Immune Gene Repertoire Research Articles

Why does the immune system of Atlantic cod lack MHC II?

MHC II, a major feature of the adaptive immune system, is lacking in Atlantic cod, and there are different scenarios (metabolic cost hypothesis or functional shift hypothesis) that might explain this loss. The lack of MHC II coincides with an increased number of genes for MHC I and Toll-like receptors (TLRs).

Increased survivorship following bacterial infection by the mosquito Aedes aegypti as compared to Anopheles gambiae correlates with increased transcriptional induction of antimicrobial peptides

Mosquitoes defend themselves from pathogens by mounting cellular and humoral innate immune responses. Bioinformatic analyses have revealed considerable divergence in immune gene repertoires between mosquito species, but interspecies empirical comparisons of immune responses are lacking. Here, we present a comparative analysis of the antimicrobial responses of two distantly related disease vectors: Aedes aegypti and Anopheles gambiae. Survival studies showed that Ae. aegypti are more proficient in surviving a bacterial infection than An. gambiae, and this correlates with Ae. aegypti’s superior ability to kill bacteria in their hemocoels. Hemocytes from both species swiftly phagocytose bacteria, but phagocytosis does not explain Ae. aegypti’s increased robustness: An. gambiae contain more circulating hemocytes and display a higher phagocytic index, but the phagocytic capacity of individual hemocytes is greater in Ae. aegypti. Then, profiling of 19 immunity genes revealed that transcriptional induction following infection is significantly elevated in Ae. aegypti when compared to An. gambiae, with the largest change seen in the transcription of cecropin and defensin. These data show that Ae. aegypti is better equipped to survive a bacterial infection than An. gambiae, and this correlates with Ae. aegypti’s increased transcriptional induction of antimicrobial peptides and other humoral immune factors in response to infection.

Immunome database for marsupials and monotremes

BackgroundTo understand the evolutionary origins of our own immune system, we need to characterise the immune system of our distant relatives, the marsupials and monotremes. The recent sequencing of the genomes of two marsupials (opossum and tammar wallaby) and a monotreme (platypus) provides an opportunity to characterise the immune gene repertoires of these model organisms. This was required as many genes involved in immunity evolve rapidly and fail to be detected by automated gene annotation pipelines.DescriptionWe have developed a database of immune genes from the tammar wallaby, red-necked wallaby, northern brown bandicoot, brush-tail possum, opossum, echidna and platypus. The resource contains 2,235 newly identified sequences and 3,197 sequences which had been described previously. This comprehensive dataset was built from a variety of sources, including EST projects and expert-curated gene predictions generated through a variety of methods including chained-BLAST and sensitive HMMER searches. To facilitate systems-based research we have grouped sequences based on broad Gene Ontology categories as well as by specific functional immune groups. Sequences can be extracted by keyword, gene name, protein domain and organism name. Users can also search the database using BLAST.ConclusionThe Immunome Database for Marsupials and Monotremes (IDMM) is a comprehensive database of all known marsupial and monotreme immune genes. It provides a single point of reference for genomic and transcriptomic datasets. Data from other marsupial and monotreme species will be added to the database as it become available. This resource will be utilized by marsupial and monotreme immunologists as well as researchers interested in the evolution of mammalian immunity.

Characterisation of immune responses in the pea aphid, Acyrthosiphon pisum

The innate immune system of insects provides effective defence against a range of parasites and pathogens. The pea aphid, Acyrthosiphon pisum, is a novel study system for investigating host–parasite interactions due to its complex associations with both well-characterised bacterial symbionts and a diversity of pathogens and parasites, including several important biological control agents. However, little is known about the cellular and humoral immune responses of aphids. Here we identify three morphologically distinct types of haemocytes in circulation that we name prohemocytes, granulocytes and oenocytoids. Granulocytes avidly phagocytose Gram negative Escherechia coli and Gram positive Micrococcus luteus while oenocytoids exhibit melanotic activity. Prohaemocytes increase in abundance immediately following an immune challenge, irrespective of the source of stimulus. Pea aphids form melanotic capsules around Sephadex beads but do not form cellular capsules. We also did not detect any antimicrobial peptide activity in the haemolymph using zone of inhibition assays. We discuss these results in relation to recent findings from the pea aphid genome annotation project that suggest that aphids have a reduced immune gene repertoire compared to other insects.

The Evolution and Regulation of the Mucosal Immune Complexity in the Basal Chordate Amphioxus

Both amphioxus and the sea urchin encode a complex innate immune gene repertoire in their genomes, but the composition and mechanisms of their innate immune systems, as well as the fundamental differences between two systems, remain largely unexplored. In this study, we dissect the mucosal immune complexity of amphioxus into different evolutionary-functional modes and regulatory patterns by integrating information from phylogenetic inferences, genome-wide digital expression profiles, time course expression dynamics, and functional analyses. With these rich data, we reconstruct several major immune subsystems in amphioxus and analyze their regulation during mucosal infection. These include the TNF/IL-1R network, TLR and NLR networks, complement system, apoptosis network, oxidative pathways, and other effector genes (e.g., peptidoglycan recognition proteins, Gram-negative binding proteins, and chitin-binding proteins). We show that beneath the superficial similarity to that of the sea urchin, the amphioxus innate system, despite preserving critical invertebrate components, is more similar to that of the vertebrates in terms of composition, expression regulation, and functional strategies. For example, major effectors in amphioxus gut mucous tissue are the well-developed complement and oxidative-burst systems, and the signaling network in amphioxus seems to emphasize signal transduction/modulation more than initiation. In conclusion, we suggest that the innate immune systems of amphioxus and the sea urchin are strategically different, possibly representing two successful cases among many expanded immune systems that arose at the age of the Cambrian explosion. We further suggest that the vertebrate innate immune system should be derived from one of these expanded systems, most likely from the same one that was shared by amphioxus.

The basis for haplotype complexity in VCBPs, an immune-type receptor in amphioxus

Innate immune gene repertoires are restricted primarily to germline variation. Adaptive immunity, by comparison, relies on somatic variation of germline-encoded genes to generate extraordinarily large numbers of non-heritable antigen recognition motifs. Invertebrates lack the key features of vertebrate adaptive immunity, but have evolved a variety of alternative mechanisms to successfully protect the integrity of "self"; in many cases, these appear to be taxon-specific innovations. In the protochordate Branchiostoma floridae (amphioxus), the variable region-containing chitin-binding proteins (VCBPs) constitute a multigene family (comprised of VCBPs 1-5), which possesses features that are consistent with innate immune-type function. A large number of VCBP alleles and haplotypes are shown to exhibit levels of polymorphism exceeding the elevated overall levels determined for the whole amphioxus genome (JGI). VCBP genes of the 2 and 5 types are distinguished further by a highly polymorphic segment (exon 2) in the N-terminal immunoglobulin domain, defined previously as a "hypervariable region" or a "hotspot." Genomic deoxyribonucleic acid (DNA) and complementary DNA (cDNA) sequences from large numbers of animals representing different populations reveal further significant differences in sequence complexity within and across VCBP2/5 haplotypes that arise through overlapping mechanisms of genetic exchange, gene copy number variation as well as mutation and give rise to distinct allelic lineages. The collective observations suggest that mechanisms were in place at the time of divergence of the cephalochordates that could selectively hyperdiversify immune-type receptors within a multigene family.

Hatching time for monotreme immunology

The sequencing of the platypus genome has spurred investigations into the characterisation of the monotreme immune response. As the most divergent of extant mammals, the characterisation of the monotreme immune repertoire allows us to trace the evolutionary history of immunity in mammals and provide insights into the immune gene complement of ancestral mammals. The immune system of monotremes has remained largely uncharacterised due to the lack of specific immunological reagents and limited access to animals for experimentation. Early immunological studies focussed on the anatomy and physiology of the lymphoid system in the platypus. More recent molecular studies have focussed on characterisation of individual immunoglobulin, T-cell receptor and MHC genes in both the platypus and short-beaked echidna. Here, we review the published literature on the monotreme immune gene repertoire and provide new data generated from genome analysis on cytokines, Fc receptors and immunoglobulins. We present an overview of key gene families responsible for innate and adaptive immunity including the cathelicidins, defensins, T-cell receptors and the major histocompatibility complex (MHC) Class I and Class II antigens. We comment on the usefulness of these sequences for future studies into immunity, health and disease in monotremes.

Prospects for understanding immune-endocrine interactions in the chicken

Despite occupying the same habitats as mammals, having similar ranges of body mass and longevity, and facing similar pathogen challenges, birds have a different repertoire of organs, cells, molecules and genes of the immune system when compared to mammals. In other words, birds are not “mice with feathers”, at least not in terms of their immune systems. Here we discuss differences between immune gene repertoires of birds and mammals, particularly those known to play a role in immune-endocrine interactions in mammals. If we are to begin to understand immune-endocrine interactions in the chicken, we need to understand these repertoires and also the biological function of the proteins encoded by these genes. We also discuss developments in our ability to understand the function of dendritic cells in the chicken; the function of these professional antigen-presenting cells is affected by stress in mammals. With regard to the endocrine system, we describe relevant chicken pituitary-adrenal hormones, and review recent findings on the expression of their receptors, as these receptors play a crucial role in modulating immune-endocrine interactions. Finally, we review the (albeit limited) work that has been carried out to understand immune-endocrine interactions in the chicken in the post-genome era.

Genomic analysis of the immune gene repertoire of amphioxus reveals extraordinary innate complexity and diversity

It has been speculated that before vertebrates evolved somatic diversity-based adaptive immunity, the germline-encoded diversity of innate immunity may have been more developed. Amphioxus occupies the basal position of the chordate phylum and hence is an important reference to the evolution of vertebrate immunity. Here we report the first comprehensive genomic survey of the immune gene repertoire of the amphioxus Branchiostoma floridae. It has been reported that the purple sea urchin has a vastly expanded innate receptor repertoire not previously seen in other species, which includes 222 toll-like receptors (TLRs), 203 NOD/NALP-like receptors (NLRs), and 218 scavenger receptors (SRs). We discovered that the amphioxus genome contains comparable expansion with 71 TLR gene models, 118 NLR models, and 270 SR models. Amphioxus also expands other receptor-like families, including 1215 C-type lectin models, 240 LRR and IGcam-containing models, 1363 other LRR-containing models, 75 C1q-like models, 98 ficolin-like models, and hundreds of models containing complement-related domains. The expansion is not restricted to receptors but is likely to extend to intermediate signal transducers because there are 58 TIR adapter-like models, 36 TRAF models, 44 initiator caspase models, and 541 death-fold domain-containing models in the genome. Amphioxus also has a sophisticated TNF system and a complicated complement system not previously seen in other invertebrates. Besides the increase of gene number, domain combinations of immune proteins are also increased. Altogether, this survey suggests that the amphioxus, a species without vertebrate-type adaptive immunity, holds extraordinary innate complexity and diversity.

The immune gene repertoire encoded in the purple sea urchin genome

Echinoderms occupy a critical and largely unexplored phylogenetic vantage point from which to infer both the early evolution of bilaterian immunity and the underpinnings of the vertebrate adaptive immune system. Here we present an initial survey of the purple sea urchin genome for genes associated with immunity. An elaborate repertoire of potential immune receptors, regulators and effectors is present, including unprecedented expansions of innate pathogen recognition genes. These include a diverse array of 222 Toll-like receptor (TLR) genes and a coordinate expansion of directly associated signaling adaptors. Notably, a subset of sea urchin TLR genes encodes receptors with structural characteristics previously identified only in protostomes. A similarly expanded set of 203 NOD/NALP-like cytoplasmic recognition proteins is present. These genes have previously been identified only in vertebrates where they are represented in much lower numbers. Genes that mediate the alternative and lectin complement pathways are described, while gene homologues of the terminal pathway are not present. We have also identified several homologues of genes that function in jawed vertebrate adaptive immunity. The most striking of these is a gene cluster with similarity to the jawed vertebrate Recombination Activating Genes 1 and 2 (RAG1/2). Sea urchins are long-lived, complex organisms and these findings reveal an innate immune system of unprecedented complexity. Whether the presumably intense selective processes that molded these gene families also gave rise to novel immune mechanisms akin to adaptive systems remains to be seen. The genome sequence provides immediate opportunities to apply the advantages of the sea urchin model toward problems in developmental and evolutionary immunobiology.

Insect immunity and its implication in mosquito-malaria interactions.

Insects' resistance to infectious agents is essential for their own survival and also for the health of the plant, animal and human populations with which they closely interact. Several of the major human diseases are spread by insects and are rapidly expanding as a result of the development of insecticide resistance in vectors and drug resistance in parasites. A vector insects' permissiveness to a pathogen, and hence the spread of the disease, will largely depend on the compatibility of the molecular interactions between the two species and the capability of the insect immune system to recognize and kill the pathogen. The innate immune system comprises a variety of components and mechanisms that can discriminate between different microorganisms and mount specific responses to control pathogenic infections. An impressive body of knowledge on the insects' innate immunity has been generated from studies in the model organism Drosophila. These studies are now guiding the exploration of the immune system in the vector mosquito of human malaria, Anopheles, and its implication in the elimination of parasites. Anopheles immune responses have been linked to parasite losses and some refractory mosquitoes can kill all parasites through specific defence mechanisms. The recently sequenced Drosophila and Anopheles genomes provide a detailed and comparative view on their immune gene repertoires that in combination with post-genomic analyses is used to further dissect the complex mechanisms of Plasmodium killing in the mosquito.

Synthetic peptide vaccines against foot-and-mouth disease. II. Comparison of the response of guinea-pigs, rabbits and mice to various formulations

The immune response of guinea-pigs to vaccination with either of two aphthovirus-specific synthetic peptides was investigated. One peptide copied the sequence of amino acids 141 to 160 from the VP1 of aphthovirus strains O 1BFS 1860 and O 1 Kaufbeuren (O peptide), the other copied the equivalent sequence from aphthovirus strain A 24 Cruzeiro (A peptide). The immune response was enhanced when the peptides were conjugated to a carried protein, but the choice of carrier protein and cross-linking agent was not critical in obtaining enhancement. The response was greatest when the peptide or peptide—carrier conjugate was adjuvanted in Freund's complete adjuvant (FCA). The O peptide was poorly immunogenic and did not confer protection against challenge with infectious virus, whereas the A peptide had good immunogenicity and did confer protection. This reflected the relative immunogenicity of the parent viruses. Rabbits, three strains of guinea-pigs and seven strains of mice were vaccinated with the O peptide conjugated to keyhole limpet haemocyanin (KLH). Considerable variation was observed between the responses of each strain and it is proposed that this relates to their repertoire of immune response genes.