Phenoloxidase system is a major defense system in many invertebrates which ultimately leads to melanization of pathogens and damaged tissues. The process of melanization depends on activation of the enzyme phenoloxidase (PO) which is controlled by the prophenoloxidase (proPO) activation system. [1]
During activation of the proPO cascade, many other immune reactions are produced, such as cytotoxic, opsonic and encapsulation activities. [2] The phenoxidase cascade plays an important role in invertebrates (especially insects) in three physiologically important processes: immune reactions, sclerotization of the cuticle and wound healing. [3]
The phenoloxidase system begins with the recognition of microbial PAMPs (pathogen-associated molecular patterns) including LPS (gram-negative bacteria), peptidoglycans (gram-positive bacteria) and β-1,3-glucans (fungi). Interaction of PAMPs with PRPs (pattern-recognition proteins) activates a series of serine proteinases and those proteolytically cleave the prophenoloxidase (proPO) zymogen and activate phenoxidase (PO). [2]
During the proPO system activation, reactive intermediates such as quinone-like intermediates, reactive oxygen (ROI) or nitrogen intermediates are produced. These have cytotoxic activity against microorganisms, prevent organism from entering of another pathogen and also assist in wound healing. [4] [5]
Active PO plays an important role in the initial stages of the melanization process. The PO catalyses a hydroxylation of monophenols (tyrosine) on diphenols and oxidation of diphenols to dichinones. The chinones non-enzymatically change their structure to dopachrome and than dopachrome isomerase changes dopachrome to indole. In the final phase of the process melanin is made by an oxidation and a polymerization. [6] [7] Melanin is rapidly deposited around the pathogen, thereby limiting its ability to damage the host organism. Storage of melanin at the site of damage also prevents further loss of hemolymph. [3]
Long-term or overproduce of substances arising during a PO cascade can lead to tissue damage and cell death at the site of the reaction. For this reason, these reactions are strictly regulated. [3]
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
Melanin is a broad term for a group of natural pigments found in most organisms. The melanin pigments are produced in a specialized group of cells known as melanocytes.
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation. It is found inside melanosomes which are synthesized in the skin melanocytes. In humans, the tyrosinase enzyme is encoded by the TYR gene.
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. This allows the innate immune system to recognize pathogens and thus, protect the host from infection.
Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils and epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.
A polydnavirus (PDV) or more recently, polydnaviriform is a member of the family Polydnaviridae of insect viruses. There are two genera in the family: Bracovirus and Ichnovirus. Polydnaviruses form a symbiotic relationship with parasitoid wasps;. The larvae of wasps in both of those groups are themselves parasitic on Lepidoptera, and the polydnaviruses are important in circumventing the immune response of their parasitized hosts. Little or no sequence homology exists between BV and IV, suggesting that the two genera have been evolving independently for a long time.
The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.
A hemocyte is a cell that plays a role in the immune system of invertebrates. It is found within the hemolymph. Hemocytes are phagocytes of invertebrates.
Sclerotization is a biochemical process that produces the rigid shell of sclerotin that comprises an insect's chitinous exoskeleton. It is prominent in the thicker, armored parts of insects and arachnids, especially in the biting mouthparts and sclerites of scorpions and beetles.
Polyphenol oxidase, an enzyme involved in fruit browning, is a tetramer that contains four atoms of copper per molecule.
Dopachrome tautomerase , also known as DCT, is a human gene. Its expression is regulated by the microphthalmia-associated transcription factor (MITF).
Priming is the first contact that antigen-specific T helper cell precursors have with an antigen. It is essential to the T helper cells' subsequent interaction with B cells to produce antibodies. Priming of antigen-specific naive lymphocytes occurs when antigen is presented to them in immunogenic form. Subsequently, the primed cells will differentiate either into effector cells or into memory cells that can mount stronger and faster response to second and upcoming immune challenges.
Resistance genes (R-Genes) are genes in plant genomes that convey plant disease resistance against pathogens by producing R proteins. The main class of R-genes consist of a nucleotide binding domain (NB) and a leucine rich repeat (LRR) domain(s) and are often referred to as (NB-LRR) R-genes or NLRs. Generally, the NB domain binds either ATP/ADP or GTP/GDP. The LRR domain is often involved in protein-protein interactions as well as ligand binding. NB-LRR R-genes can be further subdivided into toll interleukin 1 receptor (TIR-NB-LRR) and coiled-coil (CC-NB-LRR).
A quinone methide is a type of conjugated organic compound that contain a cyclohexadiene with a carbonyl and an exocyclic methylidene or extended alkene unit. It is analogous to a quinone, but having one of the double bonded oxygens replaced with a carbon. The carbonyl and methylidene are usually oriented either ortho or para to each other. There are some examples of transient synthetic meta quinone methides.
Ficolins are pattern recognition receptors that bind to acetyl groups present in the carbohydrates of bacterial surfaces and mediate activation of the lectin pathway of the complement cascade.
Prophenoloxidase (proPO) is a modified form of the complement response found in some invertebrates, including insects, crabs and worms. It is a copper-containing metalloprotein.
Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subsequent immune responses to the same antigen. The adaptive immune system and antigen-specific receptor generation are responsible for adaptive immune memory. After the inflammatory immune response to danger-associated antigen, some of the antigen-specific T cells and B cells persist in the body and become long-living memory T and B cells. After the second encounter with the same antigen, they recognize the antigen and mount a faster and more robust response. Immunological memory is the basis of vaccination. Emerging resources show that even the innate immune system can initiate a more efficient immune response and pathogen elimination after the previous stimulation with a pathogen, respectively with PAMPs or DAMPs. Innate immune memory is neither antigen-specific nor dependent on gene rearrangement, but the different response is caused by changes in epigenetic programming and shifts in cellular metabolism. Innate immune memory was observed in invertebrates as well as in vertebrates.
5,6-Dihydroxyindole is a chemical compound with the molecular formula C8H7NO2. It is an intermediate in the production of the biological pigment eumelanin. 5,6-Dihydroxyindole is biosynthesized from L-dopachrome in a reaction catalyzed by a tyrosinase enzyme and is further converted into indole-5,6-quinone. In humans, 5,6-dihydroxyindole is involved in the metabolic disorder hawkinsinuria.
Abdominal pigmentation in Drosophila melanogaster is a morphologically simple but highly variable trait that often has adaptive significance. Pigmentation has extensively been studied in Drosophila melanogaster. It has been used as a model for understanding the development and evolution of morphological phenotypes.