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Results for “Immunity, Innate”

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At least 127 records · Page 7Linked to original sources

PubMed2002

Analysis of robust innate immune response after transplantation in the absence of adaptive immunity.

BACKGROUND: Both animal models and clinical outcomes studies of transplantation suggest that antigen-independent mechanisms can alter graft survival and function. It has been suggested that antigen-independent processes interact with alloantigen-specific responses to augment the rejection reaction. A major link between antigen-specific adaptive immunity and pro-inflammatory stimuli is innate immunity. During transplantation, innate immunity may be stimulated by multiple factors, including ischemia, reperfusion, sterile injury, systemic stress, and cell death. METHODS: We investigated the hypothesis that transplantation induces a potent innate immune response in a murine model of vascularized solid organ transplantation. In our studies, we analyzed three experimental groups: (a) alymphoid group in which both the donor and recipients strains lacked an adaptive immune response due to deletion of the recombinase activating gene, thus blocking production of both T cell and B cell antigen receptors; (b) syngeneic group in which the donors and recipients were genetically identical; and (c) allogeneic group in which the donors and recipients had a complete MHC mismatch. To analyze a large number of parameters we determined the level of expression of a panel of cytokines, chemokines, receptors, and cell surface markers by RNase protection assays. In addition, serum cytokines were determined by ELISA and the infiltration of inflammatory cells was assessed by histology. RESULTS: Our results showed macrophage infiltration and up-regulation of multiple cytokines, chemokines, and chemokine receptors within the first day after transplantation in all groups, including the syngeneic and alymphoid recipients. CONCLUSIONS: Our study demonstrated a robust innate immune response that is independent of adaptive immunity and natural killer cell responses.

Animals↗

PubMed2005

Relative contributions of NK and CD8 T cells to IFN-gamma mediated innate immune protection against Listeria monocytogenes.

During the innate immune response to Listeria monocytogenes (LM), the secretion of IFN-gamma is crucial in controlling bacterial numbers. We have shown recently that CD8 T cells have the ability to rapidly secrete IFN-gamma independent of Ag, in response to IL-12 and IL-18, during a LM infection. In the current study, we compared the relative abilities of NK and CD8 T cells to provide innate immune protection. Upon transfer of either NK or memory OT-I T cells (specific for the OVA protein) into IFN-gamma-deficient hosts that were infected subsequently with wild-type LM, both cell types were found in the spleen and had the ability to secrete IFN-gamma. However, the OT-I T cells were more effective at providing innate immune protection as determined by spleen and liver LM burdens. We used immunocytochemistry to demonstrate that upon infection with LM, marginal zone macrophages were localized to the T cell area of the splenic follicle. Transferred memory OT-I T cells were also found in the T cell area of the spleen, co-localizing with the LM and macrophages. In sharp contrast, NK cells were found predominantly in the red pulp region of the spleen. In addition, memory OT-I T cells were also found to be associated with LM lesions in the liver. These results highlight the importance of CD8 T cells in innate immune responses to LM and suggest that their increased protective ability compared with NK cells is the result of their colocalization with LM and macrophages.

Adoptive Transfer↗

PubMed2006

Evaluation of the effects of probiotic supplementation from the neonatal period on innate immune development in infancy.

BACKGROUND: Activation of the innate immune system by microbial stimulation is believed to be critical for normal immune maturation, and there has been speculation that these pathways are important for inhibiting allergic-immune responses. OBJECTIVE: To assess innate immune function following a 6-month supplementation with probiotic bacteria. METHODS: Two hundred and thirty-one allergic, pregnant women were recruited into a randomized, controlled trial. The infants received either a probiotic (Lactobacillus acidophilus LAVRI-A1; Probiomics) or placebo (maltodextrin alone) daily for the first 6 months of life. Mononuclear cell samples were available from 118 infants. Functional responses to toll-like receptor (TLR) were assessed using ligands for TLR2 (Pansorbin) and TLR4/CD14 [lipopolysaccharide (LPS)] and measuring cytokine responses in the supernatants. Antigen-presenting cell function, as well as capacity for cytokine production (IL-12p70 and IL-10) was assessed. RESULTS: Infants in the probiotic group did not demonstrate differences in innate immune function compared with those in the control group. No differences were seen when cytokine responses were examined following stimulation with Pansorbin (TLR2) or LPS (TLR4). Similarly, no differences were seen in the antigen-presenting capacity of these infants. The mean fluorescence intensities of human leucocyte antigen-DR (HLA-DR) on monocytes, B cells and dendritic cells (DC) subsets were not affected, nor were the percentage of circulating DC subsets affected by a 6-month supplementation with L. acidophilus LAVRI-A1. CONCLUSIONS: Probiotic supplementation with L. acidophilus for the first 6 months of life did not alter early innate immune responses in this population at high risk of developing allergic disease.

Antigen-Presenting Cells↗

PubMed2006

Innate immunity of fish (overview).

The innate immune system is the only defence weapon of invertebrates and a fundamental defence mechanism of fish. The innate system also plays an instructive role in the acquired immune response and homeostasis and is therefore equally important in higher vertebrates. The innate system's recognition of non-self and danger signals is served by a limited number of germ-line encoded pattern recognition receptors/proteins, which recognise pathogen associated molecular patterns like bacterial and fungal glycoproteins and lipopolysaccharides and intracellular components released through injury or infection. The innate immune system is divided into physical barriers, cellular and humoral components. Humoral parameters include growth inhibitors, various lytic enzymes and components of the complement pathways, agglutinins and precipitins (opsonins, primarily lectins), natural antibodies, cytokines, chemokines and antibacterial peptides. Several external and internal factors can influence the activity of innate immune parameters. Temperature changes, handling and crowding stress can have suppressive effects on innate parameters, whereas several food additives and immunostimulants can enhance different innate factors. There is limited data available about the ontogenic development of the innate immunological system in fish. Active phagocytes, complement components and enzyme activity, like lysozyme and cathepsins, are present early in the development, before or soon after hatching.

Animals↗

PubMed2005

Interaction of mucosal microbiota with the innate immune system.

Organisms live in continuos interaction with their environment; this interaction is of vital importance but at the same time can be life threatening. The largest and most important interface between the organism and its environment is represented by surfaces covered with epithelial cells. Of these surfaces, mucosae comprise in humans approximately 300 m2, and the skin covers approximately 1.8 m2 surface of the human body. Mucosal tissues contain two effector arms of the immune system, innate and adaptive, which operate in synergy. Interaction with commensal bacteria, which outnumber the nucleated cells of our body, occurs physiologically on epithelial surfaces; this interaction could pose the risk of inflammation. The mucosal immune system has developed a complex network of regulatory signalling cascades that is a prerequisite for proper activation but also for a timely inactivation of the pathway. As demonstrated in gnotobiotic animal models of human diseases, impaired regulation of mucosal responses to commensal bacteria plays an important role in the development of several inflammatory and autoimmune diseases.

Animals↗

PubMed2004

Anticipating innate immunity without a Toll.

Earthworm innate immunity depends upon small and large leukocytes (coelomocytes) that synthesize and secrete humoral antimicrobial molecules (e.g. lysenin, fetidin, eiseniapore, coelomic cytolytic factor [CCF]; Lumbricin I). Small coelomocytes (cytotoxic) are positive (CD11a, CD45RA, CD45RO, CDw49b, CD54, beta(2)-m and Thy-1 [CD90]; CD24; TNF-alpha) but negative using other mammalian markers. Large coelomocytes (phagocytic) are uniformly negative. Specific earthworm anti-EFCC 1, 2, 3, 4 mAbs are negative for Drosophila melanogaster hemocytes and mammalian cells but positive those of earthworms. Coelomocytes contain several lysosomal enzymes involved in phagocytosis and a pattern recognition molecule (CCF) that may trigger the prophenoloxidase cascade a crucial innate immune response. Earthworms and other invertebrates possess natural, non-specific, non-clonal, and non-anticipatory immune response governed by germ line genes. Toll and Toll-like receptor signaling is essential for phagocytosis and antimicrobial peptide synthesis and secretion in insects and vertebrates but has not yet been shown to be essential in earthworm innate responses.

Animals↗

PubMed2026

Integrin-Linked Kinases 1, 4, and 5 participate in cell wall-mediated innate immunity to leaf and root pathogens.

The cell wall integrity (CWI) pathway is triggered by plasma membrane-localized receptors in plant cells and serves to orchestrate responses to cell wall damage by initiating compensatory changes under stressful environments. The essential role of CWI maintenance as part of plants' interactions with pests or pathogens and during growth is well known. Nevertheless, CWI pathways remain to be fully characterized. Here, we show that altered Integrin-Linked Kinase 1 (ILK1) expression causes widespread defects in the transcriptional program activated by the bacterial elicitor flg22, primarily in genes associated with cell wall integrity and immunity. These transcriptional deficiencies are recapitulated in mutant lines with altered ILK4 or ILK5 expression. Analysis of molecular and cellular defenses in ilk mutants revealed reduced callose accumulation in leaves treated with bacterial (elf18) and plant (pep1) elicitors and increased pathogen susceptibility. Histochemical analysis of cell-wall-associated staining across diverse cells and organs of ilk mutants revealed modified lignin-associated patterns in the root xylem and altered calcofluor staining patterns in the seed coat. All ilk mutants exhibited altered root morphology due to mechano-touch and high-NaCl stress. Based on these results, we propose that ILKs contribute to pathways connecting elicitor-triggered immune signaling with cell-wall-associated stress responses and that ILK-related defense functions may extend to the cotton root-nematode interaction, while the mechanism remains to be elucidated.

Cell Wall↗

PubMed2005

Role of Toll-like receptor-driven innate immunity in thoracic organ transplantation.

Innate immunity represents the first line of defense against microbial invasion. Recent studies have determined that a group of germline-encoded receptors, termed Toll-like receptors (TLRs), are critical for recognizing foreign motifs on microbial organisms and initiating innate responses. An exciting area of research has recently linked activation of TLRs on antigen-presenting cells (APCs) to effective antigen presentation and activation of naive T cells. Most studies have shown that TLR-dependent immune function leads to T-helper 1 (TH1) immunity, although evidence also supports that TH2 immune responses may be initiated by TLR signaling in certain contexts. In either case, innate immune signaling via TLRs leads to a productive adaptive immune response. In contrast to studies in purely infectious models, emerging data from experimental and clinical studies have provided evidence that TLR immune function is important in acute allograft rejection. Specifically, MyD88, an important TLR signal adaptor, was found to be critical for the rejection of minor-mismatched skin allografts, and important for alloimmune priming and TH1 immunity against fully allogeneic skin grafts. Furthermore, a clinical study has shown that recipients with TLR 4 polymorphisms associated with endotoxin hyporesponsiveness manifest reduce acute lung allograft rejection. Collectively, these studies demonstrate that innate immunity is important for alloimmunity. Future therapeutic modalities that target innate rather than adaptive immune mechanisms represent a promising avenue for future studies in thoracic organ transplantation.

Adaptor Proteins, Signal Transducing↗

PubMed2004

The effects of parasite-derived immune-suppressive factors on the cellular innate immune and autoimmune responses of Drosophila melanogaster.

Immune-suppressive factors (ISFs) introduced into larvae of Drosophila melanogaster during infection by virulent endoparasitic wasps effectively block the innate immune response mediated by blood cells (hemocytes) but have little influence on the autoimmune response made by a tumor strain in which the blood cells manifest a similar response but instead target and destroy endogenous tissues. Quantitative hemocyte analyses indicate that ISFs interfere with the immune effector responses downstream of nonself recognition, hemocyte activation and differentiation, because these responses were manifested by tumor hosts, in which the parasitoids developed. The data suggest that once activated to encapsulate aberrant tissues, the target specificity of the autoimmune-activated hemocytes, and the genetic program underlying tumor formation, cannot be blocked by parasitoid-derived ISFs, which effectively inhibit identical hemocyte-mediated responses during parasitization.

Animals↗

PubMed2004

Regulation of innate immunity signaling and its connection with human diseases.

Human innate immunity can respond to diverse microbial products, as well as other substances such as heat shock proteins, taxol, and unsaturated fatty acids. Mediated largely by a family of Toll-like-receptors (TLR) and associated intracellular downstream signaling molecules, human innate immune response serves multiple functions ranging from providing the first line of defense to coordinating cellular growth as well as other cellular functions. To date, about 10 distinct human TLR receptors have been identified in the human genome. Biochemical studies and genetic analyses using transgenic mice have revealed specific ligands for several TLR receptors. TLR intracellular domains could then specifically recruit several adaptor proteins including MyD88, TIRAP/MAL, TRIF, and TOLLIP. These adaptor proteins subsequently associate with a family of interleukin-1 receptor-associated kinases (IRAK1, 2, M, and 4). Recruitments of numerous downstream signaling proteins lead to activation of a range of transcription factors such as NF kappa B, AP-1, and IRFs, which are responsible for specific gene transcriptions. Human innate immunity is manifested in diverse cells and tissues. Well-coordinated innate immunity signaling enables human cells and tissues to properly respond to various substances. Improper regulations of such event have been shown to cause various diseases including asthma, atherosclerosis, and cancer. TLR receptors as well as other intracellular signaling proteins can potentially serve as therapeutic targets for numerous human diseases. This review will discuss at the molecular level, regulation of innate immunity signaling as well as its intricate connection with human diseases.

Animals↗

PubMed2004

Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep.

The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.

Amnion↗

PubMed2002

[Modification of innate immunity in humans by active components of shark liver oil].

See fish oils affect different systemic reactions innate immunity including. Innate immunity is responsible for immediate pathogen recognition and inactivation. Innate immunity decides also on the type of required immunity development. In the presented paper we have proved that supportive treatment with shark oil components normalize complement level, natural killer cells activity and reactive oxygen intermediates production by peripheral blood leukocytes of peoples suffering from active form rheumatoid arthritis.

Animals↗

PubMed1999

Exercise and cellular innate immune function.

Epidemiological evidence suggests a link between the intensity of exercise and infectious and neoplastic disease. One likely way by which exercise exerts its effect on cancer and infection is by altering the function of the immune system. Cells of the innate immune system (i.e., macrophage [Mphi], natural killer [NK] cell, and polymorphonuclear neutrophils [PMN]) are first-line defenders against cancer and infectious disease by nature of their phagocytic, cytolytic, and antimicrobial properties. The purpose of this review is to define the role of cells of the innate immune system (i.e., Mphi, PMN, and NK cells) in infection and cancer, present current information regarding the effects of acute and chronic exercise on the quantification and functional activities of these cells, and briefly to discuss potential mechanisms as to how exercise affects these cells and describe how these changes may potentially affect susceptibility to infection and cancer. The effects of exercise on the number, functions, and characteristics of cells of the innate immune system are complex and are dependent several factors, including 1) the cell function or characteristic being analyzed; 2) the intensity, duration and chronicity of exercise; 3) the timing of measurement in relation to the exercise bout; 4) the dose and type of immunomodulator used to stimulate the cell in vitro or in vivo; and 5) the site of cellular origin. Further studies are needed to determine whether the exercise-induced changes in immune function alter incidence or progression of disease. Likewise, the mechanisms as to how exercise alters innate immune function are as yet unresolved.

Exercise↗

PubMed2001

The evolution and genetics of innate immunity.

The immune system provides protection from a wide range of pathogens. One component of immunity, the phylogenetically ancient innate immune response, fights infections from the moment of first contact and is the fundamental defensive weapon of multicellular organisms. The Toll family of receptors has a crucial role in immune defence. Studies in fruitflies and in mammals reveal that the defensive strategies of invertebrates and vertebrates are highly conserved at the molecular level, which raises the exciting prospects of an increased understanding of innate immunity.

Animals↗

PubMed2006

Roles of the alternative complement pathway and C1q during innate immunity to Streptococcus pyogenes.

Complement is important for innate immunity to the common bacterial pathogen Streptococcus pyogenes, but the relative importance of the alternative and classical pathways has not been investigated. Using mice and human serum deficient in either C1q, the first component of the classical pathway, or factor B, an important component of the alternative pathway, we have investigated the role of both pathways for innate immunity to S. pyogenes. C3b deposition on four different strains of S. pyogenes was mainly dependent on factor B. As a consequence opsonophagocytosis of S. pyogenes was reduced in serum from factor B-deficient mice, and these mice were very susceptible to S. pyogenes infection. In contrast, C3b deposition was not dependent on C1q for two of the strains investigated, H372 and H305, yet opsonophagocytosis of all four S. pyogenes strains was impaired in serum deficient in C1q. Furthermore, infection in C1q-deficient mice with strain H372 resulted in a rapidly progressive disease associated with large numbers of bacteria in target organs. These results demonstrate the important role of the alternative pathway and C1q for innate immunity to S. pyogenes and suggest that C1q-mediated innate immunity to at least some strains of S. pyogenes may involve mechanisms that are independent of C3b on the bacteria.

Animals↗

PubMed2004

Alternatives to conventional vaccines--mediators of innate immunity.

Vaccines have been described as "weapons of mass protection". The eradication of many diseases is testament to their utility and effectiveness. Nevertheless, many vaccine preventable diseases remain prevalent because of political and economic barriers. Additionally, the effects of immaturity and old age, therapies that incapacitate the adaptive immune system and the multitude of strategies evolved by pathogens to evade immediate or sustained recognition by the mammalian immune system are barriers to the effectiveness of existing vaccines or development of new vaccines. In the front line of defence against the pervasiness of infection are the elements of the innate immune system. Innate immunity is under studied and poorly appreciated. However, in the first days after entry of a pathogen into the body, our entire protective response is dependant upon the various elements of our innate immune repertoire. In spite of its place as our initial defence against infection, attention is only now turning to strategies which enhance or supplement innate immunity. This review examines the need for and potential of innate immune therapies.

Humans↗

PubMed2006

Intervention of Toll-like receptor-mediated human innate immunity and inflammation by synthetic compounds and naturally occurring products.

Human innate immunity plays a pivotal role in host defense against various microbial challenges. Mediated by a family of Toll-like-receptors (TLR) and associated intracellular downstream signaling molecules, human innate immunity can specifically recognize diverse microbial products and many other non-microbial environmental cues. Beyond its role of providing first line of defense, activation of innate immunity signaling can lead to expression of diverse pro- and anti- inflammatory mediators, which are critical for regulating various cell and tissue metabolism. Alteration in innate immunity signaling may therefore lead to infection and inflammatory diseases such as atherosclerosis, diabetes, and cancer. TLR receptors as well as intracellular signaling proteins can serve as therapeutic targets for treating various inflammatory diseases. Several synthetic ligands of TLR receptors such as lipid A analogs, poly(I:C), loxoribine, oligodeoxynucleotides have been shown to be effective in regulating innate immune response. This review discusses the potential, challenge, and recent progress of developing synthetic as well as naturally occurring TLR ligands in regulating innate immunity and treating inflammatory diseases.

Biological Products↗

PubMed2004

Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis.

Innate immunity is a specific and organized immunological program engaged by peripheral organs and the CNS to maintain homeostasis after stress and injury. In neurodegenerative disorders, its putative deregulation, featured by inflammation and activation of glial cells resulting from inherited mutations or viral/bacterial infections, likely contributes to neuronal death. However, it remains unclear to what extent environmental factors and innate immunity cooperate to modulate the interactions between the neuronal and non-neuronal elements in the perturbed CNS. In the present study, we addressed the effects of acute and chronic administration of lipopolysaccharide (LPS), a Gram-negative bacterial wall component, in a genetic model of neurodegeneration. Transgenic mice expressing a mutant form of the superoxide dismutase 1 (SOD1(G37R)) linked to familial amyotrophic lateral sclerosis were challenged intraperitoneally with a single nontoxic or repeated injections of LPS (1 mg/kg). At different ages, SOD1(G37R) mice responded normally to acute endotoxemia. Remarkably, only a chronic challenge with LPS in presymptomatic 6-month-old SOD1(G37R) mice exacerbated disease progression by 3 weeks and motor axon degeneration. Closely associated with the severity of disease is the stronger and restricted upregulation of the receptor of innate immunity Toll-like receptor 2 and proinflammatory cytokines in degenerating regions of the ventral spinal cord and efferent fiber tracts of the brain from the LPS-treated SOD1(G37R) mice. This robust immune response was not accompanied by the establishment of acquired immunity. Our results provide solid evidence that environmental factors and innate immunity can cooperate to influence the course of disease of an inherited neuropathology.

Amyotrophic Lateral Sclerosis↗