What is the difference between adaptive and innate immunity

No Bcz of the lack of memory in innate immune system So upon the second exposure to a pathogen the innate will respond as if it is the first exposure , and this response can be effective or not depending on many factors.

Save my name and email in this browser for the next time I comment. Characteristics Innate Immunity Adaptive immunity 1. Presence Innate immunity is something already present in the body. Adaptive immunity is created in response to exposure to a foreign substance. Specificity Non-Specific Specific 3. Response Fights any foreign invader Fight only specific infection 4.

Response Rapid Slow weeks 5. Potency Limited and Lower potency High potency 6. Time span Once activated against a specific type of antigen, the immunity remains throughout the life. The span of developed immunity can be lifelong or short. Inheritance Innate type of immunity is generally inherited from parents and passed to offspring. Adaptive immunity is not passed from the parents to offspring, hence it cannot be inherited.

Memory Cannot react with equal potency upon repeated exposure to the same pathogen. Adaptive system can remember the specific pathogens which have encountered before.

Allergic Reaction None Immediate and Delay hypersensitivity Gnathostomes are subdivided into Chondrichthyes cartilaginous fishes and Osteichthyes bony fishes. They diverged from a jawless common ancestor with the lineage leading to other bony vertebrates. While jawless fish have an adaptive immune system based on variable lymphocyte receptors VLRs , B-like and T-like cells, Gnathostomes are the most distantly related group to mammals that have an adaptive immune system based on Igs, TCR, and MHC 3 , 6.

There are over 1, species of cartilaginous fish, which are divided into two subclasses: Elasmobranchii sharks, rays, skates, and sawfish and Holocephali chimeras 7. The Osteichthyes are a diverse group of fish that have skeletons composed of calcified bone rather than cartilage and consist of over 40, species of fish 8. They are subdivided into two classes, the Actinopterygii ray-finned fish and the Sarcopterygii lobe-finned fish Figure 1. The Actinopterygii have fins that are composed of webs of skin supported by bony spines, known as lepidotrichia.

Due to the large number of teleost species, as well their economic importance, there have been many genomic and functional immunological studies completed on teleost fish. The Sarcopterygii possess fleshy, lobed, paired fins, joined to the body by a single bone and are comprised of Actinistia coelacanths and Dipnoi lungfish 4.

The majority of immunological studies on the cartilaginous fish and lobe-finned fish are genomic analyses, with very few functional studies. However, due to their unique position in the evolution of adaptive immunity, more functional studies are now being applied to cartilaginous fish.

While there are several reviews that examine the innate or adaptive immune systems of Chondrichthyes and Actinopterygii, and some studies on Sarcopterygii 3 , 13 , 14 , a comprehensive comparison of both the innate and adaptive immune systems in all 3 classes of fish is lacking. Thus here, we will endeavor to provide a comprehensive comparison of the innate and adaptive immune systems in cartilaginous fish, lobe-finned fish focusing on coelacanths and lungfish , and ray-finned fish, with a focus on Teleost fish.

Figure 1. Schematic diagram of the evolution of jawed vertebrates and the immune system. Information sourced from multiple phylogenetic analyses 3 , 4 , 6 , 9 — R: genome duplication event. Elements of the innate immune response can be found in all multicellular organisms The innate immune system can be categorized into three defense mechanisms: 1 physical barriers, 2 cellular components, and 3 humoral responses As will be discussed, the functions of these defense mechanisms are highly conserved between fish and mammals.

The first lines of defense in the fish innate immune system are physical barriers that prevent the entry of pathogens, which includes the skin e. One of the first physical barriers encountered by a pathogen is the skin.

Fish are constantly immersed in an aquatic environment and as a result are continuously exposed to potential pathogens or other harmful agents. Therefore, the skin is extremely important in early prevention of pathogen invasion. Teleost skin has been shown to contain skin-associated lymphoid tissue SALT that consists of multiple cell types including secretory cells e.

In most teleost fish, the dermis layer of the skin consists of solid, bony scales known as leptoid scales. Interestingly, some teleost species, such as the catfish, have lost their scales during the course of evolution and instead some catfish species have regressed to having bony dermal plates covering their skin The skin of cartilaginous fish also contains many cell types, including melanocytes, lymphocytes, macrophages, and granular leukocytes The scales of cartilaginous fish are called placoid scales, also known as denticles The skin of lobe-finned fish contains keratinocytes, granulocytes and B cells Lobe-finned fish have cosmoid scales that includes a layer of dense, lamellar bone called isopedine.

An equally important function of the skin is the ability to secrete mucus, which acts as both a physical barrier, by trapping pathogens, and a chemical barrier Mucus from teleost fish contains a combination of lectins, lysozymes, complement proteins, and antimicrobial peptides AMPs ; all of which play a critical role in neutralizing pathogens 16 , While we hypothesize that skin mucus from both cartilaginous fish and lobe-finned fish contains these compounds as well, it has not been as extensively explored as in teleost fish.

Supporting this hypothesis are studies showing that a transcript for a lectin, pentraxin, was found in the skin mucus of the common skate Raja kenojei , while AMPs, including histones and S proteins, were found in the skin mucus of the African Lungfish Protopterus dolloi 20 , In addition to being involved in osmotic balance and gas exchange, the gills are also an important physical barrier, having both innate and adaptive immune components.

The physical barrier of the gills consists of the gill epithelium, a glycocalyx layer, and a mucus layer. In teleost fish, the interbranchial septum is reduced and contains a single caudal opening of the operculum, rather than multiple openings while in cartilaginous fish, the gills are supported for almost their entire length by an interbranchial septum with multiple branchial slits or gill openings Immune cells, including macrophages, neutrophils and eosinophilic granulocytes have been observed in the gill associated lymphoid tissues GIALT of teleost fish Lymphocytes have been identified in the gills of several teleost species 25 , 26 and of the nurse shark Ginglymostoma cirratum For example, B cells and T cells have been identified in the gills of rainbow trout Oncorhynchus mykiss and channel catfish Ictalurus punctatus while a specific B cell Ig transcript was observed in the gills of nurse shark see adaptive immune section for a discussion on B cells, Ig, and T cells.

Microbes present in the mucosal surface of the GIALT have been found to induce specific immunoglobulin producing B cells The gastrointestinal GI tract facilitates the absorption of nutrients, while preventing pathogen invasion through its epithelium. If a pathogen is ingested, it will encounter the GI tract, which, like the skin and gills, contains both innate and adaptive immune cellular components. Gut associated lymphoid tissue GALT can be found in both bony and cartilaginous fish; however, unlike in mammals, it is not highly organized but is composed of a diffuse network of myeloid and lymphoid cells.

Anal administration of Vibrio anguillarum to carp Cyprinus carpio and intraperitoneal injection of V. T cells have also been identified in the GALT of several teleost species 32 — In teleost fish, as in mammals, the gut microbiota plays a major role in the development and maturation of the GALT, which in turn mediates its immune response 35 , For example, resident microbiota stimulates intestinal epithelial cell proliferation in the developing zebrafish intestine, while absence of microbiota prevents differentiation of the GI tract 37 , Lymphoid aggregates, as well as macrophages and granular cells, have been found in the spiral valve of various shark and ray species 42 , Lymphocytes and macrophages appear in the gut of the Dogfish shark at hatching and their numbers increase with age, as determined by histological analysis Large accumulations of lymphoid cells have been found in the gut of the Australian lungfish Neoceratodus forsteri ; however the cellular and molecular composition of these lymphoid masses is currently unknown While there has been extensive research on the GALT of teleost fish, likely due to their economic importance, there are limited studies on the GALT of cartilaginous and lobe-finned fish and most are histological studies.

It is unknown how the GALT in these species respond to infection and if it is in a similar manner as teleost fish and mammals. In addition, while the gut microbiome of some shark species has been identified 47 , it is unknown how the microbiota effects the development of the GALT and its immune response in both cartilaginous fish and lobe-finned fish. If a pathogen passes through the physical barriers, it will encounter the cellular and humoral aspects of the innate immune system.

In bony fish, the primary sites for leukocyte production are the anterior or head kidney and thymus, while in cartilaginous fish, the primary sites include the epigonal organ, Leydig organ, thymus, and spleen Knowing the site of hematopoiesis in lobe-finned fish would allow for isolation of these cells and experiments that would lead to a better understanding of immune cells in these species. When an innate immune cell encounters a pathogen, it will recognize a pathogen-associated molecular pattern PAMP found on the pathogen.

Once recognized, the innate immune cell will become activated and can participate in several responses depending on their cell subtype including, but not limited to, phagocytosis and subsequent destruction of the pathogen, production of various cytokines and activation of the adaptive immune system via antigen presentation along with cytokine stimulation.

Macrophages are derived from hematopoietic progenitors which differentiate via circulating monocytes or via tissue resident macrophages. Differentiation of vertebrate macrophages is controlled by engagement of the colony-stimulating factor 1 receptor CSF1R CSF1R has been characterized in several teleost species, and has been identified in the elephant shark Callorhinchus milii genome 51 — Macrophages play a role in both the innate and adaptive immune systems and are key players during inflammation and pathogen infection, as well as in tissue homeostasis.

In the innate immune system, macrophages of several teleost fish species have been demonstrated to destroy pathogens through phagocytosis, the production of reactive oxygen species ROS and nitric oxide NO , and the release of several inflammatory cytokines and chemokines, similar to mammalian macrophages [reviewed in 55 — 57 ].

In the adaptive immune system, macrophages are one type of professional antigen presenting cell pAPC that can present phagocytosed materials to the T lymphocytes of the adaptive immune system through a process termed antigen presentation. Macrophages in cartilaginous fish have not been studied as in depth as in teleost fish, however, it is known that nurse shark macrophages exhibit spontaneous cytotoxicity, a nonphagocytic killing mechanism Lungfish macrophages are described to have typical vertebrate macrophage morphology 59 , Very few functional studies have been completed in lungfish, however, one study found that injection of lipopolysaccharide LPS did not change the number of macrophages in the coelomic cavity, as was expected Similar to mammals, functionally distinct subpopulations of macrophages exist in bony fish.

The best characterized macrophage phenotype in teleost fish is comparable to M1 macrophages where they can destroy pathogens via acidification, nutrient restriction, production of reactive intermediates and various cytokines and chemokines 55 — While in recent years, EVs have been extensively studied in mammals, very few studies exist in fish.

The secretion of EVs was not induced by CpG in a splenocyte culture containing mostly B cells suggesting that the EVs were likely produced by macrophages or dendritic cells in the head kidney leukocyte culture The existence of M1 and M2 cell populations, as well as EVs, have yet to be examined in cartilaginous and lobe-finned fish. The most abundant granulocytes in bony fish are neutrophils, and like macrophages, neutrophils are critical to the innate defense against pathogens Neutrophils exhibit potent antimicrobial responses through various intracellular and extracellular mechanisms including the release of granules containing cytotoxic and antimicrobial enzymes, the release of neutrophil extracellular traps NETs , phagocytosis and the production of ROS and NO [reviewed in 57 , 65 ].

Some bony fish granulocytes have a similar appearance to that of mammalian cells neutrophils or avian cells heterophils. Fish granulocytes exhibit a wide variation in morphology, numbers and types of cells between species causing much confusion regarding their nomenclature. For example, a study by Tavares-Dias et al.

Granulocytes in cartilaginous fish are classified in three types based on size, shape, and staining properties. G1 granulocytes, referred to as heterophils or fine eosinophilic granulocytes, are often the most common granulocyte in cartilaginous fish. G2 granulocytes resemble mammalian neutrophils, while G3 are referred to as coarse eosinophilic granulocytes 68 , G3 is more commonly seen in cartilaginous fish, compared to bony fish Not all species of cartilaginous fish exhibit all three types of granulocytes; for example, only G1 and G3 granulocytes have been found in Thornback rays Raya clavate and small eyed rays Raja microcellata In the African lungfish P.

Initiation of the innate immune response begins when germline-encoded intracellular or extracellular pattern recognition receptors PRRs of an immune cell bind to a PAMP found on a pathogen, such as bacteria-derived LPS, viral RNA, bacterial DNA, or a danger-associated molecular pattern DAMP found on proteins or other biomolecules that are released from stressed cells or injured cells.

Many homologs of mammalian PRRs have been identified in fish. TLRs were the first PRRs to be discovered in fish and therefore have been the most extensively studied. To date there have been 13 TLRs identified in mammals, whereas over 20 have been identified in different fish species 73 — A comparison of the TLRs found in mammals, cartilaginous fish, ray-finned fish and lobe-finned fish, as well as their ligands in mammals and when known in bony fish can be found in Table 1.

For example, a sTLR5 has been identified in bony fish, including rainbow trout, and Atlantic salmon, whereas no sTLR5 has been found in mammalian genomes 82 , 90 , Some bony fish, including the zebrafish Danio rerio , the Dabry's sturgeon Acipenser dabryanus and the yellow catfish Pelteobagrus hydrophila , possess TLR4-like genes, while TLR4 is absent in other bony fish species, as well as absent in coelacanths and cartilaginous fish 56 , 85 , TLR27 was first identified and thought to only be found in the coelacanth genome but has since been identified in the spotted gar Lepisosteus oculatus and elephant shark 78 , Table 1.

TLRs present in mammals, ray-finned fish, lobe-finned fish, and cartilaginous fish. Due to genome duplication events, several paralogs of various TLRs exist in fish. Evidence, such as an increase in the number of Hox gene clusters, indicates that an additional genome duplication event 3R occurred early in the teleost lineage, after it split from the lobe-finned lineage — MYA, while an additional round of genome duplication 4R occurred in some fish species, including salmonids, thus leading to several paralogs of genes, including TLRs 79 , The high number and large diversity of fish TLRs are likely derived from their distinct and diverse evolutionary history and environments that they occupy [reviewed in 77 ].

In addition to TLRs, differences in several other PRRs between ray-finned, lobe-finned and cartilaginous fish have been noted. Additionally, novel immune-type receptors NITRs which have been studied extensively in ray-finned fishes are missing from the coelacanth genome However, as more high quality, well-assembled, and annotated genomes become available for additional cartilaginous and lobe-finned fish, additional NITRs may be identified.

These differences indicate that not only is pathogen recognition quite diverse in fish, it can also be lineage-specific. Phagocytosis is one of the most ancient and universal tools of defense against foreign material. This mechanism of defense is observed even in unicellular eukaryotes, predating complex multicellular life 57 , 95 — Binding of a pathogen to a PRR triggers phagocytosis in cells termed phagocytes.

These include macrophages, monocytes, neutrophils and dendritic cells and are found in both bony and cartilaginous fish 57 , 95 — Recently, the existence of B cells with phagocytic ability was discovered in various teleost fish species including rainbow trout, Atlantic salmon, and Atlantic cod 99 , It is unknown if cartilaginous fish and lobe-finned fish have phagocytic B cells. After engulfment, the phagosome, containing the pathogen, binds to a lysosome, forming a phagolysosome, where the pathogen is killed by various means including the production of ROS and NO Studies in shark, skate, lungfish and teleost fish have demonstrated both ROS and NO production in various leukocytes 65 , Humoral responses are mediated by macromolecules produced by cells and released into the extracellular fluids following infection by a pathogen.

Some of the most studied humoral components in fish include the complement system, lysozyme, antimicrobial peptides, and acute phase proteins. These components have many different functions including the promotion of inflammation and phagocytosis and direct bactericidal effects. The complement system is a cascade of serum proteins that act cooperatively to mediate defense mechanisms including the elimination of pathogens through opsonization and phagocytosis and the promotion of the inflammatory response.

Figure 2 illustrates these three pathways, along with some of the associated proteins. Ultimately, these pathways induce activation of the C3 convertase, which cleaves inactive C3 into C3a, an anaphylatoxin that acts as a chemotactic factor and aids in inflammation, and C3b, which acts as an opsonin, as well as an activator of downstream complement proteins leading to the formation of the membrane attack complex , Figure 2.

The three complement pathways with associated proteins. Most of the mammalian complement components have homologs in various teleost species, including rainbow trout , zebrafish , and channel catfish , among many others, and their functions have been well-characterized [reviewed in 56 , ].

Similarly, components of all three pathways have been characterized in several cartilaginous fish species, where they have been found to have hemolytic properties — Furthermore, genes encoding complement components have been identified in lungfish , and in the coelacanth genome However, not all fish species contain all three pathways.

MBL and ficolin genes have not been identified in any cartilaginous fish studied to date, while MASP2 transcripts are lacking in the elephant shark, little skate Leucoraja erinacea and catshark Scyliorhinus canicular 54 , , In addition, the hammerhead shark contains a MASP2 transcript that contains no serine protease domain, which is necessary to initiate the lectin pathway.

This data suggests that the lectin pathway may not be present in cartilaginous fish Furthermore, some fish species contain multiple forms of various complement factors.

Multiple C3 forms have been identified in teleost fish and cartilaginous fish. For example, rainbow trout have three C3 forms, common carp have eight, and gilthead seabream S. Two C3 variants have been described in the nurse shark and the small-spotted catshark, while two C4 gene haven been identified in the elephant shark and hammerhead shark 54 , , This structural and functional diversity suggests that these fish may have an increased capacity to recognize and destroy a broader range of pathogens compared to those with fewer forms, although this remains to be demonstrated.

It is also involved in other defenses such as opsonization and phagocytosis and activation of the complement system — Two types of lysozyme have been described in vertebrates: chicken c -type and goose g -type.

Lysozyme is one of the most studied innate immune components in fish. C-type and g-type lysozymes have been reported in several teleost species where they are found in neutrophils, monocytes and to a lesser extent in macrophages of several tissues e. Recombinant r- c-type and g-type lysozymes have been found to have high bacteriolytic activity against a variety of pathogens of teleost fish such as V.

A sequence homology search of the Atlantic cod genome revealed an absence of c-type lysozyme genes; however, four g-type lysozyme genes were identified in several different tissues Intraperitoneal injection of Francisella noatunensis , an intracellular bacterium that commonly infects cod, stimulated the expression of two of the g-type lysozyme genes in the head kidney The presence of multiple g-type lysozymes may compensate for the lack of c-type lysozymes in the Atlantic cod The presence of lysozyme in the lymphomyeloid tissues of several cartilaginous fish was first discovered in A genomic investigation by Venkatesh et al.

This c-type lysozyme was characterized in the nurse shark and found to hydrolyze the cell wall of M. In addition, two g-type lysozyme genes were discovered in the coelacanth genome, although no functional studies on lysozymes have been completed in coelacanth or lungfish to date Collectively, these studies suggest that the function of lysozyme is similar in both bony and cartilaginous fish.

AMPs, also known as host defense peptides, that are generally oligopeptides with a varying number of amino acids that are generally positively charged and play a major role in the innate immune system. AMPs protect against a variety of pathogens via disruptive or pore-forming actions against bacterial membranes.

Several of these AMPs have been cloned and subsequent functional studies have demonstrated antiviral and antibacterial activities against a variety of pathogens, demonstrating that AMPs from teleost fish exhibit many if not all of the characteristics of other vertebrate AMPs — Two cathelicidin genes have been identified in rainbow trout where they displayed activities against bacteria including V.

Unlike the comprehensive studies conducted on AMPs in teleost fish, research into shark and lobe-finned fish AMPs has not been as extensive. Two AMPs have been isolated from the dogfish shark Squalus acanthias , transferrin and squalamine , which were found to have potent bactericidal activity against both Gram-negative and Gram-positive bacteria. A recent study by Heimroth et al. In both fish and mammals, tissue injury, infection and inflammation induce immune cells, such as macrophages, to secrete various cytokines into the bloodstream, which stimulate hepatocytes to produce and release acute phase proteins APPs , APPs are classified based on the extent to which their concentrations change minor, intermediate, or major and the direction of change positive or negative.

They are involved in a variety of defense activities and include coagulation factors, such as fibrinogen and prothrombin, transport proteins such as ferritin, complement components, C-reactive protein CRP and serum amyloid proteins SAP [reviewed in ]. APPs are well-conserved in arthropods, fish, amphibians, and mammals They are members of the pentraxin family of APPs, are present in the body fluids of vertebrates and invertebrates, and are commonly associated with the acute phase response of inflammation In addition to inflammation, CRP and SAP have been shown to activate the complement pathways and play a role in the clearance of apoptotic cells , Both CRP and SAP have been identified in several teleost species — where their levels in the serum have been shown to increase in response to various inflammation-inducing stimuli — Moreover, increased levels of CRP were found in the serum of sharks inhabiting a highly industrialized harbor estuary where exposure to polycyclic aromatic hydrocarbons PAHs and other contaminates was likely to lead to an inflammatory response As well, transcriptome analysis of the Indonesian coelacanth, Latimeria menadoensis , genome identified SAP encoding transcripts , however, to our knowledge, no other studies examining CRP or SAP in coelacanths or lungfish have been reported.

If a pathogen persists, despite the innate immune defenses, the adaptive immune system will be activated. As previously stated, while jawless fish have an adaptive immune system based on VLRs, B-like and T-like cells, several components of the adaptive immune system, including Igs [also known as antibodies Ab ], TCR and MHC, are believed to have arisen in the first jawed vertebrates 3 , 6.

Like the innate immune system, the adaptive immune system includes both humoral and cellular components. B cells are key elements of the humoral adaptive immune response.

The main role of B cells is to produce high affinity Ig against foreign antigen, and to act as a pAPC to present processed antigen to activate T cells. T cells are key elements of cellular adaptive immunity.

This results in a highly diverse repertoire of BCRs and TCRs able to recognize innumerable different specific antigens and is unique to the adaptive immune system. Therefore, developing B and T cells will undergo negative selection to ensure only cells that recognize foreign antigen survive. Negative selection occurs when a B cell recognizes self-antigen, inducing apoptosis or receptor editing, while positive selection occurs through antigen-independent signaling involving the BCR.

Negative selection occurs when a double positive T cells binds to MHC I or II with a high enough affinity to receive an apoptotic signal. While VDJ recombination has been characterized in fish [reviewed in , ], the process of negative and positive selection of developing B and T cells has not been fully elucidated, although these processes possibly occur in a similar manner as mammals.

There is little to no research on negative and positive selection of developing B and T cells in cartilaginous and lobe-finned fish, while there is very limited research in teleost fish. Studies into the regulation of autoimmunity would be valuable to better understand the mechanisms of negative selection in fish. The development of antibodies that specifically detect fish proteins, such as CD4 and CD8, is necessary to fully understand the homing and recirculation of B and T cells in fish.

Figure 3. Antibody diversity and isotypes are divergent in fish. A Arrangement of the heavy chain loci in bony fish and cartilaginous fish. V represents variable segments, D represents diversity segments, J represents joining segments and C represents constant domains.

B Examples of the immunoglobulin isotypes in fish. Dark blue circles represent heavy chain domains, light blue circles represent light chain domains — The Fc region mediates the effector functions of the antibody by binding to a specific class of Fc receptors and other molecules such as complement proteins with the IgH categorizing them into specific isotypes.

The variable regions of the heavy and light chain loci are assembled via somatic gene rearrangement from an array of multiple V, D, and J segments during B cell development, allowing each B cell to produce a unique Ab. In response to antigen, in combination with helper T cell interactions, B cells will secrete antigen—specific Abs.

Similar to all vertebrates except cartilaginous fish , the IgH genes of teleost fish are arranged in a translocon configuration of which multiple V segments are found upstream of several D and J segments, followed by C segments Vn-Dn-Jn-C Figure 3A Depending on the species, differences may occur such as duplication of individual V, D, or J segments, or tandem duplication of C domain exons such as that found in Atlantic salmon and zebrafish , Instead of the single translocon locus, the IgH loci of cartilaginous fish adopt a multiple mini-cluster organization, with each cluster consisting of one V, two or three Ds, and one J, followed by one set of C region exons for a specific isotype Figure 3A The clusters can be repeated as many as times in the genome, depending on the species.

While most clusters are capable of rearrangement, some clusters are partially VD-J or fully recombined VDJ or VJ in the germline, a rearrangement that is unique to cartilaginous fish IgH genes in lungfish are organized in a transiting form, having both cluster like cartilaginous fish and translocon like teleost fish configurations IgM is the most ancient antibody class found in all jawed vertebrates; with the exception of coelacanths, which is the only known jawed vertebrate that does not contain IgM in the genome — IgM is the most prevalent Ab in both bony and cartilaginous fish plasma and can be found in both secreted and transmembrane forms.

It shares a similar function in all jawed vertebrates, which includes mediating opsonization, antibody-dependent cell-mediated cytotoxicity, and complement activation, and thus contributes to both innate and adaptive immune responses 58 , , , In teleost fish, IgM is multimerized into a tetrameric form, although there have been reports of a monomeric IgM form in some teleost species , Due to an alternative splicing pathway, the transmembrane form of IgM is one domain shorter than the secreted form in teleost fish, resulting in a shortened IgM receptor on the B cell surface The J chain, which is required for IgM polymerization and secretion into the mucosa, has not been found in teleost fish, and therefore, tetrameric IgM is polymerized by interchain disulfide bonds IgM is the only teleost isotype for which sub-isotypes have been identified.

Two sub-isotypes of IgM have been identified in Atlantic salmon and brown trout Salmo trutta , reflecting the pseudotetraploid state of salmonid genomes , Both the secreted and transmembrane forms of IgM contain four C domains, except in the neonatal nurse shark, where a subclass of IgM IgM1 gj found in high amounts in the serum has only 3 C domains IgM in the serum of cartilaginous fish is found in two different states, a monomeric 7S and pentameric 19S, which are present in approximately equal amounts Pentameric IgM serves as the first line of defense, while 7S is produced later Both 7S and 19S IgM play a role in cytotoxicity reactions via phagocytosis In some cartilaginous fish species, such as the nurse shark, the J chain is present in pentameric IgM, although it may not be involved with IgM secretion, unlike the J chain in mammalian IgM , In contrast to the coelacanth, which does not contain IgM in the genome, lungfish species express multiple diverse IgM genes which vary among species , Recently the J chain was identified in the spotted lungfish IgD is found in many vertebrate classes, including teleost fish and acipenseriformes a group of fish that phylogenetically links elasmobranches, teleosts, and sturgeons.

The function of IgW and IgD, however, is poorly understood in both fish and mammals. Teleost fish contain many forms of IgD, with constant domains ranging from 2 to 16 — IgD has only been found in a transmembrane form, with the exception of the channel catfish and the Japanese puffer Takifugu rubripes , which contain both membrane and secretory forms IgD is co-expressed with IgM in most teleost fish, although they are absent in channel catfish and rainbow trout.

In rainbow trout, the ratio of IgD to IgM in the gills is much higher than other tissues. IgW in cartilaginous fish contains six to eight C domain exons, in addition to the V, D, and J segments. Multiple splice forms of IgW exist in cartilaginous fish other than the original six C domains IgW-long , including a two C domain IgW-short form and a four C domain form , , A V-less form of IgW has been identified in both the spiny dogfish S.

Two IgW transcripts have been identified in the African lungfish Similar to cartilaginous fish, lungfish IgW can be found in a long form, consisting of seven C domains homologous to IgW-long or a short form, consisting of two C domains , Two distinct loci for IgW have also been discovered in the Indonesian and African coelacanth Latimeria chalumnae IgNAR exists in both long and short forms, which can vary between species The long transmembrane and secreted forms consist of five C domains while the short transmembrane form consists of three C domains , While only a few studies have been performed, it is thought that IgT is specialized for mucosal immunity and functions analogously to mammalian IgA.

High-throughput sequencing of two species of African lungfish P. Both bony and cartilaginous fish lack bone marrow, the main site of hematopoiesis in mammals, and germinal centers GC , specialized sites where mature B cells proliferate, differentiate, and selection of high affinity BCR occurs in mammals.

Instead, in teleost fish, the main site of hematopoiesis is the anterior or head kidney. Progenitor B cells and plasma cells are found in the anterior kidney, while mature B cells and plasma blasts are found in the posterior kidney and in the spleen , It is proposed that mature B cells are released into the blood where they encounter antigen and mature into plasma blasts or plasma cells.

Plasma cells then migrate back to the anterior kidney where they may become long-lived plasma cells, supporting the storage of Ig-secreting cells , However, more work is required to fully elucidate the mechanisms regulating homing of B cells in fish.

The spleen is considered the only secondary lymphoid organ SLO in teleost fish, where expression of AID see below has been observed, suggesting that the spleen is the site for antigen stimulation In cartilaginous fish, the Leydig organ, a gland-like structure associated with the esophagus, and the epigonal organ, a structure physically attached to the gonads with a similar structure and organization as the Leydig organ, are the main sites of hematopoiesis and B cell production Lymphocytes of various sizes are abundant in these organs and form a loose follicle-like aggregate with scattered plasma cells While most cartilaginous species have both organs, some species only have one, such as the nurse shark, which only has an epigonal organ Like bony fish, RAG1 and TdT expression in the epigonal organ provides evidence that it is a site of B cell development Additionally, hematopoietic transcription factors important in B and T cell development are expressed in the Leydig and epigonal organ of the embryonic clearnose skate Raja eglanteria The WP consists of lymphocytes and mature and developing plasma cells, while the RP consists of macrophages, erythrocytes and plasma cells , Antigen stimulation, leading to Ab synthesis, has been described in the cartilaginous fish spleen , Structural analysis of the African lungfish spleen identified characteristics of a secondary lymphoid organ; the red pulp is likely the site of erythropoiesis, as well as site of plasma cell differentiation, similar to cartilaginous fish, as evidenced by mature and immature plasma cells The WP appears to be involved in immune responses Both bony and cartilaginous fish have been shown to develop immunological memory i.

One of the first studies to identify immunological memory in fish was in rainbow trout where it was demonstrated that the secondary response to trinitrophenylated-keyhole limpet hemocyannin TNP-KLH was faster and of a larger magnitude than the primary response, as determined by ELISA Several other studies in fish, including rainbow trout and turbot Psetta maxima , have since shown that neutralizing Ab can be induced against a variety of viral, bacterial and parasitic pathogens and vaccines , However, the response time of teleost IgM is much slower than in mammals, taking 3—4 weeks after immunization before specific titers are detected.

Interestingly, some fish species, such as the Atlantic cod, do not appear to produce a specific antibody response upon immunization, despite high levels of serum Abs Similar to teleost fish, the immune response time of IgM in cartilaginous fish is much longer than in mammals.

Dooley and Flajnik completed a 3 year-long immunization study in the nurse shark The results demonstrated that, following immunization, pentameric IgM, which localizes mainly in the plasma, was induced before other isotypes, but with a low-affinity interaction with antigens.

The results also demonstrated that monomeric IgM, which is capable of entering tissues, appeared after pentameric IgM and was the main Ig involved in antigen-specific responses. A significant increase in antigen-specific IgNAR titers was also observed with a high specificity to antigen following immunization.

It can take up to 28 months before the antigen-specific titer levels return to pre-immunization levels once the Ig response has reached a plateau Memory was demonstrated for both monomeric IgM and IgNAR as re-immunization after a decrease in titer induced a quicker response than the primary immunization AID in fish was first reported in channel catfish, and has since been reported in many other fish species , Teleost fish AID differs from mammals in that it has a longer cytidine deaminase motif and substitutions in its carboxy-terminal region In addition, the biochemical properties of AID from the sea lamprey, nurse shark, tetraodon, and coelacanth were recently characterized where it was found that these AIDs exhibit unique substrate specificities and optimal temperature tolerances while the lethargic enzymatic rate and affinity for ssDNA of AID are conserved However, a search of the African lungfish mucosal lymphoid tissue transcriptome for AID found no evidence of expression using cartilaginous fish, teleost fish, or tetrapod AID sequences for comparison suggesting that the African lungfish may have lost AID expression in its genome In the case of a bacterium this would be fatal to the microbe.

Mast cell: A large tissue cell that releases inflammatory mediators when damaged, and also under the influence of antibody. By increasing vascular permeability, inflammation allows complement and cells to enter the tissues from the blood. The name derives from the peculiar shapes of the nuclei. MAC: Macrophage, a large tissue cell responsible for removing damaged tissue, cells, bacteria, etc. Both PMNs and macrophages come from the bone marrow, and are therefore classed as myeloid cells.

DC: Dendritic cells present antigen to T cells, and thus initiate all T-cell-dependent immune responses. Not to be confused with follicular dendritic cells, which store antigen for B cells. The great majority of foreign materials entering the tissues are ultimately disposed of by this mechanism.

Cytotoxicity: Macrophages can kill some targets perhaps including tumor cells without phagocytosing them, and there are a variety of other cells with cytotoxic abilities. NK natural killer cell: A lymphocyte-like cell capable of killing some targets, notably virus-infected cells and tumor cells, but without the receptor or the fine specificity characteristic of true lymphocytes. Antigen: Strictly speaking, a substance that stimulates the production of antibody.

However, the term is applied to substances that stimulate any type of adaptive immune response. Its ability to recognize individual antigens through its specialized surface receptors and to divide into numerous cells of identical specificity and long lifespan makes it the ideal cell for adaptive responses. Two major populations of lymphocytes are recognized: T and B.

Antibody: Is a major fraction of serum proteins, often called immunoglobulin. It is made up of a collection of very similar proteins each able to bind specifically to different antigens, and resulting in a very large repertoire of antigen-binding molecules. Antibodies can bind to and neutralize bacterial toxins and some viruses directly but they also act by opsonization and by activating complement on the surface of invading pathogens. Opsonization: A phenomenon whereby antibodies bind to the surface of bacteria, viruses or other parasites, and increase their adherence and phagocytosis.

Antibody also activates complement on the surface of invading pathogens. Adaptive immunity thus harnesses innate immunity to destroy many microorganisms. Complement: As mentioned above, complement is often activated by antibody bound to microbial surfaces.