Immune System Of Invertebrates Research Articles

Invertebrate Immune Systems–Specific, Quasi-Specific, or Nonspecific?

Until recently, it was widely accepted that invertebrates fail to show a high degree of specificity and memory in their immune strategies. Recent reports have challenged this view such that our understanding of the capabilities of the invertebrate immune systems needs to be reassessed. This account critically reviews the available evidence that suggests the existence of a high degree of memory and specificity in some invertebrates and seeks mechanistic explanations of such observations. It is postulated that elevated levels of phagocytosis may be a partial explanation for this phenomenon.

How do invertebrates generate a highly specific innate immune response?

High immune specificity is usually considered an exclusive property of vertebrate adaptive immunity. Surprisingly, similar specificities were recently discovered in the invertebrates, which lack the adaptive system. Here, we propose alternative mechanisms for invertebrate specificity, including (i) high genetic diversity of receptors or effectors, (ii) synergistic interactions among immune components, and (iii) dosage effects. The latter two mechanisms act at the protein level, where they could mediate a much higher functional diversity than contained genetically. This may be essential considering the limited genetic diversity of invertebrate immunity genes. They may also contribute to immunological priming—an increased responsiveness of the invertebrate immune system after parasite challenge comparable to vertebrate immune memory. Similar processes are likely to act in the innate system of vertebrates and enhance the effectiveness of adaptive immunity.

Biological Inspiration for Artificial Immune Systems

Artificial immune systems (AISs) to date have generally been inspired by naive biological metaphors. This has limited the effectiveness of these systems. In this position paper two ways in which AISs could be made more biologically realistic are discussed. We propose that AISs should draw their inspiration from organisms which possess only innate immune systems, and that AISs should employ systemic models of the immune system to structure their overall design. An outline of plant and invertebrate immune systems is presented, and a number of contemporary systemic models are reviewed. The implications for interdisciplinary research that more biologically-realistic AISs could have is also discussed.

Extraordinary diversity among members of the large gene family, 185/333, from the purple sea urchin, Strongylocentrotus purpuratus

BackgroundRecent analysis of immune-related genes within the sea urchin genome revealed a number of large gene families with vertebrate homologues, such as the Toll-like and NOD/NALP-like receptor families and C-type lectins in addition to a rudimentary complement system. Therefore, the immune response of the purple sea urchin appears to be more complex than previously believed. Another component of the sea urchin immune response is an unusual family of mRNAs, known as 185/333, which is strongly upregulated in response to pathogen challenge. The work presented here indicates that this family of transcripts is derived from an unexpectedly diverse gene family.ResultsThe 185/333 genes are small (< 2 kb) with only two exons. Their extraordinary diversity was exemplified by 121 unique sequences identified from 171 cloned genes. Sequences from the second exons were aligned optimally by introducing large gaps, which defined blocks of sequence known as elements. Genes were defined by the presence or absence of elements. Phylogenetic analysis defined five intron types which, when combined with the exon element patterns resulted in 31 gene patterns, 14 of which were not described previously. Sequence diversity was present in all elements, and was higher in the intron than the exons. Repeats within the sequence facilitated multiple alignments, of which two were analyzed in detail. Although the two alignments differed in length, number of elements, and number of patterns, both were about equally accurate at describing the 185/333 sequences. The genes were closely linked and flanked by short repeats. The repeats within and between the genes may promote their diversification through gene conversion, recombination, and meiotic mispairing.ConclusionThe diversity of the 185/333 gene family represents an intriguing addition to what is known about the S. purpuratus immune response, and provides further evidence that invertebrate immune systems are neither simple nor static.

Insect Immunity Shows Specificity in Protection upon Secondary Pathogen Exposure

Immunological memory in vertebrates, conferring lasting specific protection after an initial pathogen exposure, has implications for a broad spectrum of evolutionary, epidemiological, and medical phenomena . However, the existence of specificity in protection upon secondary pathogen exposure in invertebrates remains controversial . To separate this functional phenomenon from a particular mechanism, we refer to it as specific immune priming. We investigate the presence of specific immune priming in workers of the social insect Bombus terrestris. Using three bacterial pathogens, we test whether a prior homologous pathogen exposure gives a benefit in terms of long-term protection against a later challenge, over and above a heterologous combination. With a reciprocally designed initial and second-exposure protocol (i.e., all combinations of bacteria were tested), we demonstrate, even several weeks after the clearance of a first exposure, increased protection and narrow specificity upon secondary exposure. This demonstrates that the invertebrate immune system is functionally capable of unexpectedly specific and durable induced protection. Ultimately, despite general broad differences between vertebrates and invertebrates, the ability of both immune systems to show specificity in protection suggests that their immune defenses have found comparable solutions to similar selective pressures over evolutionary time.

Nitric oxide: an antiparasitic molecule of invertebrates

Since Furchgott, Ignarro and Murad won the Nobel prize in 1998 for their work on the role of nitric oxide (NO) as a signaling molecule, many reports have shown the seemingly limitless range of body functions controlled by this compound. In vertebrates, the role of NO as a defense against infection caused by viruses, bacteria, and protozoan and metazoan parasites has been known for several years. New evidence, however, shows that NO is also important in defending invertebrates against parasites. This discovery is a breakthrough in the understanding of how the invertebrate immune system works, and it has implications for the emerging field of invertebrate ecological immunology.

ECAM is waiting for eCAM

ECAM is waiting for eCAM

GENETIC CORRELATION BETWEEN MELANIZATION AND ANTIBACTERIAL IMMUNE RESPONSES IN A NATURAL POPULATION OF THE MALARIA VECTOR ANOPHELES GAMBIAE

The immune system of invertebrates can mount different responses, including melanotic encapsulation and several antibacterial defense mechanisms. Variation of the efficacies of these responses is generally considered to be a product of the evolutionary pressure on each response due to infection by parasites. However, potential interactions and trade-offs among the different responses of the immune system could constrain the evolutionary potential of each response. In a natural population of the mosquito Anopheles gambiae, we measured the genetic association between the melanization response and an antibacterial response in two environmental qualities (well-fed and undernourished larvae). In both environments the two immune responses were positively genetically correlated: in full-sib families that were most likely to melanize a bead, injected bacteria were most likely to be cleared. Thus, our data do not support the idea of a trade-off among different outcomes of the invertebrate immune system, but rather that some families are overall immunologically superior to others.

Induction of antiviral immunity by double-stranded RNA in a marine invertebrate.

Vertebrates mount a strong innate immune response against viruses, largely by activating the interferon system. Double-stranded RNA (dsRNA), a common intermediate formed during the life cycle of many viruses, is a potent trigger of this response. In contrast, no general inducible antiviral defense mechanism has been reported in any invertebrate. Here we show that dsRNA induces antiviral protection in the marine crustacean Litopenaeus vannamei. When treated with dsRNA, shrimp showed increased resistance to infection by two unrelated viruses, white spot syndrome virus and Taura syndrome virus. Induction of this antiviral state is independent of the sequence of the dsRNA used and therefore distinct from the sequence-specific dsRNA-mediated genetic interference phenomenon. This demonstrates for the first time that an invertebrate immune system, like its vertebrate counterparts, can recognize dsRNA as a virus-associated molecular pattern, resulting in the activation of an innate antiviral response.

Evaluation of an innate immune reaction to parasites in earthworms

Encapsulation is an essential process of the invertebrate immune system and includes the prophenoloxidase (proPO) cascade. We present an assay for evaluating this immune response, now newly adapted to earthworms. Coelomic fluid is withdrawn and coelomocytes are stained with l-Dopa. We studied assay repeatability and the correlation between number of PO-active cells and infection level of the parasitic protozoan Monocystis sp. in the earthworm Lumbricus terrestris. Our study showed high assay repeatability although the expected negative relationship between PO-active coelomocytes and parasite load was not observed; yet a suggestion toward a positive relationship was detected. This finding is contrary to previous assumptions that presume coelomocyte concentrations to be the independent variable determining parasite load.

Invertebrate immune systems – not homogeneous, not simple, not well understood

The approximate 30 extant invertebrate phyla have diversified along separate evolutionary trajectories for hundreds of millions of years. Although recent work understandably has emphasized the commonalities of innate defenses, there is also ample evidence, as from completed genome studies, to suggest that even members of the same invertebrate order have taken significantly different approaches to internal defense. These data suggest that novel immune capabilities will be found among the different phyla. Many invertebrates have intimate associations with symbionts that may play more of a role in internal defense than generally appreciated. Some invertebrates that are either long lived or have colonial body plans may diversify components of their defense systems via somatic mutation. Somatic diversification following pathogen exposure, as seen in plants, has been investigated little in invertebrates. Recent molecular studies of sponges, cnidarians, shrimp, mollusks, sea urchins, tunicates, and lancelets have found surprisingly diversified immune molecules, and a model is presented that supports the adaptive value of diversified non-self recognition molecules in invertebrates. Interactions between invertebrates and viruses also remain poorly understood. As we are in the midst of alarming losses of coral reefs, increased pathogen challenge to invertebrate aquaculture, and rampant invertebrate-transmitted parasites of humans and domestic animals, we need a better understanding of invertebrate immunology.

GENETIC CORRELATION BETWEEN MELANIZATION AND ANTIBACTERIAL IMMUNE RESPONSES IN A NATURAL POPULATION OF THE MALARIA VECTOR ANOPHELES GAMBIAE

The immune system of invertebrates can mount different responses, including melanotic encapsulation and several antibacterial defense mechanisms. Variation of the efficacies of these responses is generally considered to be a product of the evolutionary pressure on each response due to infection by parasites. However, potential interactions and trade-offs among the different responses of the immune system could constrain the evolutionary potential of each response. In a natural population of the mosquito Anopheles gambiae, we measured the genetic association between the melanization response and an antibacterial response in two environmental qualities (well-fed and undernourished larvae). In both environments the two immune responses were positively genetically correlated: in full-sib families that were most likely to melanize a bead, injected bacteria were most likely to be cleared. Thus, our data do not support the idea of a trade-off among different outcomes of the invertebrate immune system, but rather that some families are overall immunologically superior to others.

Comparative immunology.

Comparative Immunology has gained wide acceptance in biology, as an offspring of immunology and an amalgam of immunology and zoology. The prescient experiments of Metchnikoff on phagocytosis in invertebrates during the 19th century served to splinter immunology into its two main components: cellular and humoral. There is much interest in the immune system of invertebrates as representing early models or precursors of the innate system of vertebrates that by contrast possess the innate system as well as the more highly evolved adaptive system. With respect to mechanisms, we think of the invertebrate system as innate, natural, non-specific, non-anticipatory, and non-clonal. Innate immunity operates through leukocytes that are not components of the macrophage T and B interrelationships that characterize vertebrate adaptive immunity that is adaptive, induced, specific, anticipatory, and clonal. This symposium on invertebrate immunology has provided an overview of what is current and crucial to understanding the larger field of comparative immunology. Comparative immunology is now an established field, here since Metchnikoff but officially since about 1977, with a journal (Developmental and Comparative Immunology) (DCI) and an International Society of Developmental and Comparative Immunology (ISDCI). During this short but vigorous history several national, adherent societies have been organized in Japan, Italy and Germany with sporadic interest in a national group in the USA. Nevertheless, comparative immunology is here as vital to zoology in general and to immunology in particular as we delve deeper into unique but also shared characteristics.

Isolation and characterization of an IL-1-like protein from Manduca sexta.

Invertebrates such as insects have similar immune systems when compared to vertebrates, which are composed of humoral and cell-mediated responses (Pathak, 1993). Humoral response involves the synthesis and release of antibacterial peptides such as lysozyme, cecropins, and attacins. Cell-mediated response involves phagocytosis, nodule formation, and encapsulation of foreign antigens. Phagocytosis is an ancient form of host defense, a process in which a cell, usually macrophage, ingests a foreign antigen. This process can be observed in both vertebrates and invertebrate immune systems. In insects, plasmatocytes and granular hemocytes are the main cells with phagocytic activity. However, invertebrates do not have antigen-specific lymphocytes and do not produce specific immune recognition molecules (immunoglobins) (Abbas et al., 1997). Some invertebrate species contain macrophage-like cells capable of producing cytokine-like molecules similar to that of vertebrate (Beck and Habicht, 1986; Ellis, 1996). Cytokines are low molecular weight proteins, some examples are the members of the interleukin (IL) family, tumor necrosis factor (TNF), and interferon (INF) to name a few. Their role in the vertebrate immune response includes control of cellular proliferation and differentiation, and regulation of hematopoiesis (Abbas et al., 1997).KeywordsA375 CellElution VolumeForeign AntigenSingle Protein BandApproximate Molecular WeightThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Identification and Characterization of a DrosophilaNuclear Proteasome Regulator: A HOMOLOG OF HUMAN 11 S REGγ (PA28γ)

We report the cloning and characterization of a Drosophila proteasome 11 S REGgamma (PA28) homolog. The 28-kDa protein shows 47% identity to the human REGgamma and strongly enhances the trypsin-like activities of both Drosophila and mammalian 20 S proteasomes. Surprisingly, the Drosophila REG was found to inhibit the proteasome's chymotrypsin-like activity against the fluorogenic peptide succinyl-LLVY-7-amino-4-methylcoumarin. Immunocytological analysis reveals that the Drosophila REG is localized to the nucleus but is distributed throughout the cell when nuclear envelope breakdown occurs during mitosis. Through site-directed mutagenesis studies, we have identified a functional nuclear localization signal present in the homolog-specific insert region. The Drosophila PA28 NLS is similar to the oncogene c-Myc nuclear localization motif. Comparison between uninduced and innate immune induced Drosophila cells suggests that the REGgamma proteasome activator has a role independent of the invertebrate immune system. Our results support the idea that gamma class proteasome activators have an ancient conserved function within metazoans and were present prior to the emergence of the alpha and beta REG classes.

Lectins, as non-self-recognition factors, in crustaceans

Invertebrate immune system must rely on non-self-recognition molecules to ensure efficient defence responses against infectious pathogens that continuously threaten their survival. Lectins from the hemolymph of invertebrates, including crustaceans, have been regarded as potential molecules involved in immune recognition and microorganism phagocytosis through opsonization. This report presents an overview on the molecular characterisation, physiological role, synthesis and induction upon infection of arthropod lectins, with special emphasis on crustaceans. Although the participation of arthropod lectins in immune surveillance is not fully demonstrated, some recent reports in insects and horseshoe crabs appear to support this concept more convincingly. Unfortunately, such unambiguous evidences have not been thus far demonstrated in crustaceans. The results obtained in related arthropod groups could, however, be predictable for crustaceans. The precise mechanisms underlying non-self-recognition represent the basis to prevent and control infections as well as to stimulate animal resistance. This is particularly relevant for cultivated aquatic species, especially penaeid shrimps, which are frequently constrained by recurrent diseases that often provoke great economic losses.

Fly immunity: great expectations.

Preliminary analysis of the Drosophila genome sequence reveals important similarities and differences between the functioning of mammalian and invertebrate immune systems.

Serpent regulates Drosophila immunity genes in the larval fat body through an essential GATA motif.

Insects possess a powerful immune system, which in response to infection leads to a vast production of different antimicrobial peptides. The regulatory regions of many immunity genes contain a GATA motif in proximity to a kappaB motif. Upon infection, Rel proteins enter the nucleus and activate transcription of the immunity genes. High levels of Rel protein-mediated Cecropin A1 expression previously have been shown to require the GATA site along with the kappaB site. We provide evidence demonstrating that the GATA motif is needed for expression of the Cecropin A1 gene in larval fat body, but is dispensable in adult fat body. A nuclear DNA-binding activity interacts with the Cecropin A1 GATA motif with the same properties as the Drosophila GATA factor Serpent. The GATA-binding activity is recognized by Serpent-specific antibodies, demonstrating their identity. We show that Serpent is nuclear in larval fat body cells and haemocytes both before and after infection. After overexpression, Serpent increases Cecropin A1 transcription in a GATA-dependent manner. We propose that Serpent plays a key role in tissue-specific expression of immunity genes, by priming them for inducible activation by Rel proteins in response to infection.

Plasmatocyte Spreading Peptide Is Encoded by an mRNA Differentially Expressed in Tissues of the MothPseudoplusia includens

It has long been known that blood cells (hemocytes) are an essential component of the invertebrate immune system, yet little is known about the molecules mediating their function. Recently, we identified plasmatocyte spreading peptide (PSP1) from the mothPseudoplusia includenswhich regulates the trafficking and adhesion of a hemocyte subclass called plasmatocytes. Here, we report the cloning of a cDNA (p15) that encodes a PSP1 precursor protein. Northern blot analysis revealed that a homologous prepro-PSP1 mRNA is expressed in fat body, and that other PSP1-related transcripts are expressed in nervous tissue and hemocytes. Coupledin vitrotranscription/translation reactions indicated thatp15produces a protein recognized by a PSP1 polyclonal antibody. Immunoblotting experiments further revealed that a putative pro-PSP1 protein is present inP. includensplasma and fat body.

Identification and cloning of an integrin β subunit from hemocytes of the freshwater crayfishPacifastacus leniusculus

We have cloned and sequenced a beta subunit of integrin from a cDNA library of crayfish hemocytes. This beta integrin shows great similarity to beta integrin subunits from other animals; the highest is towards beta pat-3 from Caenorhabditis elegans followed by beta PS from Drosophila melanogaster. By immunoblotting with antibodies raised towards a synthetic peptide corresponding to a part of the cytoplasmic region of the deduced protein sequence, it was shown that the integrin is present in the membrane of the hemocytes. This is the first integrin found in hemocytes of an invertebrate animal and this finding opens the door for further investigations on integrins and their role in the invertebrate immune system.