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Results for “Adaptive Immunity”

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At least 271 records · Page 15Linked to original sources

PubMed2004

In vivo recognition by the host adaptive immune system of microencapsulated xenogeneic cells.

BACKGROUND: Microencapsulation is under consideration as a means of enabling pancreatic islet transplantation. To understand better the ongoing destructive host response, we examined whether the adaptive immune system of the recipient recognized polymer-encapsulated xenogeneic cells implanted intraperitoneally. METHODS: Balb/c mice were implanted with xenogeneic Chinese hamster ovary cells, inside and outside poly(hydroxyethyl methacrylate-methyl methacrylate) microcapsules, and responses were compared with xenografted Chinese hamster skin (positive control). Capsules were localized within an agarose rod. Splenocyte proliferation upon rechallenge in vitro, antibody titer in serum, and Th1/2 polarization (assessed by interleukin-4 and interferon-gamma in supernatants of antigen-challenged splenocytes and immunoglobulin [Ig]G1 and IgG2a antibody isotypes in serum) were measured. RESULTS: Encapsulation did not prevent a strong recipient antibody response. Splenocyte proliferation in vitro did not differ after priming by implanted cells, inside or outside capsules. Thus, the capsule membrane did not prevent indirect recognition of shed antigens. However, after 10 days of implantation, proliferation was lower than that induced by skin grafts, although this difference disappeared by 2 months. This transient T-cell suppression was unexpected because encapsulated cell viability was already compromised by 10 days. The influence of Th1/2 bias did not explain the observed suppression. Cells inside capsules elicited a consistent Th2 response, whereas cells outside capsules elicited a mixed response, and skin xenografts showed an initial Th2 response that became mixed by 2 months. CONCLUSIONS: Encapsulation does not prevent host immune responses, but the inflammatory response to the implanted biomaterials or xenogeneic cells may be responsible both for encapsulated cell death and transient T-cell suppression.

Animals↗

PubMed2004

On the origins of adaptive immunity: innate immune receptors join the tale.

Among members of the Ig superfamily (IgSF), antigen receptors have the unique capacity to rearrange their variable domains, thereby creating an extensive repertoire for antigen recognition. It is assumed that antigen receptors evolved from a non-rearranging IgSF member by insertion of a transposable element. Although the nature of this predecessor is unknown, two multigene families of innate immune receptors that bear a close structural resemblance to antigen receptor chains have been identified in mammals and bony fish, respectively: signal-regulatory proteins (SIRPs) and novel immune-type receptors (NITRs). Members of both families encode V-set Ig domains with a typical antigen receptor-like joining (J) motif and possess the potential to signal through immunoreceptor tyrosine-based inhibition motifs (ITIMs) or immunoreceptor tyrosine-based activation motifs (ITAMs). By analogy to the T-cell receptor (TCR) and certain innate receptors [e.g. killer cell inhibitory receptors (KIRs)] that recognize MHC molecules, SIRP members regulate immune function by interaction with broadly expressed 'self' ligands. We propose the existence of an evolutionary and functional link between innate and adaptive immune receptors that sheds light on the nature of the antigen receptor predecessor(s).

Amino Acid Sequence↗

PubMed2003

Evasion of innate and adaptive immunity by flaviviruses.

After a virus infects an animal, antiviral responses are generated that attempt to prevent dissemination. Interferons, antibody, complement, T and natural killer cells all contribute to the control and eradication of viral infections. Most flaviviruses, with the exception of some of the encephalitic viruses, cause acute disease and do not establish persistent infection. The outcome of flavivirus infection in an animal is determined by a balance between the speed of viral replication and spread, and the immune system response. Although many of the mechanistic details require further elucidation, flaviviruses have evolved specific tactics to evade the innate and adaptive immune response. A more thorough understanding of these principles could lead to improved models for viral pathogenesis and to strategies for the development of novel antiviral agents.

Animals↗

PubMed2006

Innate and adaptive immune responses of the central nervous system.

The central nervous system (CNS) is an immunologically specialized organ. The blood-brain barrier regulates the passage of molecules and cells into the CNS. Robust immune responses occur in the CNS even though there is normally an absence of MHC molecules, lack of normal lymphatic drainage, and reduced immune surveillance. This review discusses the immunological elements of the healthy CNS and the pattern of responses that evolve during innate and adaptive immunity in this organ. We also discuss the contribution of astrocytes, cerebrovascular endothelial cells, microglia, macrophages, and dendritic cells to the integrity and pathology of the CNS during CD4+ T-cell autoimmune responses directed against neuroantigens.

Animals↗

PubMed2006

Toxoplasma gondii infection reveals a novel regulatory role for galectin-3 in the interface of innate and adaptive immunity.

In attempts to investigate the role of galectin-3 in innate immunity, we studied galectin-3-deficient (gal3-/-) mice with regard to their response to Toxoplasma gondii infection, which is characterized by inflammation in affected organs, Th-1-polarized immune response, and accumulation of cysts in the central nervous system. In wild-type (gal3+/+) mice, infected orally, galectin-3 was highly expressed in the leukocytes infiltrating the intestines, liver, lungs, and brain. Compared with gal3+/+, infected gal3-/- mice developed reduced inflammatory response in all of these organs but the lungs. Brain of gal3-/- mice displayed a significantly reduced number of infiltrating monocytes/macrophages and CD8+ cells and a higher parasite burden. Furthermore, gal3-/- mice mounted a higher Th1-polarized response and had comparable survival rates on peroral T. gondii infection, even though they were more susceptible to intraperitoneal infection. Interestingly, splenic cells and purified CD11c+ dendritic cells from gal3-/- mice produced higher amounts of interleukin-12 than cells from gal3+/+ mice, possibly explaining the higher Th1 response verified in the gal3-/- mice. We conclude that galectin-3 exerts an important role in innate immunity, including not only a pro-inflammatory effect but also a regulatory role on dendritic cells, capable of interfering in the adaptive immune response.

Animals↗

PubMed2003

Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions.

BACKGROUND: Antigen-presenting cells (APCs) such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation in the course of adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Nicotine has been shown to increase the growth of atherosclerotic lesions. Therefore, we investigated whether nicotine can stimulate APCs and their T cell-stimulatory capacity using human monocyte-derived DCs and murine bone marrow-derived DCs as APCs. METHODS AND RESULTS: Nicotine dose-dependently (10(-8) to 10(-4) mol/L) induced DC expression of costimulatory molecules (ie, CD86, CD40), MHC class II, and adhesion molecules (ie, LFA-1, CD54). Moreover, nicotine induced a 7.0-fold increase in secretion of the proinflammatory T(H)1 cytokine interleukin-12 by human DCs. These effects were abrogated by the nicotinic receptor antagonist alpha-bungarotoxin and mecamylamine, respectively. The effects of nicotine were mediated in part by the phosphorylation of the PI3 kinase downstream target Akt and the mitogen-activated kinases ERK and p38 MAPK. Nicotine-stimulated APCs had a greater capacity to stimulate T-cell proliferation and cytokine secretion, as documented by mixed lymphocyte reactions and ovalbumin-specific assays with ovalbumin-transgenic DO10.11 mice. In a murine model of atherosclerosis, nicotine significantly enhanced the recruitment of DCs to atherosclerotic lesions in vivo. CONCLUSIONS: Nicotine activates DCs and augments their capacity to stimulate T-cell proliferation and cytokine secretion. These effects of nicotine may contribute to its influence on the progression of atherosclerotic lesions.

Animals↗

PubMed2006

[Crosstalk between innate and adaptive immunity].

Most of microorganisms are detected and destroyed within hours by innate immunity which does not generate lasting protective immunity. Innate immunity is mainly mediated by macrophages, dendritic cells and NK cells. Adaptive response is mediated by antigen-specific lymphocytes, which generate specific immunological memory, providing long-lasting protection. Th1 cells produce interferon (IFN)-gamma which mediate cell-mediate immunity, while Th2 cells help B cell to produce antibody via IL-4, 5, 6 production. Tr cells producing IL-10 are responsible for termination of excessive immune inflammations. IFN are divided into two main classes: type I IFN such as IFN-alpha, beta and type II IFN (IFN -gamma), both of which serve not only to bridge the gap between innate and adaptive immunity but also to shape subsequent development of adaptive immunity.

Animals↗

PubMed2003

Innate inhibition of adaptive immunity: Mycobacterium tuberculosis-induced IL-6 inhibits macrophage responses to IFN-gamma.

In humans and in mice, control of the intracellular pathogen, Mycobacterium tuberculosis (Mtb), requires IFN-gamma. Although the adaptive immune response results in production of substantial amounts of IFN-gamma in response to Mtb, the immune response is unable to eradicate the infection in most cases. We have previously reported evidence that Mtb inhibits macrophage responses to IFN-gamma, suggesting that this may limit the ability of IFN-gamma to stimulate macrophages to kill Mtb. We have also observed that uninfected macrophages, adjacent to infected macrophages in culture, exhibit decreased responses to IFN-gamma. Here we report that IL-6 secreted by Mtb-infected macrophages inhibits the responses of uninfected macrophages to IFN-gamma. IL-6 selectively inhibits a subset of IFN-gamma-responsive genes at the level of transcriptional activation without inhibiting activation or function of STAT1. Inhibition of macrophage responses to IFN-gamma by IL-6 requires new protein synthesis, but this effect is not attributable to suppressor of cytokine signaling 1 or 3. These results reveal a novel function for IL-6 and indicate that IL-6 secreted by Mtb-infected macrophages may contribute to the inability of the cellular immune response to eradicate infection.

Animals↗

PubMed2000

A mechanism for the impaired IFN-gamma production in C-C chemokine receptor 2 (CCR2) knockout mice: role of CCR2 in linking the innate and adaptive immune responses.

We have recently shown that mice with a targeted disruption of CCR2, the receptor for monocyte chemoattractant protein-1, have markedly impaired recruitment of macrophages to sites of inflammation. An unexpected finding in the CCR2(-/-) mice was a dramatic decrease in the production of IFN-gamma after challenge with purified protein derivative of Mycobacterium bovis. In this study, we have investigated the mechanism of this cytokine production defect. In vitro, direct activation of splenocytes with CD3/CD28 Abs failed to reveal any differences in IFN-gamma production between CCR2(+/+) and CCR2(-/-) mice. However, after immunization, the number of Ag-specific, IFN-gamma-producing cells in the draining lymph nodes was decreased by 70% in the CCR2(-/-) mice, suggesting an in vivo trafficking defect. Direct measurement of cell trafficking with fluorescently labeled CFA revealed a marked decrease in the number of monocytes/macrophages migrating to the site of immunization and to the draining lymph nodes in the CCR2(-/-) mice. The data suggest that impaired trafficking of APCs in the CCR2(-/-) mice contributes to the defect in IFN-gamma production. These data support the idea that CCR2-positive monocytes/macrophages are critical in linking the innate and adaptive immune responses.

Adaptation, Physiological↗

PubMed2003

Interleukin-12 and the regulation of innate resistance and adaptive immunity.

Interleukin-12 (IL-12) is a heterodimeric pro-inflammatory cytokine that induces the production of interferon-gamma (IFN-gamma), favours the differentiation of T helper 1 (T(H)1) cells and forms a link between innate resistance and adaptive immunity. Dendritic cells (DCs) and phagocytes produce IL-12 in response to pathogens during infection. Production of IL-12 is dependent on differential mechanisms of regulation of expression of the genes encoding IL-12, patterns of Toll-like receptor (TLR) expression and cross-regulation between the different DC subsets, involving cytokines such as IL-10 and type I IFN. Recent data, however, argue against an absolute requirement for IL-12 for T(H)1 responses. Our understanding of the relative roles of IL-12 and other factors in T(H)1-type maturation of both CD4+ and CD8+ T cells is discussed here, including the participation in this process of IL-23 and IL-27, two recently discovered members of the new family of heterodimeric cytokines.

Adaptation, Physiological↗

PubMed1998

Regulation of adaptive immunity by natural killer cells.

Natural killer (NK) cells are well recognized as cytolytic effector cells of the innate immune system. In the past several years, the structure and function of NK cell receptors for the major histocompatibility complex (MHC) class I molecules and other ligands have been the subject of extensive studies. These studies. These studies have focused largely on the mechanisms of target cell recognition for lysis. Another aspect of NK cell function that seems to be underappreciated is their role in immune regulation. Since NK cells produce a number of immunologically relevant cytokines, it has been suggested that these cells may modulate the development of the adaptive immune response. But, is it the only mechanism by which NK cells interact with cells involved in the induction of antigen-specific responses? This article reviews some older and more recent studies and attempts to place NK cells in the context of potent immune regulators of T cell responses.

Animals↗

PubMed2002

Links between innate and adaptive immunity via type I interferon.

Type I interferon (IFN-alpha/beta) is expressed rapidly following exposure to a wide variety of infectious agents and plays a key role in innate control of virus replication. Recent studies have demonstrated that dendritic cells both produce IFN-alpha/beta and undergo maturation in response to IFN-alpha/beta. Moreover, IFN-alpha/beta has been shown to potently enhance immune responses in vivo through the stimulation of dendritic cells. These findings indicate that IFN-alpha/beta serves as a signal linking innate and adaptive immunity.

Adjuvants, Immunologic↗

PubMed2005

Phagocytosis: the convoluted way from nutrition to adaptive immunity.

Phagocytosis, the process by which cells internalize large particulate materials from their milieu and sequester them in phagosomes, plays a role in a variety of cell functions ranging from nutrition in ameba to innate and adaptive immunity in mammals. Recent findings revealed unexpected characteristics of phagosomes, highlighting how this complex organelle may have evolved, from Dictyostelium to human, to become a key player in our ability to mount an efficient immune response against a variety of intracellular pathogens.

Animals↗

PubMed2000

The role of adaptive immunity in atherosclerosis.

Atherosclerosis is an inflammatory disease induced by a lipid metabolic disturbance at sites of hemodynamic strain in the vasculature. Studies in both man and experimental animal models show an involvement of innate and adaptive immune mechanisms in the disease process. Our recent studies in apoE-knockout mice show that the level of hypercholesterolemia affects the functional properties of the immune response. Modulating immune activity by injections of polyclonal immunoglobulins inhibits disease progression, suggesting that immunomodulation may be useful to treat atherosclerosis. Analysis of T cell receptor (TCR) mRNA in atherosclerotic lesions shows expansions of T cells expressing TCR-V beta 6, a receptor type that is also expressed by T cells recognizing oxidized low density lipoprotein (oxLDL). This suggests that oxLDL is an autoantigen that induces strong, local T cell responses in the plaque. Further characterization of this and other candidate antigens, such as heat shock proteins and macromolecular components of Chlamydia pneumoniae, may provide important information on which specific interference with the disease process could be based.

Animals↗

PubMed2006

Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+ cells.

Peripheral cellular immunity was recently shown to play a critical role in brain plasticity and performance. The antigenic specificity of the participating T cells, however, was not investigated, and nor was their relevance to psychological stress. Here we show, using a mouse model, that adaptive immunity mitigates maladaptation to the acute psychological stress known to trigger abnormal behaviors reminiscent of human post-traumatic stress disorder. Assessment of behavioral adaptation (measured by the acoustic startle response and avoidance behavior) in mice after their exposure to predator odor revealed that maladaptation was several times more prevalent in T cell-deficient mice than in their wild-type counterparts. A single population of T cells reactive to central nervous system (CNS)-associated self-protein was sufficient to endow immune-deficient mice with the ability to withstand the psychological stress. Naturally occurring CD4+CD25+ regulatory T cells were found to suppress this endogenous anti-stress attribute. These findings suggest that T cells specific to abundantly expressed CNS antigens are responsible for brain tissue homeostasis and help the individual to cope with stressful life episodes. They might also point the way to development of immune-based therapies for mental disorders, based either on up-regulation of T cells that partially cross-react with self-antigens or on weakening of the activity of regulatory T cells.

Adaptation, Physiological↗

PubMed2005

Glassy dynamics in the adaptive immune response prevents autoimmune disease.

The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system's search for antibodies, a balance has evolved between binding affinity and specificity.

Animals↗

PubMed2006

Glycolipid alpha-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice.

alpha-Galactosylceramide (alpha-GalCer) is the prototype compound for studying the presentation of glycolipids on CD1d molecules to natural killer T (NKT) lymphocytes. A single i.v. dose of glycolipid triggers a cascade of events involving the production of several cytokines over the course of a day, a short-lived activation of NKT and natural killer (NK) cells, and a more prolonged adaptive T cell immune response if certain antigens are given together with alpha-GalCer. We find that a recently described analogue, alpha-C-galactosylceramide (alpha-C-GalCer), more potently induces these innate and adaptive immune responses in mice. alpha-C-GalCer acts as a more effective trigger for IL-12 and IFN-gamma production, although it minimally elicits IL-4 and TNF-alpha release into the serum. Also, alpha-C-GalCer better mobilizes NKT and natural killer cells to resist B16 melanoma. To help understand these effects, we find that alpha-C-GalCer binds more stably to dendritic cells than alpha-GalCer and that dendritic cells loaded with alpha-C-GalCer induce larger and more long lasting NKT cell responses in vivo. When glycolipid is targeted to dendritic cells in spleen together with antigens in dying cells, such as irradiated tumor cells, alpha-C-GalCer is active as an adjuvant for T cell-mediated immunity at lower doses, just 20 ng per mouse, where it is also able to up-regulate the required CD40L costimulatory molecule on NKT cells. Therefore, alpha-C-GalCer represents a glycolipid that binds more stably to dendritic cells and acts as a more effective link between innate and adaptive immunity in vivo.

Animals↗

PubMed2004

Type I interferon as a link between innate and adaptive immunity through dendritic cell stimulation.

Type I interferon (IFN-alpha/beta) is expressed rapidly after infection and plays a key role in innate defense against pathogens. Recent studies have shown that a connection exists between IFN-alpha/beta and antigen-presenting dendritic cells (DCs) at two levels. Firstly, a specific DC precursor, the plasmacytoid pre-DC (p-preDC), was identified as a cell type able to secrete very high amounts of IFN-alpha/beta following stimulation with infectious agents. Secondly, IFN-alpha/beta has been shown to act as a differentiation/maturation factor for DCs. These findings will be discussed in association with evidence indicating that IFN-alpha/beta can enhance and modulate immune responses in vivo. Taken together, the available data suggest that IFN-alpha/beta serves as a link between the innate response to infection and the adaptive immune response.

Animals↗