Fish Immunology (1+1)

Unit 3- Nonspecific immunity

3.3. Nonspecific Humoral defence
Teleost fish have been shown to possess non-specific humoral defense substances which are physicochemical and functionally similar to mammals, but still different features.
Antimicrobial polypeptides
Antimicrobial polypeptides are small molecular peptides which are active against microorganisms and have been identified as a component of the innate immune response and been found in the tissues of teleost fishes, These peptides have been found in the mucus, liver and gill tissue of teleost fish. These low molecular weight polypeptides have the ability to break down cell wall of both Gram-positive and Gram-negative bacteria and also some of the evolutionarily conserved cationic, bactericidal polypeptides have been found.
Complement
Fish complement, in general, exhibits highest activity between 15 ⁰C and 25 ⁰C and can remain active at temperatures as low as 0 ¬- 4 ⁰C which is in contrast to mammalian complement with an optimal temperature of 37 ⁰C.
The complement system in teleosts, as well as that in higher vertebrates, can be activated in three ways:
The classical pathway which is triggered by antibody binding to the cell surface, but can also be activated by proteins such as ligand-bound C-reactive protein or directly by viruses, bacteria and virus-infected cells
The alternative pathway, which is independent of antibodies and is activated di¬rectly by foreign microorganisms, and
The lectin pathway, which is activated by the binding of a protein complex consisting of mannose/mannan-binding lectin in bacterial cells.
Cytokines
A cascade of pro-inflammatory cytokines is released as part of the non-specific innate immune response. The major drawback in identifying fish cytokines is the low sequence identity compared to their mammalian counterparts. The low sequence identities also limit the detection of proteins of fish cytokines by using the antibodies of human cytokines. In general, however, fish appear to possess a repertoire of cytokines similar to that of mammals.

Several cytokine homologues that are observed in fish species are
tumour necrosis factor-a (TNFa) and TNFb,
interleukin-1b (IL-1b), IL-2, IL-4, IL-6, IL-10, IL-11, IL-12, IL-15, IL-18, IL-21, IL-22, IL-26, IFN-g and
chemokines IL-8 or CXCL8, gIP-10, CK-1 and CK-2.
Tumor necrosis factor (TNF)
TNF-α and -β are impor¬tant activators of macrophages leading to increased respiratory activity, phagocytosis and nitric oxide production.
Interleukins (IL)
IL present in tel¬eost fish species are involved in the regulation of immunity through the stimulation of T cells. The expression of the IL-1 receptor in fish appears to be in the ante¬rior kidney, spleen, liver and gills after stimula¬tion with LPS and TNF-α, suggesting a role for the IL-1 receptor in regulating IL-1β during the inflammatory response. The expression of the IL-1 receptor in fish appears to be found in all tissues and is regulated in the ante¬rior kidney, spleen, liver and gills after stimula¬tion with LPS and TNF-α, suggesting a role for the IL-1 receptor in regulating IL-1β during the inflammatory response.
Chemokines
Chemokines are a superfamily of cytokines, produced by different cell types that have, among other functions, chemoattractant properties stimulating the recruitment, activation, and adhesion of cells to sites of infection or injury.
Chemokines play a key role in the movement of immune effector cells to sites of infection and it is becoming increasingly clear that their function is also necessary to translate an innate immune response into an acquired adaptive response.
Innate immune stimuli activate toll receptors and set in motion the expression of chemokines from resident tissue macrophages and dendritic cells and, modulate the expression of chemokine receptors on dendritic cells. These changes in chemokine/chemokine-receptor expression direct the movement of antigen-loaded dendritic cells from the tissue into lymphoid tissue to activate native T and B cells and initiate the adaptive response.
Interferon (INF)
INFα and β are cytokines with a nonspecific anti¬viral function that is based on the inhibition of nu¬cleic acid replication within infected cells. INF plays an important role in the defence against viral infec¬tion in vertebrate host cells, which secrete INFα/β upon recognition of viral nucleic acid. These INFs protect other cells from viral infection by binding to different receptors, which results in the induction of several hundred genes that are stimulated by INF (ISGs).
Protease inhibitors
Several protease inhibitors are present in the serum and other body fluids of fish. The main function of protease inhibi¬tors is to maintain body fluid homeostasis. These molecules are involved in acute phase reactions and defence against pathogens that secrete pro¬teolytic enzymes. The most widely studied of the protease inhibitors is the α-2 macroglobulin, which has a high specificity for inhibiting the physical encapsulation of protease.
Lysozyme
Lysozyme is a bacteriolytic enzyme that is widely distributed throughout the body and is part of the nonspecific defence mechanisms in most animals. lysozyme has been detected in se¬rum, secretions, mucous membranes and tissues rich in leucocytes, mainly the kidney and intestine. Apparently, the main sources of lysozyme are monocytes/macrophages and neutrophils. The bactericidal ac¬tion of this enzyme involves the hydrolyzation of the peptidoglycan of bacterial cell walls resulting in cell lysis. Furthermore, this enzyme is known to trigger an opsonin of the complement system and phagocytic cells.
Natural antibodies
Natural antibodies are produced in fish at a level that is regulated in the absence of antigenic stimu¬lation of cells that are equivalent to B1 cells. These natural antibodies are found in high levels in the serum of fish, where they provide im¬mediate and broad protection against bacterial and viral pathogens, making these factors key compo¬nents of nonspecific immunity. Natural antibodies are also linked to adaptive immunity. Teleost fish are capable of generating specific IgM-type natural antibodies against various antigens. The intensity of this response, however, has been shown to vary between different species and environmental con¬ditions.
Pentraxins
C-reactive protein (CRP) and serum amyloid protein (SAA) are present in the body fluids of vertebrates and invertebrates and are commonly associated with the acute phase response of inflammation. Different stimuli, such as tissue damage, trauma or infection, generate various patterns of CRP production in teleost fish, in which either the level of CRP is decreased in serum (negative acute phase protein) or the level of CRP is increased in serum (positive acute phase protein). Although the pentraxinas of teleosts have a recognized role in defence mechanisms.
Transferrin
Iron is an essential element in the establishment of infection by many pathogens, but the availability of iron in the tissue fluids of vertebrates is extremely low due to its high affinity for the blood protein transferrin. Transferrin is a globular glycopro¬tein with a high iron chelator activity. This protein is the major iron ion transport protein in animals and plants. Only bacteria with high affinity systems for iron absorption are able to maintain sufficient iron levels to grow in the host.