A. P. Desbois
2.2 IMMUNE SYSTEM IN FISHES
18 Fish Vaccines
Antigens and Immune Responses in Fishes 19
heterogeneous organization of poikilothermic animals, which include jawless fish and jawed fish.
Their physiology and immune system development vary among them, and it is particularly influ- enced via environmental parameters, not like warm-blooded vertebrates. Outside parameters like photoperiodism, temperature, and concentration of oxygen in water influences the maturation and functioning of each innate (e.g., supplement, lysozyme pastime) and adaptive immunity in fish (4).
Apart from antimicrobial immune reactions, environmental factors have an impact on some of the changes that are inherited and evolved via genetic changes. The primary mechanism through which the adaptive immunity diversifies its repertoires of lymphocyte-based antigen receptor is genetic recombination (5). The roles of various genes and organs involved in the defense mechanism of jawed and jawless fishes are discussed right here so that they will provide complete information on the development of the fish immune system.
2.2.1 ImmunItyof agnatHans
No matter the diversification, many features of fish immunity, i.e., immune gene expression, inflam- mation, wound recovery, antigen sample receptors, signaling, and trafficking of lymphocytes, remain conserved across the vertebrate lineage. These features are by and large performed through the cell and humoral factors of immunity. The Agnathans lack hematopoietic organs, i.e., spleen, thymus, or kidney. However, they have a unique strip of medullary tissue present in the trunk referred to as the immune body (6). The dedicated organs for immunity have not been detected so far. However, a number of areas of lamprey typhlosole and renal folds carry hematopoietic stem cells (HSC) and lymphoid-like cells and differentiated cells including thrombocyte-, granulocyte-, monocyte-, and lymphocyte-like cells have additionally been detected (7). The humeral elements like antimicrobial peptide coding genes, i.e., cathelicidin genes have been detected in Atlantic hagfish (Myxine glutinosa) (8). Other innate immunity-associated genes, such as reactive oxygen species modulator I, peroxire- doxin coding gene, and NFκB inhibitor gene, are being detected in the immune body and other tissues, which imply the presence of a well-advanced innate protection mechanism (9). The lamprey oral gland is additionally determined to secrete many defenses related to functional proteins, e.g., interferon- prompted lethality protein-19 and disintegrins. The components present in the supplement activation pathway have been detected in lamprey (10). The homologous components like C3, MBL, and MBL associated serum protease (MAPS) of the lectin pathway and the alternative pathway had been iden- tified from lamprey and/or hagfish, but the cytolysis in terms of serum protein is named “lamprey pore-forming protein.” The biomarkers of adaptive immunity (11), i.e., MHC, T cell receptors (TCRs), and B cell receptors (BCRs), are absent in primitive forms, but in spaces, there are a lot of leucine-rich repeats indicating an alternative pathway. Some of the research has located precise agglutinin-based reminiscence for antigen reputation in Atlantic lamprey and agglutinin-secreting cells within the gut.
The lamprey has particular lymphocytes-expressing genes encoding B-cell signaling additives. The VDJ recombination system, which is required for developing a diversified repertoire of Ig, is absent in Agnathans. The lymphoid cells have determined a specific complex leucine rich repeats (LRR) mol- ecule known as variable lymphocyte receptors (VLR), which undergoes subsequent assembly through an entirely novel genomic mechanism in which massive banks of LRR cassettes are used to build the
“diversity” area of the receptor molecules (12). The fundamental composition of these VLR consists of a conserved sign peptide, an N-terminal LRR (LRRNT), followed by nine variable and tremen- dously numerous LRRs, a connecting peptide, a C-terminal LRR (LRRCT), a conserved C terminus (GPI)-anchor site, and a hydrophobic tail. Upon antigen induction, there is the marked proliferation of hematopoietic lymphoid cells and increased VLR protein receptors for variable antigen detection.
2.2.2 ImmunItyof osteIcHtHyes
Fishes have a resilient innate immunity which helps them to continue to exist and adapt to the unfavorable conditions. The kidney, thymus, and spleen are important lymphoid organs in fish (13).
Head kidney plays a chief role in hematopoiesis and antimicrobial activity. The pattern of fish
20 Fish Vaccines lymphoid organs is unique with the kind of fish and its development also varies among marine and freshwater fishes (14). For example, the kidney, thymus, and spleen are the largest lymphoid organs in teleost fishes. In the case of freshwater teleost, the kidney is the primary lymphoid organ and the spleen is the secondary organ. In marine fishes, it develops in the order of kidney, spleen, and thymus. In marine water teleost fishes, the anterior kidney is the first organ to appear followed by spleen and thymus. But, in each case, the thymus is the primary organ to have lymphoid cells accompanied via the kidney and spleen.
2.2.3 fIsH Innate ImmunIty
Nonspecific immunity is observed in all residing organisms and is the primary line of defense against all pathogens. It also plays a crucial function in the activation of the adaptive immune response. The cell of the innate body recognizes and generically responds to pathogens. It also pos- sesses memory as the host evolves its innate immune components based on the evolutionary experi- ence of its ancestors encountering comparable pathogens. Innate immunity is commonly divided into three compartments: surface barrier, humoral factors, and cellular elements. As in the first line of protection, it is not astonishing that most people of the wide-spectrum parameters of innate immunity are conserved across species and taxa. In all jawed vertebrates, the innate immune system features a rapid reaction toward invading pathogens and tissue damage. But, it cannot provide per- fectly directed, specific protection from individual pathogens or long-term period immunological reminiscence.
2.2.3.1 Surface Barrier
Mucus, skin, gills, and gastrointestinal (GI) tract act as the first line of barrier to any diseases.
The layer of mucus found in pores and skin, gills, and GI tract entrap microorganisms with the aid of continuously sloughing and inhibiting colonization. The mucus of fish is toxic to certain microorganisms because of the presence of a few humoral factors. The rate of mucus production will increase in reaction to infection or physical or chemical irritants (15). The dermis of fish skin consists of nonkeratinized living cells and the integrity of those cells plays an important function in maintaining osmotic stability and excluding microorganisms. Speedy healing is likewise observed in the epidermis of fishes (16). The large surface area of delicate gill epithelium is taken into consid- eration as a crucial course of pathogen entry. The gills are covered via mucus production and highly responsive epithelium, resulting in hyperplasia, often seen in numerous gill infections. Phagocytic cells line the branchial capillaries and lymphoid cells on the caudal edge of the intrabronchial sep- tum. GI tract is lined by the mucus membrane and additionally the digestive enzymes, bile, and low pH of the stomach give an extremely adverse environment for pathogens, typically based on their pattern recognition specificities or effector functions.
2.2.3.2 Humoral Factors
They have a protective function that inhibits microorganisms and neutralizes the host enzymes on which pathogens depend. The classification of humoral parameters is based on their pattern recog- nition factors or effector functions.
2.2.3.2.1 Growth Inhibitors
Growth inhibitors act either on crucial vitamins or interfere with microbial metabolism. Transferrin (TF) in serum exerts bacteriostatic and fungistatic effects. TF, protein with high iron-binding capability, is a crucial element for the growth of microorganisms and preventing the utilization of iron by microorganisms (17). Pathogenic bacteria can produce siderophores to overcome this defense mechanism and the hyperferremic activity acts as a counter-reaction established in fish species. TF is also an acute-phase protein cited in inflammatory reaction to get rid of iron from damaged tissues (18) and an activator of fish macrophages (19). Interferons are virus-inducible
Antigens and Immune Responses in Fishes 21
cytokines that induce the expression of different antiviral proteins (20). The lysozyme variants (types I and II), purified from the head kidney of rainbow trout, has antibacterial impact gram –ve bacterial fish pathogens (1). INF α and β have nonspecific antiviral characteristics that cause the inhibition of nucleic acid replication. They induce the expression of interferon-stimulated genes inducing Mx, Viperin, ISG 15, and PKR. IFN-γ promotes Th 1 responses via CD4 + Th 1 and natural killer (NK) cells. It provides defense against intracellular pathogens. Fish IFN modulates cytokine and chemokine expression, and induces proinflammatory cytokines (IL-1, IL-6, IL-12, and TNF).
2.2.3.3 Cellular Factors
Cellular factors include monocytes, macrophages, granulocytes, neutrophils, dendritic cells, and NK cells. When an innate immune system recognizes a pathogen through its pathogen-associated molecular pattern, these immune cells get activated and cause phagocytosis and destruction of pathogens (21).
2.2.3.3.1 Macrophages
Macrophages are differentiated via circulating monocytes or through tissue-resident macrophages like kupffer cells in the liver, glial cells in the brain, and so on. Its differentiation is controlled by the CSF receptor 1 (22). It was first recognized inside the elephant shark (Callorhinchus milii) genome.
Macrophages in teleost play a role in both innate and adaptive immunity. In the innate immune reactions, they destroy pathogens via phagocytosis, reactive oxygen species, nitric oxide production, and the release of anti-inflammatory cytokines and chemokines. In teleost fish species, classically activated macrophages (M1) produce TNF, IL-1b, ROS, and NO (23), and kill pathogens through engulfment and production of toxic reactive intermediates, phagolysosomal acidification, and limit- ing nutrient availability. M2 are alternatively activated macrophages and are immunosuppressant and anti-inflammatory.
2.2.3.3.2 Fish Gill
Diseases associated with gills harm and cause enormous losses in the aquaculture industry not only via an extended mortality rate among fish but additionally through impaired growth and also with the aid of increased remedial and sanitation costs. Damage to gill tissues is especially character- ized by infection and increased epithelial cells hyperplasia or hypertrophy. A gill epithelium of salmonids has a better variety of MHC class II positive cells (24), whereas a low wide variety of macrophages-like cells has been detected in the gill epithelium of presumably healthy salmonid fish (25) cytokines including interleukin (IL)-10.