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Results for “ancestral immunity”

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At least 19 recordsLinked to original sources
PubMed2005

Adipose tissues as an ancestral immune organ: site-specific change in obesity.

Close relationships have been demonstrated between adipose tissue and the inflammatory/immune system. Furthermore, obesity is increasingly considered as a state of chronic inflammation. Cytofluorometric analysis reveals the presence of significant levels of lymphocytes in the stroma-vascular fraction of white adipose tissues. In epididymal (EPI) fat, lymphocytes display an "ancestral" immune system phenotype (up to 70% of natural killer (NK), gammadelta+ T and NKT cells among all lymphocytes) whereas the inguinal (ING) immune system presents more adaptive characteristics (high levels of alphabeta+ T and B cells). The percentage of NK cells in EPI fat was decreased in obese mice fed with a high-fat diet, whereas gammadelta positive cells were significantly increased in ING fat. These data support the notion that adipose tissue may elaborate immunological mechanisms to regulate its functions which might be altered in obesity.

Adipose Tissue↗
PubMed1991

ACTH-like molecules in gastropod molluscs: a possible role in ancestral immune response and stress.

The presence of immunoreactive ACTH molecules on phagocytic cells from the freshwater snails Planorbarius corneus and Lymnaea stagnalis was shown by cytofluorimetric analysis. The role of ACTH in phagocytosis and in the release of biogenic amines, two biological responses that may be taken as ancestral types of immune response and stress, respectively, has also been evaluated. ACTH markedly increased the phagocytosis of Staphylococcus aureus by P. corneus haemocytes and caused the release of biogenic amines from such cells into the serum. These data, as well as tracing the ancestral physiological role of ACTH, favour the hypothesis that immune and neuroendocrine systems share a common evolutionary origin.

Adrenocorticotropic Hormone↗
PubMed2006

Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex.

The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used the Monodelphis domestica (gray short-tailed opossum) sequence to construct the first map of a marsupial major histocompatibility complex (MHC). The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral "immune supercomplex" that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes.

Animals↗
PubMed2004

Recognition strategies in the innate immune system of ancestral chordates.

Many components of the innate immune system in vertebrates can be reliably traced to urochordates and successful strategies for the detection and elimination of pathogens are present at that level of animal evolution, but the issue of where and how the adaptive immune system emerged is still obscure. There is a paucity of evidence for a gradual transition from the innate immune system of invertebrates to the recombinatorial immune system of higher vertebrates. None of the classical elements of MHC based transplantation immunity (MHC, TCR) or humoral immunity (Ig) have been found in urochordates or Agnathans. Nevertheless there is abundant evidence for adaptive immune responses in the agnathans. This remarkable paradox raises a number of questions. How do these ancestral chordates discriminate between the constituents of the external world and the constituents of "self"? Are these strategies universal within the animal kingdom and among chordates, or are different strategies used by representatives of the different taxonomic groups? The current state of our knowledge indicates that the immune system of lower chordates is very different from that of cartilaginous fishes. Pure homology hunting for vertebrate-specific immuno-relevant molecules in invertebrates is therefore of limited value. A more promising approach may involve unbiased functional screening methods. To understand better the evolution of adaptive immune systems, more comparative data from jawless vertebrates (lamprey or hagfish) and a representative of Acrania (e.g. Amphioxus) are clearly needed.

Animals↗
PubMed1996

Primordial emergence of the recombination activating gene 1 (RAG1): sequence of the complete shark gene indicates homology to microbial integrases.

The rearrangement of antibody and T-cell receptor gene segments is indispensable to the vertebrate immune response. All extant jawed vertebrates can rearrange these gene segments. This ability is conferred by the recombination activating genes I and II (RAG I and RAG II). To elucidate their origin and function, the cDNA encoding RAG I from a member of the most ancient class of extant gnathostomes, the Carcharhine sharks, was characterized. Homology domains identified within shark RAG I prompted sequence comparison analyses that suggested similarity of the RAG I and II genes, respectively, to the integrase family genes and integration host factor genes of the bacterial site-specific recombination system. Thus, the apparent explosive evolution (or "big bang") of the ancestral immune system may have been initiated by a transfer of microbial site-specific recombinases.

Amino Acid Sequence↗
PubMed2000

The evolution of vertebrate antigen receptors: a phylogenetic approach.

Classical T cells, those with alpha beta T-cell receptors (TCRs), are an important component of the dominant paradigm for self-nonself immune recognition in vertebrates. alpha beta T cells recognize foreign peptide antigens when they are bound to MHC molecules on the surfaces of antigen-presenting cells. gamma delta T cells bear a similar receptor, and it is often assumed that these T cells also require specialized antigen-presenting molecules for immune recognition, which we term "indirect antigen recognition." B-cell receptors, or immunoglobulins, bind directly to antigens without the help of a specialized antigen-presenting molecule. Phylogenetically, it has been assumed that T-cell receptors and the genes that encode them are a monophyletic group, and that "indirect" antigen recognition evolved before the split into two types of TCR. Recently, however, it has been proposed that gamma delta-TCRs bind directly to antigens, as do immunoglobulins (Ig's). This calls into question the null hypothesis that indirect antigen recognition is a common characteristic of TCRs and, by extension, the hypothesis that all TCR gene sequences form a monophyletic group. To determine whether alternative explanations for antigen recognition and other historical relationships among TCR genes might be possible, we performed phylogenetic analyses on amino acid sequences of the constant and variable regions which encode the basic subunits of TCR and Ig molecules. We used both maximum-parsimony and genetic distance-based methods and could find no strong support for the hypothesis of TCR monophyly. Analyses of the constant region suggest that TCR gamma or delta sequences are the most ancient, implying that the ancestral immune cell was like a modern gamma delta T cell. From this gamma delta-like ancestor arose alpha beta T cells and B cells, implying that indirect antigen recognition is indeed a derived property of alpha beta-TCRs. Analyses of the variable regions are complicated by strong selection on antigen-binding sequences, but imply that direct antigen binding is the ancestral condition.

Animals↗
PubMed1986

Ontogeny of gut-associated lymphoid tissue (GALT) in the dogfish Scyliorhinus canicula L.

Cartilaginous fish occupy a fundamental position in vertebrate phylogeny and it is likely that this group has retained some of the ancestral immune mechanisms. The ontogeny of GALT has received little attention in elasmobranchs and this study correlates this development with morphological differentiation, development of other lymphoid organs, exposure to seawater and transition from yolk dependence to exogenous food as a source of nutrient. GALT was first represented by individual lymphocyte-like and macrophage-like cells in the lamina propria. In later stages accumulations and intraepithelial leucocytes were recorded prior to hatching. The size of accumulations and the number of lymphocyte and macrophage-like cells infiltrating the lamina propria and epithelium increased in fish as they became dependent upon an exogenous diet. Although GALT developed after the thymus and lymphoid-like tissue in the kidney and at approximately the same time as the epigonal, Leydig and spleen, the source of cells populating the gut is unknown. Plasma cells and granulocytes were not observed in the developing fish until 6 months post-hatch after which the fish had a similar GALT distribution and content to the adult fish.

Animals↗
PubMed2000

Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space.

According to the remodeling theory of aging we proposed several years ago, the current data on human immunosenescence depicts a complex scenario where clonotypical immunity deteriorates, while ancestral innate/natural immunity is largely conserved or even up-regulated with age. Under an evolutionary perspective, antigens are the cause of a persistent life-long antigenic stress, responsible for the accumulation of effector CD8+/CD28- T cells, the decrease of naive T cells (CD95-) and the marked shrinkage of T cell repertoire with age. Concomitantly, NK cytotoxicity, chemotaxis, phagocytosis and complement activities remain unaffected or negligibly affected, in comparison to clonotypical immunity. Thus, immunosenescence is not a random deteriorative phenomenon but appears to inversely recapitulate an evolutionary pattern. On the whole, immunosenescence can be envisaged as the result of the continuous challenge of the unavoidable exposure to a variety of potential antigens (viruses, bacteria, but also food and self molecules among others). From this perspective antigens are nothing else than a particular type of stressor and immunosenescence appears to be the price paid to immunological memory, i.e. one of the main characteristics of the most evolutionary recent and sophisticated type of immunity. Together with the age-related thymic involution, and the consequent age-related decrease of thymic output of new T cells, this situation leaves the body practically devoid of virgin T cells, and thus likely more prone to a variety of infectious and non infectious diseases.

Aged↗
PubMed2003

Centenarians as a model for healthy aging.

For over 10 years we have studied centenarians as a model to address the biological basis of aging and longevity, with particular attention to immunology and genetics. The most important findings can be summarized as follows. (i) Human immunosenescence represents a complex remodelling, whereby clonotypical immunity deteriorates, while ancestral, innate immunity is largely preserved. (ii) Continuous exposure to antigens causes a lifelong, chronic antigenic stress, which is responsible, together with the involution of the thymus, for the accumulation of memory/effector T cells and the exhaustion of naïve T cells. (iii) Aging is characterized by a peculiar chronic inflammatory status that we propose to call 'inflammaging', which appears to be under genetic control, is detrimental for longevity and is more evident in men than in women. Inflammaging, i.e. the up-regulation of a variety of anti-stress responses at the cellular and molecular level, is the consequence of the ability of the body to adapt to and counteract the effects of a variety of stressors, which causes the accumulation of molecular and cellular scars. Inflammaging is considered the common and most important driving force of age-related pathologies, such as neurodegeneration, atherosclerosis, diabetes and sarcopenia, among others, all of which share an inflammatory pathogenesis. (iv) Possible strategies to counteract the major effects of immunosenescence and inflammaging, such as the systematic reduction of the lifelong antigenic load, the elimination of chronic infections, thymic rejuvenation and preventative treatment with anti-inflammatory drugs in people with a pro-inflammatory genotype, are envisaged.

Aged↗
PubMed2002

Basal metabolic rate and the evolution of the adaptive immune system.

Vertebrates have evolved an adaptive immune system in addition to the ancestral innate immune system. It is often assumed that a trade-off between costs and benefits of defence governs the evolution of immunological defence, but the costs and benefits specific to the adaptive immune system are poorly known. We used genetically engineered mice lacking lymphocytes (i.e. mice without adaptive, but with innate, immunity) as a model of the ancestral state in the evolution of the vertebrate immune system. To investigate if the magnitude of adaptive defence is constrained by the energetic costs of producing lymphocytes etc., we compared the basal metabolic rate of normal and lymphocyte-deficient mice. We found that lymphocyte-deficient mice had a higher basal metabolic rate than normal mice with both innate and adaptive immune defence. This suggests that the evolution of the adaptive immune system has not been constrained by energetic costs. Rather, it should have been favoured by the energy savings associated with a combination of innate and adaptive immune defence.

Adaptation, Physiological↗
PubMed2006

Evolution of an obligate social cheater to a superior cooperator.

Obligate relationships have evolved many times and can be parasitic or mutualistic. Obligate organisms rely on others to survive and thus coevolve with their host or partner. An important but little explored question is whether obligate status is an evolutionarily terminal condition or whether obligate lineages can evolve back to an autonomous lifestyle. The bacterium Myxococcus xanthus survives starvation by the social development of spore-bearing fruiting bodies. Some M. xanthus genotypes defective at fruiting body development in isolation can nonetheless exploit proficient genotypes in chimaeric groups. Here we report an evolutionary transition from obligate dependence on an altruistic host to an autonomous mode of social cooperation. This restoration of social independence was caused by a single mutation of large effect that confers fitness superiority over both ancestral genotypes, including immunity from exploitation by the ancestral cheater. Thus, a temporary state of obligate cheating served as an evolutionary stepping-stone to a novel state of autonomous social dominance.

Acetyltransferases↗
PubMed2005

Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans.

Genetic and functional genomic approaches have begun to define the molecular determinants of pathogen resistance in Caenorhabditis elegans. Conserved signal transduction components are required for pathogen resistance, including a Toll/IL-1 receptor domain adaptor protein that functions upstream of a conserved p38 MAP kinase pathway. We suggest that this pathway is an ancestral innate immune signaling pathway present in the common ancestor of nematodes, arthropods and vertebrates, which is likely to predate the involvement of canonical Toll signaling pathways in innate immunity. We anticipate that the study of pathogen resistance in C. elegans will continue to provide evolutionary and mechanistic insights into the signal transduction and physiology of innate immunity.

Animals↗
PubMed2005

Still waiting for the toll?

Multicellular organisms including invertebrates and vertebrates live in various habitats that may be aquatic or terrestrial where they are constantly exposed to deleterious pathogens. These include viruses, bacteria, fungi, and parasites. They have evolved various immunodefense mechanisms that may protect them from infection by these microorganisms. These include cellular and humoral responses and the level of differentiation of the response parallels the evolutionary development of the species. The first line of innate immunity in earthworms is the body wall that prevents the entrance of microbes into the coelomic cavity that contains fluid in which there are numerous leukocyte effectors of immune responses. When this first barrier is broken, a series of host responses is set into motion activating the leukocytes and the coelomic fluid. The responses are classified as innate, natural, non-specific, non-anticipatory, non-clonal (germ line) in contrast to the vertebrate capacity that is considered adaptive, induced, specific, anticipatory and clonal (somatic). Specific memory is associated with the vertebrate response and there is information that the innate response of invertebrates may under certain conditions possess specific memory. The invertebrate system when challenged affects phagocytosis, encapsulation, agglutination, opsonization, clotting and lysis. At least two major leukocytes, small and large mediate lytic reactions against several tumor cell targets. Destruction of tumor cells in vitro shows that phagocytosis and natural killer cell responses are distinct properties of these leukocytes. This has prompted newer searches for immune function and regulation in other systems. The innate immune system of the earthworm has been analyzed for more than 40 years with every aspect examined. However, there are no known entire sequences of the earthworm as exists in these other invertebrates. Because the earthworm lives in soil and has been utilized as a successful monitor for pollution, there are studies that reveal up and down regulation of responses in the immune system after exposure to a variety of environmental pollutants. Moreover, there are partial sequences that appear in earthworms after exposure to environmental pollutants such as cadmium and copper. There are now attempts to define the AHR receptor crucial for intracellular signaling after exposure to pollutants, but without linking the signals to changes in the immune system. There are several pathways for signal transduction, including JAK/STAT, TOLL, TRAF PIP3, known in invertebrates and vertebrates. For resistance to pathogens, conserved signal transduction components are required and these include a Toll/IL-1 receptor domain adaptor protein that functions upstream of a conserved p38 MAP kinase pathway. This pathway may be an ancestral innate immune signaling pathway found in a putative common ancestor of nematodes, arthropods and even vertebrates. It could also help us to link pollution, innate immunity and transduction in earthworms.

Animals↗
PubMed2024

Conservation of antiviral systems across domains of life reveals immune genes in humans.

Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.

Humans↗
PubMed1997

Short-range linkage relationships of the valyl-tRNA synthetase gene in Fugu rubripes.

The class III region of the human major histocompatibility complex (MHC) is gene-dense, averaging one gene every 10-20 kilobases (kb). Its gene order has been compared with other organisms. To extend this analysis further in another non-mammalian vertebrate, the compact genome of Fugu rubripes was investigated for the existence of orthologues of these class III genes and their relative arrangements. Orthologues of the Mr 70000 heat shock protein (HSP70) and valyl-tRNA synthetase genes have been isolated. They do not seem to be closely physically linked as compared with mammals (supported by longer-range analysis using pulsed field gel electrophoresis). Random shotgun sequencing of the two Fugu cosmids containing the gene encoding valyl-tRNA synthetase revealed sequences resembling genes encoding tenascin-X, the nuclear antigen A/Ro of Sjogren's syndrome, and the Landsteiner-Wiener blood group glycoprotein. These linkage relationships recapitulate some mammalian data, albeit imperfectly. Tenascin-X has been located both in the human and mouse Mhc class III regions. Three copies of a sequence found in the gene encoding Sjogren's syndrome nuclear antigen A/Ro have been identified in the human Mhc class I region; the mouse Mhc class I region contains one copy. It is postulated that a fragmented gene pattern had existed prior to convergence in the ancestral mammalian immune response-related Mhc region, and that some of these genes had belonged to the same linkage group.

Animals↗
PubMed2004

CD91 up-regulates upon immune stimulation in Xenopus adult but not larval peritoneal leukocytes.

CD91, the endocytic receptor for alpha2-macroglobulin (alpha2M), mediates the internalization of certain heat shock proteins (hsps) and the cross-presentation of peptides they chaperone by antigen-presenting cells. The phylogenetic conservation of the immunologically active CD91 ligands, alpha2M and hsps, is consistent with the idea of an ancestral system of immune surveillance. We have further explored this hypothesis by taking advantage of the frog Xenopus, and asked how conserved is CD91 and whether the expression of CD91 is differentially modulated during immune responses of class I-positive adult and naturally class I-negative larvae. We have identified a Xenopus CD91 gene homologue that displays high sequence identity (>65%) with other CD91 homologues and contains an additional distinctive cytoplasmic NPXY motif. Phylogenetic analysis indicates that CD91 homologues branch as a monophyletic group distinct from other LDLRs; this suggests an origin of CD91 contemporary with that of metazoans. A 14-kb transcript is detected by Northern blotting in most adult and larval tissues, including lymphoid tissues. RT-PCR study reveals that CD91 is expressed in most cell types, including adult macrophages, B and T cells as well as in splenocytes and thymocytes from naturally MHC class I negative larvae. CD91 is markedly up-regulated in vivo by adult peritoneal leukocytes following bacterial and viral stimulation; it is constitutively expressed on class I-negative larval peritoneal leukocytes at high levels and cannot be further upregulated by such stimulation. These data are in agreement with a conserved role of CD91 in immunity.

Amino Acid Sequence↗
PubMed2001

The ancestral complement system in sea urchins.

The origin of adaptive immunity in the vertebrates can be traced to the appearance of the ancestral RAG genes in the ancestral jawed vertebrate; however, the innate immune system is more ancient. A central subsystem within innate immunity is the complement system, which has been identified throughout and seems to be restricted to the deuterostomes. The evolutionary history of complement can be traced from the sea urchins (members of the echinoderm phylum), which have a simplified system homologous to the alternative pathway, through the agnathans (hagfish and lamprey) and the elasmobranchs (sharks and rays) to the teleosts (bony fish) and tetrapods, with increases in the numbers of complement components and duplications in complement pathways. Increasing complexity in the complement system parallels increasing complexity in the deuterostome animals. This review focuses on the simplest of the complement systems that is present in the sea urchin. Two components have been identified that show significant homology to vertebrate C3 and factor B (Bf), called SpC3 and SpBf, respectively. Sequence analysis from both molecules reveals their ancestral characteristics. Immune challenge of sea urchins indicates that SpC3 is inducible and is present in coelomic fluid (the body fluids) in relatively high concentrations, while SpBf expression is constitutive and is present in much lower concentrations. Opsonization of foreign cells and particles followed by augmented uptake by phagocytic coelomocytes appears to be a central function for this simpler complement system and important for host defense in the sea urchin. These activities are similar to some of the functions of the homologous proteins in the vertebrate complement system. The selective advantage for the ancestral deuterostome may have been the amplification feedback loop that is still of central importance in the alternative pathway of complement in higher vertebrates. Feedback loop functions would quickly coat pathogens with complement leading to phagocytosis and removal of foreign cells, a system that would be significantly more effective than an opsonin that binds upon contact as a result of simple diffusion. An understanding of the immune response of the sea urchin, an animal that is a good estimator of what the ancestral deuterostome immune system was like, will aid us in understanding how adaptive immunity might have been selected for during the early evolution of the vertebrates and how it might have been integrated into the pre-existing innate immune system that was already in place in those animals.

Amino Acid Sequence↗