SEARCH · PubMed Health

Results for “Innate Immunity Recognition”

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 685 records · Page 38Linked to original sources

PubMed2004

Functional convergence of invertebrate and vertebrate cytokine-like molecules based on a similar lectin-like activity.

It is generally accepted that the action of cytokines results from their binding to specific receptors. However, many cytokines possess lectin-like activity that may be essential for the expression of their full biological activities. This review focuses on the physiological relevance of the lectin-like activity of cytokines during the innate immune response in mammals, using TNF as an illustrative example. Moreover, we will show that TNF displays functional analogies with a defense molecule from the earthworm Eisenia foetida termed CCF. These analogies are not reflected by primary sequence homology between CCF and TNF but are particularly based on a similar lectin-like activity/domain. Hence, from a phylogenetic point of view, the lectin-like activity/domain of CCF and TNF may represent an essential recognition mechanism that has been functionally conserved during the innate immune response of invertebrates and vertebrates as a result of convergent evolution.

Animals↗

PubMed2005

Manifold mechanisms of Toll-like receptor-ligand recognition.

Toll-like receptors recognize a diverse range of molecules derived from pathogens as well as host cells. As the number and diversity of TLR ligands and host factors increase, more questions are being raised. Here, we review recent advances toward understanding the molecular and cellular mechanisms underlying TLR-mediated direct or indirect recognition of their diverse range of ligands, including lipids, proteins, and nucleic acids. The elucidation of such mechanisms may represent a key for developing novel immunotherapeutics for infectious diseases, allergies, or cancer and to intervene in immunological disorders such as autoimmune diseases.

Animals↗

PubMed2004

Increase of Escherichia coli inoculum doses induces faster innate immune response in primiparous cows.

The objective of the current study was to evaluate the dynamics of infection and the immunological response to varying numbers of Escherichia coli injected into the mammary glands of primiparous cows during the periparturient period. Primiparous cows have been shown to be more resistant to intramammary E. coli challenge, and an increase of the inoculum dose by 2 log10 units induced a more rapid clinical response and clearance of the organisms. Recognition of lipopolysaccharide (LPS) is a key event in the innate immunity response to gram-negative infection and is mediated by the accessory molecules CD14 and LPS-binding protein (LBP). Primiparous cows were inoculated with 1 x 10(4) (Group A; n=8) or 1 x 10(6) (Group B; n=8) cfu E. coli P4:O32 in their 2 left quarters during the periparturient period. Clinical examination and analysis of blood and milk parameters, including IL-8, complement fragment 5a (C5a), LBP, and soluble CD14 (sCD14), were performed from d -4 to d +3 relative to infection. Primiparous cows in Group B initiated a more rapid clinical response following intramammary infection (IMI), resulting in typical clinical signs and changes in blood and milk parameters approximately 3 h earlier compared with primiparous cows in Group A. Based on average milk production in the noninfected quarters on d +2 postinoculation, all heifers reacted as moderate responders. Distinct differences in the kinetic patterns of rectal temperature, somatic cell count (SCC), IL-8, C5a, LBP, and sCD14 were observed between both groups during the early phase of inflammation. Both C5a and IL-8 increased before cellular influx into the infected glands, followed by increases in sCD14 and LBP. In conclusion, primiparous cows are able to clear an intramammary E. coli infection efficiently. Moreover, increasing the inoculum dose induces a more rapid inflammatory reaction, mainly because of early activation of the innate host immune response.

Animals↗

PubMed2005

The complex mechanism of antibody-mediated clearance of Bordetella from the lungs requires TLR4.

Although the antibacterial effects of Abs are well studied in in vitro systems, the in vivo effects of Abs cannot always be accurately predicted. Complicated cross-talk between different effector functions of Abs and various arms of the immune system can affect their activities in vivo. Using the mouse respiratory pathogen Bordetella bronchiseptica, we examined the mechanisms of Ab-mediated clearance of bacteria from the respiratory tract. Interestingly, although TLR4 was not necessary for protective immunity following infection, it was required for rapid bacterial clearance in mice that were vaccinated or adoptively transferred Abs. TLR4 was important for the rapid recruitment of neutrophils that are necessary for Ab-mediated bacterial clearance via a mechanism that requires both FcgammaR and CR3. These data are consistent with a model in which TLR4-mediated inflammatory responses aid in the recruitment of neutrophils, which phagocytose Ab- and complement-opsonized bacteria via FcgammaRs and CR3. Although pattern recognition receptors are known to be involved in innate immunity and the generation of adaptive immunity, their contributions to specific adaptive immune functions should be considered in ongoing efforts to improve vaccine-induced protective immunity.

Adoptive Transfer↗

PubMed2005

Natural cytotoxicity receptors: pattern recognition and involvement of carbohydrates.

Natural cytotoxicity receptors (NCRs), expressed by natural killer (NK) cells, trigger NK lysis of tumor and virus-infected cells on interaction with cell-surface ligands of these target cells. We have determined that viral hemagglutinins expressed on the surface of virus-infected cells are involved in the recognition by the NCRs, NKp44 and NKp46. Recognition of tumor cells by the NCRs NKp30 and NKp46 involves heparan sulfate epitopes expressed on the tumor cell membrane. Our studies provide new evidence for the identity of the ligands for NCRs and indicate that a broader definition should be applied to pathological patterns recognized by innate immune receptors. Since nonmicrobial endogenous carbohydrate structures contribute significantly to this recognition, there is an imperative need to develop appropriate tools for the facile sequencing of carbohydrate moieties.

Epitopes↗

PubMed2006

Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in young Haitian children.

BACKGROUND: Mannose-binding lectin (MBL) is a component of the innate immune response and binds microbial surfaces through carbohydrate recognition domains. MBL deficiency may contribute to susceptibility to a variety of infectious diseases, particularly in young children. MBL binds to the Cryptosporidium sporozoite and may be important in resistance to cryptosporidiosis. METHODS: We studied the association of serum MBL levels and cryptosporidiosis in a case-control study of young Haitian children with cryptosporidiosis versus children who were control subjects. RESULTS: Ninety-nine children were enrolled, as follows: 49 children with cryptosporidiosis, 41 healthy controls, and 9 children with diarrhea from other causes. Case children were more malnourished than controls, and 49% had persistent or chronic diarrhea. At enrollment, mean serum MBL levels were markedly lower in children with cryptosporidiosis (P = .002), as was the number of children with an MBL deficiency of < or = 70 ng/mL (P = .005). In multivariate analysis, the association of cryptosporidiosis and MBL deficiency persisted (P = .002; adjusted odds ratio, 22.4), as did the association of cryptosporidiosis with general malnutrition. The subset of children with cryptosporidiosis and MBL deficiency were more likely to be male (P = .025). CONCLUSIONS: MBL may be an important component of innate immune protection against Cryptosporidium infection in young children. Additional studies are necessary to determine whether MBL intestinal losses, deficient epithelial expression, and/or genetic polymorphisms in the MBL gene contribute to MBL deficiency in cryptosporidiosis and other enteric infections in young children.

Case-Control Studies↗

PubMed2006

[Recognition of viral nucleic acids and regulation of type I IFN expression].

Recognition of viral nucleic acids with pattern recognition receptors (PRRs) is the first step to induce innate immune system. Type I interferons (IFNs), central mediators in the antiviral innate immunity, are responsible for induction of cytokines and chemokines that disrupt virus replication. Recent studies indicated that there are at least two distinct pathways for the induction of type I IFN by viral infection. Toll-like receptors (TLRs) are extracellular and endosomal PRRs for microbial pathogens whereas retinoic acid inducible gene-I(RIG-I) and melanoma differentiation-associated gene 5(MDA5) are novel intracellular PRRs for viral dsRNA. In this report we describe the distinct mechanisms inducing type I IFNs through TLRs and RIG-I/MDA5 pathways.

Animals↗

PubMed2002

Innate immunity: the missing link in neuroprotection and neurodegeneration?

Innate immunity was previously thought to be a nonspecific immunological programme that was engaged by peripheral organs to maintain homeostasis after stress and injury. Emerging evidence indicates that this highly organized response also takes place in the central nervous system. Through the recognition of neuronal fingerprints, the long-term induction of the innate immune response and its transition to an adaptive form might be central to the pathophysiology and aetiology of neurodegenerative disorders. Paradoxically, this response also protects neurons by favouring remyelination and trophic support afforded by glial cells.

Animals↗

PubMed2001

Toll-like receptors: cellular signal transducers for exogenous molecular patterns causing immune responses.

Innate immunity initiates protection of the host organism against invasion and subsequent multiplication of microbes by specific recognition. Germ line-encoded receptors have been identified for microbial products such as mannan, lipopeptide, peptidoglycan (PGN), lipoteichoic acid (LTA), lipopolysaccharide (LPS), and CpG-DNA. The Drosophila Toll protein has been shown to be involved in innate immune response of the adult fruitfly. Members of the family of Toll-like receptors (TLRs) in vertebrates have been implicated as pattern recognition receptors (PRRs). Ten TLRs are known and six of these have been demonstrated to mediate cellular activation by distinct microbial products. TLR4 has been implicated as activator of adaptive immunity, and analysis of systemic LPS responses in mice led to the identification of LPS-resistant strains instrumental in its identification as a transmembrane LPS signal transducer. Structural similarities between TLRs and receptor molecules involved in immune responses such as CD14 and the IL-1 receptors (IL-1Rs), as well as functional analysis qualified TLR2 as candidate receptor for LPS and other microbial products. Targeted disruption of the TLR9 gene in mice led to identification of TLR9 as CpG-DNA signal transducer. Involvement of TLR5 in cell activation by bacterial flagellin has been demonstrated. Further understanding of recognition and cellular signaling activated through the ancient host defense system represented by Toll will eventually lead to means for its therapeutic modulation.

Amino Acid Sequence↗

PubMed2004

Structural and functional anatomy of the globular domain of complement protein C1q.

C1q is the first subcomponent of the classical pathway of the complement system and a major connecting link between innate and acquired immunity. As a versatile charge pattern recognition molecule, C1q is capable of engaging a broad range of ligands via its heterotrimeric globular domain (gC1q) which is composed of the C-terminal regions of its A (ghA), B (ghB) and C (ghC) chains. Recent studies using recombinant forms of ghA, ghB and ghC have suggested that the gC1q domain has a modular organization and each chain can have differential ligand specificity. The crystal structure of the gC1q, molecular modeling and protein engineering studies have combined to illustrate how modular organization, charge distribution and the spatial orientation of the heterotrimeric assembly offer versatility of ligand recognition to C1q. Although the biochemical and structural studies have provided novel insights into the structure-function relationships within the gC1q domain, they have also raised many unexpected issues for debate.

Animals↗

PubMed2005

Contribution of Toll-like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration.

Toll-like receptors (TLRs) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLRs. When the receptors are activated, cells bearing TLRs produce various proinflammatory cytokines in a MyD88-dependent manner. Liver regeneration following partial hepatectomy (PH) requires innate immune responses, particularly interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) production by Kupffer cells, although the recognition and activation processes are still unknown. We investigated whether TLR/MyD88 signaling is critical for induction of innate immune responses after PH. In Myd88(-/-) mice after PH, induction of expression of immediate early genes involved in hepatocyte replication and phosphorylation of STAT3 in the liver, and production of TNF-alpha/IL-6 by and activation of NF-kappaB in the Kupffer cells were grossly subnormal and were associated with impaired liver regeneration. However, TLR2, 4 and 9, which recognize gram-negative and -positive bacterial products, are not essential for NF-kappaB activation and IL-6 production after PH, which excludes a possible contribution of TLR2/TLR4 or TLR9 to MyD88-mediated pathways. In conclusion, the TLR/MyD88 pathway is essential for incidental liver restoration, particularly its early phase.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Endotoxin and mammalian host responses during experimental disease.

Endotoxin is an integral component of the outer membrane of Gram-negative bacteria and a prime example of unique and highly conserved bacterial surface molecules that engage with the innate immune system of the mammalian host via pattern recognition receptors on a range of host cells. The results of this interaction, which may be beneficial or detrimental to the development and welfare of the host, are reviewed, focusing on the different sensitivities and consequences in a range of hosts of experimental exposure to endotoxin, the disease outcomes and recent developments in our understanding of the mechanisms involved.

Animals↗

PubMed2003

Innate immunity in breast carcinoma.

The innate immune response, which depends on so-called pattern-recognition receptors (PRRs) is an evolutionarily old immune response able to elicit a defensive response against a vast array of pathogens. The purpose of this review is to revisit the role of innate immunity in breast carcinoma from the oldest therapeutic approach using bacillus Calmette-Guerin to the recent findings on the manipulation of the PRR pathways with unmethylated cytosine-guanosine dinucleotides (CpG motifs). Encouraging results have been obtained in prevention and local treatment of murine mammary tumors using tumor cells engineered to express stably mycobacterial antigens or directly using CpG-containing oligonucleotides. The experimental findings raise the possibility of successful anti-tumor management through stimulation of innate immunity in women at high risk of developing breast cancer and in breast cancer patients with reasonable immunological performance and low tumor load.

Animals↗

PubMed2005

Old meets new: the interaction between innate and adaptive immunity.

The innate immune system is an ancient and diverse collection of defenses, including the recognition of pathogens through the use of germline-encoded pathogen receptors. The adaptive immune system, encompassing T and B cell responses, is a more recent development that utilizes somatically recombined antigen receptor genes to recognize virtually any antigen. The adaptive immune system has the advantage of flexibility and immunologic memory but it is completely dependent upon elements of the innate immune system for the initiation and direction of responses. Appropriate innate and acquired immune system interactions lead to highly efficient recognition and clearance of pathogens, but maladaptive interactions between these two systems can result in harmful immunologic responses including allergy, autoimmunity, and allograft rejection.

Animals↗

PubMed2003

Macrophage migration inhibitory factor and host innate immune responses to microbes.

Among innate immune cells, macrophages play an essential role in the sensing and elimination of invasive microorganisms. Binding of microbial products to pathogen-recognition receptors stimulates macrophages to release cytokines and other effector molecules that orchestrate the host innate and adaptive immune responses. Recently, the protein known as macrophage migration inhibitory factor (MIF) has emerged as a pivotal mediator of innate immunity. First identified as a T-cell cytokine, MIF was rediscovered as a protein released by pituitary cells after exposure to endotoxin [lipopolysaccharide (LPS)] or bacteria and in response to stress. Monocytes, macrophages and lymphocytes constitutively express MIF, which is rapidly released after stimulation with bacterial endotoxins and exotoxins, and cytokines. MIF induces powerful proinflammatory biological responses and has been shown to be an important effector molecule of septic shock. High levels of MIF have been detected in the circulation of patients with severe sepsis and septic shock. Inhibition of MIF activity with neutralizing anti-MIF antibodies or deletion of the Mif gene led to a marked reduction in cytokine production and protected mice from lethal bacterial sepsis and toxic shock induced by Gram-negative endotoxin or Gram-positive exotoxins. Investigations into the mechanisms whereby MIF modulates innate immune responses to endotoxin and Gram-negative bacteria have shown that MIF up-regulates the expression of Toll-like receptor 4 (TLR4), the signal-transducing molecule of the LPS receptor complex. Thus, MIF enables cells, such as the macrophage, that are at the forefront of the host antimicrobial defences, to sense promptly the presence of invading Gram-negative bacteria and mount an innate immune response. Given that it is a pivotal regulator of innate immune responses to bacterial infections, MIF appears to be a perfect target for novel therapeutic interventions in patients with severe sepsis.

Humans↗

PubMed2006

An endogenous peptide signal in Arabidopsis activates components of the innate immune response.

Innate immunity is initiated in animals and plants through the recognition of a variety of pathogen-associated molecules that in animals are called pathogen-associated molecular patterns and in plants are called elicitors. Some plant pathogen-derived elicitors have been identified as peptides, but peptide elicitors derived from the plant itself that activate defensive genes against pathogens have not been previously identified. Here, we report the isolation and characterization of a 23-aa peptide from Arabidopsis, called AtPep1, which activates transcription of the defensive gene defensin (PDF1.2) and activates the synthesis of H(2)O(2), both being components of the innate immune response. The peptide is derived from a 92-aa precursor encoded within a small gene that is inducible by wounding, methyl jasmonate, and ethylene. Constitutive expression of the AtPep1 precursor gene PROPEP1 in transgenic Arabidopsis plants causes a constitutive transcription of PDF1.2. When grown in soil, the transgenic plants exhibited an increased root development compared with WT plants and an enhanced resistance toward the root pathogen Pythium irregulare. Six paralogs of PROPEP1 are present in Arabidopsis, and orthologs have been identified in species of several agriculturally important plant families, where they are of interest for their possible use in crop improvement.

Acetates↗

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↗

PubMed2005

New insights into alternative mechanisms of immune receptor diversification.

The clonal commitment, selection, and expansion of B and T lymphocytes expressing diversified receptors provide the underlying basis for the jawed vertebrates adaptive immune response. At the core of this process is the rearrangement and somatic modification of segmental genetic elements that encode the constituent components of immunoglobulins and T-cell antigen receptors. No evidence has been found for a similar mechanism outside of jawed vertebrates; however, invertebrates and jawless vertebrates are subjected to continuous exposure to pathogenic bacteria, viruses, and parasites. The invertebrates and jawless vertebrates as well as jawed vertebrates all encode a variety of mediators of innate immunity. Several reports of extensive germline diversification of conventional innate receptors, as well as molecules that resemble innate receptors but undergo germline and somatic modification, have been made recently. The range of such molecules, which include the fibrinogen-related proteins (FREPs) in a mollusc, variable region-containing chitin-binding proteins (VCBPs) in a cephalochordate, variable lymphocyte receptors (VLRs) in jawless vertebrates, and novel immune-type receptors (NITRs) in bony fish, encompasses both the immunoglobulin gene superfamily (IgSF) and leucine-rich repeat (LRR) proteins. Although these molecules vary markedly in form and likely in function, growing evidence suggests that they participate in various types of host defense and thereby represent significant alternatives to current paradigms of innate and adaptive immune receptors. Unusual genetic mechanisms for diversifying recognition proteins may be a widespread characteristic of animal immunity.

Adaptation, Physiological↗