PubMed Health⌕ Search

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 55 records · Page 3Linked to original sources
PubMed2006

Toll like receptors and acute allograft rejection.

Toll like receptors (TLR) are critical innate immune receptors expressed on a variety of cells including dendritic cells that are activated by the presence of invading pathogens. However, there is emerging evidence that TLR signaling participates in inflammation that may occur in the absence of overt infection. In solid organ transplantation there is increasing evidence, both in experimental and human studies, that TLR activation is involved in the innate immune recognition of allografts. Further investigation of how innate immunity impacts solid organ transplantation may lead to improved therapies for transplant recipients.

Acute Disease↗
PubMed2000

Innate immune system recognition of microbial pathogens.

The long-term goal of our laboratory is to understand vertebrate host recognition of microbial pathogens. Although our work is primarily curiosity driven, it is certainly true that understanding how a host recognizes microbial pathogens should have some medical application. Probably more than 50,000 people die each year in the United States of septic shock or the systemic inflammatory response syndrome, and there is no good therapy for this problem. Understanding the molecular basis of its origin should suggest novel therapeutic approaches.

Antigens, Bacterial↗
PubMed2004

Selective induction of pentraxin 3, a soluble innate immune pattern recognition receptor, in infectious episodes in patients with haematological malignancy.

Pentraxins are a superfamily of conserved proteins induced in response to microbial and inflammatory stimuli. Members of this family include C-reactive protein (CRP) and serum amyloid P component, collectively known as the classical short pentraxins, and the more recently discovered pentraxin 3 (PTX3), a member of the closely related subfamily of the long pentraxins. PTX3 has been shown to be produced in response to microbial infections, and highly elevated levels were reported in patients with sepsis. In this study, PTX3 levels were evaluated in sera of a group of patients with haematological malignancy. Our findings indicate that serum PTX3 was elevated in only 1/11 afebrile episodes, despite evidence of mucositis (median 1.39), in 10/10 episodes of blood stream or target organ infections (median 7.2) but, surprisingly, was normal in 5/5 episodes of invasive aspergillosis (median 1.39). The data suggest that serum PTX3 levels are elevated selectively in response to infection. These disparate responses require further study.

C-Reactive Protein↗
PubMed2004

The role of scavenger receptors in pathogen recognition and innate immunity.

Scavenger receptors represent a large family of structurally unrelated distinct gene products, expressed by myeloid and selected endothelial cells and able to recognise modified low-density lipoproteins. They also bind and internalise a variety of microbial pathogens, as well as modified or endogenous molecules derived from the host, and contribute to a range of physiological or pathological processes.

Animals↗
PubMedDate not supplied

A role for innate immunity in type 1 diabetes?

Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and gammadelta T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes.

Animals↗
PubMed2001

Toll-like receptors control activation of adaptive immune responses.

Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-kappaB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.

Adaptor Proteins, Signal Transducing↗
PubMed2002

How instruction and feedback can select the appropriate T helper response.

The decision of the immune system to trigger immune responses that are, respectively, induced by Th1 or Th2 effectors is a critical one, because it profoundly influences disease outcome. We have recently constructed a mathematical model of Th1-Th2-pathogen interactions that shows that the major decisional events can often be successfully determined by the intrinsic behaviour of the T helper system itself. For certain dangerous types of pathogens, however, which replicate rapidly or have developed strategies to evade the immune response, additional stimuli may be necessary. As a possible mechanism for the decision-making process innate immune recognition has been proposed. Here we present an enlarged version of our model, which incorporates signals created from the innate immune system after pathogen recognition. The model analysis suggests that there is fault-tolerance of the T helper system to incorrect Th1 signals. In the presence of incorrect Th1 stimuli an initial Th1 response is shifted to the correct Th2-dominated response owing to the intrinsic T helper dynamics. By contrast, according to our model there is no fault-tolerance for incorrect Th2 signals. In fact, if timing is unimportant then Th2 signals are superfluous since the intrinsic T helper dynamics provide an automatic switch to Th2 if Th1 effectors fail to control the pathogen. Th2 signals may, however, be required to accelerate the onset of the Th2 response. Additionally, we discuss the role of feedback where successful pathogen destruction leads to up-regulation of activation of the effective T helper type. As one possibility we examine the role of CpG motifs as indicators for successful pathogen destruction. Differences between instructive and feedback mechanisms are highlighted.

Animals↗
PubMed2003

Evolution of complement as an effector system in innate and adaptive immunity.

For a long time, the complement system in mammals has been regarded as a biological system that plays an essential role in innate immunity. More recently, it has been recognized that the complement system contributes heavily to the generation and development of an acquired immune response. In fact, this ancient mechanism of defense has evolved from a primitive mechanism of innate immune recognition in invertebrate species to that of an effector system that bridges the innate with the adaptive immune response in vertebrate species. When and how did complement evolve into a shared effector system between innate and adaptive immunity? To answer this question, our group is interested in understanding the role of complement in innate and adaptive immune responses in an evolutionary relevant species: the teleost fish. The attractiveness of this species as an animal model is based on two important facts. First, teleost fish are one of the oldest animal species to have developed an adaptive immune response. Second, the complement system of teleost fish offers a unique feature, which is the structural and functional diversity of its main effector protein, C3, the third component of the complement system.

Animals↗
PubMed2004

Dynamic changes in the localization of MAPK cascade components controlling pathogenesis-related (PR) gene expression during innate immunity in parsley.

The activation of mitogen-activated protein kinase (MAPK) cascades is an important mechanism for stress adaptation through the control of gene expression in mammals, yeast, and plants. MAPK activation has emerged as a common mechanism by which plants trigger pathogen defense responses following innate immune recognition of potential microbial pathogens. We are studying the non-host plant defense response of parsley to attempted infection by Phytophthora species using an experimental system of cultured parsley cells and the Phytophthora-derived Pep-13 peptide elicitor. Following receptor-mediated recognition of this peptide, parsley cells trigger a multifaceted innate immune response, involving the activation of three MAPKs that have been shown to function in the oxidative burst-independent activation of defense gene expression. Using this same experimental model we now report the identification of a MAPK kinase (MAPKK) that functions upstream in this pathway. This kinase, referred to as PcMKK5 based on sequence similarity to Arabidopsis thaliana AtMKK5, is activated in parsley cells following Pep-13 treatment and functions as an in vivo activator of all three MAPKs previously shown to be involved in this response. Gain- and loss-of-function mutant versions of PcMKK5, when used in protoplast co-transfection assays, demonstrated that kinase activity of PcMKK5 is required for PR gene promoter activation following Pep-13 treatment. Furthermore, using specific antibodies and immunofluorescent labeling, we demonstrate that activation of MAPKs in parsley cells correlates with an increase in their nuclear localization, which is not detectable for activated PcMKK5. These results suggest that activation of gene expression through MAPK cascades during innate immune responses in plants involves dynamic changes in the localization of the proteins involved, which may reflect the distribution of key protein substrates for the activated MAPKs.

Arabidopsis↗
PubMed2005

Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess.

Toll-like receptor 2 (TLR2) is a pattern recognition receptor (PRR) that plays an important role in innate immune recognition of conserved structural motifs on a wide array of pathogens, including Staphylococcus aureus. To ascertain the functional significance of TLR2 in the context of central nervous system (CNS) parenchymal infection, we evaluated the pathogenesis of S. aureus-induced experimental brain abscess in TLR2 knockout (KO) and wild-type (WT) mice. The expression of several proinflammatory mediators, including inducible nitric oxide synthase, tumor necrosis factor alpha, and macrophage inflammatory protein-2, was significantly attenuated in brain abscesses of TLR2 KO mice compared to WT mice during the acute phase of infection. Conversely, interleukin-17 (IL-17), a cytokine produced by activated and memory T cells, was significantly elevated in lesions of TLR2 KO mice, suggesting an association between innate and adaptive immunity in brain abscess. Despite these differences, brain abscess severity in TLR2 KO and WT animals was similar, with comparable mortality rates, bacterial titers, and blood-brain barrier permeability, implying a role for alternative PRRs. Expression of the phagocytic PRRs macrophage scavenger receptor type AI/AII and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was increased in brain abscesses of both TLR2 KO and WT mice compared to uninfected animals. However, LOX-1 induction in brain abscesses of TLR2 KO mice was significantly attenuated compared to WT animals, revealing that the TLR2-dependent signal(s) influence LOX-1 expression. Collectively, these findings reveal the complex nature of gram-positive bacterial recognition in the CNS which occurs, in part, through engagement of TLR2 and highlight the importance of receptor redundancy for S. aureus detection in the CNS.

Animals↗
PubMed2004

Innate immune responses in peptidoglycan recognition protein L-deficient mice.

Peptidoglycan recognition proteins (PGRPs) constitute a family of innate immune recognition molecules. In Drosophila, distinct PGRPs bind to peptidoglycans on gram-positive or gram-negative bacteria and provide essential signals upstream of the Toll and Imd pathways required for immunity against infection. Four PGRPs, PGRP-L, -S, -Ialpha, and -Ibeta, are expressed from three genes in mammals. In this paper, we provide direct evidence that the longest family member, PGRP-L, is a secreted serum protein with the capacity to multimerize. Using gene targeting to create PGRP-L-deficient mice, we demonstrate little contribution by PGRP-L to systemic challenge using gram-negative bacteria (Escherichia coli, slightly less susceptible), Gram-positive bacteria (Staphylococcus aureus), or yeast (Candida albicans). Peritoneal macrophages from PGRP-L-deficient mice produced decreased amounts of the inflammatory cytokines interleukin 6 and tumor necrosis factor alpha when stimulated with E. coli or lipopolysaccharide, but comparable amounts when stimulated with S. aureus, C. albicans, or their cell wall components. Additionally, these cells produced similar amounts of cytokines when challenged with gram-positive or -negative peptidoglycans. In contrast to its critical role in immunity in flies, PGRP-L is largely dispensable for mammalian immunity against bacteria and fungi.

Animals↗
PubMed2006

Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR-independent production of IFN-beta.

Vaccinia virus (VV) has been used extensively as a vaccine vehicle in the clinical application for infectious diseases and cancer. Previous studies have suggested that the unique potency of VV-based vaccine lies in its effective activation of the innate immune system. However, how VV activates innate immune pathways remains largely unknown. In this study, we showed that VV elicited innate immune response through both Toll-like receptor (TLR)-dependent and -independent pathways. The TLR pathway was mediated by TLR2 and MyD88, leading to the production of proinflammatory cytokines, whereas activation of the TLR-independent pathway resulted in the secretion of IFN-beta. More importantly, both TLR-dependent and -independent pathways were required for activating innate and adaptive immunity to VV in vivo. These findings represent the first evidence that innate immune recognition of VV is mediated by TLR2, demonstrate that one pathogen can target both TLR and non-TLR innate immune pathways to work together in achieving efficient activation of host defense, and suggest potential new strategies for the design of effective vaccines.

Animals↗
PubMed2000

Immune-type diversity in the absence of somatic rearrangement.

Immunoglobulin gene diversity has been characterized to varying degrees in modern representatives of all of the major radiations of cartilaginous fish. A pattern of overall chromosomal relationships of the various types of joined and unjoined Ig gene clusters is suggested in which the essential features are: (a) both Ig heavy and light-chain gene clusters occur on multiple chromosomes, (b) various classes of Ig are interspersed, (c) not all individual gene loci appear to be closely linked (Fig. 2). The cluster-type Ig gene system appears to be a series of (potentially) individually regulated loci analogous in part to the olfactory receptor gene system (BUCK and AXEL 1991) and markedly distinct from Ig loci in other vertebrate groups and TCR genes. Such a system would be ideal for the creation of variation in both form and function in a large number of clusters while preserving or partially preserving specificity in a number of other gene clusters. The full range of joined genes and the relative number of joined genes (as relates to unjoined genes), have yet to be determined. Nevertheless, a number of conclusions can be drawn: (a) four distinct forms of heavy-chain joining have been identified (VDD-J, VD-DJ, V-D-DJ, and VDJ; Fig. 1); (b) light-chain genes, which possess only two recombining elements, can be found in either unjoined (V-J) or joined (VJ) forms (Fig. 1); (c) physical linkage between individual joined and unjoined genes has not been established, although such investigations have not been pursued in a significantly rigorous manner as to rule out this possibility; (d) joined light-chain genes are expressed and can be somatically mutated. Can germline joining be viewed as an ancestral character? The answer to this needs to be considered in the context of an overall system in which the level of structural and functional redundancy is extremely high. Joining is an adaptation that is unique to multicluster gene families. The phenomenon overcomes the possibility of not generating a specific form of a receptor, a major shortcoming of conventional rearranging Ig and TCR gene systems. The limitation of encoding specific receptors is compensated through large numbers of additional gene clusters that retain the capacity to rearrange and generate new specificities. Commitment of a V region to diverse, fixed specificity also is a property of the NITR genes, which although not related closely to Ig in a structural sense, may reflect an analogous phenomena. The possibility that immune-type diversity is achieved in the absence of somatic rearrangement and that remnants of such systems could be operative in immune recognition in contemporary vertebrates is of extraordinary significance in terms of our overall understanding of the relationships between adaptive and innate immune recognition.

Animals↗
PubMed2000

Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex.

The membrane protein complex CD19/CD21 couples the innate immune recognition of microbial antigens by the complement system to the activation of B cells. CD21 binds the C3d fragment of activated C3 that becomes covalently attached to targets of complement activation, and CD19 co-stimulates signaling through the antigen receptor, membrane immunoglobulin. CD21 is also expressed by follicular dendritic cells and mediates the long-term retention of antigen that is required for the maintenance of memory B cells. Understanding of the biology of this receptor complex has been enriched by analyses of genetically modified mice; these analyses have uncovered roles not only in positive responses to foreign antigens, but also in the development of tolerance to self-antigens. Studies of signal transduction have begun to determine the basis for the coreceptor activities of CD19. The integration of innate and adaptive immune recognition at this molecular site on the B cell guides the appropriate selection of antigen by adaptive immunity and emphasizes the importance of this coreceptor complex.

Animals↗
PubMed2003

[Antiinfective host defense mechanism: toll-like receptors and innate immunity].

The innate immune system has evolved as the first line of defense against invading microorganisms. The recent discovery of the toll-like receptors(TLRs) has rapidly expanded our knowledge of molecular events that initiate host-pathogen interactions. The TLRs, which are expressed on the surface of cells, involved in innate immune recognition, including macrophages and dendritic cells, have a crucial role in the detection of microbial infection. Signals initiated by the interaction of TLRs with pathogen-associated molecular patterns (PAMPs) induce activation of the inflammatory and antimicrobial innate immune response. Ten members of the TLR family have been identified, and they appear to recognize PAMPs, including lipopolysaccharide, peptidoglycan, and bacterial DNA. There has been considerable interest in how adaptive immune responses are controlled by the innate immune system. Recent studies have suggested that TLRs may control the induction of Th1 responses and that a separate system of recognition regulates the Th2 response. Thus TLR signaling represents a key component in the innate immune response to microbial infection.

Animals↗