SEARCH · PubMed Health

Results for “Adaptive Immunity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources

PubMed1998

Identification of the mouse IgG3 receptor: implications for antibody effector function at the interface between innate and adaptive immunity.

Mouse IgG3 appears early in immune responses independently of T cell help and, as such, is an early effector molecule of the immune system. Yet, a specific IgG3 cellular receptor remains undefined. In transfection experiments, mouse Fc gammaRI was clearly able to bind immune complexes of IgG3, whereas mouse Fc gammaRII could not. Furthermore, macrophages from mice expressing Fc gammaRII and Fc gammaRIII but lacking Fc gammaRI were unable to phagocytose IgG3 immune complexes, thus identifying mouse Fc gammaRI as the sole receptor for IgG3 immune complexes. Competition studies demonstrated that monomeric mouse IgG3 could inhibit IgG2a binding to mouse Fc gammaRI with an ID50 approximately 10(-7) M (fivefold lower than IgG2a). The identification of mouse Fc gammaRI as the IgG3 receptor establishes Fc gammaRI as a participant in events at the interface between innate and adaptive immunity, implying a greater role for this receptor in the development of normal and pathologic immune responses than previously recognized.

Animals↗

PubMed2005

Plasmacytoid dendritic cells act as the most competent cell type in linking antiviral innate and adaptive immune responses.

Appropriate in vivo control of plasmacytoid dendritic cell (pDC) recruitment and activation is a fundamental requirement for defense against viral infection. During this process, a pivotal event that influences the outcome of viral infection is the production of high levels of type I interferon by pDCs. In particular, recent research findings showed that pDCs not only shape the nature of innate resistance, but are also responsible for the successful transition from innate to adaptive immunity for viral resistance. In addition, pDCs can differentiate into antigen presenting cells that may regulate tolerance to a given pathogen. Importantly, in a series of recent clinical studies, pDCs appeared to be defective in number and function in conditions of chronic viral diseases such as infected with HIV-1, HBV or HCV. pDC-associated clinical antiviral therapy is also emerging. This review describes research findings examining the functional and antiviral properties of in vivo pDC plasticity.

Animals↗

PubMed2006

Regulation of innate and adaptive immune responses by the related cytokines IL-12, IL-23, and IL-27.

The functional characterization and subsequent purification of T cell growth factor/interleukin (IL)-2 in the early 1980s established this secreted protein as a key mediator of immune cell activation and provided the prototype that enabled the discovery of numerous cytokines over the ensuing two decades. While soluble immunoregulatory factors were initially identified functionally as biological activities present in the culture supernatants of activated lymphocytes/monocytes, this methodology shifted radically following the completion of the human genome sequence. Computer-generated structural modeling algorithms have replaced functional assays and biochemical purification as the initial means of discovering new cytokines. To date, a total of 31 interleukins, as well as over a dozen other related hematopoietic factors, have been identified. These cytokines and their receptors may be grouped on the basis of structural homologies as well as by shared ligand and receptor subunits. The challenge now at hand is to define the biological functions of the newly identified cytokines and to elucidate the common and divergent roles of related family members. This point is well illustrated by the IL-12/IL-23/IL-27 family, whose members share ligand and receptor subunits and play somewhat overlapping roles in innate and adaptive immune responses. These three cytokines are not entirely redundant, as they may preferentially activate naïve or memory T cells, induce discrete T cell cytokine profiles, contribute to distinct stages of host immune responses to infectious agents, and differentially promote autoimmunity. Further elucidation of the unique functions of the IL-12 family members may lead to improved immunodiagnostics and therapies.

Adaptation, Physiological↗

PubMed2004

Heterogeneity of TLR-induced responses in dendritic cells: from innate to adaptive immunity.

Toll-like receptors (TLR) mediate recognition of several microbial products. Accumulating evidence indicates that TLR are capable of inducing distinct responses in dendritic cells and other antigen-presenting cells, and can direct T-helper cell differentiation in opposing directions. The generation of such varied responses is achieved through the selective utilization of adaptor molecules that link TLR to distinct signal transduction pathways. The ability of TLR to activate and guide innate and adaptive immunity has the potential to be exploited for practical application that may lead to the development of more successful immunotherapies and vaccination strategies. A review of recent literature, unpublished observations, and future challenges is presented here.

Dendritic Cells↗

PubMed2004

A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the APC that functions to enhance adaptive immune responses against CD91-targeted antigens.

Dendritic cells (DC) and other APCs rely on a number of specialized receptors to facilitate the uptake and intracellular accumulation of Ags. In this capacity, APCs use receptor-mediated endocytosis to enhance Ag presentation and the stimulation of Ag-specific T cells. Studies have demonstrated that the targeted delivery of Ags in vivo to CD91/the low-density lipoprotein receptor-related protein (CD91/LRP) induces enhanced activation of the adaptive immune system. However, the APC that mediates these augmented, Ag-specific responses remains to be characterized. In this study, we show that a subset of CD11c(+) lineage-negative (lin(-)) DC expresses the scavenger receptor CD91/LRP and that these rare APC are primarily responsible for the T cell activation that occurs following CD91/LRP-mediated Ag uptake in whole blood. The targeting of Ags to CD91/LRP results in enhanced receptor-mediated uptake within both lin(-) DCs and monocytes, and this uptake results in markedly increased T cell activation. Finally, purified cellular populations were used to demonstrate that CD11c(+) lin(-) DC, but not monocytes, are capable of stimulating T cell activation following CD91/LRP-mediated Ag uptake. Therefore, CD11c(+) lin(-) DC use CD91/LRP to facilitate the uptake and subsequent presentation of an array of Ags complexed within the CD91/LRP ligand, the activated form of alpha2-macroglobulin (alpha2M*).

Antigen Presentation↗

PubMed2000

Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity.

The immunological consequences of apoptosis have been hotly debated. Apoptosis was originally described as a set of cellular morphological changes that occur in the absence of inflammation but the term has been redefined on the basis of a set of conserved molecular events that include the activation of caspases. Though the apoptosis occurring during normal development is immunologically bland or even tolerizing, the apoptotic death after viral infection or after the ligation of Fas can trigger powerful innate and adaptive immune responses. The molecular machinery at the nexus of apoptosis and inflammation includes caspase-1 --an activator of IL-1beta and IL-18 - as well as the double-stranded-RNA-dependent protein kinase pathway and RNaseL pathway, which are key effectors of antiviral immunity. New proapoptotic vaccines induce immune responses that may be able to prevent or treat infectious disease and cancer.

Animals↗

PubMed2002

Roles of heat-shock proteins in innate and adaptive immunity.

Heat-shock proteins (HSPs) are the most abundant and ubiquitous soluble intracellular proteins. In single-cell organisms, invertebrates and vertebrates, they perform a multitude of housekeeping functions that are essential for cellular survival. In higher vertebrates, their ability to interact with a wide range of proteins and peptides--a property that is shared by major histocompatibility complex molecules--has made the HSPs uniquely suited to an important role in organismal survival by their participation in innate and adaptive immune responses. The immunological properties of HSPs enable them to be used in new immunotherapies of cancers and infections.

Animals↗

PubMed2005

gammadelta T cells link innate and adaptive immune responses.

While most T cells use a CD3-associated alpha/beta T cell receptor as antigen recognition structure, a second population of T cells expresses the alternative gamma/delta T cell receptor. gamma/delta T cells are a minor population in the peripheral blood but constitute a major population among intestinal intraepithelial lymphocytes. Most gamma/delta T cells recognize ligands which are fundamentally different from the short peptides that are seen by alpha/beta T cells in the context of MHC class I or class II molecules. Thus, human Vdelta2 T cells recognize small bacterial phosphoantigens, alkylamines and synthetic aminobisphosphonates, whereas Vdelta1 T cells recognize stress-inducible MHC-related molecules MICA/B as well as several other ligands. At the functional level, gamma/delta T cells rapidly produce a variety of cytokines and usually exert potent cytotoxic activity, also towards many tumor cells. In this article, we discuss the role of gamma/delta T cells as a bridge between the innate and the adaptive immune system, based on the interpretation that gamma/delta T cells use their T cell receptor as a pattern recognition receptor. Our increasing understanding of the ligand recognition and activation mechanisms of gamma/delta T cells also opens new perspectives for the development of gamma/delta T cell-based immunotherapies.

Adaptation, Physiological↗

PubMed2004

Chemokine receptor 5 is dispensable for innate and adaptive immune responses to Listeria monocytogenes infection.

Chemokine receptor 5 (CCR5) binds macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, RANTES, and members of the monocyte chemotactic protein family and is also a receptor for human immunodeficiency virus (HIV). CCR5 ligands can suppress HIV-1 entry into cells. In humans, homozygous mutations of the ccr5 gene confer resistance to HIV-1 infection. The role of CCR5 in defense against microbial infection is unclear. In this study we examined the innate and adaptive immune responses of CCR5-deficient mice to the intracellular bacterial pathogen Listeria monocytogenes. We found that migration of monocytic cells, formation of L. monocytogenes-containing lesions, and bacterial clearance occurred normally in the spleens and livers of CCR5-deficient animals. Activation of macrophages and dendritic cells during the first 3 days postinfection was normal in the absence of CCR5, as demonstrated by intact expression of inducible nitric oxide synthase (iNOS) and production of the cytokines tumor necrosis factor alpha, gamma interferon, and interleukin-12. Priming of L. monocytogenes-specific CD8 T cells also occured independently of CCR5 expression. Previously immunized, CCR5-deficient animals mounted normal secondary CD8 T-cell responses and cleared bacteria from infected organs similarly to wild-type controls, suggesting that CCR5 is dispensable for migration and activation of memory CD8 T cells. Our data indicate that CCR5-mediated chemotaxis is not required for defense against infection with L. monocytogenes.

Animals↗

PubMed2002

Memorizing innate instructions requires a sufficiently specific adaptive immune system.

During its primary encounter with a pathogen, the immune system has to decide which type of immune response is most appropriate. Based on signals from the innate immune system and the immunological context in which the pathogen is presented, responding lymphocytes will adopt a particular phenotype, e.g. secrete a particular profile of cytokines. Once stimulated, lymphocytes store the appropriate type of response by differentiating from a naive to a memory phenotype. This allows the appropriate type of immune reaction to be regenerated upon re-stimulation of those memory clones. We developed a computer simulation model in which cross-reacting effector/memory clones contribute to the immunological context of pathogens. If a pathogen is recognized by both naive clones and pre-existing effector/memory clones, the naive lymphocytes adopt the effector mechanism of the memory clone. The adaptive immune system thereby stores immunological decisions and somatically learns to induce the right type of immune response to pathogens sharing epitopes. The influence of effector/memory lymphocytes may be detrimental when they cross-react to new pathogens that require a different kind of immune response. Here, we show that the immune system needs to be sufficiently specific to avoid such mistakes and to profit from the information that is stored in effector/memory lymphocytes. Repertoire diversity is required to reconcile this specificity with reactivity against many pathogens.

Aged↗

PubMed2001

The role of complement in inflammation and adaptive immunity.

Major advances in our understanding of the immunobiology of complement were made within the past 5 years primarily due to the development of gene-targeting technology. New strains of mice bearing specific deficiencies in serum complement proteins or their receptors were developed using this approach. Characterization of these mice has provided new and exciting insights into the biology of the complement system. In this review, we discuss recent results on two important aspects of the complement system, i) host protection and inflammation, and ii) regulation of B lymphocytes of adaptive immunity. While these two roles appear distinct, they are linked. We discuss how natural antibody and classical pathway complement work together in host protection against bacterial infection on the one hand but, on the other, they co-operate to induce inflammation as observed in reperfusion injury. Significantly, the lymphocytes that produce natural antibody, the B-1 lymphocytes, are regulated in part by the complement system.

Animals↗

PubMed2005

Phagocytosis: at the crossroads of innate and adaptive immunity.

Phagocytosis, the process by which cells engulf large particles, requires a substantial contribution of membranes. Recent studies have revealed that intracellular compartments, including endocytic organelles and the endoplasmic reticulum (ER), can engage in fusion events with the plasma membrane at the sites of nascent phagosomes. The finding that ER proteins are delivered to phagosomes, where degraded peptides are loaded onto major histocompatibility complex (MHC) class II molecules, has significantly enhanced our understanding of the immune functions associated with these organelles. Although it is well known that pathogens are killed in phagosomes, the contribution of ER proteins to phagosomes has provided a novel pathway for the loading of exogenous peptides onto MHC class I molecules, a process known as cross-presentation. Thus, phagocytosis has evolved from a nutritional function in unicellular organisms to play key roles in both innate and adaptive immunity in vertebrates.

Animals↗

PubMed1998

Natural killer and T cells of innate and adaptive immunity: lymphoid compartments with different requirements for common gamma chain-dependent cytokines.

A group of cytokines, including interleukin-2, -4, -7, -9 and -15, are related through the usage of a shared receptor subunit, the common cytokine receptor gamma chain, gamma c. gamma c-dependent cytokines critically affect the development and maintenance of the lymphoid system. This review will highlight our current knowledge on the gamma c-dependent cytokine network and on the non-redundant roles that these cytokines play in the development and homeostasis of T and natural killer cells involved in innate and adaptive immunity.

Animals↗

PubMed2005

RNA interference: more than a research tool in the vertebrates' adaptive immunity.

In recent years, RNA silencing, usage of small double stranded RNAs of approximately 21 - 25 base pairs to regulate gene expression, has emerged as a powerful research tool to dissect the role of unknown host cell factors in this 'post-genomic' era. While the molecular mechanism of RNA silencing has not been precisely defined, the revelation that small RNA molecules are equipped with this regulatory function has transformed our thinking on the role of RNA in many facets of biology, illustrating the complexity and the dynamic interplay of cellular regulation. As plants and invertebrates lack the protein-based adaptive immunity that are found in jawed vertebrates, the ability of RNA silencing to shut down gene expression in a sequence-specific manner offers an explanation of how these organisms counteract pathogen invasions into host cells. It has been proposed that this type of RNA-mediated defence mechanism is an ancient form of immunity to offset the transgene-, transposon- and virus-mediated attack. However, whether 1) RNA silencing is a natural immune response in vertebrates to suppress pathogen invasion; or 2) vertebrate cells have evolved to counteract invasion in a 'RNA silencing' independent manner remains to be determined. A number of recent reports have provided tantalizing clues to support the view that RNA silencing functions as a physiological response to regulate viral infection in vertebrate cells. Amongst these, two manuscripts that are published in recent issues of Science and Immunity, respectively, have provided some of the first direct evidences that RNA silencing is an important component of antiviral defence in vertebrate cells. In addition to demonstrating RNA silencing to be critical to vertebrate innate immunity, these studies also highlight the potential of utilising virus-infection systems as models to refine our understanding on the molecular determinants of RNA silencing in vertebrate cells.

Animals↗

PubMed2004

HIV-1 gp120 binding to dendritic cell receptors mobilize the virus to the lymph nodes, but the induced IL-4 synthesis by FcepsilonRI+ hematopoietic cells damages the adaptive immunity--a review, hypothesis, and implications.

HIV-1 is equipped with the envelope gp160 glycoprotein for interaction with Langerhans cells (LCs) and dendritic cells (DCs), the members of the innate immune system, which confront the virus at the portal of virus entry in the human body. These cells are equipped with receptors by which they bind and endocytose the virus. The gp120 glycoprotein is used for binding to CD4 receptor and CCR5 co-receptor of T helper 2 (Th2) cells and the virions shed gp120 is able to induce FcepsilonRI+ hematopoietic cells to produce IL-4, which inactivate the host adaptive immune response. The properties of gp120s various functional domains are analyzed together with the regulatory viral proteins, which are involved in the damage to T and B cells during HIV-1 replication. The interaction of HIV-1 virions through their gp120 with LCs and DCs at the portal of virus entry will be discussed. A hypothesis will be presented that the understanding of the role of the different functional domains of gp120 in the life cycle of the virus and during AIDS will help in the design of approaches to prevent and abrogate HIV-1 infection and AIDS.

CD4 Antigens↗

PubMed2007

Shigella's ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?

Shigella, a Gram-negative invasive enteropathogenic bacterium, causes the rupture, invasion and inflammatory destruction of the human colonic epithelium. This complex and aggressive process accounts for the symptoms of bacillary dysentery. The so-called invasive phenotype of Shigella is linked to expression of a type III secretory system (TTSS) injecting effector proteins into the epithelial cell membrane and cytoplasm, thereby inducing local but massive changes in the cell cytoskeleton that lead to bacterial internalization into non-phagocytic intestinal epithelial cells. The invasive phenotype also accounts for the potent pro-inflammatory capacity of the microorganism. Recent evidence indicates that a large part of the mucosal inflammation is initiated by intracellular sensing of bacterial peptidoglycan by cytosolic leucine-rich receptors of the NOD family, particularly NOD1, in epithelial cells. This causes activation of the nuclear factor kappa B and c-JunNH(2)-terminal-kinase pathways, with interleukin-8 appearing as a major chemokine mediating the inflammatory burst that is dominated by massive infiltration of the mucosa by polymorphonuclear leukocytes. Not unexpectedly, this inflammatory response, which is likely to be very harmful for the invading microbe, is regulated by the bacterium itself. A group of proteins encoded by Shigella, which are injected into target cells by the TTSS, has been recently recognized as a family of potent regulators of the innate immune response. These enzymes target key cellular functions that are essential in triggering the inflammatory response, and more generally defense responses of the intestinal mucosa. This review focuses on the mechanisms employed by Shigella to manipulate the host innate response in order to escape early bacterial killing, thus ensuring establishment of its infectious process. The escape strategies, the possible direct effect of Shigella on B and T lymphocytes, their impact on the development of adaptive immunity, and how they may help explain the limited protection induced by natural infection are discussed.

Animals↗

PubMed2003

Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone.

Women mount more vigorous antibody- and cell-mediated immune responses following either infection or vaccination than men. The incidence of most autoimmune diseases is also higher in women than in men; however, during pregnancy many autoimmune diseases go into remission, only to flare again in the early post-partum period. Successful pregnancy requires that the female immune system tolerate the presence of a semi-allogeneic graft for 9 months. Oral contraceptive use can increase susceptibility to certain genital tract infections and sexually transmitted diseases in women. Moreover, treatment of mice and rats with female sex hormones is required to establish animal models of genital tract Chlamydia, Neisseria and Mycoplasma infection. This review describes what is currently known about the effects of the female sex hormones oestradiol and progesterone on innate and adaptive immune responses in order to provide a framework for understanding these sex differences. Data from both human and animal studies will be reviewed.

Autoimmunity↗

PubMed2003

Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.

Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.

Antigen Presentation↗