SEARCH · PubMed Health

Results for “Immunity, Innate”

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 163 records · Page 9Linked to original sources

PubMed1999

The immune system in the elderly: III. Innate immunity.

The capability to cope with infectious agents and cancer cells resides not only in adaptive immune responses against specific antigens, mediated by T and B lymphocytes clonally distributed, but also in natural immune reactions. These innate defence mechanisms include chemotaxis, phagocytosis, natural cytotoxicity, cell interactions, and soluble mediators or cytokines. However, specific and natural immune mechanisms are always closely linked and interconnected, providing the primary defense against pathogens. The Authors discuss the main changes observed with advancing age in granulocytes and natural killer (NK) cell activity, in the expression and function of adhesion molecules, and in the pattern of cytokine production. Since phagocytic function is the primary mechanism through which the immune system eliminates most extracellular pathogenic microorganisms, analysis of this function is of clinical importance. Neutrophils from aged subjects often exhibit a diminished phagocytic capacity, as well as a depressed respiratory burst, notwithstanding an activated state. The activity of NK cells during aging has been studied extensively and different results have been reported. The most consistent data indicate an increase in cells with high NK activity with advancing age. Cells from healthy centenarians can efficiently kill target cells. This finding seems to suggest that innate immunity and in particular NK cell activity, is not heavily deteriorated with age. Conversely, a low NK activity is a predictor of impending morbidity. Immunosenescence is associated with increased expression of several cell adhesion molecules (CAM) resulting in an augmented capacity to adhere. Finally, also the cytokine network, responsible for differentiation, proliferation, and survival of lymphoid cells, undergoes complex changes with age. The main findings are a Th1 to Th2 cytokine production shift and an increased production of proinflammatory cytokines, which could explain many aspects of age-associated pathological events, such as atherosclerosis and osteoporosis.

Aged↗

PubMed2003

[Role of the innate immune response in the brain].

There is an innate immune system in the brain. It is inducible in a transient manner from the structures that are devoid of blood brain barrier and thereafter within parenchymal microglia during systemic infection. Transcriptional activation of genes encoding proteins of the innate immunity also takes place in diseases of the central nervous system. This recent discovery raised the hypothesis that inflammation and innate immunity may be involved in the etiology of neurodegenerative disorders. Nevertheless, this system is able to trigger the release of neurotrophic factors and to protect neuronal elements during brain infection and trauma. The innate immune response may play a critical role in protecting neurons and be a possible cause of neurodegeneration. The fate of this newly identified cascade of events is therefore likely to have a determinant impact on the central nervous system during infection and injury.

Blood-Brain Barrier↗

PubMed2006

Innate immunity and inflammation--New frontiers in comparative cardiovascular pathology.

Innate immunity and inflammation play key roles in a wide range of pathology - including heart disease and vasculopathies. Current thinking suggests "damage" rather than "foreignness" as the actual trigger of the immune system, which has caused a dramatic change in how we tend to view the etiopathology of most types of heart disease. The future potential of certain anti-inflammatory therapeutic strategies in addressing heart disease is intriguing. Still, the Janus face of immunity/inflammation cannot be over emphasized as adverse manipulation of these systems may prove ineffectual or worse, damaging. Knowledge on functional characteristics of individual immune mediators is undoubtedly a central theme, but in depth understanding of the multiple biological actions of these molecules, as well as their contextual function, is the corner stone in deciding on potential future targets for pharmacologic manipulation. Animal models of human heart disease are currently being investigated and clinical trials conducted to gain further knowledge in this essential area of cardiovascular research, but the scarcity of cardiovascular research focusing on signaling molecules and pathways of innate immunity is still evident. Genomic and proteomic research in heart disease is going through its formative years, and much is still unknown about the complex pathway dynamics utilized by the innate immune system. This review will provide an overview of the current literature focusing on innate immunity and the heart, and hopefully will spark an interest in further basic as well as clinical research. As more information on cardiovascular immunity becomes available, this will provide a better understanding and thus act as the foundation for potential development of new treatment strategies for treatment of cardiovascular disorders.

Animals↗

PubMed2003

Innate immune response against nonsegmented negative strand RNA viruses.

Innate immune response represents the hallmark of host defense against foreign pathogens, including viruses. Not only does this response combat viruses during initial stages of infection, but it shapes the adaptive immune response as well. This review focuses on this critical host defense mechanism, the innate immune response, in the context of infection by nonsegmented negative strand RNA viruses of the Paramyxoviridae family. We specifically focus on the two critical transcription factors, nuclear factor-kappaB (NF-kappaB) and interferon (IFN) regulatory factor-3 (IRF-3), that play an important role in establishing an innate antiviral state. The antiviral cytokine IFN-alpha/beta (IFN type I) produced following viral infection as a result of activation of NF-kappaB or IRF-3 or both exerts an antiviral state by inducing the Janus kinases/signal transducer and activator (Jak-Stat) pathway. In that context, our review discusses various strategies adopted by these viruses to counteract and evade the antiviral action of IFN I for replicative advantages, especially after modulation of the Jak-Stat antiviral pathway. Understanding this interplay between the innate immune response and viral replication is fundamental to probing into the molecular basis of host-virus interaction.

DNA-Binding Proteins↗

PubMed2004

Mini-review: the role of peptidoglycan recognition in innate immunity.

The importance of peptidoglycan detection in the host innate immune response has long been underestimated. However, the recent identification of proteins involved in the sensing of peptidoglycan in both mammals and Drosophila has revealed that the detection of this microbial motif is key to the defense response. In Drosophila, the peptidoglycan-recognition proteins (PGRP) are the initial sensors of infecting bacteria that then trigger a cascade ultimately leading to the expression of antimicrobial peptides. In mammals, PGRP also exist and although they bind peptidoglycan, the role of these proteins in innate immune responses remains to be clearly defined. In contrast, the Nod proteins (Nod1 and Nod2), which are also involved in peptidoglycan sensing, appear to play a key role in innate immunity against bacteria by triggering host defense responses through the activation of the transcription factor, NF-kappaB. Interestingly, mutations in Nod2 are related to increased susceptibility to Crohn's disease, thereby implicating defective bacterial sensing in the development at this chronic disease. In this review, we will focus on the recent findings concerning mammalian and Drosophila proteins involved in peptidoglycan recognition and the putative role of these proteins in the innate immune defense response.

Animals↗

PubMed2003

Human cord blood leukocyte innate immune responses to defense collagens.

The innate immune system provides critical protection during initial infections before the generation of an appropriate adaptive (antibody or T cell mediated) immune response. These early defense mechanisms may be particularly critical for neonates in whom the adaptive immune system is not fully operational. Pattern recognition molecules target potential pathogens for destruction by the innate immune system, and likely facilitate the initiation of a pathogen-specific immune response. Defense collagens, such as C1q, MBL and SPA, comprise a family of such proteins that, via specific interactions with phagocytic cells, play a role in this first line of defense. To begin to assess the importance of these innate defense mechanisms in neonates, cord blood plasma and leukocytes were isolated, and responses to these components of the innate defense system were assessed. C1q enhanced the phagocytosis of targets suboptimally opsonized with either IgG or complement components, and this enhancement of phagocytosis was blocked by anti-CD93/C1qRP MAb by 57% to 68%. Flow cytometric analysis demonstrated that neonatal monocytes and neutrophils expressed CD93/C1qRP similarly to adult cells, with several-fold greater expression on monocytes than on neutrophils and essentially no expression on lymphocytes. Superoxide production in response to multivalent C1q by neonatal neutrophils was also comparable to adult cells. We also confirm that C1q and MBL are present in neonate circulation. Thus, the data demonstrate that these recognition and effector mechanisms of the innate system are functional in the newborn and similar to that of adult cells.

Adult↗

PubMed2005

Dissecting innate immune responses with the tools of systems biology.

Systems biology strives to derive accurate predictive descriptions of complex systems such as innate immunity. The innate immune system is essential for host defense, yet the resulting inflammatory response must be tightly regulated. Current understanding indicates that this system is controlled by complex regulatory networks, which maintain homoeostasis while accurately distinguishing pathogenic infections from harmless exposures. Recent studies have used high throughput technologies and computational techniques that presage predictive models and will be the foundation of a systems level understanding of innate immunity.

Animals↗

PubMed2003

Innate immunity: sensing the environment and regulating the regulators.

PURPOSE OF REVIEW: Innate immune cells act as sensors for environmental pathogens and key regulators of pathogen-specific T-cell effector responses. The expression of Toll-like receptors is essential for these functions. Innate immunity is a rapidly evolving field. Great progress has been made in the past year in characterizing the signaling pathways downstream of Toll-like receptors, and the role of Toll-like receptors in the regulation of pathogen responses. RECENT FINDINGS: The ability to control the activation of regulatory T cells has emerged as a key function of innate immunity. Regulatory T cells are involved in the induction of tolerance and the prevention of harmful immune pathology, particularly T-cell responses directed against self-antigens. Toll-like receptor-mediated interactions between pathogen-stimulated innate immune cells and regulatory T cells result in the release of suppression by regulatory T cells, thus allowing pathogen-specific responses. However, pathogenic microorganisms may exploit this interaction to evade the host's response. In addition, recent studies raise the possibility that regulatory T cells may express some Toll-like receptor family members, thereby responding directly to pathogens. SUMMARY: A deeper understanding of the complex role of innate immune cells as sensors of the environment and regulators of pathogen responses will probably influence the current models of immune regulation, particularly those centered on the role of the environment in shaping immune responses.

CD4-Positive T-Lymphocytes↗

PubMed2005

Innate immunity: New approaches to understanding its clinical significance.

Immunologists view innate immunity as evolution's ancient host response to infectious agents. Unlike vertebrates, in which antibodies and T-cell subsets rely on somatic mutations, molecular participants of innate immunity are encoded in the genome. Despite its heritage, many of innate immunity's sentinel molecules, intracellular transcriptional controls, and effector molecules participate in the pathogenesis of numerous complex human diseases. Toll-like receptors (TLRs), an important starting point, contact the environment and provide specific sensing for an important component of innate immunity. TLRs, found on macrophages, dendritic cells, and endothelial cells, recognize specific microbial molecular patterns. Beginning with these sentinel molecules, the process leads through intracytoplasmic mediators of transcription control and culminates with an array of host immune responses. Effector molecules include cytokines and the complement system. Polymorphisms within TLR genes might contribute to the pathogenesis of complex diseases. Disease associations linked to single nucleotide polymorphisms are in the early stage of experimental discovery; important clinical insights are emerging. Along these lines, studies of asthma provide an excellent example of how ancient ligand-receptor interactions and TLR polymorphisms provide new understanding of a common disease. New knowledge could facilitate the development of novel therapies.

Asthma↗

PubMed2002

The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice.

The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by antibody-antigen complexes on the bacterial surface and has been considered predominately to be an effector of the adaptive immune response, whereas the alternative and mannose-binding lectin pathways are activated directly by bacterial cell surface components and are considered effectors of the innate immune response. Recently, a role has been suggested for the classical pathway during innate immunity that is activated by natural IgM or components of the acute-phase response bound to bacterial pathogens. However, the functional importance of the classical pathway for innate immunity to S. pneumoniae and other bacterial pathogens, and its relative contribution compared with the alternative and mannose-binding lectin pathways has not been defined. By using strains of mice with genetic deficiencies of complement components and secretory IgM we have investigated the role of each complement pathway and natural IgM for innate immunity to S. pneumoniae. Our results show that the proportion of a population of S. pneumoniae bound by C3 depends mainly on the classical pathway, whereas the intensity of C3 binding depends on the alternative pathway. Furthermore, the classical pathway, partially targeted by the binding of natural IgM to bacteria, is the dominant pathway for activation of the complement system during innate immunity to S. pneumoniae, loss of which results in rapidly progressing septicemia and impaired macrophage activation. These data demonstrate the vital role of the classical pathway for innate immunity to a bacterial pathogen.

Animals↗

PubMed2025

Innate immune sensing and signaling: Co-opted for genome surveillance? Implications for tumorigenesis.

Innate immune signaling is traditionally associated with the response to pathogenic infection. However, emerging evidence suggests that nuclear innate immune sensors and their downstream pathways may also serve as a critical mechanism for genome surveillance. This review explores a model in which DNA sensors such as mouse IFI204 and IFI205 (IFI16 in humans) localize to replication forks, where they detect endogenous aberrant DNA structures and initiate an interferon-stimulated gene (ISG) transcriptional program. A key output of this transcriptional program is ISG15, which we find conjugated to fork-associated proteins and facilitates recruitment of the replication fork protection complex, thereby stabilizing replication forks under physiological conditions. We discuss how nuclear innate immune sensors mediate replication stress sensing and examine the broad consequences of downstream ISG transcription across diverse contexts-including its impact on genome stability and its dual roles in modulating tumor cell behavior and the tumor microenvironment. These findings suggest that the innate immune system, through its nuclear DNA sensing arm, may be evolutionarily co-opted for genome surveillance and may influence tumor initiation and therapy resistance. Understanding how innate immune signaling intersects with replication stress could offer mechanistic insights into tumor development and reveal novel therapeutic targets.

Humans↗

PubMed2005

Immune response in human visceral leishmaniasis: analysis of the correlation between innate immunity cytokine profile and disease outcome.

We investigated the cytokine profile of cells of the innate immune response and its association with active (ACT), asymptomatic (AS) and cured (CUR) human visceral leishmaniasis (VL), as well as noninfected (NI) subjects. The frequency of cytokine-producing cells was determined after short-term in vitro incubation of whole peripheral blood samples with soluble Leishmania antigen (SLA). Our data demonstrated a predominant type 2 cytokine profile in NI and ACT. In NI, we observed an increase of IL-4+ neutrophils, IL-10+ eosinophils besides a decrease of tumour necrosis factor (TNF)-alpha+ eosinophils/monocytes. Yet in ACT, we observed an increase of IL-4+ neutrophils and natural killer (NK) cells and IL-10+ monocytes, a reduced frequency of IL-12+ and IFN-gamma+ eosinophils and lower levels of TNF-alpha+ and IL-12+ monocytes. AS presented a mixed profile, characterized by an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, of IL-12+ eosinophils/monocytes, as well as increase of IL-4+ neutrophils and NK cells and IL-10+ eosinophils/monocytes. In contrast, CUR was characterized by a type 1 response with an increase of IFN-gamma+ neutrophils/eosinophils and NK cells, associated with an increase in IL-12+ monocytes. In conclusion, we show a correlation between innate immune cytokine patterns and clinical status of VL, suggesting that these cells, in addition to other factors, may contribute to the cytokine microenvironment in which Leishmania-specific T cells are primed and to disease outcome.

Adolescent↗

PubMed2006

MyD88 innate immune function in a zebrafish embryo infection model.

Innate immunity signaling mechanisms during vertebrate embryogenesis are largely unknown. To study Toll-like receptor (TLR) signaling function in the zebrafish embryo model, we designed an experimental setup for antisense morpholino knockdown under conditions of bacterial infection. Clearance of Salmonella enterica serovar Typhimurium Ra bacteria was significantly impaired after knockdown of myeloid differentiation factor 88 (MyD88), a common adaptor protein in TLR and interleukin-1 receptor signaling. Thereby, we demonstrate for the first time that the innate immune response of the developing embryo involves MyD88-dependent signaling, which further establishes the zebrafish embryo as a model for the study of vertebrate innate immunity.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Innate immunity: an overview.

Though sometimes portrayed as "new," the science of innate immunity made its start more than 100 years ago. Recent progress has reflected the application of new methods to old problems. In particular, genetic dissection of innate immune pathways has been pursued with great success in model organisms. This has opened the way to an understanding of innate immune sensing. The effector arm of innate immunity has also been tackled, largely though the use of biochemical methods.

Animals↗

PubMed2006

Essential role of MAPK phosphatase-1 in the negative control of innate immune responses.

TLR-induced innate immunity and inflammation are mediated by signaling cascades leading to activation of the MAPK family of Ser/Thr protein kinases, including p38 MAPK, which controls cytokine release during innate and adoptive immune responses. Failure to terminate such inflammatory reactions may lead to detrimental systemic effects, including septic shock and autoimmunity. In this study, we provide genetic evidence of a critical and nonredundant role of MAPK phosphatase (MKP)-1 in the negative control of MAPK-regulated inflammatory reactions in vivo. MKP-1-/- mice are hyperresponsive to low-dose LPS-induced toxicity and exhibit significantly increased serum TNF-alpha, IL-6, IL-12, MCP-1, IFN-gamma, and IL-10 levels after systemic administration of LPS. Furthermore, absence of MKP-1 increases systemic levels of proinflammatory cytokines and exacerbates disease development in a mouse model of rheumatoid arthritis. When activated through TLR2, TLR3, TLR4, TLR5, and TLR9, bone marrow-derived MKP-1-/- macrophages exhibit increased cytokine production and elevated expression of the differentiation markers B7.2 (CD86) and CD40. MKP-1-deficient macrophages also show enhanced constitutive and TLR-induced activation of p38 MAPK. Based on these findings, we propose that MKP-1 is an essential component of the intracellular homeostasis that controls the threshold and magnitude of p38 MAPK activation in macrophages, and inflammatory conditions accentuate the significance of this regulatory function.

Animals↗

PubMed2003

Recent insights into the role of the innate immune system in the development of alcoholic liver disease.

The innate immune system is responsible for the rapid, initial response of the organism to potentially dangerous stresses, including pathogens, tissue injury, and malignancy. Pattern-recognition receptors of the toll-like receptor (TLR) family expressed by macrophages provide a first line of defense against microbial invasion. Activation of these receptors results in a stimulus-specific expression of genes required to control the infection, including the production of inflammatory cytokines and chemokines, followed by the recruitment of neutrophils to the site of infection. The early stages in the development of alcoholic liver disease (ALD) follow a pattern characteristic of an innate immune response. Kupffer cells, the resident macrophages in the liver, are activated in response to bacterial endotoxins (lipopolysaccharide, LPS), leading to the production of inflammatory and fibrogenic cytokines, reactive oxygen species, as well as the recruitment of neutrophils to the liver. One mechanism by which chronic ethanol can turn the highly regulated innate immune response into a pathway of disease is by disrupting the signal transduction cascades mediating the innate immune response. Recent studies have identified specific modules in the TLR-4 signaling cascade that are disrupted after chronic ethanol exposure, including CD14 and the mitogen-activated protein kinase family members, ERK1/2 and p38. Enhanced activation of these TLR-4 dependent signaling pathways after chronic ethanol likely contributes to the development of alcoholic liver disease.

Cytokines↗

PubMed2007

[Innate immunity: structure and function of TLRs].

The innate immune system provides the first line of defence against infection. Through a limited number of germline-encoded receptors called pattern recognition receptors (PRRs), innate cells recognize and are activated by highly conserved structures expressed by large group of microorganisms called pathogen-associated molecular patterns (PAMPs). PRRs are involved either in recognition (scavenger receptors, C-type lectins) or in cell activation (Toll-like receptors or TLR, helicases and NOD molecules). TLRs play a pivotal role in cell activation in response to PAMPs. TLR are type I transmembrane proteins characterized by an intracellular Toll/IL 1 receptor homology domain that are expressed by innate immune cells (dendritic cells, macrophages, NK cells), cells of the adaptive immunity (T and B lymphocytes) and non immune cells (epithelial and endothelial cells, fibroblasts). In all the cell types analyzed, TLR agonists, alone or in combination with costimulatory molecules, induce cell activation. The crucial role played by TLR in immune cell activation has been detailed in dendritic cells. A TLR-dependent activation of dendritic cells is required to induce their maturation and migration to regional lymph nodes and to activate naïve T cells. The ability of different cell types to respond to TLR agonists is related to the pattern of expression of the TLRs and its regulation as well as their intracellular localization. Recent studies suggest that the nature of the endocytic and signaling receptors engaged by PAMPs may determine the nature of the immune response generated against the microbial molecules, highlighting the role of TLRs as molecular interfaces between innate and adaptive immunity. In this review are summarized the main biological properties of the TLR molecules.

Epithelial Cells↗

PubMed2005

Psoriasis: dysregulation of innate immunity.

The current understanding of the function of natural killer (NK) T cells in innate immunity and their potential to control acquired specific immunity, as well as the remarkable efficacy of antitumour necrosis factor-alpha biological treatments in psoriasis, forces us to refine the current T-cell hypothesis of psoriasis pathogenesis, and to give credit to the role of innate immunity. Psoriasis might be envisioned to be a genetically determined triggered state of otherwise dormant innate immunity. This aggravated state of innate immunity is represented by the activity of NK T cells, dendritic cells, neutrophils and keratinocytes, leading to the recruitment and activation of preferentially type 1 T cells, possibly in an antigen-independent way. Keratinocytes in psoriasis then are sensitive to the effects of T-cell activation and cytokine production, interferon (IFN)-gamma, by responding with psoriasiform hyperplasia. The chronic inflammation of psoriatic lesions suggests that this might be due to a deficiency in downregulation processes (e.g. a defect in the regulatory T-cell repertoire) and/or the persistence of an unknown trigger resulting in an exaggerated innate immune response.

Antigens↗