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Results for “Adaptive Immunity”

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At least 163 records · Page 9Linked to original sources

PubMed2005

Turning down the system: counter-regulatory mechanisms in bone and adaptive immunity.

Major advances have been made in recent years toward the identification of transcription factors that control cell-type-specific gene expression in the skeletal and adaptive immune systems. However, the identification of factors necessary and sufficient to drive production of effector cell proteins such as matrix components and cytokines represents the first step toward understanding how cells in bone and the adaptive system achieve their highly specialized functions. Here, we provide selected examples of counter-regulatory mechanisms that serve to turn down cells involved in extracellular matrix biosynthesis and adaptive immunity at the level of the transcription factors Runx2 and nuclear factor for the activation of T cells.

Animals↗

PubMed2004

The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation.

Dendritic cell (DC) maturation is an innate response that leads to adaptive immunity to coadministered proteins. To begin to identify underlying mechanisms in intact lymphoid tissues, we studied alpha-galactosylceramide. This glycolipid activates innate Valpha14(+) natural killer T cell (NKT) lymphocytes, which drive DC maturation and T cell responses to ovalbumin antigen. Hours after giving glycolipid i.v., tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were released primarily by DCs. These cytokines induced rapid surface remodeling of DCs, including increased CD80/86 costimulatory molecules. Surprisingly, DCs from CD40(-/-) and CD40L(-/-) mice did not elicit CD4(+) and CD8(+) T cell immunity, even though the DCs exhibited presented ovalbumin on major histocompatibility complex class I and II products and expressed high levels of CD80/86. Likewise, an injection of TNF-alpha up-regulated CD80/86 on DCs, but CD40 was required for immunity. CD40 was needed for DC interleukin (IL)-12 production, but IL-12p40(-/-) mice generated normal ovalbumin-specific responses. Therefore, the link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation ("signal one") and costimulation ("signal two") to generate functioning CD4(+) T helper cell 1 and CD8(+) cytolytic T lymphocytes.

Animals↗

PubMed2006

Gamma delta T cells facilitate adaptive immunity against West Nile virus infection in mice.

West Nile (WN) virus causes fatal meningoencephalitis in laboratory mice, and gammadelta T cells are involved in the protective immune response against viral challenge. We have now examined whether gammadelta T cells contribute to the development of adaptive immune responses that help control WN virus infection. Approximately 15% of TCRdelta(-/-) mice survived primary infection with WN virus compared with 80-85% of the wild-type mice. These mice were more susceptible to secondary challenge with WN virus than the wild-type mice that survived primary challenge with the virus. Depletion of gammadelta T cells in wild-type mice that survived the primary infection, however, does not affect host susceptibility during secondary challenge with WN virus. Furthermore, gammadelta T cells do not influence the development of Ab responses during primary and at the early stages of secondary infection with WN virus. Adoptive transfer of CD8(+) T cells from wild-type mice that survived primary infection with WN virus to naive mice afforded partial protection from lethal infection. In contrast, transfer of CD8(+) T cells from TCRdelta(-/-) mice that survived primary challenge with WN virus failed to alter infection in naive mice. This difference in survival correlated with the numeric and functional reduction of CD8 memory T cells in these mice. These data demonstrate that gammadelta T cells directly link innate and adaptive immunity during WN virus infection.

Adoptive Transfer↗

PubMed2005

Kinetics of adaptive immunity to Haemophilus influenzae type b meningitis in transgenic mice: evidence from diverse expression of double T1/T2 transgenes and Th1/Th2-related cytokines.

To investigate the kinetic changes in adaptive immunity during experimental Haemophilus influenzae type b (Hib) meningitis, we established a murine meningitis model based on T1/T2 doubly transgenic mice. These mice carry two transgenes that express two distinct cell-surface markers: a human Thy1 transgene (hThy1) under the control of the murine IFN-gamma promoter, and a murine Thy1.1 transgene (mThy1.1) under the control of the murine IL-4 promoter, designated T1 and T2, respectively. Mice infected with Hib displayed severest symptoms and lowest total splenocyte counts on day 3 after infection. Simultaneously, we examined the significantly low percentage of CD19+ B cells, the relatively high level of CD4+ T cells and significantly high percentage of CD8+ T cells in Hib-infected mice. Furthermore, we observed the early induction of both Th1 and Th2 responses, in terms of the augmentation of Th1 cells (IFN-gamma-producing CD4+ T cells) and Th2 cells (IL-4-producing CD4+ T cells) in Hib-infected mice. On day 7 after infection, the Th1 response gradually declined and the Th2 response rather sustained. Two weeks after infection, both Th1 and Th2 cells were barely detectable. Moreover, we demonstrated using an antigen-specific re-stimulation test to analyze the effector function of lymphocyte subsets that CD8+ T cells contributed to more predominantly production of IFN-gamma than CD4+ T cells did; and CD4+ T cells partly contributed to the secretion of IL-4 from flowcytometry of intracellular cytokine staining. Our results support that these transgenic mice provide an available model to dissect the complex kinetic change of adaptive immunity in bacterial infectious diseases.

Adaptation, Physiological↗

PubMed2004

Inverse trend between estimated worldwide frequency of major cancers and inferred infectious burdens of populations: possible role of adaptive immune system.

Regions of the world subjected to heavy infectious burdens seem to show lower incidence of cancer. The index of infectious burden in this study has been chosen to be poverty, i.e., low GDP, high infantile mortality, poor hygienic conditions, inaccessibility to modern medical infra-structures, etc. When estimates of observed cancer incidence is plotted against the GDP of 24 regions of the world, a trend line is obtained: low GDP (a proxy for high infectious burden) tends to be associated with low incidence of cancer whereas high GDP values herald higher cancer occurrences. Similarly, countries with high infantile mortality rates tend to have a lower incidence of cancer and vice versa. The data are explained in terms of the so-called "hygiene hypothesis": frequent infectious onslaughts, especially in childhood, challenge the immune system and build a strong adaptive immune system and immunological memory which prepare the body to tackle further battles down the line, such as cancer. Within this framework, the role of other factors such as diet, selenium, hardness of water, etc. in the aetiology of cancer is also briefly examined. For rigorous verification of this observation, age-adjusted cancer incidence rates for various countries must be used even though such data are not available for all the countries examined here [Bulletin of World Health Organization 62(2) (1984) 163]; where data are available [Age-adjusted death rates for cancer for selected sites (A classification) in 51 countries in 1974, Segi Institute of Cancer Epidemiology, Nagoya, Japan (Feb. 1979); Global Geocancerology, Churchill Livingstone, New York, 1986], the same trend is also observed for the age-adjusted cancer death rates, which may be used as an index of age-adjusted cancer incidence, subject to qualifications discussed in the text.

Developing Countries↗

PubMed2004

The evolution of alloimmunity and the genesis of adaptive immunity.

Infectious agents select for host immune responses that destroy infectious nonself yet maintain tolerance to self. Here we propose that retroviruses and other host-antigen associated pathogens (HAAPs) select for the genetic, biochemical, and cell biological properties of alloimmunity, also known as the histocompatibility or tissue rejection response. This hypothesis predicts the major observations regarding histocompatibility responses, including: (i) their existence in animals as diverse as sponges and humans; (ii) extreme polymorphism and balanced allele frequencies at histocompatibility loci, including the human MHC and blood group loci; (iii) the frequency dependent selection of histocompatibility alleles; (iv) the ancient age of many alloantigenic polymorphisms; (v) the high ratio of nonsynonymous mutations to synonymous mutations at histocompatibility loci; (vi) disassortative mating based on MHC alleles; (vii) the inability to explain the existence and continuing selection of histocompatibility alleles by other more conventional biochemical and genetic paradigms; and (viii) the susceptibility of HAAPs, particularly retroviruses such as HIV (human immunodeficiency virus), to histocompatibility reactions. In addition, the hypothesis that HAAPs select the forms and molecules of alloimmunity offers simple explanations for the evolution of histocompatibility systems over time, the initial selection of hypervariable immune mechanisms, and the genesis of adaptive immunity.

Alleles↗

PubMed2005

The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces.

Secretory antibodies of the immunoglobulin A (IgA) class form the first line of antigen-specific immune protection against inhaled, ingested, and sexually transmitted pathogens and antigens at mucosal surfaces. Epithelial transcytosis of polymeric IgA (pIgA) is mediated by the polymeric immunoglobulin receptor (pIgR). At the apical surface, the extracellular ligand-binding region of pIgR, known as secretory component (SC), is cleaved and released in free form or as a component of secretory IgA (SIgA). SC has innate anti-microbial properties, and it protects SIgA from proteolytic degradation. Expression of pIgR is regulated by microbial products through Toll-like receptor signaling and by host factors such as cytokines and hormones. Recent studies of the structure of the extracellular ligand-binding domain of pIgR have revealed mechanisms by which it binds pIgA and other ligands. During transcytosis, pIgA has been shown to neutralize pathogens and antigens within intracellular vesicular compartments. The recent identification of disease-associated polymorphisms in human pIgR near the cleavage site may help to unravel the mystery of how pIgR is cleaved to SC. The identification of novel functions for SC and SIgA has expanded our view of the immunobiology of pIgR, a key component of the mucosal immune system that bridges innate and adaptive immune defense.

Animals↗

PubMed2002

The administration of cortisone to female B6A mice during their immune adaptive period causes anovulation and the formation of ovarian cysts.

PROBLEM: Female mice that are injected with estradiol-17beta (E2) and testosterone during the 7-day immune adaptive period are infertile at adulthood. To determine whether the resultant infertility can be caused by steroids other than estrogens/ androgens, this study examined the effect of injecting cortisone, alone, and in combination with E2 and testosterone, on reproductive function. METHOD OF STUDY: Neonatal (C57BL/6J x A/J)F1 B6A female mice were injected from 3 to 6 days of age with sesame oil:ethanol (9:1; v:v), alone, or containing 20 microgg cortisone acetate, 20 microg E2, or 20 microg testosterone. Two additional groups were given 20 microg cortisone acetate in combination with 20 microg E2 or 20 microg testosterone. At adulthood the animals were killed, the stage of vaginal estrus determined, the ovaries examined for the presence of corpora lutea and follicular cysts, and circulating levels of progesterone, E2, and testosterone were measured by radioimmunoassay (RIA). RESULTS: It was found that injections of cortisone seriously compromise reproductive development. For example, 11% of cortisone-injected animals had ovaries that lacked corpora lutea. In addition, 39% of cortisone-injected females had ovaries with follicular cysts. Cortisone-injected females also had low levels of circulating progesterone (18 ng/mL versus 30 ng/mL for the sesame oil-injected females). CONCLUSION: It is concluded that the deleterious effect of steroids on reproductive function, when administered during the immune adaptive period, is not restricted to estrogens and androgens. It is proposed that injections of cortisone alter T-lymphocyte subsets, which contributes to anovulation and the production of follicular cysts.

Animals↗

PubMed2006

Immune adaptive response induced by Bicotylophora trachinoti (Monogenea: Diclidophoridae) infestation in pompano Trachinotus marginatus (Perciformes: Carangidae).

Fish have developed protective strategies against monogeneans through immunological responses. In this study, immune adaptive response to parasites was analysed in the pompano Trachinotus marginatus infested by Bicotylophora trachinoti. Hosts were pre-treated with formalin and after 10 days assigned to one of the following experimental treatments: (1) fish infested with remaining eggs of B. trachinoti; (2) fish infested with remaining eggs of B. trachinoti and experimentally re-infested by exposure to T. marginatus heavily infested with B. trachinoti. Samples were collected at 0, 15, and 30 days. Gills were dissected to check the presence of B. trachinoti. Blood was collected for haematological and biochemical assays. Spleen and head-kidney were dissected for phagocytosis assay. The spleen-somatic index was also calculated. Re-infested fish showed a faster and higher parasite infestation than infested ones. The parasite mean abundance at 15 days was 24.86+/-13.32 and 11.67+/-8.57 for re-infested and infested fish, respectively. In both groups, hosts showed an immune adaptive response to parasite infestation that was marked by an increased number of leukocytes. Also, phagocytosis (%) in spleen and head-kidney cells was stimulated after parasite infestation (92.50+/-3.73 and 66.00+/-9.54, respectively), becoming later depressed (77.39+/-6.69 and 53.23+/-9.14, respectively). These results support the hypothesis that monogenean infestation induces a biphasic response of the non-specific defence mechanisms in the pompano T. marginatus. This response is marked by an initial stimulation followed by a later depression of the non-specific defence mechanisms.

Animals↗

PubMed2005

Mast cells in the development of adaptive immune responses.

Mast cells are so widely recognized as critical effector cells in allergic disorders and other immunoglobulin E-associated acquired immune responses that it can be difficult to think of them in any other context. However, mast cells also can be important as initiators and effectors of innate immunity. In addition, mast cells that are activated during innate immune responses to pathogens, or in other contexts, can secrete products and have cellular functions with the potential to facilitate the development, amplify the magnitude or regulate the kinetics of adaptive immune responses. Thus, mast cells may influence the development, intensity and duration of adaptive immune responses that contribute to host defense, allergy and autoimmunity, rather than simply functioning as effector cells in these settings.

Animals↗

PubMed2005

[A state of innate and adaptive immunity in children with schizophrenia and in the high-risk group for the disease].

Leukocyte elastase (LE) activity, alpha1-proteinase inhibitor (alpha1-PI), C-reactive protein (CRP) as the indices of innate immunity and the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein (Aab-BMP) as the indices of adaptive immunity have been studied in the blood serum of 40 children at high risk for schizophrenia and in 32 children with schizophrenia. In the high-risk group, an increase both of the LE activity, CRP content and variance of alpha1-PI concentrations, indicating the activation of innate immunity, was found. LE activity correlated with severity of schizotypal diathesis. The development of schizophrenic process is accompanied by generalization of the immune response: along with activation of the innate immunity, there was activation of immunity acquired as an increase of the level of autoantibodies to neuroantigenes. It is suggested that activation of innate and adaptive immunity is related to the processes determining the disturbances of the nervous system development.

Autoantibodies↗

PubMed2006

Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function.

BACKGROUND: Dendritic cells (DCs) are central to the initiation and regulation of the adaptive immune response during infection. Modulation of DC function may therefore allow evasion of the immune system by pathogens. Significant depression of the host's systemic immune response to both concurrent infections and heterologous vaccines has been observed during malaria infection, but the mechanisms underlying this immune hyporesponsiveness are controversial. RESULTS: Here, we demonstrate that the blood stages of malaria infection induce a failure of DC function in vitro and in vivo, causing suboptimal activation of T cells involved in heterologous immune responses. This effect on T-cell activation can be transferred to uninfected recipients by DCs isolated from infected mice. Significantly, T cells activated by these DCs subsequently lack effector function, as demonstrated by a failure to migrate to lymphoid-organ follicles, resulting in an absence of B-cell responses to heterologous antigens. Fractionation studies show that hemozoin, rather than infected erythrocyte (red blood cell) membranes, reproduces the effect of intact infected red blood cells on DCs. Furthermore, hemozoin-containing DCs could be identified in T-cell areas of the spleen in vivo. CONCLUSION: Plasmodium infection inhibits the induction of adaptive immunity to heterologous antigens by modulating DC function, providing a potential explanation for epidemiological studies linking endemic malaria with secondary infections and reduced vaccine efficacy.

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↗

PubMed2004

Toll-like receptors: linking innate and adaptive immunity.

Detection of and response to microbial infections by the immune system depends largely on a family of pattern-recognition receptors called Toll-like receptors (TLRs). These receptors recognize conserved molecular products derived from various classes of pathogens, including Gram-positive and -negative bacteria, DNA and RNA viruses, fungi and protozoa. Recognition of ligands by TLRs leads to a series of signaling events resulting in induction of acute responses necessary to kill the pathogen. TLRs are also responsible for the induction of dendritic cell maturation, which is responsible and necessary for initiation of adaptive immune responses. Although TLRs control induction of adaptive immunity, it is not clear at this point how responses are appropriately tailored by individual TLRs to the advantage of the host.

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↗

PubMed2025

Implications of EGFR expression on EGFR signaling dependency and adaptive immunity against EGFR-mutated lung adenocarcinoma.

BACKGROUND: In EGFR-mutated lung adenocarcinoma (EGFRm LUAD), EGFR mutations do not necessarily result in increased EGFR expression (EGFR-exp), which differs among patients. However, the factors influencing EGFR-exp and the impact of EGFR-exp on tumor characteristics in patients with EGFRm LUAD remain unclear. PATIENTS AND METHODS: Whole-exome and RNA sequencing were performed for patients with early- and advanced-stage EGFRm LUAD. The patients were classified into low or high EGFR-exp groups based on the median transcripts per million. We retrospectively examined the association between EGFR-exp, genomic characteristics, downstream EGFR signaling activity, tumor microenvironment (TME) status, and clinical outcomes. RESULTS: This study included 450 and 45 patients in the early- and advanced-stage cohorts, respectively. In both cohorts, the EGFR-exp low group exhibited a lower incidence of TP53 co-mutations and EGFR amplification and a higher incidence of EGFR subclonal mutations than the EGFR-exp high group. Furthermore, downstream EGFR signaling pathways, such as the MAPK signaling, were less activated in the EGFR-exp low group. However, this group showed significantly enriched adaptive immune response pathways (Q < 0.0001) and an immune-inflamed TME. Additionally, a low EGFR-exp was a significantly favorable factor for postoperative relapse (odds ratio [OR], 0.6; P = 0.04). However, in the advanced-stage cohort, a low EGFR-exp was a significant risk factor for non-responders to osimertinib (OR, 17.5; P = 0.03). CONCLUSIONS: In EGFRm LUAD, significant associations were observed between EGFR-exp levels and both EGFR signaling pathways and adaptive immune status, which in turn influence clinical outcomes. This large-scale multi-omics analysis highlights the heterogeneity among patients with EGFRm LUAD and emphasizes the need to assess EGFR-exp levels alongside mutation status for optimal treatment strategies in EGFRm LUAD.

Humans↗

PubMed2004

Toll-like receptor control of the adaptive immune responses.

Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms. Toll-like receptors (TLRs) have recently emerged as a key component of the innate immune system that detect microbial infection and trigger antimicrobial host defense responses. TLRs activate multiple steps in the inflammatory reactions that help to eliminate the invading pathogens and coordinate systemic defenses. In addition, TLRs control multiple dendritic cell functions and activate signals that are critically involved in the initiation of adaptive immune responses. Recent studies have provided important clues about the mechanisms of TLR-mediated control of adaptive immunity orchestrated by dendritic cell populations in distinct anatomical locations.

Adaptation, Physiological↗

PubMed2004

Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response.

While the initiation of the adaptive and innate immune response is well understood, less is known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane receptor of the immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these animal models RAGE does not play a role in the adaptive immune response. However, deletion of RAGE provides protection from the lethal effects of septic shock caused by cecal ligation and puncture. Such protection is reversed by reconstitution of RAGE in endothelial and hematopoietic cells. These results indicate that the innate immune response is controlled by pattern-recognition receptors not only at the initiating steps but also at the phase of perpetuation.

Animals↗