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Results for “Adaptive immunity”

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PubMed1998

Innate immune recognition and control of adaptive immune responses.

The immune system of higher vertebrates consists of two components: innate and adaptive. The innate immune system relies on a set of germ-line encoded receptors that recognize conserved molecular patterns found only in microorganisms. The adaptive immune system uses somatically generated antigen receptors which are clonally distributed on the two types of lymphocytes: T cells and B cells. These antigen receptors are generated by random processes and, as a consequence, the general design of the adaptive immune system is based on clonal selection of lymphocytes expressing receptors with particular specificities. Here we discuss the essential role of the innate immune system in the clonal selection of lymphocytes and activation of the adaptive immune responses.

Animals↗
PubMed2002

Adaptive immunity is severely impaired by open-heart surgery.

OBJECTIVE: The influence of open-heart surgery on antigen-specific immunity, also called adaptive immunity, remains to be clarified. We explored the effects of open-heart surgery on adaptive immunity. METHODS: In 8 consecutive adult patients undergoing elective cardiac surgery with cardiopulmonary bypass, we measured the T cell-response to purified protein derivative (PPD) antigen perioperatively. We separately measured the proliferation of T cells and the antigen presentation of antigen-presenting cells (APCs) using a cross-reaction system. RESULTS: T cell response to PPD antigen was severely impaired by open-heart surgery. Compared to preoperative values, T cell response to PPD antigen fell to 5.7 +/- 4.4% immediately after surgery, 4.5 +/- 3.2% on postoperative day (POD) 1, to 22.4 +/- 24.6% on POD 3 and to 50.1 +/- 34.3% on POD 7. T cell proliferation on POD1 decreased to 29 +/- 26%. APC antigen-presentation on POD 1 also decreased to 31 +/- 36%. CONCLUSIONS: Open-heart surgery impaired both T cell proliferation and the antigen-presentation. Such synergistic impairment severely impaired adaptive immunity. This impairment was both severer and longer than we anticipated based on previous studies using the response of T cells to lectin as a marker of cell-mediated immunity.

Aged↗
PubMed2004

C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity.

C-reactive protein (CRP) is an acute-phase serum protein and a member of the pentraxin protein family. Its host defense functions predate the adaptive immune system by millions of years. Our current understanding of CRP interactions with complement and with Fcgamma receptors (FcgammaR) have led to an increased appreciation of the regulatory role of CRP in inflammation and autoimmunity. This review outlines the role of CRP in infection, inflammation, and autoimmune disease. We provide a description of recent studies, which suggest that CRP acts through FcgammaR to reduce inflammation and protect from certain autoimmune diseases. A general description of the proposed function of CRP is provided as a framework for future investigation.

Adaptation, Physiological↗
PubMed2002

Analysis of robust innate immune response after transplantation in the absence of adaptive immunity.

BACKGROUND: Both animal models and clinical outcomes studies of transplantation suggest that antigen-independent mechanisms can alter graft survival and function. It has been suggested that antigen-independent processes interact with alloantigen-specific responses to augment the rejection reaction. A major link between antigen-specific adaptive immunity and pro-inflammatory stimuli is innate immunity. During transplantation, innate immunity may be stimulated by multiple factors, including ischemia, reperfusion, sterile injury, systemic stress, and cell death. METHODS: We investigated the hypothesis that transplantation induces a potent innate immune response in a murine model of vascularized solid organ transplantation. In our studies, we analyzed three experimental groups: (a) alymphoid group in which both the donor and recipients strains lacked an adaptive immune response due to deletion of the recombinase activating gene, thus blocking production of both T cell and B cell antigen receptors; (b) syngeneic group in which the donors and recipients were genetically identical; and (c) allogeneic group in which the donors and recipients had a complete MHC mismatch. To analyze a large number of parameters we determined the level of expression of a panel of cytokines, chemokines, receptors, and cell surface markers by RNase protection assays. In addition, serum cytokines were determined by ELISA and the infiltration of inflammatory cells was assessed by histology. RESULTS: Our results showed macrophage infiltration and up-regulation of multiple cytokines, chemokines, and chemokine receptors within the first day after transplantation in all groups, including the syngeneic and alymphoid recipients. CONCLUSIONS: Our study demonstrated a robust innate immune response that is independent of adaptive immunity and natural killer cell responses.

Animals↗
PubMed1990

Innate and adaptive immune responses in a social conflict paradigm.

Social conflict stress was examined for its effects on in vitro and in vivo immunity in mice. Adaptive immunity, as measured by the generation of primary IgM antibody responses to the T-dependent antigen keyhold limpet hemocyanin, was suppressed following chronic (greater than 1 day), but not acute (less than 1 day), stress periods while the IgM response to the T-independent antigen polyvinylpyrrolidone was not affected. In vitro proliferative responses of splenocytes to the T cell mitogen concanavalin A and the B cell mitogen lipopolysaccharide were unaffected. Acute (less than 1 day) stress dramatically increased innate immunity as measured by a luminol-dependent chemiluminescence assay of phagocytic cell function. DBA/2J mice averaged a 269% increase in phagocytosis as compared to a 412% increase in C57BL/6J. This differential effect of stress on immune responsiveness indicates that alterations in innate immunity in addition to adaptive immunity should also be considered when evaluating neuroendocrine and immune interactions in response to stress.

Animals↗
PubMed1997

A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.

Induction of the adaptive immune response depends on the expression of co-stimulatory molecules and cytokines by antigen-presenting cells. The mechanisms that control the initial induction of these signals upon infection are poorly understood. It has been proposed that their expression is controlled by the non-clonal, or innate, component of immunity that preceded in evolution the development of an adaptive immune system in vertebrates. We report here the cloning and characterization of a human homologue of the Drosophila toll protein (Toll) which has been shown to induce the innate immune response in adult Drosophila. Like Drosophila Toll, human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat (LRR) domain, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-kappaB pathway. We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-kappaB and the expression of NF-kappaB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the co-stimulatory molecule B7.1, which is required for the activation of naive T cells.

Amino Acid Sequence↗
PubMed2006

Sendai virus infection induces efficient adaptive immunity independently of type I interferons.

Adaptive immunity in response to virus infection involves the generation of Th1 cells, cytotoxic T cells, and antibodies. This type of immune response is crucial for the clearance of virus infection and for long-term protection against reinfection. Type I interferons (IFNs), the primary innate cytokines that control virus growth and spreading, can influence various aspects of adaptive immunity. The development of antiviral immunity depends on many viral and cellular factors, and the extent to which type I IFNs contribute to the generation of adaptive immunity in response to a viral infection is controversial. Using two strains (Cantell and 52) of the murine respiratory Sendai virus (SeV) with differential abilities to induce type I IFN production from infected cells, together with type I IFN receptor-deficient mice, we examined the role of type I IFNs in the generation of adaptive immunity. Our results show that type I IFNs facilitate virus clearance and enhance the migration and maturation of dendritic cells after SeV infection in vivo; however, soon after infection, mice clear the virus from their lungs and efficiently generate cytotoxic T cells independently of type I IFN signaling. Furthermore, animals that are unresponsive to type I IFN develop long-term anti-SeV immunity, including CD8+ T cells and antibodies. Significantly, this memory response is able to protect mice against challenge with a lethal dose of virus. In conclusion, our results show that primary and secondary anti-SeV adaptive immunities are developed normally in the absence of type I IFN responsiveness.

Animals↗
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↗
PubMed2002

Cutting edge: recruitment of the ancestral fyn gene during emergence of the adaptive immune system.

The adaptive immune system (AIS) is characterized by the MHC molecules and the rearranging Ag receptors, and was established in a common ancestor of jawed vertebrates. Fyn, a Src-family tyrosine kinases, is important for normal development and function of T lymphocytes and neuronal cells. Indeed, as the result of an alternative splicing of a distinct exon 7, fyn encodes for two isoforms, FynT in T lymphocytes and FynB in the brain. How this alternative splicing of fyn transcripts has emerged and evolved in relation to the setting of the AIS remains to be established. In this study, we show that exon capture in a vertebrate ancestor by the fynT-like gene has yielded a novel fyn-encoded isoform, fynB. Unexpectedly, the newly established AIS recruited the ancestral Fyn isoform, FynT, whereas the CNS expresses the most recent one, FynB. These results shed new light on the emergence of the AIS.

Adaptation, Physiological↗
PubMed2000

Enhanced immunogenicity of aldehyde-bearing antigens: a possible link between innate and adaptive immunity.

Innate immunity directs the adaptive immune response by identifying antigens that are associated with infectious agents. Although some microbial antigens can be recognized by innate immune receptors, most cannot, and these require identification by some other means. The introduction of aldehydes into antigens by glycolaldehyde, which can be produced by activated neutrophils reacting with serine, or by the oxidation of an N-linked oligosaccharide with NaIO4, enhances by several orders of magnitude their immunogenicity in mice. The augmented immunogenicity requires the presence of an aldehyde on the antigen, and is not dependent on protein aggregation. An in vitro correlate of augmented immunogenicity is the enhanced presentation of glycolaldehyde-modified antigen to T cells by macrophages and bone marrow-derived dendritic cells. The potential clinical importance of this form of antigen modification is twofold: glycolaldehyde renders a model self antigen immunogenic, and it converts a relatively non-immunogenic malaria antigen, merozoite surface protein-1, into an effective immunogen. Thus, the tagging of antigens by the addition of aldehydes, which may be an innate immune mechanism to facilitate their recognition by the adaptive immune system, may have a role in the genesis of autoimmunity and the development of vaccines.

Acetaldehyde↗
PubMed2006

Complement component C3 is required for protective innate and adaptive immunity to larval strongyloides stercoralis in mice.

This study examines the role of complement components C3 and C5 in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. Larval survival in naive C3(-/-) mice was increased as compared with survival in wild-type mice, whereas C3aR(-/-) and wild-type mice had equivalent levels of larval killing. Larval killing in naive mice was shown to be a coordinated effort between effector cells and C3. There was no difference between survival in wild-type and naive C5(-/-) mice, indicating that C5 was not required during the innate immune response. Naive B cell-deficient and wild-type mice killed larvae at comparable levels, suggesting that activation of the classical complement pathway was not required for innate immunity. Adaptive immunity was equivalent in wild-type and C5(-/-) mice; thus, C5 was also not required during the adaptive immune response. Larval killing was completely ablated in immunized C3(-/-) mice, even though the protective parasite-specific IgM response developed and effector cells were recruited. Protective immunity was restored to immunized C3(-/-) mice by transferring untreated naive serum, but not C3-depleted heat-inactivated serum to the location of the parasites. Finally, immunized C3aR(-/-) mice killed larvae during the adaptive immune response as efficiently as wild-type mice. Therefore, C3 was not required for the development of adaptive immunity, but was required for the larval killing process during both protective innate and adaptive immune responses in mice against larval S. stercoralis.

Animals↗
PubMed2003

Analysis of differential immune responses induced by innate and adaptive immunity following transplantation.

The roles of innate and adaptive immunity in allograft rejection remain incompletely understood. Previous studies analysing lymphocyte deficient or syngeneic graft recipients have identified subsets of inflammatory chemokines and cytokines induced by antigen independent mechanisms. In the current study, we analysed a panel of 60 inflammatory parameters including serum cytokines, intragraft chemokines and cytokines, receptors, and cellular markers. Our results confirmed the up-regulation of a subset of markers by innate mechanisms and also identified a subset of parameters up-regulated only in the context of an adaptive response. Thus, we successfully differentiated markers of the innate and adaptive phases of rejection. Current paradigms emphasize that innate signals can promote a subsequent adaptive response. Interestingly, in our studies, expression of the markers induced by innate mechanisms was markedly amplified in the allogeneic, but not syngeneic or lymphocyte deficient, recipients. These results suggest that inflammatory mediators can have functional overlap between the innate and adaptive responses, and that the adaptive component of the rejection process amplifies the innate response by positive feedback regulation.

Analysis of Variance↗
PubMed2003

The art of war: Innate and adaptive immune responses.

Research over the last several years has greatly advanced our understanding of the mechanisms by which the immune system functions. There exist two main branches of immunity, termed innate and adaptive immunity. Innate immunity uses the genetic memory of germline-encoded receptors to recognize the molecular patterns of common pathogens. Adaptive immunity, akin to somatic memory, is a complex system by which the body learns to recognize a pathogen's unique antigens and builds an antigen specific response to destroy it. The effective development of the overall immune response depends on careful interplay and regulation between innate and adaptive immunity. Here we review our current understanding of how these integrated systems distinguish targets against which a response is appropriate and neutralize potentially pathogenic challenges.

Animals↗
PubMed1998

Skin delivery of a hybrid liposome/ISCOM vaccine implicates a role for adjuvants in rapid modulation of inflammatory cells involved in innate immunity before the enhancement of adaptive immune responses.

There is now compelling evidence that intradermal vaccination with an efficacious adjuvanted antigen triggers a series of coordinated responses characterized initially by the rapid mobilization and recruitment of granulocytes to the lung. Activation of effector cells of the innate immune system is intended to provide surveillance and temporary protective cover at vulnerable mucosal sites while both T and B cell precursors, as well as haematopoietic progenitor cells, are undergoing dramatic reductions in numbers during the first 2-4 days post-vaccination. Some of these events recapitulate those seen after infection with a pathogen. Initial decreases in cell numbers in the thymus and bone marrow (BM) are followed by rapid increases in cellular proliferation in these organs, probably in response to peripheral signals. Vaccine-induced cell death (by apoptosis) in the thymus may provide one of many stimuli needed to up-regulate BM production of progenitor cells, and cells of the B, myeloid and monocytic lineages so that depleted peripheral compartments are replenished. Reconstitution of the latter cell population is critical in ensuring sufficient numbers of APC are generated to deal with extraneous antigen resulting from either vaccination or proliferation of a pathogen. Ultimately, these APC, as effector cells of the innate immune system, must provide pattern recognition of dangerous pathogens and serve to activate appropriate T cell responses. Vaccination not only educates both the innate and adaptive arms of the immune response but also more interestingly, appears to regulate subsequent innate immune responses following exposure to a lethal challenge dose of bacteria. Under these conditions, the rate of loss of BM precursors is greatly attenuated in mice previously vaccinated with adjuvanted antigen compared to unvaccinated controls or mice that had received only antigen. Mice intradermally vaccinated with adjuvanted antigen also displayed increased rates of granulocyte and monocyte recruitment in the lung and spleen. These events occurred very rapidly within 12-36 h of challenge and may be crucial in providing complete protection in vaccinated mice against a challenge dose that was otherwise lethal for unvaccinated controls. Therefore, an important characteristic of an efficacious intradermal vaccine may be the ability to deplete T and B precursors in the thymus and BM lymphoid compartments followed by increased rates of haematopoiesis to re-supply peripheral requirements for granulocytes/monocytes, and T and B cells. Adaptive immunity elicited by intradermal vaccination is, therefore, dependent upon prior activation of the innate immune system.

Adjuvants, Immunologic↗
PubMed2006

Basophils: a potential liaison between innate and adaptive immunity.

Activation of innate immunity is closely associated to development of protective adaptive immune response. Significant advances have been made to reveal such links between innate immunity and Th1 type adaptive immune responses. By contrast, the role of innate immunity in the development of Th2 type adaptive immune responses is still not well understood. Production of IL-4, a key cytokine in the induction of Th2 immunity, by innate type cells represents an attractive mechanism for such an innate link to Th2 immunity. We have recently reported that in the course of infection with the intestinal nematode, Nippostrongylus brasiliensis, a robust basophil accumulation in the liver/spleen occurs and that these basophils display enhanced IL-4 production. Thus, the basophils is an attractive candidate to mediate the innate-adaptive link for Th2 responses and understanding the control of the tissue homing patterns and cytokine responses of basophils in the course of infections may shed important light on the in vivo induction of Th2 adaptive immunity.

Animals↗
PubMed2025

Comparative Analysis of Mammalian Adaptive Immune Loci Revealed Spectacular Divergence and Common Genetic Patterns.

Adaptive immune responses are mediated by the production of adaptive immune receptors, antibodies, and T-cell receptors, which bind antigens, thus causing their neutralization. Unlike other proteins, adaptive immune receptors are not fully encoded in the germline genome and result from a complex of somatic processes collectively called V(D)J recombination affecting germline immunoglobulin (IG) and T-cell receptor (TR) loci consisting of template genes. While various existing studies report extreme diversity of antibodies and T-cell receptors, little is known about the diversity of germline IG and TR loci. To overcome this gap, the first comparative analysis of full-length sequences of IG/TR loci across 46 mammalian species from 13 taxonomic orders was performed. First, germline gene counts were shown to correlate in immunoglobulin heavy chain immunoglobulin heavy chain (IGH)/immunoglobulin lambda (IGL) loci and T-cell receptor alpha (TRA)/T-cell receptor beta (TRB) and anticorrelate in immunoglobulin kappa (IGK)/IGL, possibly indicating coevolution between corresponding chains. Second, structures of IG/TR loci were analyzed, and it was shown that IG/TR loci formed by long arrays of high multiplicity repeats are more common for species that have experienced population bottlenecks. Finally, haplotypes of IG/TR loci with little or no sequence similarity within a species were found, suggesting that they may have a limited potential for homologous recombination. These results demonstrate that IG/TR loci are rapidly evolving genomic regions whose structural variation is shaped by the population history of the species and open new perspectives for immunogenomics studies.

Animals↗