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Results for “Adaptive Immunity”

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At least 307 records · Page 17Linked to original sources

PubMed2003

Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: therapeutic opportunities and controversies.

Monocyte chemoattractant protein (MCP)-1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small-molecule antagonists of the receptor of MCP-1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP-1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP-1/CCL2(-/-) and CCR2(-/-) mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP-1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP-1/CCL2/CCR2 axis in disease.

Adaptation, Physiological↗

PubMed2000

Adaptive immunity and enhanced CD8+ T cell response to Listeria monocytogenes in the absence of perforin and IFN-gamma.

Single Ag-specific CD8+ T cells from IFN-gamma-deficient (GKO) or perforin-deficient (PKO) mice provide substantial immunity against murine infection with Listeria monocytogenes. To address the potential for redundancy between perforin and IFN-gamma as CD8+ T cell effector mechanisms, we generated perforin/IFN-gamma (PKO/GKO) double-deficient mice. PKO/GKO-derived CD8+ T cells specific for the immunodominant listeriolysin O (LLO91-99) epitope provide immunity to LM infection similar to that provided by Ag-matched wild-type (WT) CD8+ T cells in the liver but reduced in the spleen. Strikingly, polyclonal CD8+ T cells from immunized PKO/GKO mice were approximately 100-fold more potent in reducing bacterial numbers than the same number of polyclonal CD8+ T cells from immunized WT mice. This result is probably quantitative, because the frequency of the CD8+ T cell response against the immunodominant LLO91-99 epitope is >4.5-fold higher in PKO/GKO mice than WT mice at 7 days after identical immunizations. Moreover, PKO/GKO mice can be immunized by a single infection with attenuated Listeria to resist >80,000-fold higher challenges with virulent organisms than naive PKO/GKO mice. These data demonstrate that neither perforin nor IFN-gamma is required for the development or expression of adaptive immunity to LM. In addition, the results suggest the potential for perforin and IFN-gamma to regulate the magnitude of the CD8+ T cell response to infection.

Animals↗

PubMed2004

The LILR family: modulators of innate and adaptive immune pathways in health and disease.

Leukocyte immunoglobulin (Ig)-like receptors [LILRs, also known as Ig-like transcripts (ILTs)] are a family of inhibitory and stimulatory receptors encoded within the leukocyte receptor complex and are expressed by immune cell types of both myeloid and lymphoid lineage. Several members of the LILR family recognize major histocompatibility complex class I. The immunomodulatory role of LILR receptors indicates that they may exert an influence on signaling pathways of both innate and adaptive immune systems. LILR activity can also influence the antigen-presenting properties of macrophages and dendritic cells and may thus play a role in T-cell tolerance. The wide-ranging effects of LILR signaling on immune cell activity imply that these receptors are likely to play an important role in a range of clinical situations including pregnancy, transplantation, and arthritis (including the human leukocyte antigen B27-associated spondyloarthropathies). In this review, we summarize current knowledge on the nature and function of LILRs, focusing on their regulation of immune cell activity and their potential role in disease.

Animals↗

PubMed2000

TNF-alpha blockade by a dimeric TNF type I receptor molecule selectively inhibits adaptive immune responses.

Tumor necrosis factor-alpha (TNF-alpha) is a mediator of severe inflammatory processes, including rheumatoid arthritis. Suppression of TNF with a soluble type I or type II receptor molecule (TNF-RI or TNF-RII) has the potential to decrease cytokine levels and modulate inflammatory diseases in humans. However, it has recently been reported that treatment of mice with a TNF-RI:Fc immunoadhesin protein augmented Gram positive infections and subsequent mortality. To determine if TNF-alpha blockade with soluble TNF-alpha receptors might alter immune system function, assays were assessed in rodents treated with a dimeric form of the p55 TNF-RI, Tumor Necrosis Factor-binding protein (TNFbp). Administration of TNFbp resulted in suppression of primary and secondary IgG antibody responses and cell-mediated immune function. No treatment-related differences were detected in immune-enhancing assays or non-specific immune function parameters. Bacterial host resistance assays with Listeria monocytogenes, Staphylococcus aureus or Escherichia coli showed an increase in tissue colony counts only with L. monocytogenes challenged animals following TNFbp administration. These results suggest that TNFbp has the capacity to inhibit adaptive immune function in experimental animal models. Studies suggest that while reducing TNF-alpha is important in controlling cytokine-dependent disease states, maintenance of a threshold level may be critical for normal immune function.

Animals↗

PubMed2004

IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals.

Dendritic cells (DCs) are the professional APCs of the immune system, enabling T cells to perceive and respond appropriately to potentially dangerous microbes, while also being able to maintain T cell tolerance toward self. In part, such tolerance can be determined by IL-10 released from certain types of regulatory T cells. IL-10 has previously been shown to render DCs unable to activate T cells and it has been assumed that this process represents a general block in maturation. Using serial analysis of gene expression, we show that IL-10 pretreatment of murine bone marrow-derived DCs alone causes significant changes in gene expression. Furthermore, these cells retain the ability to respond to Toll-like receptor agonists, but in a manner skewed toward the selective induction of mediators known to enhance local inflammation and innate immunity, among which we highlight a novel CXCR2 ligand, DC inflammatory protein-1. These data suggest that, while the presence of a protolerogenic and purportedly anti-inflammatory agent such as IL-10 precludes DCs from acquiring their potential as initiators of adaptive immunity, their ability to act as initiators of innate immunity in response to Toll-like receptor signaling is enhanced.

Amino Acid Motifs↗

PubMed2003

A CD40 bridge between innate and adaptive immunity.

In this issue of Immunity, Brodeur et al. show that C4b binding protein (C4BP), a regulator component of the classical complement (C) pathway, can bind to CD40 receptors on B cells and activate them. This suggests a novel way by which CD40 may function to bridge innate and adaptive immune responses.

Animals↗

PubMed2005

Bruton's Tyrosine Kinase is involved in innate and adaptive immunity.

Btk is a cytoplasmic tyrosine kinase, which is mainly involved in B cell receptor signalling. Gene targeting experiments revealed that Btk is important for B cell development and function. However, Btk is not only expressed in B cells, but also in most other haematopoietic lineages except for T cells and plasma cells. Recently we found that Btk is involved in Toll-like receptor signalling. Toll-like receptors play an important role in innate immunity. They are highly expressed on mast cells, macrophages and dendritic cells, which are essential for the recognition and consequently for the elimination of microbial pathogens. Therefore Btk might play an important role for the function of immunocompetent cells of innate as well as adaptive immunity.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2003

Use of intracellular cytokine staining and bacterial superantigen to document suppression of the adaptive immune system in injured patients.

OBJECTIVE: To determine the percentages of major T lymphocyte subsets in the circulating peripheral blood mononuclear cell population in patients with major traumatic injury at early and late time points and to determine the expression of coreceptors and cytokine production by these T cell subsets. SUMMARY BACKGROUND DATA: Prior studies suggest that serious injury in humans suppresses the adaptive immune system as revealed by diminished proliferation and altered cytokine production in response to polyclonal T cell activation. However, the contribution of individual cell types to this immune dysfunction has not been well characterized. METHODS: The percentage of circulating CD4+ and CD8+ T cells and the relative density of CD4 and CD8 coreceptor expression was determined by flow cytometry in 17 consecutive trauma patients (injury severity score > 20) within 24 hours of injury and at day 7. Intracellular expression of the cytokines interleukin 2 (IL-2), interferon gamma (IFNgamma), IL-4, and IL-10 were also studied after stimulation with bacterial superantigen (SEB). Patients were compared with age- and sex-matched controls and to themselves for differences between early and late cytokine expression. RESULTS: The percentage of circulating CD4+ and CD8+ T cells was decreased versus controls at day 1 and further decreased by day 7 following injury. CD4 and CD8 cell surface expression was also decreased at days 1 and 7. CD4+ T cells in injured patients responded to SEB activation with decreased expression of IFNgamma and IL-2 on day 1 versus controls (P < 0.05) and of all 4 cytokines by day 7 (P < 0.05), while CD8+ T cells showed diminished expression of IFNgamma and IL-2 only at both time points. When day 1 and day 7 cytokine expression results were compared in the same patients, CD4+ T cells showed diminished expression of IFNgamma, IL-2, and IL-4 by day 7 (P < 0.05), but maintained expression of IL-10. CD8 T cells showed diminished expression of IFNgamma only. CONCLUSIONS: Severe injury induces a loss of circulating CD4+ and CD8+ T lymphocytes and diminished coreceptor expression by these cells. Both T cell subsets show progressive loss of immunostimulatory cytokine production with maintenance of potentially suppressive IL-10 production. These events may have negative consequences for host defense.

Adult↗

PubMed2005

Respiratory syncytial virus and T cells: interplay between the virus and the host adaptive immune system.

Respiratory syncytial virus (RSV) is a major cause of morbidity in young infants and is increasingly recognized as an important cause of serious illness/morbidity in the elderly. This agent has also been implicated both in the etiopathogenesis of asthma/airway hyperreactivity and in the exacerbation of wheezing episodes in individuals with asthma. This review deals with our current knowledge of the host adaptive immune response to RSV, focusing on the interaction of the virus with T lymphocytes. Current information on the impact of RSV infection on the function of responding CD4 (+) and, in particular, CD8 (+) T lymphocytes will be reviewed; and the potential implications of this virus/immune cell interaction on the development of RSV-induced disease in the respiratory tract will be discussed. In addition, the long-standing conundrum concerning the development of an effective vaccine against RSV will be discussed in the context of the vaccine-induced enhanced disease during RSV infection and the interplay between the virus and immune/memory T cells in the development of pulmonary injury in vaccinated individuals after the RSV infection.

CD4-Positive T-Lymphocytes↗

PubMed2001

KIR: diverse, rapidly evolving receptors of innate and adaptive immunity.

KIR genes have evolved in primates to generate a diverse family of receptors with unique structures that enable them to recognize MHC-class I molecules with locus and allele-specificity. Their combinatorial expression creates a repertoire of NK cells that surveys the expression of almost every MHC molecule independently, thus antagonizing the spread of pathogens and tumors that subvert innate and adaptive defense by selectively downregulating certain MHC class I molecules. The genes encoding KIR that recognize classical MHC molecules have diversified rapidly in human and primates; this contrasts with conservation of immunoglobulin- and lectin-like receptors for nonclassical MHC molecules. As a result of the variable KIR-gene content in the genome and the polymorphism of the HLA system, dissimilar numbers and qualities of KIR:HLA pairs function in different humans. This diversity likely contributes variability to the function of NK cells and T-lymphocytes by modulating innate and adaptive immune responses to specific challenges.

Alleles↗

PubMed2004

Granulocyte chemotactic protein-2 mediates adaptive immunity in part through IL-8Rbeta interactions.

Chemokines constitute a large family of structurally related proteins that play a role in leukocyte migration and differentiation. Indeed, the early expression of human CXC chemokine receptor 1 (hCXCR1) and hCXCR2 [homologous to mouse interleukin (IL)-8Rbeta] ligands by the epithelium is a hallmark of the mucosal host defense. Mice lack IL-8; however, granulocyte chemotactic protein-2 (GCP-2)/lipopolysaccharide-induced CXC chemokine, a murine homologue of human GCP-2, has 32% and 61% sequence identity to human IL-8 and GCP-2, respectively, and binds hCXCR1, hCXCR2, and mouse IL-8Rbeta. To better understand the role of GCP-2 in adaptive immunity and as a nasal adjuvant, we characterized the exogenous effects of this CXC chemokine on cellular and humoral mucosal immune responses. GCP-2 significantly enhanced serum immunoglobulin G (IgG) and mucosal IgA antibodies through increased cytokine secretion by CD4+ T cells. These alterations in humoral and cellular responses were preceded by an increase in the number of B cells in the nasal tract, a decrease in the number of CD4+ T cells in the nasal tract as well as cervical lymph nodes, and an increase in the number of neutrophils in the nasal tract 12 h after GCP-2 immunization. This chemokine also modulated CD28 expression by CD4+ T cells during CD3epsilon stimulation of wild-type mice. GCP-2 increased CD80 and CD86 expression on B cells during in vitro stimulation in a dose-dependent manner. In contrast, cytokine and costimulatory molecule enhancement by GCP-2 was not induced by lymphocytes from IL-8Rbeta-/- mice, suggesting that GCP-2 modulates cellular immunity in part through IL-8Rbeta interactions.

Adaptation, Physiological↗

PubMed2004

Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: importance of the Kupffer cell network.

Mammalian cells recognize LPS from Gram-negative bacteria via the Toll-like receptor 4 (TLR4) complex. During experimental Salmonella infection, C3H/HeJ mice carrying a dominant-negative mutation in TLR4 exhibited delayed chemokine production, impaired NO generation, and attenuated cellular immune responses. However, dramatically enhanced bacterial growth within the Kupffer cell network before the recruitment of inflammatory cells appeared to be primarily responsible for the early demise of Salmonella-infected TLR4-deficient mice. LPS-TLR4 signaling plays an essential role in the generation of both innate and adaptive immune responses throughout the course of infection with Gram-negative bacteria. Alternative pattern-recognition receptors cannot completely compensate for the loss of TLR4, and compensation occurs at the expense of an increased microbial burden.

Animals↗

PubMed2005

Interleukin-15 enhances innate and adaptive immune responses to blood-stage malaria infection in mice.

Compared to C57BL/6 wild-type mice, interleukin-15(-/-) (IL-15(-/-)) mice showed delayed clearance of Plasmodium chabaudi AS infection, lower type 1 cytokine production, impaired dendritic cell and NK cell functions, and lower titers of malaria-specific antibodies. Thus, IL-15 supports early control and timely resolution of blood-stage malaria through promotion of Th1-dependent innate and adaptive immune responses.

Animals↗

PubMed2004

Relative proportions of T-cell subpopulations and cytokines that mediate and regulate the adaptive immune response in patients with aggressive periodontitis.

BACKGROUND: Both the virulence factors of periodontopathic bacteria and the immune response against them have been involved in tissue destruction observed in periodontal disease. Considering the regulatory role of cytokines produced by T cells, the purpose of this study was to compare the CD3+, CD4+, and CD8+ subpopulations of T cells, and to characterize the mRNA of cytokines involved in the adaptive immune response in a group of healthy/gingivitis 1 (HI/G1) individuals and aggressive periodontitis (AgP) patients. METHODS: The percentages of T-cell subpopulations were analyzed in 10 gingival samples of HI/G1 individuals and 10 gingival samples of AgP patients by immunohistochemistry. The presence of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-10, IL- 13, and transforming growth factor (TGF)-beta was measured by reverse transcription polymerase chain reaction (RT-PCR) of mRNA extracted from complete gingival biopsies. RESULTS: Significant differences were found in CD3+ and CD4+ cell counts between both groups. The parameters were lower in the gingival biopsies from AgP patients while CD8+ counts were similar in both groups. The cytokine mRNA analysis showed constant expression of IL-2 and IFN-gamma in all cases. The mRNA of IL-5 and IL-10 was present in the majority of HI/G1 (N = 10, N = 9, respectively) but was not in the AgP group (N = 2, N = 1). IL-13 and TGF-beta were only detected in HI/G1 (N = 2, N = 3) and IL-4 was not detected in any of the individuals. CONCLUSIONS: These results indicate that the role of the CD8+ subpopulation in aggressive periodontitis lesions is limited. On the other hand, cytokines IL-2 and IFN-gamma may not be relevant in the progression of aggressive periodontitis.

Alveolar Bone Loss↗

PubMed2006

Patients with Hereditary Hemorrhagic Telangectasia (HHT) exhibit a deficit of polymorphonuclear cell and monocyte oxidative burst and phagocytosis: a possible correlation with altered adaptive immune responsiveness in HHT.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare genetic disease characterized by mutations occurring in the endoglin and ALK-1, two receptors of transforming growth factor-beta1. From a pathogenic point of view, a possible involvement of the immune system in HHT has been suggested since a mononuclear cell infiltrate was found around the area of telangiectases. Up until now, no information has been available about the role played by leukocytes in HHT and the mechanisms elicited by secretion of their mediators. However, the fact that a deficit of adaptive immunity in HHT has been reported in a companion paper in this issue will represent a great contribution to the understanding of HHT pathogenesis. The purpose of this study was to evaluate whether patients with HHT manifest also alterations in the innate immune response. Therefore, the phenotype of T, B and natural killer lymphocytes, serum immunoglobulin levels, phagocytosis and oxidative burst activity exerted by polymorphonuclear cells (PMN) and monocytes (MO) were analyzed in 22 patients. Twenty individuals demonstrated single or multiple deficits of PMN and MO functions, while the immunophenotype of lymphocytes and serum concentrations of immunoglobulins were normal. To the best of our knowledge, this is the first demonstration of a reduction in PMN and MO functions in HHT, thus suggesting a higher susceptibility to infectious complications in these patients. The relationship between innate immune deficits and T helper 1 and monocyte-derived cytokine dysfunction in HHT, as previously reported, is discussed.

Adult↗

PubMed2001

The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity.

Since we live in a dirty environment, we have developed many host defenses to contend with microorganisms. The epithelial lining of our skin, gastrointestinal tract and bronchial tree produces a number of antibacterial peptides, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities. Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune responses. The epithelial cells are a source of constitutively produced beta defensin (HBD1) and proinflammatory cytokine-inducible beta defensins (HBD2 and -3) and cathelicidin (LL37). The neutrophils-derived antimicrobial peptides are released on demand from their cytoplasmic granules. They include the enzymes cathepsin G and chymase, azurocidin, a defensins and cathelicidin. In contrast, C5a and C3b are produced by activation of the serum complement cascade. The antimicrobial moieties direct the migration and activate target cells by interacting with selected G-protein-coupled seven-transmembrane receptors (GPCRs) on cell surfaces. The beta defensins interact with the CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinity FPRL-1 receptors. The neutrophil-derived cathepsin G acts on the high-affinity FMLP receptor (GPCR) known as FPR, while the receptors for chymase and azurocidin have not been identified as yet. The serum-derived C5a uses a GPCR known as C5aR to mediate its chemotactic and cell-activating effects. Consequently, all these ligand-receptor interactions in addition to mediating chemotaxis also activate receptor-expressing cells to produce other mediators of inflammation.

Animals↗

PubMed2005

Editing at the crossroad of innate and adaptive immunity.

Genetic information can be altered through the enzymatic modification of nucleotide sequences. This process, known as editing, was originally identified in the mitochondrial RNA of trypanosomes and later found to condition events as diverse as neurotransmission and lipid metabolism in mammals. Recent evidence reveals that editing enzymes may fulfill one of their most essential roles in the defense against infectious agents: first, as the mediators of antibody diversification, a step crucial for building adaptive immunity, and second, as potent intracellular poisons for the replication of viruses. Exciting questions are raised, which take us to the depth of the intimate relations between vertebrates and the microbial underworld.

Animals↗

PubMed2004

Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs.

Microglia are the resident macrophage-like population in the CNS. Microglia remain quiescent until injury or infection activates the cells to perform effector inflammatory and APC functions. Our previous studies have shown that microglia infected with a neurotropic strain of Theiler's murine encephalomyelitis virus secreted innate immune cytokines and up-regulated costimulatory molecules and MHC class II, enabling the cells to present viral and myelin Ags to CD4+ T cells. Recently, TLRs have been shown to recognize pathogen-associated molecular patterns and initiate innate immune responses upon interaction with infectious agents. We examined TLR expression on brain microglia and their functional responses upon stimulation with various TLR agonists. We report that mouse microglia express mRNA for all of the recently identified TLRs, TLR1-9, used for recognition of bacterial and viral molecular patterns. Furthermore, stimulation of quiescent microglia with various TLR agonists, including LPS (TLR4), peptidoglycan (TLR2), polyinosinic-polycytidylic acid (TLR3), CpG DNA (TLR9), and infection with viable Theiler's murine encephalomyelitis virus, activated the cells to up-regulate unique patterns of innate and effector immune cytokines and chemokines at the mRNA and protein levels. In addition, TLR stimulation activated up-regulation of MHC class II and costimulatory molecules, enabling the microglia to efficiently present myelin Ags to CD4+ T cells. Thus, microglia appear to be a unique and important component of both the innate and adaptive immune response, providing the CNS with a means to rapidly and efficiently respond to a wide variety of pathogens.

Animals↗