this type of response, while several ance of B-lymphocytes and immunoglobulins is late additives and immunostimulants can enhance their in marine species compared to species, efficiency (Magnadottir, 2006, 2010). and larvae have reached about 20–30 mm in length The aim of this review is to provide some back- when IgM is first expressed (Chantanachookhin ground on the immune system of fish, describing the et al., 1991; Magnadottir et al., 2005). In addition, ontogeny and core components, the nonspecific and Dalmo (2005) mentioned that the transfer of mater- adaptive immune mechanisms and elements that nal to and embryos has been demon- promote their actions as immunomodulators. strated in several species. Further, Magnadottir et al. (2005) suggest that the primary role of maternal anti- bodies is to protect the eggs against vertical transfer 2. Ontogeny of the immune system of certain or that maternal IgM may aid phagocytosis or the activation of complement path- The ontogeny of the immune system of teleost ways in early developmental stages; IgM may even fish has been studied in various species, includ- function simply as a nutritional yolk protein. ing ( mykiss), Finally, complement component C3 has been (Ictalurus punctatus), (Danio rerio) and found in unfertilised eggs in the spotted wolfish grouper (Acanthistius brasilianus). Teleosts have (Anarhichas minor Olafsen) indicating maternal been described as primitive models of hematopoi- transfer (Ellingsen et al., 2005). Using immunohisto- esis. The first hematopoietic organ is called the -in chemistry techniques, C3 has been found in several termediate cell mass (ICM). In kili (Pseudepiplatys different organs and tissues of developing and annulatus) and rainbow trout, hematopoiesis exists halibut (Lange et al., 2004a,b). These studies suggest for a short period in the yolk sac and then shifts to that complement may play a role in the generation of the ICM (Zapata et al., 2006). With respect to the different organs and not only in the defence against development of the organs involved in the immune invading pathogens (Dalmo, 2005). 487 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503

3. Lymphoid organs 2006). In rainbow trout, the kidney is well-devel- oped after hatching, when it mainly produces red The thymus, kidney (anterior and middle) and blood cells and granulocytes. Studies suggest the spleen are the largest lymphoid organs in teleosts presence of lymphoid cells that release IgM between (Zapata et al., 2006). In freshwater teleosts, the 12 and 14 days post fertilization (dpf) (Castillo et thymus is the first organ to become lymphoid, but al., 1993) and have also shown two variants of IgM before this event, the anterior kidney may contain by ELISA in embryos eight days before the end of hematopoietic progenitors, but not lymphocytes the incubation period (Sanchez et al., 1995). This (Lam et al., 2004). finding suggests that a source of B cells exists before the end of the incubation period in the kidney or in other hematopoietic sites. Structurally, the anterior 3.1. Thymus kidney is composed of a network of reticular fibres that provide support for tissue and are found This organ has two lobes, is homogeneous, and is scattered among hematopoietic system cells that represented by a thin sheet of oval lymphoid tissue line the sinusoid reticuloepithelium (Press et al., that is arranged subcutaneously in the dorsal com- 1994). The main cells found in the anterior kidney missure of the and is lined by mucous are , which aggregate into structures tissue of the pharyngeal epithelium (Ellis, 2001). called melanomacrophage centers (MMCs), and The structure that characterizes the thymus of lymphoid cells, which are found at all develop- fish is a capsule that surrounds the lymphoid bark mental stages and exist mostly as Ig+ cells (B cells) tissue. Basically, the thymus can be considered as (Press et al., 1994). Reticular cells play an important an aggregation of macrophages that promote the role in supplying the interactions necessary for the encapsulated proliferation of T cells (Davis et al., function of lymphoid cells (Press et al., 1994) and 2002). The differentiation of the thymic structure endothelial cells of sinusoids. The latter system is is highly variable in teleosts, and in many spe- the main component for blood filtering due to its cies, it is not possible to observe a clear differ- ability to perform endocytosis (Danneving et al., entiation between the cortex and medulla that is 1994). found in higher vertebrates (Bowden et al., 2005). Furthermore, myeloid cells and eosinophilic granu- lar cells can be found in this organ. Other studies 3.3. Spleen described the appearance of focal epithelial nests, known as Hassal’s corpuscles (Zapata et al., 2006). The spleen is composed of a system of splenic The thymus is responsible for the production of ellipsoids, MMCs and lymphoid tissue. In most spe- T cells. In zebrafish, thymus development involves cies, ellipsoids are clustered together and are organ- neural crest cells derived from the neuroectoderm, ized around the other two components (Ferguson, which migrate to the third and fourth pharyngeal 1989). The ellipsoids are thick-walled pouches and interact with the endoderm (Trede that open in the pulp and result from the et al., 2001). The early development of the thymus of the splenic arterioles. The cells along the walls has been studied in several teleost fish species, and are actively involved in the phagocy- development time differs between species accord- tosis of . Usually in the form of antibodies ing to the effects of temperature on growth. The or metabolic products, antigens may be detained relationship between growth and development is for long periods of time, which has an important dynamic, with physiological age expressed as de- role in immunological memory. The spleen in ze- gree days, and is not a factor for differences in his- brafish remains a small organ that contains large torical temperature (Bowden et al., 2005). amounts of eritroblast at 30 days post fertilization. At three months, when lymphoblasts are evident in the spleen, emerging ellipsoids are involved in 3.2. Kidney the capture of . A similar developmental pattern has been described for other teleost spleen, The kidney in teleost fish is the equivalent of the such as that of the Atlantic salmon, grouper and marrow in vertebrates and is the largest site catfish (Dos Santos et al., 2000; Petrie-Hanson and of until adulthood (Zapata et al., Ainsworth, 2000). 488 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article

4. Cells involved in immune response is able to react to different attacks (thickening and cellular hyperplasia), and its integrity is essential for Fish possess populations that are anal- osmotic balance and to prevent the entry of foreign ogous to T cells, B cells, cytotoxic cells (similar to agents (Hibiya, 1994). On the other hand, defending natural killer cells), macrophages and polymorpho- cells are present, such as lymphocytes, macrophages nuclear leukocytes. The immune system of teleosts and eosinophilic granular cells (Sveinbjornsson et has sub-populations of T lymphocytes that exhibit al., 1996; Ellis, 2001; Fischer et al., 2006). differential responses to mitogens, B cell acute al- lograft reactions, mixed leukocyte reactions and co- operative interactions between T cells, B cells and 5.2. Nonspecific cellular cytotoxicity macrophages that are essential for the production of antibodies. Moreover, elasmobranch and teleost fish In , nonspecific response situations are are the most primitive groups that possess the Major mainly executed by cytotoxic cells, known as natu- Histocompatibility Complex (MHC) and T cell re- ral killer cells. Although the nonspecific cytotoxic ceptor (TCR) (Manning and Nakanishi, 1996). cells of catfish are morphologically distinct from the large granular lymphocytes of mammals, they are suggested to be functionally similar (Evans and 5. Nonspecific immunity Jaso-Friedmann, 1992). These cells are able to elim- inate a range of spontaneously xenogeneic targets, In fish, the innate response has been considered including parasites in fish and traditional targets an essential component in combating pathogens of natural killer cells in mammals (Hasegawa et al., due to limitations of the , 1998). Unlike the natural killer cells of mammals, their poikilothermic nature, their limited repertoire the nonspecific cytotoxic cells of catfish are agranu- of antibodies and the slow proliferation, maturation lar, small lymphocytes that are commonly found in and memory of their lymphocytes (Whyte, 2007). It lymphoid tissues, such as the anterior kidney and is commonly divided into three compartments: the spleen, but are rarely found in the blood (Shen et al., epithelial/mucosal barrier, the humoral parameters 2002). In addition to the case in catfish, nonspecific and the cellular components. The epithelial and cytotoxic cells have shown activity in other fish spe- mucosal barrier of the , and alimentary cies, including rainbow trout (Greenle et al., 1991), tract is an extremely important disease barrier in common (Cyprinus carpio) (Hinuma et al., fish, being constantly immersed in media contain- 1980; Suzumura et al., 1994), damsel fish (Dascyllus ing potentially harmful agents (Magnadottir, 2010). albisella) (McKinney and Achmale, 1994) and tila- This type of response requires a series of mecha- pia (Oreochromis spp.) (Faisal et al., 1989). nisms that involve humoral factors, cell and tissue, antimicrobial peptides and complement factors. Humoral factors may be cellular receptors or mol- 5.3. Antimicrobial peptides ecules that are soluble in plasma and other body fluids (Magnadottir, 2006; Subramanian et al., 2007; Studies of the integument and integument secre- Subramanian et al., 2008) tions of fish (Hellio et al., 2002) have demonstrated an important role for this system in defence against viruses and bacteria (Ellis, 2001; Chinchar 5.1. Physical barriers et al., 2004; Maier et al., 2008). These peptides have been found in the , and tissue Flakes, skin mucus and gills act as the first bar- of teleost fish (Birkemo et al., 2003). These low rier to infection (Ingram, 1980; Shepard, 1994; Ellis, molecular weight polypeptides have the ability to 2001). The mucus of fish contains lectins, pentrax- break down bacterial walls (Ellis, 2001). ins, lysozymes, complement proteins, antibacterial peptides and immunoglobulin M (IgM), which have an important role in inhibiting the entry of patho- 5.4. Phagocytosis gens (Alexander and Ingram, 1992; Rombout et al., 1993; Aranishi and Nakane, 1997; Boshra et al., 2006; Phagocytosis is one of the most important Saurabh and Sahoo, 2008). In addition, the processes in poikilothermic because it is 489 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503 the process that is least influenced by tempera- erful chemokine to macrophages and neutrophils ture (Blazer, 1991; Lange and Magnadottir, 2003; that have receptors for C3, the central complement Magnadottir et al., 2005). The main cells involved molecule which is a part of all three pathways, and in phagocytosis in fish are neutrophils and macro- which remains attached to the bacteria, favouring phages (Secombes and Fletcher, 1992). These cells phagocytosis (Jenkins and Ourth, 1993). Teleost remove bacteria mainly by the production of reac- C3 is composed of a disulfide-linked two-chain (a tive species during a respiratory burst. In and b) glycoprotein containing a thioester bond addition, neutrophils possess myeloperoxidase in comparable to C3 from several species their cytoplasmic granules, which in the presence (Magdanottir et al., 2005). of halide and hydrogen peroxide kills bacteria by halogenation of the bacterial cell wall. Moreover, these cells have lysozymes and other hydrolytic 5.6. Tumor necrosis factor (TNF) enzymes in their lysosomes (Fischer et al., 2006). Similarly, macrophages can produce nitric oxide Several studies in fish have provided direct evi- in mammals and can be as potent as antibacte- dence suggesting that TNF-α and -β are impor- rial agents, peroxynitrites and hydroxyl groups tant activators of macrophages. Studies in rainbow (Secombes and Fletcher, 1992). trout, turbot, bream (Sparus aurata), (Carassius auratus) and catfish have shown that TNF causes the activation of macrophages, leading 5.5. Complement to increased respiratory activity, phagocytosis and nitric oxide production (Yin et al., 1997; Mulero The complement system in teleosts, as well as and Meseguer, 1998; Tafalla et al., 2001). that in higher vertebrates, can be activated in three ways: the classical pathway, which is triggered by antibody binding to the cell surface (Holland and 5.7. Interferon (INF) Lambris, 2002), the alternative pathway, which is independent of antibodies and is activated di- INFα and β are cytokines with a nonspecific anti- rectly by foreign microorganisms, and the lectin viral function that is based on the inhibition of nu- pathway, which is activated by the binding of a cleic acid replication within infected cells. INF plays protein complex consisting of mannose/mannan- an important role in the defence against viral infec- binding lectin in bacterial cells (Sakai, 1992). tion in vertebrate host cells, which secrete INFα/β However, the mechanisms and molecules involved upon recognition of viral nucleic acid (Robertsen, in this system in teleosts are not well understood, 2006). These INFs protect other cells from viral with the exception of the genetic sequence of the infection by binding to different receptors, which mannose-binding lectin protease that is associated results in the induction of several hundred genes with serum (Matsushita et al., 1998; Nikoskelainen that are stimulated by INF (ISGs). Some of these et al., 2002). Studies suggest that the alternative genes encode antiviral proteins, such as protein MX complement pathway is of great importance in (MX), protein kinase dsRNA activated (PKR) and the innate immune response in teleost fish (Yano, 2,5-oligoadenylate synthetase (OAS) (De Veer et 1996). The activity of complement-opsonized tel- al., 2001; Samuel, 2001). Two interferons (INFα-1 eosts has been documented in a variety of species, and INFα-2) have been cloned from the Atlantic such as (Matsuyama et al., 1992), salmon and were characterized with respect to their catfish (Jenkins and Ourth, 1993) and salmonids sequence, gene structure, promoters and induction (Lammens et al., 2000). Salmonid antibodies, in of antiviral activity of interferon-stimulated genes the presence of complement proteins, are able to (ISG) (Killeng et al., 2007; Rokenes et al., 2007). neutralize enveloped viruses, including the infec- The INFα-1 Atlantic salmon induces the expression tious hematopoietic necrosis virus (IHNV) and of MX and ISGs, and both have similar properties the viral haemorrhagic septicaemia virus (VHSV) to INFα/β and INFγ in mammals (Rokenes et al., (Lorenzen and La Patra, 1999). In bacterial infec- 2007). Furthermore, INFα-1 in Atlantic salmon in- tions, complement activation by lipopolysaccharide duces a potent antiviral activity against infectious found in the cell wall of gram-negative pathogenic pancreatic necrosis virus (IPNV) in cells. However, bacteria stimulates C5a factor production, a pow- this cytokine does not protect Atlantic salmon cells 490 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article against infectious salmon anaemia virus (ISAV), also involved in the cascade leading to an inflam- suggesting that this virus must have developed matory response for this type of bacteria (Savan mechanisms to counteract the antiviral activity of and Sakai, 2006). Further, cytokines involved in INF (Killeng et al., 2007). Moreover, INFα-2 ex- leukocyte differentiation, including pressed recombinantly in Atlantic salmon was also colony stimulating factor (CSF) (Arma et al., 2004), confirmed to confer antiviral activity against IPNV macrophage-CSF (Hanington et al., 2007) and IL-7 (Ooi et al., 2008). Some authors suggest that rain- (Kono et al., 2008), are all identified in fish. On the bow trout have at least three INFs (Zou et al., 2007). other hand, chemokines are also present and in Rainbow trout (INF1 (rtl INF1) and INF2 (rtl INF2) some fish species considerable numbers of genes show sequences similar to INFα-1 and INF-2 in have now been identified (DeVries et al., 2006); Atlantic salmon. Rainbow trout INF 3 (rtl INF 3) is however, many have no clear homologues in other related to INFα in mammals and fish, as shown by vertebrate groups and their function remains to be the conservation of four cysteine residues. The rtl determined (Secombes, 2008). INF1 and 2 proteins have been shown to regulate the production of MX, inhibiting the proliferation of VHSV in cell lines from the gonad of rainbow 5.10. Protease inhibitors trout (GTR 2). Moreover, rtl INF 3 has been proven to be a poor inducer of antiviral activity. It is worth Several protease inhibitors are present in the noting that these three INFs in rainbow trout show serum and other body fluids of fish (Bowden et differential expression across cells and tissues, sug- al. 1997). The main function of protease inhibi- gesting that they have different functions in the fish tors is to maintain body fluid homeostasis. These immune system (Zou et al., 2007). molecules are involved in acute phase reactions and defence against pathogens that secrete pro- teolytic enzymes (Magdanottir, 2010). The most 5.8. Interleukins (IL) widely studied of the protease inhibitors is the α-2 macroglobulin, which has a high specificity for IL-1 in mammals is comprised of 10 ligands inhibiting the physical encapsulation of protease and 10 protein receptor molecules and plays an (Armstrong and Quigley, 1999). important role in and host defence (Dinarello, 1997). IL-1β has been detected in 13 tel- eost fish species and is involved in the regulation of 5.11. Lysozyme immunity through the stimulation of T cells. The function of IL-1β in these fish species is analo- Lysozyme is a bacteriolytic that is widely gous to mammalian IL-1β (Mathew et al., 2002; distributed throughout the body and is part of the Magnadottir, 2010). In teleost fish, IL-1 receptors nonspecific defence mechanisms in most animals. have been cloned and sequenced from the rainbow In salmonids, lysozyme has been detected in se- trout and Atlantic salmon. The expression of the rum, secretions, mucous membranes and tissues IL-1 receptor in salmon appears to be constitutive rich in leucocytes, mainly the kidney and intestine in all tissues tested and is regulated in the ante- (Grinde et al., 1988; Lie et al., 1989). Apparently, rior kidney, spleen, liver and gills after stimula- the main sources of lysozyme are monocytes/ tion with LPS and TNF-α, suggesting a role for macrophages and neutrophils. However, recent the IL-1 receptor in regulating IL-1β during the studies have detected this enzyme in the granules inflammatory response (Sangrador-Vegas et al., of the eosinophilic granular cells of the intestine 2000; Subramaniam et al., 2002). (Sveinbjornsson et al., 1996). The bactericidal ac- tion of this enzyme involves the hydrolyzation of the peptidoglycan of bacterial cell walls resulting 5.9. Others cytokines and chemokines in cell lysis. Lysozyme was initially associated with the defence against Gram-positive bacteria, but has As described above, TNF-α and IL-1β are cy- been found to lyse Gram-negative bacteria as well. tokines involved in the induction of inflamma- Furthermore, this enzyme is known to trigger an tory responses to Gram negative bacteria in fish. opsonin of the complement system and phagocytic In addition, it has been demonstrated that IL-6 is cells (Magnadottir, 2006). 491 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503

5.12. Natural antibodies 5.14. Transferrin

Natural antibodies are produced in fish at a level is an essential element in the establishment that is regulated in the absence of antigenic stimu- of infection by many pathogens, but the availability lation of cells that are equivalent to B1 cells (Boes, of iron in the tissue fluids of vertebrates is extremely 2000). These natural antibodies are found in high low due to its high affinity for the blood protein levels in the serum of fish, where they provide im- transferrin. Only bacteria with high affinity systems mediate and broad protection against bacterial and for iron absorption are able to maintain sufficient viral pathogens, making these factors key compo- iron levels to grow in vivo (Ellis, 2001; Stafford and nents of nonspecific immunity. Natural antibodies Belosevic, 2003). Transferrin is a globular glycopro- are also linked to adaptive immunity. Teleost fish tein with a high iron chelator activity. This protein is are capable of generating specific IgM-type natural the major iron ion transport protein in animals and antibodies against various antigens. The intensity plants. Transferrin has a high degree of genetic poly- of this response, however, has been shown to vary morphism in all species and is found in the serum between different species and environmental con- and secretions of all vertebrates. Pathogenic bacteria ditions (Whyte, 2007). have developed a set of mechanisms to obtain iron from the host, even from transferrin. However, be- cause of the high degree of genetic polymorphism 5.13. Pentraxins and the ability of certain bacterial pathogens to obtain iron from transferring, this protein may be C-reactive protein (CRP) and serum amyloid restricted to certain genotypes. In protein (SAA) are present in the body fluids of (Oncorhynchus kisutch), three genotypes have been vertebrates and and are commonly identified with respect to transferrin: AA, AC and associated with the acute phase response of in- CC. In some strains of coho salmon that originate flammation (Bayne and Gerwick, 2001; Wu et al., in Oregon, increasing resistance against bacterial 2003). The expression of CRP has been reported in kidney disease has been associated with the C allele several teleost fish species, including rainbow trout of transferrin (Suzumoto et al., 1997). However, the (Hoover et al., 1998), catfish (Szalai et al., 1992), latter has not been confirmed for two strains of coho Atlantic salmon, common cod (Gadus morhua), salmon that are native to British Columbia (Withler halibut (Hippoglossus hippoglossus) and dog fish and Evelyn, 1990). ( malabaricus) (Lund and Olafsen, 1998). The levels of these proteins are increased upon tis- sue injury, trauma or infection. These proteins play 6. Specific immunity an active role in the immune system (Cook et al., 2003), activation of the classical complement path- The specific immune response occurs through way (De Haas et al., 2000) and the removal of ap- mechanisms that involve a complex network of spe- optotic cells (Nauta et al., 2003). Different stimuli, cialized cells, proteins, genes and biochemical mes- such as tissue damage, trauma or infection, have sages that provide the means necessary for the body been shown to generate various patterns of CRP to respond specifically to antigens, antibodies and production in teleost fish, in which either the level effector cells with high specificity and affinity. of CRP is decreased in serum (negative acute phase protein) (Szalai et al., 1994; Liu et al., 2004) or the level of CRP is increased in serum (positive acute 6.1. Antibodies phase protein) (Kodama et al., 2004). Although the pentraxinas of teleosts have a recognized role in The predominant immunoglobulin in teleosts is defence mechanisms, studies performed by Cook a tetramer of the IgM and contains eight an- et al. (2003, 2005) have demonstrated their role in tigenic combining sites (Acton et al., 1971). Some immune function through the activation of comple- teleosts have a monomer of IgM in their serum, al- ment-mediated lysis in sheep erythrocytes. These though the factors leading to its expression are still authors note that the phagocytosis of beads soaked unknown (Wilson and Warr, 1992). The binding with pentraxinas possibly occurs through the action affinities of monomeric and tetrameric IgM in rain- of a surface receptor expressed in phagocytes. bow trout are similar, but tetrameric IgM activates 492 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article complement more effectively than the monomeric difference in the antibodies. However, the response form due to a structural difference in the Fc portion to suboptimal levels of antigen suggests that perhaps of the molecule (Elcombe et al., 1985). IgD was the B cells with high affinity receptors were selected as second immunoglobulin isotype identified in fish, memory B cells (Morrison and Nowak, 2002). specifically catfish, due to sequence similarity with IgD in mammals, its location immediately under the IgM gene and its expression in B cells (Wilson et al., 6.3. Cellular Cytotoxicity 1997). Moreover, the concentration of IgM in the serum of salmonids is extremely low compared to The leukocytes of fish are capable of generating that of other teleosts such as Japanese (Anguilla cellular cytotoxicity reactions, which has been dem- japonica) (Uchida et al., 2000), cyprinids (Vilain et onstrated in several fish species. However, the cells al., 1984) and some (Scapigliati et al., that are responsible for cell-mediated cytotoxicity in 1997). However, the amounts of IgM in the serum of fish are difficult to characterize due to the lack of (Salmo trutta) and rainbow trout that appropriate tools for cellular and molecular recogni- are infected or acclimated to high temperature (19 °C) tion (Fisher et al., 2006). In mammals, the adaptive reach values similar to those of the common cod and immune response implemented by CD8+ cytotoxic haddock (Melanogrammus aeglefinus). In addition, T lymphocytes has been shown to be critical in com- IgM levels in salmon and (Gadus morhua) bating various viral infections. These lymphocytes vary with size (Sanchez et al., 1993; Magnadottir et recognize and kill cells with virus-derived peptides al., 1999), temperature (Sanchez et al., 1993) and using class I MHC molecules. Several studies indicate water quality season (Olesen and Jorgensen, 1986; that this mechanism of cell death also exists in fish. Magnadottir et al., 2001). Teleost antibodies are found The sequencing of fish homologues of MHC class I in the skin (Hatten et al., 2001), intestine (Rombout and CD3+ T cells suggests that CD8+ MHC class I et al., 1986), gill mucus (Lumsden et al., 1993), bile presentation is similar to that which occurs in high- (Jenkins et al., 1994) and systemically in the plasma. er vertebrates (Fisher et al., 2006). Furthermore, we The immune response of the skin and gills is impor- found a direct monoclonal antibody against the re- tant because these organs are in direct contact with combinant protein Onmy-UBA*501, the MHC class I the environment. Specific antibodies can be gener- molecule of rainbow trout, which are expressed in the ated in the skin (Cain et al., 2000), intestine, (Jones same cell types as classical mammalian MHC mam- et al., 1999) and gills (Lumsden et al., 1993) without malian class I molecules (Dijkstra et al., 2003). Like necessarily generating a systemic response. other vertebrates, fish acquire immunocompetency during ontogeny. In sea (Dicentrarchus labrax L.), T cells appear early in larval development, at least 6.2. Immunological memory five days after the start of incubation (Dos Santos et al., 2000). Fisher et al. (2006) have demonstrated in Fish develop a memory response before a second rainbow trout that transcripts of CD8+ T cells and exposure to an antigen (Arkoosh and Kaattari, 1991; MHC class I are detectable one week after insemina- Whittington et al., 1994). Rainbow trout respond tion, while TCR mRNA in T cells appears one week to suboptimal doses of both T lymphocytes in an after insemination. MHC class I molecules and CD8 antigen-dependent and independent manner after are expressed from the larval stage, suggesting that an initial exposure to the same antigen (Arkoosh very young fish can be vaccinated to develop cellu- and Kaattari, 1991). It is remarkable that it takes two lar immunity. In fact, up to 14 days after the end of exposures before the fish responds to the second incubation young trout can destroy skin allografts, administration of T-dependent antigens, whereas a process accompanied by infiltration of cytotoxic T-independent antigen requires only one exposure. T lymphocytes (Tatner and Manning, 1983). Additionally, while response is faster and of larger magnitude than the primary response, the number of antigen-specific B cells in the spleen is directly pro- 6.4. Cytokines involved in adaptive portional to the frequency of B-cell specific antigen immunity precursors. This finding suggests that the secondary response is caused by the expansion of the pool of Cytokines have been described in adaptive im- memory B cells (Kattari, 1992) and not a specific munity in fish and with the recent discovery of CD4 493 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503 in teleosts in it seems likely these cytokines will of circulating IgM as a response to elevated levels drive the activation and differentiation of T helper of pathogens that are expected in an environment cell subsets to release different cytokine repertoires rich in particles. Increased salinity also affects im- (Secombes, 2008). As stated above, type I and type mune parameters by increasing the activity of lytic II IFN are present that could potentially drive Th1 enzymes, the respiratory burst of macrophages and cell differentiation, with IFN-g a potential effector the circulating levels of IgM. However, the reason of Th1 responses altogether with IL-12 (Yoshiura why these changes are associated with salinity is et al., 2003; Nascimento et al., 2007), IL-15 (Wang currently unknown, but some authors suggest that et al., 2007) and IL-18 (Huising et al., 2004; Zou increases in salinity levels cause an increased bur- et al., 2004). In relation to Th2-type cytokines, a den of pathogens from the environment to generate molecule which is claimed to be a homologue of a more favourable osmotic environment (Bowden, IL-4 has been found recently; however, it has no 2008). Changes in environmental pH levels show obvious similarity to known vertebrate IL-4 genes conflicting results for immune system parameters, (Li et al., 2007). However, the presence of the tran- such as levels of lysozyme and IgM in the circula- scription factor that drives Th2 cell differentiation, tion. Finally, stress in fish as a result of population GATA3, suggests that Th2 responses may exist in density associated with cultivation and produc- fish, although this remains to be proven (Secombes, tion management can increase circulating cortisol 2008). Finally, both IL-10 (Zou et al., 2003; Pinto levels, generating a decrease in specific and non- et al., 2006) and TGF-β (Hardie et al., 1998) are specific immunity and, therefore, making the fish present in fish, and thus may form the effectors of prone to opportunistic pathogens (Brydges et al., potential T regulatory cells. 2009; Ramsay et al., 2009).

7. Environmental effect on immune 8. Compounds that modulate the immune response system in fish

The immune system and response of fish can be Another approach to immunoprophylactic con- greatly influenced by various external factors like trol is the use of probiotics and immunostimulants temperature, light, water quality, salinity and dif- including specific dietary manipulation (Magnottir, ferent stress inducers (Magnadottir, 2010). 2010). These compounds are defined as chemicals, Decreases in temperature, which are important drugs, stress generators or other actions that raise due to the poikilothermic nature of fish, affect the nonspecific defence mechanisms or the specific im- rate of their physiological functions (Hayward et mune response (Anderson, 1992) and include nu- al., 2009; e.g., enzymatic activity). In the rainbow cleotides, glucans and probiotics. These treatments trout, photoperiod has also been shown to impact are primarily aimed at enhancing the innate system the immune response through a reduction in the and therefore are of value as general preventive number of circulating leukocytes that is caused by measures in aquaculture (Magnadottir, 2010). increasing daylight hours; in turn, leukocytes are increased to reduce the hours of exposure to this factor. An increase in the photoperiod can also gen- 8.1. Nucleotides erate increases in the activity of lysozyme and the circulating levels of IgM. Furthermore, oxygen lev- Nucleotides are composed of a purine or pyrimi- els in the environment may modulate the immune dine base, a ribose or deoxyribose sugar and one response; depresses the respiratory burst or more phosphate groups. The term nucleotide in activity of macrophages and lowers the levels of this context refers not only to a specific form of the circulating antibodies, which in turn, are elevated compound, but also to all forms that contain purine by hyperoxia (Watts et al., 2001; Bowden, 2008). or pyrimidine bases (Rudolph, 1994). These com- On the other hand, increased levels of suspended pounds are essential in many physiological and bio- solids in the fish environment help to raise hemat- chemical functions, among which are included the ocrit levels to compensate for the diminished abil- encoding and decoding of genetic information, the ity of the gills to capture oxygen. This factor also mediating of energy and cell signals, increases the activity of lysozyme and the levels and also forming components of coenzymes, al- 494 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article losteric effectors and cellular agonists (Carver et al., 2008). Glucan-linked glucans β1-3 and β1-6 are 1995; Cosgrove, 1998). Nucleotide supplementation the major components of the cell walls of yeasts of fish was introduced by the studies of Burrells et al. and mycelial fungi. These polysaccharides are not (2001a,b), which indicated that dietary supplemen- antigenic to animals (Ballou, 1982), but have been tation with nucleotides confers increased resistance proven to be potent activators of nonspecific mech- on salmonids to viral, bacterial and parasitic diseases anisms of antibacterial defences in fish (Di Luzio, and improves the effectiveness of vaccination and 1985; Sherwood et al., 1987). The injection of glu- the ability to osmoregulate. Futher, the binding of cans generates improvements in the fish innate these compounds to Toll- like receptor 9 (TLR-9) immune response by increasing the activity of mac- is thought to stimulate the activity of intracellular rophages, complement activation and levels of lytic bacterial DNA and trigger innate and adaptative re- enzymes (Jeney and Anderson, 1993; Jorgensen et sponses (Dalmo, 2005). With respect to the innate al., 1993; Ai et al., 2007). Furthermore, several stud- immune response, it is known that dietary nucle- ies have shown that injection of glucans improves otides may influence the activity of macrophages antibacterial defences and efficiency of vaccination (Gil, 2002) and natural killer cell (Carver et al., 1990). (Yano et al., 1991; Rorstad et al., 1993). Similarly, Sakai et al. (2001) demonstrated in common carp when administered orally, these compounds are that exogenous nucleotides may influence the hu- capable of stimulating the immune response and moral and cellular components of the innate immune disease resistance (Siwicki et al., 1994). Engstad and system by increasing the complement lytic activity Robertsen (1995) inoculated Atlantic salmon with of enzymes and the production of the superoxide an Aeromonas salmonicida that contained anion by anterior kidney phagocytes. Li et al. (2004) glucans in its formulation; six weeks after inocula- reported that hybrid (Morone saxatilis) tion, there was a greater antibody response in the that were fed diets supplemented with nucleotides vaccine-inoculated fish compared to the fish that had a higher production of oxidative radicals from were vaccinated with a preparation that contained the neutrophils in their blood compared to fish that only the bacteria. were fed a normal . In addition, nucleotides also influence the activity of lymphocytes and im- munoglobulin production (Jyonouchi et al., 1993; 8.3. Probiotics Navarro et al., 1996). Ramadan et al. (1994), were the first to observe the effect of dietary supplementa- Probiotics are organisms or substances that con- tion with nucleotides, and described a stimulatory tribute to the intestinal microbial balance. Fuller effect on the humoral and cellular immune response (1989) defined probiotics as live microbial feed in after intramuscular injection or bath with supplements which exert beneficial effects on the formalin-killed Aeromonas hydrophila. Antibody host by improving its intestinal microbi- titres and lymphocyte mitogenic responses of fish al balance. Research on the use of probiotics in supplemented with nucleotides were significantly aquatic animals has increased the demand for sus- higher in fish that were fed the diet. Similar tainable aquaculture (Gatesoupe, 1999). Many of phenomena have been observed in rainbow trout the probiotics used in aquaculture belong to the (Burrells et al., 2001b; Leonardi et al., 2003), hybrid Lactobacillus, the genus Bacillus, photosynthetic striped bass (Li et al., 2004) and Atlantic salmon bacteria or yeasts, although other genera or spe- (Burrells et al., 2001b). However, the mechanisms cies have also been employed, including nitrifying of action of these compounds are still not well un- bacteria, streptococci and Roseobacter (Wang et derstood. al., 2008). These have been tested in aquaculture with generally good results (Panigrahi et al., 2005; Aly et al., 2008; Ma et al., 2009). The benefits of 8.2. Glucans supplements include improvements in feed values, contribution to enzymatic , inhibition of One of the most used substances in immunos- pathogenic microorganisms, anti-mutagenic and timulation experiments in fish are various forms of anti-carcinogenic activity, growth-promoting fac- β-glucans from different sources, normally intro- tors and an augmentation of the immune response duced in the feed but also by intraperitoneal injec- (Wang and Xu, 2006; Wang, 2007). Studies have tion or as a vaccine adjuvant (Dalmo and Bogwald, shown that the use of Bacillus sp. in cropping 495 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503 systems has improved the water quality, survival, Aly SM, Abdel-Galil Ahmed Y, Abdel-Aziz Ghareeb growth rate and health status of juvenile giant A, Mohamed MF (2008): Studies on Bacillus subti- prawn (Penaeus monodon) and also reduced the lis and Lactobacillus acidophilus, as potential pro- amount of pathogenic vibrios (Dalmine et al., 2001). biotics, on the immune response and resistance of Moreover, probiotics may also stimulate the innate tilapia nilotica (Oreochromis niloticus) to challenge defence through TLR, other cellular receptors or infections. Fish and Immunology 25, 128– humoral factors (Magnadottir, 2010). 136. Anderson DP (1992): Immunostimulants, adjuvants and vaccine carriers in fish: applications to aquaculture. 9. Concluding remarks Annual Review of Fish Disease 2, 281–307. Aranishi F, Nakane M (1997): Epidermal proteases of the In the last years, great progress has been made Japanese eel. and Biochemistry 16, in understanding the immune response of fish 471–478. which has benefitted the growing aquaculture Arkoosh MR, Kaattari SL (1991): Development of im- industry worldwide. One critical element of this munological memory in rainbow trout (Oncorhynchus area of research has been established: the immu- mykiss). I. An immunochemical and cellular analysis nomodulation of larval fish. The production of fish of the B cell response. Developmental and Compara- larvae is often hampered by high mortality rates tive Immunology 15, 279–293. and economic loss due to infectious diseases. As Arma NR, Hirono I, Aoki T (2004): Characterization of is well known, in fish the innate response has been expressed genes in kidney cells of Japanese considered an essential component in combating Paralichthys olivaceus treatment with ConA/PMA and pathogens due to limitations of the adaptive im- LPS. Fish Pathology 39, 189–196. mune system. Therefore, the immunomodulation Armstrong PB, Quigley JP (1999): α-2-Macroglobulin: of larval fish has been proposed as a potential meth- an evolutionarily conserved arm of the innate immune od for improving larval survival by increasing the system. Developmental and Comparative Immunology innate responses of developing animals until their 23, 375–390. adaptive immune response is sufficiently developed Ballou CE (1982): Yest cell wall and cell surface. In: to mount an effective response to the Strathern JN, Jones EW, Broach JR (eds.): The Mo- (Dalmo, 2005). This is a crucial point in further lecular Biology of the Yeast Saccharomyces: Metabo- research that is currently focused on increasing the lism and Gene Expression. Cold Spring Harbor survival of larval fish. Finally, Dalmo (2005) suggest Laboratories, New York, USA. 335–360. that the development of strategies to control patho- Bayne CJ, Gerwick L (2001): The acute phase response gen load and immuno-prophylactic measures must and innate immunity of fish. Developmental and Com- be implemented further to realise the full potential parative Immunology 25, 725–743. of the production of marine fish larvae and thus Birkemo GA, Luders T, Andersen O, Nes IF, Nissen- improve the overall production of adult fish Meyer J (2003): Hipposin, a histone-derived antimi- crobial peptide in (Hippoglossus hippoglossus L.). Journal of Biochemistry, Molecular REFERENCES Biology and Biophysics 1646, 207–215. Blazer VS (1991): Piscine macrophage function and nu- Acton RT, Weinheimer PF, Hall SJ, Niedermeier W, Shel- tritional influences: A review. Journal of Aquatic ton E, Bennett JC (1971): Tetrameric immune mac- Animal Health 3, 77–86. roglobulins in three orders of bony . Proceedings Boes M (2000): Role of natural and immune IgM anti- of the National Academy of Sciences of the United bodies in immune responses. Molecular Immunology States of America 68, 107–111. 37, 1141–1149. Ai Q, Mai K, Zhang L, Tan B, Zhang W, Xu W, Li H (2007): Boshra H, Li J, Sunyer JO( 2006): Recent advances on Effects of dietary [beta]-1, 3 glucan on innate immune the complement system of teleost fish. Fish and Shell- response of large yellow croaker, Pseudosciaena crocea. fish Immunology 20, 239–262. Fish and Shellfish Immunology 22, 394–402. Brydges NM, Boulcott P, Ellis T, Braithwaite VA ( 2009): Alexander JB, Ingram GA (1992): Noncellular nonspe- Quantifying stress responses induced by different han- cific defense mechanisms of fish. Annual Review of dling methods in three species of fish. Applied Animal Fish Disease 2, 249–279. Behaviour Science 116, 295–301. 496 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article

Bowden TJ (2008): Modulation of the immune system Dalmin G, Kathiresan K, Purushothaman A (2001): Ef- of fish by their environment. Fish and Shellfish Im- fect of probiotics on bacterial population and health munology 25, 373–383. status of in culture ecosystem. Indian Bowden TJ, Butler R, Bricknell IR, Ellis AE (1997): Serum Journal of Experimental Biology 39, 939–942. trypsininhibitory activity in five species of farmed fish. Dalmo RA, Bogwald J (2008): β-glucans as conductors Fish and Shellfish Immunology 7, 377–385. of immune symphonies. Fish and Shellfish Immunol- Bowden TJ, Cook P, Rombout JHWM (2005): Develop- ogy 25, 384–396. ment and function of the thymus in teleosts. Fish and Danneving BH, Lauve A, McPress LC, Landsverk T Shellfish Immunology 19, 413–427. (1994): Receptor-mediated endocytosis and phagocy- Burrells C, William PD, Forno PF (2001a):. Dietary nu- tosis by rainbow trout head kidney sinusoidal cells. cleotides: a novel supplement in fish feeds. 1. Effects Fish and Shellfish Immunology 4, 3–18. on resistance to diseases in salmonids. Aquaculture Davis JM, Clay H, Lewis JL, Ghori N, Herbomel P, 199, 159–169. Ramakrishnan L (2002): Real-time visualization of Burrells C, William PD, Southage PJ, Wadsworth SL mycobacterium-macrophage interactions leading ini- (2001b): Dietary nucleotides: a novel supplement in tiation of granuloma formation in zebrafish embryos. fish feeds. 2. Effects on vaccination, salt water transfer, Immunity 17, 693–702. growth rate and physiology of Atlantic salmon. Aqua- De Haas CJ, van Leeuwen EMM, van Bommel T, Verhoef culture 199, 171–184. J, van Kessel KPM, van Strijp JAG (2000): Serum amy- Cain KD, Jones DR, Raison RL (2000): Characterisation loid P component bound to Gram-negative bacteria of mucosal and systemic immune responses in rainbow prevents lipopolysaccharide-mediated classical path- trout (Oncorhynchus mykiss) using surface plasmon way complement activation. Infection and Immunity resonance. Fish and Shellfish Immunology 10, 651– 68, 1753–1759. 666. De Veer MJ, Holko M, Frevel M, Walker E, Der S, Paran- Carver JD, Cox WI, Barness LA (1990): Dietary nucle- jape JM, Silverman RH, Williams BRG (2001): Func- otide effects upon murine natural killer cell activity tional classification of interferon-stimulated genes and macrophage activation. Journal of Parenteral and identified using microarrays. Journal of Leukocyte Enteral Nutrition 14, 18–22. Biology 69, 912–920. Castillo A, Sanchez C, Dominguez J, Kaattari SL, Villena DeVries ME, Kelvin AA, Xu L, Ran L, Robinson J, Kelvin AJ (1993): Ontogeny of IgM and IgM-bearing cells in DJ (2006): Defining the origins and evolution of the rainbow trout. Developmental and Comparative Im- chemokine/chemokine receptor system. Journal of munology 17, 419–424. Immunology 176, 401–415. Chantanachookhin C, Seikai T, Tanaka M (1991): Com- Dijkstra JM, Kollner B, Aoyagi K, Sawamoto Y, Kuroda parative study of the ontogeny of the lymphoid organs A, Ototake M (2003): The rainbow trout classical MHC in three species of marine fish. Aquaculture 99, 143– class I molecule Onmy-UBA) 501 is expressed in simi- 155. lar cell types as mammalian classical MHC class I mol- Chinchar VG, Bryan L, Silphadaung U, Noga E, Wade ecules. Fish and Shellfish Immunology 14, 1–23. D, Rollins-Smith L (2004): Inactivation of viruses in- Di Luzio NR (1985): Update on the immunomodulating fecting ectothermic animals by and piscine activities of glucans. Seminars in Immunopathology antimicrobial peptides. Virology 323, 268–275. 8, 387–400. Cook MT, Hayball PJ, Birdseye L, Bagley C, Nowak BF, Dinarello CA (1997): Interleukin-1. Cytokine Growth Hayball JD (2003): Isolation and partial characteriza- Factor Review 8, 253–265. tion of a pentraxin-like protein with complement- Dos Santos NM, Romano N, de Sousa M, Ellis AE, Rom- fixing activity from snapper ( auratus, ) bout JH (2000): Ontogeny of B and T cells in sea bass serum. Developmental and Comparative Immunology (Dicentrarchus labrax, L.). Fish and Shellfish Immu- 27, 579–588. nology 10, 583–596. Cook MT, Hayball PJ, Nowak BF, Hayball JD (2005): The Elcombe BM, Chang RJ, Taves CJ, Winkelhake JL (1985): opsonising activity of a pentraxin-like protein isolated Evolution of antibody structure and effector functions: from snapper (Pagrus auratus, Sparidae) serum. Devel- comparative hemolytic activities of monomeric and tetra- opmental and Comparative Immunology 29, 703–712. meric IgM from rainbow trout, Salmo gairdnerii. Com- Cosgrove M (1998): Nucleotides. Nutrition 14, 748–751. parative Biochemistry and Physiology 80, 697–706. Dalmo RA (2005): Ontogeny of the fish immune system. Ellingsen T, Strand C, Monsen E, Bogwald J, Dalmo RA Fish and Shellfish Immunology 19, 395–396. (2005): The ontogeny of complement component C3 497 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503

in the spotted wolfish (Anarhichas minor Olafsen). Hatten F, Fredriksen A, Hordvik I, Endresen C (2001): Fish and Shellfish Immunology 18, 351–358. Presence of IgM in cutaneous mucus, but not in gut Ellis AE (2001): Innate host defence mechanism of fish mucus of Atlantic salmon, Salmo salar. Serum IgM is against viruses and bacteria. Developmental and Com- rapidly degraded when added to gut mucus. Fish and parative Immunology 25, 827–839. Shellfish Immunology 11, 257–268. Engstad RE, Robertsen B (1995): Effects of structurally Hayward CJ, Bott NJ, Nowak BF (2009): Seasonal epiz- different yeast B glucans on immune responses in At- ootics of sea lice, Caligus spp., on southern bluefin lantic salmon (Salmo salar). Journal of Marine Bio- , Thunnus maccoyii (Castelnau), in a long-term technology 3, 203–207. farming trial. Journal of Fish Disease 32, 101–106. Evans D, Jaso-Friedmann L (1992): Nonspecific cytotoxic Hellio C, Pons AM, Beaupoil C, Bourgougnon N, Gal YL cells as effectors of immunity in fish. Annual Review (2002): Antibacterial, antifungal and cytotoxic activi- of Fish Disease 2, 109. ties of extracts from fish epidermis and epidermal Faisal M, Ahmed G, Peters II, Cooper EL (1989): Natu- mucus. International Journal of Antimicrobial Agents ral citotoxicity of tilapia leukocytes. Disease of Aquatic 20, 214–2199. Organims 7, 17–22. Hibiya T (ed.) (1994): An Atlas of Fish Histology. Normal Ferguson HW (1989): Systemic Pathology of Fish. A text and and Pathological Features. Gustav Fischer Verlag, atlas comparative tissue response in diseases of teleost. Stuttgart, Germany. 5–125. Iowa state University Press. Ames. Iowa, USA. 5–103. Hinuma S, Abo T, Kumagai K, Hata M (1980): The potent Fischer U, Utke K, Somamoto T, Kollner B, Ototake M, activity of fresh water fish kidney cells in cell-killing. Nakanishi T (2006): Cytotoxic activities of fish leuco- I. Characterization and species distribution of cyto- cytes. Fish and Shellfish Immunology 20, 209–226. . Developmental and Comparative Immunol- Fuller R (1989): Probiotic in man and animals. Journal ogy 4, 653–666. of Applied Bacteriology 66, 365–378. Holland MC, Lambris JD (2002):. The complement sys- Gatesoupe FJ (1999): The use of probiotics in aquacul- tem of teleosts. Fish and Shellfish Immunology 12, ture. Aquaculture 180, 147–165. 399–420. Gil A (2002): Modulation of the immune response medi- Hoover GJ, El-Mowafi A, Simko E, Kocal TE, Ferguson ated by dietary nucleotides. European Journal of Clin- HW, Hayes MA (1998): Plasma proteins of rainbow ical Nutrition 56, S1–S4. trout (Oncorhynchus mykiss) isolated by binding to Greenlee AD, Brown RA, Ristlow SS (1991): Nonspecific lipopolysaccharide from Aeromonas salmonicida. citotoxic cells of Rainbow trout (Oncorhynchus mykiss) Comparative Biochemistry and Physiology 120, 559– kill Yac-1 targets by both necrotic and apoptotic mech- 569. anisms. Developmental and Comparative Immunology Huising MO, Stet RJM, Savelkoul HFJ, Verburg-van Ke- 15, 153–164. menade BML (2004): The molecular evolution of the Grinde B, Lie O, Poppe T, Salte R (1988): Species and interleukin-1 of cytokines; IL-18 in teleost fish. individual variation in lysozyme activity in fish of in- Developmental and Comparative Immunology 28, terest in aquaculture. Aquaculture 68, 299–304. 395–413. Hanington PC, Wang T, Secombes CJ, Belosevic M (2007): Ingram GA (1980): Substances involved in the natural Growth factors of lower vertebrates: characterization resistance of fish to infection a review. Journal of Fish of goldfish Carassius( auratus L.) macrophage colony- Biology 16, 23–60. stimulating factor-1. Journal of Biological Chemistry Jeney G, Anderson DP (1993): Glucan injection or bath 282, 31865–31872. exposure given alone or in combination with a bacte- Hardie LJ, Laing KJ, Daniels GD, Grabowski PS, Cun- ria enhance the nonspecific defense mechanisms in ningham C, Secombes CJ (1998): Isolation of the first rainbow trout (Oncorhynchus mykiss). Aquaculture piscine transforming growth factor β gene: analysis 116, 315–329. reveals tissue specific expression and a potential reg- Jenkins JA, Ourth DD (1993): Opsonic effect of the al- ulatory sequence in rainbow trout (Oncorhynchus ternative complement pathway on mykiss). Cytokine 10, 555–563. peripheral blood phagocytes. Veterinary Immunology Hasegawa S, Nakayasu C, Yoshitomi T, Nakanishi T, Immunopathology 39, 447–459. Okamoto N (1998): Specific cell-mediated cytotoxic- Jenkins PG, Wrathmell AB, Harris JE, Pulsford AL ity against an allogeneic target cell line in isogeneic (1994): Systemic and mucosal immune response to crucian carp. Fish and Shellfish Immunology enterically delivered antigen in Oreochromis mossam- 8, 303–313. bicus. Fish and Shellfish Immunology 4, 255–271.

498 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article

Jones DR, Hannan CM, Russel-Jones GJ, Raison RL Lange SR, Bambir S, Dodds AW, Magnadottir B (2004b): (1999): Selective B cell non-responsiveness in the gut An immunohistochemical study on complement com- of the rainbow trout (Oncorhynchus mykiss). Aquac- ponent C3 in juvenile Atlantic halibut (Hippoglosus ulture 172, 29–39. hippoglossus L.). Developmental and Comparative Im- Jorgensen JB, Sharp GJ, Secombes CJ, Robertsen B munology 28, 593–601. (1993): Effect of yeast cell wall glucan on the bacterial Leonardi M, Sandino AM, Klempau A (2003): Effect of activity of rainbow trout macrophages. Fish and Shell- a nucleotide-enriched diet on the immune system, fish Immunology 3, 267–277. plasma cortisol levels and resistance to infectious pan- Jyonouchi, H, Zhang L, Tomita Y (1993): Studies of im- creatic necrosis (IPN) in juvenile rainbow trout (On- munomodulating actions of RNA/nucleotides: RNA/ corhynchus mykiss). Bulletin of the European Nucleotides enhance in vitro immunoglobulin produc- Association of Fish Pathologists 23, 52–59. tion by human peripheral blood mononuclear cells in Li P, Lewis DH, Gatlin DM (2004): Dietary oligonucle- response to T-dependent stimuli. Pediatric Research otide from yeast RNA influences immune responses 33, 458–465. and resistance of hybrid striped bass (Morone chrysops Kaattari SL (1992): Fish B lymphocytes: Defining their × M. saxatilis) to infection. Fish form and function. In: Faisal M, Hetrick FM (eds.): and Shellfish Immunology 16, 561–569. Annual Review of Fish Diseases. Vol. 2. Pergamon, Li JH, Shao JZ, Xiang LX, Wen Y (2007): Cloning, char- Tarrytown, NY, USA. 161–180. acterization and expression analysis of pufferfish inter- Kileng O, Brundtland MI, Robertsen B (2007): Infectious leukin-4 cDNA: the first evidence of Th2-type cytokine salmon anemia virus is a powerful inducer of key genes in fish. Molecular Immunology 44, 2078–2086. of the type I interferon system of Atlantic salmon, but Lie O, Evensen O, Sorensen A, Froysadal E (1989): Study is not inhibited by interferon. Fish and Shellfish Im- on lysozyme activity in some fish species. Disease of munology 23, 378–389. Aquatic Organism 6, 1–5. Kodama H, Matsuoka Y, Tanaka Y, Liu YC, Iwasaki T, Liu Y, Iwasaki T, Watarai S, Kodama H (2004): Effect of Watarai S (2004): Changes of C-reactive protein levels turpentine oil on C-reactive protein (CRP) production in rainbow trout (Oncorhynchus mykiss) sera after ex- in rainbow trout (Oncorhynchus mykiss). Fish and posure to anti-ectoparasitic chemicals used in aqua- Shellfish Immunology 17, 203–210. culture. Fish and Shellfish Immunology 16, 589–597. Lorenzen N, LaPatra SE (1999): Immunity to rhabdovi- Kono T, S, Sonoda K, Savan R, Secombes CJ, Sakai rus in rainbow trout: the antibody response. Fish and M (2008): Characterization and expression analysis of Shellfish Immunology 9, 345–360. an interleukin-7 homologue in the Japanese pufferfish, Lumsden JS, Ostland VE, Byrne PJ, Ferguson HW (1993): Fugu rubripes. FEBS Journal 275, 1213–1226. Detection of a distinct gill-surface antibody response Lam SH, Chua HL, Gong Z, Lam TJ, Sin Y (2004): De- following horizontal infection and bath challenge of velopment and maturation of the immune system in Salvelinusfontinalis with Flavobactewium zebrafish, Danio rerio: a gene expression profiling, in branchiophilum, the causative agent of bacterial gill situ hybridization and immunological study. Develop- disease. Disease of Aquatic Organism 16, 21–27. mental and Comparative Immunology 28, 9–28. Lund V, Olafsen JA (1998): A comparative study of pen- Lammens M, Decostere A, Haaesebrouck F (2000): Ef- traxin-like proteins in different fish species. Develop- fects of Flavobaterium psychrophilium strains and mental and Comparative Immunology 22, 185–194. their metabolites on the oxidative activity of rainbow Ma CW, Cho YS, Oh KH (2009): Removal of pathogenic trout Oncorhynchus mykiss phagocytes. Disease of bacteria and nitrogens by Lactobacillus spp. JK-8 and Aquatic Organisms 41, 173–179. JK-11. Aquaculture 287, 266–270. Lange S, Magnadottir B (2003): Spontaneous haemolytic Maier VH, Dorn KV, Gudmundsdottir BK, Gudmunds- activity of Atlantic halibut (Hippoglossus hippoglossus son GH (2008): Characterisation of cathelicidin gene L.) and sea bass (Dicentrarchus labrax) serum. Com- family members in divergent fish species. Molecular parative Biochemistry and Physiology, Molecular Biol- Immunology 45, 3723–3730. ogy 136, 99–106. Magnadottir B (2006): Innate immunity of fish (over- Lange SR, Bambir S, Dodds AW, Magnadottir B (2004a): view). Fish and Shellfish Immunology 20, 137–151. The ontogeny of complement component C3 in At- Magnadottir B (2010): Immunological control of fish dis- lantic cod (Gadus morhua L.) an immunohistochem- eases. Journal of Marine Biotechnology 12, 361–379. ical study. Fish and Shellfish Immunology 16, Magnadottir B, Jonsdottir H, Helgason S, Bjornsson B, 359–367. Jorgensen TO, Pilstrom L (1999): Humoral immune 499 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503

parameters in Atlantic cod (Gadus morhua L.). II. The Nauta AJ, Daha M, van Kooten C, Roos A (2003): Rec- effects of size and gender under different environmen- ognition and clearance of apoptotic cells: a role for tal conditions. Comparative Biochemistry and Physi- complement and pentraxins. Trends in Immunology ology 122B, 181–188. 24, 148–154. Magnadottir B, Jonsdottir H, Helgason S, Bjornsson B, Navarro J, Ruiz-Bravo A, Jimenez-Varela M, Gil A (1996): Jorgensen TO, Pilstrom L (2001): Immuneparameters Modulation of antibody-forming cell and mitogen- of immunised cod (Gadus morhua L). Fish and Shell- driven lymphoproliferative responses by dietary nu- fish Immunology 10, 75–89. cleotides in mice. Immunology Letters 53, 141–145. Magnadottir B, Lange S, Gudmundsdottir S, Bogwald J, Nikoskelainen S, Lehtinen J, Lilius EM (2002): Bacterio- Dalmo RA (2005): Ontogeny of humoral immune pa- lytic activity of rainbow trout (Oncorhynchus mykiss) rameters in fish. Fish and Shellfish Immunology 19, complement. Developmental and Comparative Im- 429–439. munology 26, 797–804. Manning MJ, Nakanishi T (1996): Cellular defenses. In: Olesen NJ, Jorgensen PEV (1986): Quantification of se- Iwama GK, Nakanishi T (eds.): Fish Fisiology. XV. The rum immunoglobulin in rainbow trout Salmo gaird- fish immune system. Academic press. London, Eng- neri under various environmental conditions. Disease land. 159–205. of Aquatic Organism 1, 183–189. Mathew JA, Guo YX, Goh KP, Chan J, Verburg van Ke- Ooi EL, Verjan N, Hirono I, Nochi T, Kondo H, Aoki T, menade BM, Kwang J (2002): Characterisation of a Kiyono H, Yuki Y. (2008): Biological characterisation monoclonal antibody to carp IL-1beta and the devel- of a recombinant Atlantic salmon type I interferon opment of a sensitive capture ELISA. Fish and Shellfish synthesized in Escherichia coli. Fish and Shellfish Im- Immunology 13, 85–95. munology 24, 506–513. Matsushita M, Endo Y, Nonaka M, Fujita T (1998): Com- Panigrahi A, Kiron V, Puangkaew J, Kobayashi T, Satoh plement-related serine proteases in and ver- S, Sugita H (2005): The viability of probiotic bacteria tebrates. Current Opinion in Immunology 10, 29–35. as a factor influencing the immune response in rain- Matsuyama H, Yano T, Yamakawa T, Nakao M (1992): bow trout Oncorhynchus mykiss. Aquaculture 243, Opsonic effect of the third complement component 241–254. (C3) of carp (Cyprinus carpio) on phagocytosis by neu- Petrie-Hanson L, Ainsworth AJ (2000): Differential cy- trophils. Fish and Shellfish Immunology 2, 69–78. tochemical staining characteristics of channel catfish McKinney EC, Achmale MC (1994): with leukocytes identify cell populations in lymphoid or- neurofibromatosis exhibit cytotoxicity in toward tu- gans. Veterinary Immunology and Immunopathology mor targets. Developmental and Comparative Immu- 73, 129–144. nology 18, 305–313. Pinto RD, Nascimento DS, Reis MIR, do Vale A, dos Morrison RN, Nowak B (2002): The antibody response Santos NMS (2006): Molecular characterization, 3D of teleost fish. Seminars in Avian and Exotic Med- modelling and expression analysis of sea bass (Dicen- icine 11, 46–54. trarchus labrax) interleukin-10. Molecular Immunol- Mulero V, Meseguer J (1998): Functional characterisa- ogy 44, 2066–2075. tion of a macrophage-activating factor produced by Press CM, Dannevig BH, Landsverk T (1994): Immune leucocytes of gilthead seabream (Sparus aurata L.). and enzyme histochemical phenotypes of lymphoid Fish and Shellfish Immunology 8, 143–156. and nonlymphoid cells within the spleen and head Mulero I , Garcia Ayala A, Meseguer J, Mulero V (2007): kidney of Atlantic salmon (Salmo salar L.). Fish and Maternal transfer of immunity and ontogeny of au- Shellfish Immunology 4, 79–93. tologous immunocompetence of fish: A mini review. Ramadan A, Afifi NA, Moustafa M, Samy AM (1994): Aquaculture 268, 244–250. The effect of ascogen on the immune response of tila- Nakanishi T. (1986): Seasonal changes in the humoral pia fish to Aeromonas hydrophila vaccine. Fish and immune response and the lymphoid tissues of the ma- Shellfish Immunology 5, 159–165. rine teleost, Sebastiscus marmoratus. Veterinary Im- Ramsay JM, Feist GW, Varga ZM, Westerfield M, Kent munology and Immunopathology 12, 213–221. ML, Schreck CB (2009): Whole-body cortisol response Nascimento DS, do Vale A, Toma’s AM, Zou J, Secombes of zebrafish to acute net handling stress. Aquaculture CJ, dos Santos NMS (2007): Cloning, promoter analysis 297, 157–162. and expression in response to bacterial exposure of sea Razquin BE, Castillo A, Lopez-Fierro P, Alvarez F, Zapata bass (Dicentrarchus labrax L.) interleukin-12 p40 and A, Villena A (1990): Ontogeny of IgM-producing cells in p35 subunits. Molecular Immunology 44, 2277–2791. the lymphoid organs of rainbow trout, Salmo gardnieri

500 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article

Richardson: an immunological and enzyme-histochem- Savan R, Sakai M (2006): Genomics of fish cytokines. Com- ical study. Journal of Fish Biology 36, 159–173. parative Biochemistry and Physiology D 1, 9–101. Robertsen B (2006): The interferon system of teleost fish. Scapigliati G, Chausson F, Cooper EL, Scalia D, M Maz- Fish and Shellfish Immunology 20, 172–191. zini (1997): Qualitative and quantitative analysis of Rokenes TP, Larsen R, Robertsen B (2007): Atlantic salmon serum immunoglobulins of four Antarctic fish species. ISG15: expression and conjugation to cellular proteins Polar Biology 18, 209–213. in response to interferon, double-stranded RNA and vi- Schroder MB, Villena AJ, Jorgensen TO (1998): Ontogeny rus infections. Molecular Immunology 44, 950–959. of lymphoid organs and immunoglobulin producing Rombout JH, Blok LJ, Lamers CHJ (1986): Immunization cells in Atlantic cod (Gadus morhua L.). Developmen- of carp ( Cyprinus carpio) with a Vibrio anguillarum tal and Comparative Immunology 22, 507–517. bacterin: Indications for a common mucosal immune Secombes CJ (2008): Will advances in fish immunology system. Developmental and Comparative Immunology change vaccination strategies? Fish and Shellfish Im- 10, 341–351. munology 25, 409–416. Rombout JH, Taverne N, van de Kamp M, Taverne-Thiele Secombes CJ, Fletcher TC (1992): The role of phagocytes AJ (1993): Differences in mucus and serum immu- in the protective mechanisms of fish. Annual Review noglobulin of carp (Cyprinus carpio L.). Developmen- of Fish Disease 2, 53–71. tal and Comparative Immunology 17, 309–317. Shen L, Stuge TB, Zhou H, Khayat M, Barker KS, Quin- Rombout JH, Huttenhuis HBT, Picchietti S, Scapigliati iou SM, Wilson M, Bengten E, Chinchar VG, Clem S (2005): Phylogeny and ontogeny of fish leucocites. LW, Miller NW (2002): Channel catfish cytotoxic cells: Fish and Shellfish Immunology 19, 441–455. a mini-review. Developmental and Comparative Im- Rorstad G, Aasjord PM, Robertsen B (1993): Adjuvant munology 26, 141–149. effect of a yeast glucan in vaccines against furunculo- Shephard KL (1994): Functions for fish mucus. Reviews sis in Atlantic salmon (Salmo salar). Fish and Shellfish in Fish Biology 4, 401–429. Immunology 3, 179–190. Sherwood ER, Williams DL, McName RB, Jones EL, Rudolph FB (1994): The biochemistry and physiology of Browder IW, Di Luzio NR (1987): Enhancement of nucleotides. Journal of Nutrition 124, 124S–127S. interleukin 2 production by soluble glucan. Journal of Sakai DK (1992): Repertoire of complement in immu- Immunopharmacology 9, 261–267. nological defense mechanisms of fish. Annual Review Siwicki AK, Anderson DP, Rumsey GL (1994): Dietary intake of Fish Disease 2, 223–247. of immunostimulants by rainbow trout affects non specific Sakai M, Taniguchi K, Mamoto K, Ogawa H, Tabata M immunity and protects against furunculosis. Veterinary (2001): Immunostimulant effects of nucleotide isolated Immunology and Immunopathology 41, 125–139. from yeast RNA on carp, Cyprinus carpio L. Journal Stafford JL, Belosevic M (2003): Transferrin and the in- of Fish Disease 24, 433–438. nate immune response of fish: identification of a novel Samuel CE (2001): Antiviral actions of interferons. Clin- mechanism of macrophage activation. Developmental ical Microbiology Review 14, 778–809. and Comparative Immunology 27, 539–554. Sanchez C, Babin M, Tomillo J, Ubeira FM, Dominguez Subramaniam S, Stansberg C, Olsen L, Zou J, Secombes J (1993): Quantification of low levels of rainbow trout CJ, Cunningham C (2002): Cloning of a Salmo salar immunoglobulin by enzyme immunoassay using two interleukin-1 receptor-like cDNA. Developmental and monoclonal antibodies. Veterinary Immunology and Comparative Immunology 26, 415–431. Immunopathology 36, 65–74. Subramanian S, Mackinnon SL, Ross NW (2007): A com- Sanchez C, Alvarez A, Castillo A, Zapata A, Villena A, parative study on innate immune parameters in the Dominguez J (1995): Two different subpopulations of epidermalmucus of various fish species. Comparative Ig-bearing cells in lymphoid organs of rainbow trout. Biochemistry and Physiology B 148, 256–263. Developmental and Comparative Immunology 19, Subramanian S, Ross NW, Mackinnon SL (2008): Com- 79–86. parison of antimicrobial activity in the epidermal mucus Sangrador-Vegas A, Martin SA, O’Dea PG, Smith TJ (2000): extracts of fish. Comparative Biochemistry and Physiol- Cloning and characterization of the rainbow trout (On- ogy B 150, 85–92. corhynchus mykiss) type II interleukin-1 receptor cDNA. Suzumura E, Kurata O, Okamoto N, Ykeda Y (1994): European Journal of Biochemistry 267, 7031–703. Characteristics of natural killer cells in carp. Fish Pa- Saurabh S, Sahoo PK (2008): Lysozyme: an important thology 29, 199–203. defence molecule of fish innate immune system. Aqua- Suzumoto BK, Schreck CB, Mclntyre JD (1997): Relative culture Research 39, 223–239. resistances of three transferrin genotypes of coho 501 Review Article Veterinarni Medicina, 56, 2011 (10): 486–503

salmon (Oncorhynchus kisutch) and their hemato- Wang YB, Li JR, Lin J (2008): Probiotics in aquaculture: logical responses to bacterial kidney disease. Journal challenges and outlook. Aquaculture 281, 1–4. of the Fisheries Research Board of Canada 34, 1–8. Watts M, Munday BL, Burke CM (2001): Immune re- Sveinbjornsson B, Olsen R, Paulsen S (1996): Immuno- sponses of teleost fish. Australian Veterinary Journal cytochemical localization of lysozyme in intestinal 79, 570–574. eosinophilic granule cells (EGCs) of Atlantic salmon, Whittington RJ, Munday BL, Akhlaghi M, Reddacliff GL, Salmo salar L. Journal of Fish Disease 19, 349–355. Carson J (1994): Humoral and peritoneal cell responses Szalai AJ, Norcum MT, Bly JE, Clem LW (1992): Isolation of rainbow trout (Oncorhynchus mykiss) to ovalbumin, of an acute-phase and phosphorylcholine-reactive Vibrio anguillarum and Freund’s complete adjuvant pentraxin from channel catfish (Ictalurus punctatus). following intraperitoneal and bath immunisation. Fish Comparative Biochemistry and Physiology B 102, and Shellfish Immunology 4, 475–488. 535–543. Whyte SK (2007): The innate immune response of finfish Szalai AJ, Bly JE, Clem LW (1994): Changes in serum e A review of current knowledge. Fish and Shellfish concentrations of channel catfish (Ictalurus punctatus) Immunology 23, 1127–1151. phosphorylcholine-reactive protein (PRP) in response Wilson MR, Warr GW (1992): Fish immunoglobulins to inflammatory agents, low temperature-shock and and the genes that encode them. Annual Review of infection by the fungus Saprolegnia sp. Fish and Shell- Fish Disease 2, 201–221. fish Immunology 4, 323–336. Wilson MR, Bengten E, Miller N, Clem LW, Du Pasquier Tafalla C, Figueras A, Novoa B (2001): Viral hemorrhagic L, Warr GW (1997): A novel chimeric Ig heavy chain septicemia virus alters turbot Scophthalmus maximus from a teleost fish shares similarities to IgD. Proceed- macrophage nitric oxide production. Disease of ings of the National Academy of Sciences of the United Aquatic Organism 47, 101–107. States of America 94, 4593–4597. Tatner MF, Manning MJ (1983): The ontogeny of cel- Willett C, Cortes, A Zuasti A, Zapata A. (1999): Early lular immunity in the rainbow trout, Salmo gairdneri hematopoiesis and developing lymphoid organs in the Richardson, in relation to the stage of development of zebrafish. Developmental Dynamics 214, 323–336. the lymphoid organs. Developmental and Comparative Withler RE, Evelyn TP (1990): Genetic variation in re- Immunology 7, 69–75. sistance to bacterial kidney disease within and between Trede NS, Zapata A, Zon LI (2001): for lymphoid two strains of coho salmon from British Columbia. genes. Trends in Immunology 22, 302–307. Transactions of the American Fisheries Society 119, Uchida D, Hirose H, Chang PK, Aranishi F, Hirayabu E, 1003–1009. Mano N, Mitsuya T, Prayitno SB, Natori M (2000): Wu Y, Wang S, Peng X (2003): Serum acute phase re- Characterization of Japanese eel immunoglobulin M sponse (APR)-related proteome of to trauma. and its level in serum. Comparative Biochemestry and Fish and Shellfish Immunology 16, 381–389. Physiology B 127, 525–532. Yano T (1996): The nonspecific immune system: Hu- Vilain C, Wetzel MC, Du Pasquier L, Charlemagne J moral defence. In: Iwama G, Nakanishi T (eds.): The (1984): Structural and functional analysis of spontane- Fish Immune System: Organism, Pathogen and Envi- ous antinitrophenyl antibodies in three cyprinid fish ronment. Academic Press, San Diego. 105–157. species: carp (Cyrinus carpio), goldfish (Carassius au- Yano T, Matsuyama H, Mangindaan REP (1991): Polysac- ratus) and (Tinca tinca). Developmental and charide induced protection of carp Cyprinus carpio Comparative Immunology 8, 611–622. against bacterial infection. Journal of Fish Disease 14, Wang YB (2007): Effect of probiotics on growth perform- 577–582. ance and digestive enzyme activity of the shrimp Pe- Yin Z, Lam TL, Sin YM (1997): Cytokine-mediated an- naeus vannamei. Aquaculture 269, 259–264. timicrobial immune response of catfish, Clarias garie- Wang YB, Xu ZR (2006): Effect of probiotics for common pinus, as a defence against Aeromonas hydrophila. Fish carp (Cyprinus carpio) based on growth performance and Shellfish Immunology 7, 93–104. and digestive enzyme activities. Animal Feed Science Yoshiura Y, Kiryu I, Fujiwara A, Suetake H, Suzuki Y, and Technology 127, 283–292. Nakanishi T (2003): Identification and characteriza- Wang T, Holland J, Bols N, Secombes CJ (2007): Molecu- tion of Fugu orthologues of mammalian interleukin-12 lar and functional characterisation of interleukin-15 in subunits. Immunogenetics 55, 296–306. rainbow trout Oncorhynchus mykiss: a potent inducer Zapata A, Diez B, Cejalvo T, Gutierrez-De Frias C, Cortes of interferon-gamma expression in spleen leucocytes. A (2006): Ontogeny of the immune system of fish. Fish Journal of Immunology 179, 1475–1488. and Shellfish Immunology 20, 126–136.

502 Veterinarni Medicina, 56, 2011 (10): 486–503 Review Article

Zou J, Clarke M, Secombes CJ (2003): Characterisation, Zou J, Tafalla C, Truckle J, Secombes CJ (2007): Identi- expression and promoter analysis of an interleukin 10 fication of a second group of type I IFNs in fish sheds homologue in the puffer fish, Fugu rubripes. Immu- light on IFN evolution in vertebrates. Journal of Im- nogenetics 55, 325–335. munology 179, 3859–3871. Zou J, Bird S, Truckle J, Bols N, Horne M, Secombes CJ (2004): Identification and expression analysis of an Received: 2010–10–27 IL-18 homologue and its alternatively spliced form in Accepted after corrections: 2011–11–02 rainbow trout Oncorhynchus mykiss. European Journal of Biochemistry 271, 1913–1923.

Corresponding Author: Moran, Universidad Austral de Chile, Faculty of Veterinary Science, Department of Pharmacology, Valdivia, Chile Tel. +56 63 221936, E-mail: [email protected]

503