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Results for “Immunity, Innate”

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At least 343 records · Page 19Linked to original sources

PubMed2005

Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility.

C reactive protein, the first innate immunity receptor identified, and serum amyloid P component are classic short pentraxins produced in the liver. Long pentraxins, including the prototype PTX3, are expressed in a variety of tissues. Some long pentraxins are expressed in the brain and some are involved in neuronal plasticity and degeneration. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. PTX3 acts as a functional ancestor of antibodies, recognizing microbes, activating complement, and facilitating pathogen recognition by phagocytes, hence playing a nonredundant role in resistance against selected pathogens. In addition, PTX3 is essential in female fertility because it acts as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility.

Animals↗

PubMedDate not supplied

Interaction of mannan-binding lectin with Trichinella spiralis glycoproteins, a possible innate immune mechanism.

Complex and variable glycoconjugates presented by parasitic nematodes during infection are very important in the host-parasite interplay. Predominantly carbohydrate-rich antigens are involved in the stimulation and modulation of the stage-specific immune response of the host. The non-specific innate immune system, however, acts as the first line of host defence against pathogens, before the appearance of antigen-specific responses. The functional entities of the innate system are lectins that recognize the surface ligands of pathogens: mannan-binding lectin (MBL) is a key recognition element involved in binding oligosaccharide structures exposed on microorganisms. In the present study we investigated whether MBL binds to the parasitic nematode Trichinella spiralis (T. spiralis). Since the parasite is coated with mannose-containing glycans, these structures could represent potential ligands for MBL and contribute to activation of the innate immune response of the host. Histochemical staining revealed MBL on the surface and internal organs of T. spiralis muscle larvae. MBL bound in a mannose-inhibitable manner to both crude extracts of T. spiralis muscle larvae and larvae excretory/secretory products. Western blot analyses showed that MBL recognized glycoproteins from all stages of T. spiralis. In vitro complement activation assays suggested that MBL is capable of fixing complement components on T. spiralis crude extract coated plates and activating the complement cascade through the 'lectin pathway'.

Animals↗

PubMed2004

The Paneth cell and the innate immune response.

PURPOSE OF REVIEW: Innate immune defense of the small intestine is mediated in part by antimicrobial peptides and proteins secreted by Paneth cells, epithelial cells positioned at the base of the crypts of Lieberkuhn. Recent studies have yielded better understanding of the role that Paneth cells may play in host defense. Emerging data suggest that these cells may contribute to the pathophysiology of several human diseases. A wealth of data has also emerged on the regulatory pathways of Paneth cell functions and structure-function analysis on Paneth cell antimicrobials. This review discusses new reports in these areas. RECENT FINDINGS: Studies of transgenic and knockout mice have supported a pivotal role of Paneth cell defensins in protection from oral bacterial pathogens. Other studies suggest that Paneth cells may be the targets of virulence mechanisms of bacterial pathogens. New observations also suggest that Paneth cell dysfunction may contribute to the clinical phenotype of Crohn disease, necrotizing enterocolitis, and, perhaps, intestinal manifestations of cystic fibrosis. SUMMARY: Paneth cells are emerging as key mediators of innate host defense in the small intestine. The antimicrobial activity of Paneth cell secretory products on transient and resident microbes in the gut may have a profound influence on health. The possible role of Paneth cell dysfunction in human disease and a better understanding of Paneth cell regulatory pathways are areas poised for significant advances in the near future.

Journal Article↗

PubMed2005

Innate immune traits differ between Meishan and Large White pigs.

A panel of innate immune traits were compared between Meishan and Large White pigs. These pigs were of similar age and kept under the same environmental conditions to reduce non-genetically derived variation in immune traits. The animals were all apparently healthy and were not experimentally challenged with any pathogen during the study. The measures only required a small blood sample. Total white cell counts were similar between the pig breeds. However, the numbers of lymphocytes, neutrophils and monocytes differed significantly, with Meishans having higher neutrophil and monocyte counts and lower lymphocyte counts. Flow cytometric methods were used to determine quantitatively the characteristics and function of neutrophils and monocytes. Meishan neutrophils were smaller and less complex than Large White neutrophils, and phagocytosis of Escherichia coli and the ensuing oxidative burst was lower in Meishan neutrophils compared to Large White neutrophils. Monocyte phagocytosis of E. coli was significantly less than that of neutrophils in both breeds but the function of Meishan monocytes as measured by phagocytosis and tumour necrosis factor alpha (TNFalpha) release did not differ from that of Large White monocytes. Levels of acute phase proteins also differed between the breeds with a significantly higher proportion of Meishans having elevated serum amyloid A levels. However, Meishans had lower alpha(1)-acid glycoprotein levels than Large Whites and haptoglobin levels were similar. Such differences in innate immune traits may have implications in the resistance to infection by a broad range of pathogens and subsequent disease effects in these breeds. Further studies are warranted to investigate the genes underlying these traits.

Acute-Phase Proteins↗

PubMedDate not supplied

Ecotoxicology and innate immunity in fish.

This review summarizes the scattered literature on the effects of toxicants on the external and internal innate immunity of fish. Insecticides, heavy metals and surfactants have been the most frequently examined toxicants, whereas dioxins, furans and polychlorinated biphenyls have been tested less frequently. Studies to date have been conducted at the levels of cells in vitro, of fish in the laboratory and microcosms, and also of fish in the field. Among innate immune parameters, phagocyte respiratory burst appears especially sensitive to toxicants. Toxicant-induced alterations in external mucous production have also been observed repeatedly. Field studies have occasionally examined changes to melano-macrophage centers, but the meaning of such changes is not clear. Advances in basic knowledge of fish innate immunity should lead to improvements in monitoring fish health and predicting the impact of toxicants on fish populations, which is a fundamental ecotoxicological goal.

Acute-Phase Proteins↗

PubMed2005

Melanogenesis and associated cytotoxic reactions: applications to insect innate immunity.

Insects transmit the causative agents for such debilitating diseases as malaria, lymphatic filariases, sleeping sickness, Chagas' disease, leishmaniasis, river blindness, Dengue, and yellow fever. The persistence of these diseases provides testimony to the genetic capacity of parasites to evolve strategies that ensure their successful development in two genetically diverse host species: insects and mammals. Current efforts to address the problems posed by insect-borne diseases benefit from a growing understanding of insect and mammalian immunity. Of considerable interest are recent genomic investigations that show several similarities in the innate immune effector responses and associated regulatory mechanisms manifested by insects and mammals. One notable exception, however, is the nearly universal presence of a brown-black pigment accompanying cellular innate immunity in insects. This response, which is unique to arthropods and certain other invertebrates, has focused attention on the elements involved in pigment synthesis as causing or contributing to the death of the parasite, and has even prompted speculation that the enzyme cascade mediating melanogenesis constitutes an ill-defined recognition mechanism. Experimental evidence defining the role of melanin and its precursors in insect innate immunity is severely lacking. A great deal of what is known about melanogenesis comes from studies of the process occurring in mammalian systems, where the pigment is synthesized by such diverse cells as those comprising portions of the skin, hair, inner ear, brain, and retinal epithelium. Fortunately, many of the components in the metabolic pathways leading to the formation of melanin have been found to be common to both insects and mammals. This review examines some of the factors that influence enzyme-mediated melanogenic responses, and how these responses likely contribute to blood cell-mediated, target-specific cytotoxicity in immune challenged insects.

Animals↗

PubMed2003

"Eat me" and "don't eat me" signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system.

A full innate immune system (e.g. complement system, scavenger receptors, Toll-like receptors (TLR)) has been described in the CNS and is thought to be an extremely efficient army designed to fight against invading pathogens and toxic cell debris such as apoptotic cells and amyloid fibrils. The binding of soluble or secreted innate immune molecules on pathogen-associated molecular patterns (PAMPs) as well as apoptotic cell-associated molecular patterns (ACAMPs) provide several "eat me" signals to promote the safe disposal of the intruders by professional and amateur phagocytes. These patterns are deciphered by receptors (pattern recognition receptors, PRRs; e.g. CR3) that control phagocytosis and associated inflammatory response depending on the meaning of these signals. Importantly, in order to avoid excessive collateral damage of surrounding cells, it is increasingly evident that "don't eat me" signals (coined herein as self-associated molecular patterns, SAMPs; e.g. complement regulatory proteins, CD200) are of paramount importance to signal a robust anti-inflammatory response and promote tissue repair. Further knowledge of the innate immune response in the CNS will greatly help to delineate the novel therapeutic routes to protect from CNS inflammation and neurodegeneration.

Animals↗

PubMed2002

Stereotyped and specific gene expression programs in human innate immune responses to bacteria.

The innate immune response is crucial for defense against microbial pathogens. To investigate the molecular choreography of this response, we carried out a systematic examination of the gene expression program in human peripheral blood mononuclear cells responding to bacteria and bacterial products. We found a remarkably stereotyped program of gene expression induced by bacterial lipopolysaccharide and diverse killed bacteria. An intricately choreographed expression program devoted to communication between cells was a prominent feature of the response. Other features suggested a molecular program for commitment of antigen-presenting cells to antigens captured in the context of bacterial infection. Despite the striking similarities, there were qualitative and quantitative differences in the responses to different bacteria. Modulation of this host-response program by bacterial virulence mechanisms was an important source of variation in the response to different bacteria.

Bacteria↗

PubMed2001

Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules.

The innate immune system recognizes microorganisms through a series of pattern recognition receptors that are highly conserved in evolution. Insects have a family of 12 peptidoglycan recognition proteins (PGRPs) that recognize peptidoglycan, a ubiquitous component of bacterial cell walls. We report cloning of three novel human PGRPs (PGRP-L, PGRP-Ialpha, and PGRP-Ibeta) that together with the previously cloned PGRP-S, define a new family of human pattern recognition molecules. PGRP-L, PGRP-Ialpha, and PGRP-Ibeta have 576, 341, and 373 amino acids coded by five, seven, and eight exons on chromosomes 19 and 1, and they all have two predicted transmembrane domains. All mammalian and insect PGRPs have at least three highly conserved C-terminal PGRP domains located either in the extracellular or in the cytoplasmic (or in both) portions of the molecules. PGRP-L is expressed in liver, PGRP-Ialpha and PGRP-Ibeta in esophagus (and to a lesser extent in tonsils and thymus), and PGRP-S in bone marrow (and to a lesser extent in neutrophils and fetal liver). All four human PGRPs bind peptidoglycan and Gram-positive bacteria. Thus, these PGRPs may play a role in recognition of bacteria in these organs.

Amino Acid Sequence↗

PubMed2004

The potential for Toll-like receptors to collaborate with other innate immune receptors.

Cells of the innate immune system express a large repertoire of germ-line encoded cell-surface glycoprotein receptors including Toll-like receptors (TLRs). TLRs recognize conserved motifs on microbes and induce inflammatory signals. Evidence suggests that individual members of the TLR family or other non-TLR surface antigens either physically or functionally interact with each other and cumulative effects of these interactions instruct the nature and outcome of the immune response to a particular pathogen.

Humans↗

PubMed2006

Neurotoxicity from innate immune response is greatest with targeted replacement of E4 allele of apolipoprotein E gene and is mediated by microglial p38MAPK.

Inheritance of APOE alleles is associated with varying clinical outcomes in several neurodegenerative diseases that are associated with innate immune response in brain. We tested the hypothesis that inheritance of different APOE alleles would significantly modulate neurotoxicity arising from glial innate immune response. We first used dissociated cultures of wild-type (wt) murine neurons and glia derived from mice with targeted replacement (TR) of the epsilon2, epsilon3, or, epsilon4 APOE allele. Our results showed that the vast majority of bystander damage to wt neurons derived from microglia was greatest with TR APOE4 glia, intermediate from TR APOE3 glia, and least from TR APOE2 glia and preceded detectable NO secretion. Microglial p38MAPK-dependent cytokine secretion followed a similar pattern of TR APOE dependence. In hippocampal slice cultures, innate immune activation had a similar pattern of TR APOE-dependence and produced postsynaptic neuronal damage in TR APOE4 and TR APOE3 but not TR APOE2 cultures that was p38MAPK dependent. These findings suggest a new mechanism by which inheritance of different APOE alleles may influence the outcome of neurodegenerative diseases associated with microglial innate immune response.

Alleles↗

PubMed2005

Do pathogen exposure and innate immunity cause brain diseases?

It had long been thought that the central nervous system was isolated from the immune system owing to the blood-brain barrier and that this organ was unable to mount an immune reaction of its own when challenged by invading pathogens. It is now clear that the immune system has a profound impact on the central nervous system, because immune molecules found in the blood stream are able to stimulate cells within the brain. Moreover, recent studies have demonstrated that cells within the central nervous system have the capacity to produce molecules of the innate immune system and that this organ is able to generate a proper immune reaction. This topic has been extensively studied in recent years, and it is becoming clear that the innate immune system is an important modulator of the fate of neurons. Indeed, the precise role(s) of the innate immune response in neurodegenerative diseases is currently under intensive debate. In this review paper, we present evidence either supporting or opposing a role for the innate immune response in these events. The mechanisms by which pathogens interact with the brain and whether such an interaction leads to neurodegenerative disorders are also discussed.

Animals↗

PubMed2002

Innate immunity in the Aegean: ancient pathways for today's survival.

A workshop on innate immunity that took place this past autumn in Fira, Santorini, as part of the Aegean Conferences, provided tantalizing evidence about the early origin and evolutionary conservation of humoral and cellular components of innate immunity from sponges, flies and sea squirts to man, uncovered mechanistic aspects of its fundamental role in defense against disease, as well as the serious consequences of misdirected responses, and revealed the untapped potential of novel therapeutic approaches.

Animals↗

PubMed2004

Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes.

There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.

Diabetes Mellitus, Type 2↗

PubMed2004

STAT4 is a critical mediator of early innate immune responses against pulmonary Klebsiella infection.

Bacterial pneumonia is a leading cause of morbidity and mortality in the U.S. An effective innate immune response is critical for the clearance of bacteria from the lungs. IL-12, a key T1 cytokine in innate immunity, signals through STAT4. Thus, understanding how STAT4 mediates pulmonary immune responses against bacterial pathogens will have important implications for the development of rational immunotherapy targeted at augmenting innate immunity. We intratracheally administered Klebsiella pneumoniae to wild-type BALB/c and STAT4 knockout (STAT4-/-) mice. Compared with wild-type controls, STAT4-/- mice had decreased survival following intratracheal Klebsiella administration, which was associated with a higher lung and blood bacterial burden. STAT4-/- animals also displayed impaired pulmonary IFN-gamma production and decreased levels of proinflammatory cytokines, including the ELR- CXC chemokines IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma. Although total lung leukocyte populations were similar between STAT4-/- and wild-type animals following infection, alveolar macrophages isolated from infected STAT4-/- mice had decreased production of proinflammatory cytokines, including IFN-gamma, compared with infected wild-type mice. The intrapulmonary overexpression of IFN-gamma concomitant with the systemic administration of IFN-gamma partially reversed the immune deficits observed in STAT4-/- mice, resulting in improved bacterial clearance from the blood. Collectively, these studies demonstrate that STAT4 is required for the generation of an effective innate host defense against bacterial pathogens of the lung.

Adjuvants, Immunologic↗

PubMed2006

Trauma: the role of the innate immune system.

Immune dysfunction can provoke (multiple) organ failure in severely injured patients. This dysfunction manifests in two forms, which follow a biphasic pattern. During the first phase, in addition to the injury by trauma, organ damage is caused by the immune system during a systemic inflammatory response. During the second phase the patient is more susceptible for sepsis due to host defence failure (immune paralysis). The pathophysiological model outlined in this review encompasses etiological factors and the contribution of the innate immune system in the end organ damage. The etiological factors can be divided into intrinsic (genetic predisposition and physiological status) and extrinsic components (type of injury or "traumaload" and surgery or "intervention load"). Of all the factors, the intervention load is the only one which, can be altered by the attending emergency physician. Adjustment of the therapeutic approach and choice of the most appropriate treatment strategy can minimize the damage caused by the immune response and prevent the development of immunological paralysis. This review provides a pathophysiological basis for the damage control concept, in which a staged approach of surgery and post-traumatic immunomonitoring have become important aspects of the treatment protocol. The innate immune system is the main objective of immunomonitoring as it has the most prominent role in organ failure after trauma. Polymorphonuclear phagocytes and monocytes are the main effector-cells of the innate immune system in the processes that lead to organ failure. These cells are controlled by cytokines, chemokines, complement factors and specific tissue signals. The contribution of tissue barrier integrity and its interaction with the innate immune system is further evaluated.

Journal Article↗

PubMed2003

Innate immunity: from lymphocyte mitogens to Toll-like receptors and back.

Innate immunity, our inborn immediate defence mechanism, was thought for a long time to be non-specific and, consequently, research into innate mechanisms often took second place to research into adaptive immunity. In recent decades, however, the spotlight has shone on groundbreaking advances into mechanisms of innate immunity; from the hypothesis that mitogen receptors distinguish between 'self' and 'very-different-from-self' in the mid-1970s to the refining of the concept by Janeway in 1989, the identification of Toll-like molecules as mitogen receptors, and finally the cloning of the first mammalian Toll-like receptor (TLR) in 1997. We now know that innate immune activation has a role in the control of adaptive immune responses, and many more TLRs and their ligands have been characterised.

Animals↗

PubMed2006

Innate immune recognition of viral infection.

Induction of the antiviral innate immune response depends on recognition of viral components by host pattern-recognition receptors. Members of the Toll-like receptor family have emerged as key sensors that recognize viral components such as nucleic acids. Toll-like receptor signaling results in the production of type I interferon and inflammatory cytokines and leads to dendritic cell maturation and establishment of antiviral immunity. Cells also express cytoplasmic RNA helicases that function as alternative pattern-recognition receptors through recognition of double-stranded RNA produced during virus replication. These two classes of pattern-recognition receptor molecules are expressed in different intracellular compartments and induce type I interferon responses via distinct signaling pathways.

Adaptor Proteins, Signal Transducing↗