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Results for “Adaptive Immunity”

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At least 937 records · Page 52Linked to original sources

PubMed2006

A review of CpGs and their relevance to aquaculture.

CpG oligodeoxynucleotides (ODN) have been described as functioning as natural adjuvants because they promote professional antigen presenting cell (APC) function and co-stimulate lymphocytes. The majority of studies into the immune effects of CpG ODN to date have been carried out on mammals where they are proving very successful at stimulating innate and adaptive immune responses in a variety of species as well as protecting them from bacterial, viral and protozoan pathogens. Fish also possess the ability to raise both innate and adaptive immune responses to invading pathogens and interest in the effect of CpG ODN on the piscine immune system is growing. Various studies have now been carried out to elicit the effects of CpG ODN on diverse fish species showing that 31 different B-class CpG ODN exert various immune responses both in vivo and in vitro in salmonids, cyprinids and pleuronectiformes. These responses include activation of macrophages, proliferation of leucocytes and stimulation of cytokine expression. CpG ODN have also been shown to be protective against bacterial and viral challenge as well as against pathogenic amoebae. As would be expected these effects are all dependent on not only the ODN sequence and length but on the concentration and the species in which it is being used. This review provides the first comprehensive overview of all CpG ODN tested in fish to date and brings together all the work carried out in this field.

Adjuvants, Immunologic↗

PubMed2002

Immunology of viral-vector-mediated gene transfer into the brain: an evolutionary and developmental perspective.

The immune system imposes limitations on gene transfer into the brain. Viral vectors injected into the brain's ventricular system elicit innate and adaptive immune responses. However, when injected directly into the brain parenchyma, they elicit only transient inflammation owing to the absence of dendritic cells, which transport antigen to lymph nodes and present it to naive T cells to initiate adaptive immune responses. This article explores the evolutionary and developmental basis of brain immune responses and their implications for viral-vector-mediated neurological gene therapy. Elucidating the cellular and molecular basis of these differential reactions is essential to the long-term success of neurological gene therapy.

Animals↗

PubMed2005

Papillomavirus virus-like particles induce cytokines characteristic of innate immune responses in plasmacytoid dendritic cells.

Human papillomavirus (HPV) virus-like particles (VLP) are being extensively tested as vaccines for the prevention of HPV-associated cervical cancer. Dendritic cells (DC) acquire and present antigens, initiating innate and adaptive immune responses. It has been shown previously that DC of the myeloid lineage are capable of generating adaptive immune responses to HPV VLP in vitro. However, the capacity of plasmacytoid DC (pDC) to acquire HPV VLP and the nature of the immune response generated have not been reported. In this study we found that freshly isolated as well as CpG-matured pDC bind papillomavirus VLP and that internalization occurs preferentially in the immature pDC. In contrast to myeloid DC, pDC did not undergo phenotypic maturation upon exposure to HPV16 VLP. However, HPV16 VLP induced pDC to secrete of IFN-alpha and IL-6, both cytokines that play a role in the generation of antibody responses, as well as TNFalpha and IL-8. Given that VLP do not contain viral nucleic acids, these results indicate that viral capsids alone may be capable of inducing cytokine production by pDC. Finally, CpG-activated pDC, but not pDC exposed to HPV16 VLP, activated lymphocytes to secrete IL-10 and low levels of IFN-gamma. Together these findings suggest a possible immunogenic effect of pDC in the setting of VLP vaccination.

Animals↗

PubMed2005

Role of vasoactive intestinal peptide in inflammation and autoimmunity.

Vasoactive intestinal peptide (VIP), a peptide produced by immune cells, exerts a wide spectrum of immunological functions that control the homeostasis of the immune system. In the last decade, VIP has been clearly identified as a potent anti-inflammatory factor, both in innate and adaptive immunity. In innate immunity, this peptide inhibits the production of inflammatory cytokines and chemokines from macrophages, microglia and dendritic cells. In addition, VIP reduces the expression of co-stimulatory molecules on antigen-presenting cells, and therefore reduces stimulation of antigen-specific CD4 T-cells. In terms of adaptive immunity, VIP promotes T-helper (Th)2-type responses, and reduces inflammatory Th1-type responses. Several of the molecular mechanisms involved in the inhibition of cytokine and chemokine expression, and in the preferential development and/or survival of Th2 effectors are known. Therefore, VIP and its analogs have been proposed as promising alternative candidates to existing therapies for the treatment of acute and chronic inflammatory and autoimmune diseases. The aim of this review is to update knowledge of the cellular and molecular events that are relevant to VIP function in the immune system. The central functions that VIP plays in cellular processes is being recognized and attention is being focused on this important peptide with regard to exciting new candidates for therapeutic intervention and drug development.

Animals↗

PubMed2003

A review of the influence of aqueous humor on immunity.

Regulation of immunity within the immune-privileged ocular microenvironment is a dynamic interaction of anatomical features, factors, and cells that work toward suppressing the induction inflammation. Immunosuppressive neuropeptides found in aqueous humor are central to this immunoregulation. These neuropeptides are alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, calcitonin gene-related peptide, and somatostatin. Along with transforming growth factor-beta2, the neuropeptides target specific cells and pathways in innate and adaptive immunity. These aqueous humor factors prevent pathogen-induced inflammation and activation of Th1 cells, while promoting induction of regulatory T cells. Therefore, the ocular microenvironment, through the constitutive production of immunosuppressive factors found in aqueous humor, maintains immune privilege by manipulating regional innate and adaptive immunity away from inflammatory responses.

Aqueous Humor↗

PubMed2006

Immunotargeting with CD154 (CD40 ligand) enhances DNA vaccine responses in ducks.

Engagement of CD154 on activated T cells with CD40 on antigen-presenting cells (APCs) potentiates adaptive immune responses in mammals. Soluble multimeric forms of CD154 have been used as an adjuvant or in immunotargeting strategies to enhance vaccine responses. The objective of our study was to examine the ability of duck CD154 (DuCD154) to enhance DNA vaccine responses in the duck hepatitis B model. Constructs were generated to express the functional domain of DuCD154 (tCD154), truncated duck hepatitis B virus (DHBV) core antigen (tcore) and chimera of tcore fused to tCD154 (tcore-tCD154). Expression in LMH cells demonstrated that all proteins were secreted and that tCD154 and tcore-tCD154 formed multimers. Ducks immunized with the plasmid ptcore-tCD154 developed accelerated and enhanced core-specific antibody responses compared to ducks immunized with ptcore or ptcore plus ptCD154. Antibody responses were better sustained in both ptcore-tCD154- and ptcore plus ptCD154-immunized ducks. Core-specific proliferative responses of duck peripheral blood mononuclear cells were enhanced in ducks immunized with ptcore-tCD154 or ptcore alone. This study suggests that the role of CD154 in the regulation of adaptive immune responses had already evolved before the divergence of birds and mammals. Thus, targeting of antigens to APCs with CD154 is an effective strategy to enhance DNA vaccine responses not only in mammalian species but also in avian species.

Adjuvants, Immunologic↗

PubMed2002

[beta]-defensins in lung host defense.

Host defenses at the mucosal surface of the airways evolved to present many layers of protection against inhaled microbes. Normally, the intrapulmonary airways are sterile. Airway secretions contain numerous factors with antimicrobial activity that contribute to innate defenses. Many protein and peptide components exert bacteriostatic or bacteriocidal effects against a wide variety of organisms and may act in synergistic or additive combinations. The beta-defensins are a relatively recently described family of peptide antimicrobials that are widely expressed at mucosal surfaces, including airway and submucosal gland epithelia. These small cationic peptides are products of individual genes that exhibit broad-spectrum activity against bacteria, fungi, and some enveloped viruses. Their expression in airway epithelia may be constitutive or inducible by bacterial products or pro-inflammatory cytokines. beta-defensins also act as chemokines for adaptive immune cells, including immature dendritic cells and T cells via the CCR6 receptor, and provide a link between innate and adaptive immunity. Alterations in the function of the beta-defensins may contribute to disease states. Here we review much of the biology of the beta-defensins, including gene discovery, genomic organization, molecular structure, regulation of expression, and function.

Amino Acid Sequence↗

PubMed2026

Transcriptomic responses of gill and intestinal tissues in Nile tilapia (Oreochromis niloticus) to bacterial infection following sequential nanoimmersion and hydrogel-based multivalent vaccination.

Bacterial pathogens, including Flavobacterium oreochromis, Aeromonas veronii, Streptococcus agalactiae, and Edwardsiella tarda, represent major infectious threats to Nile tilapia (Oreochromis niloticus). A multivalent vaccination strategy integrating cationic nanoemulsion immersion with oral hydrogel boosters was developed to investigate tissue-specific immune responses at the transcriptomic level. Gill tissues were collected following immersion challenge and intestinal tissues following intraperitoneal injection challenge, reflecting the physiologically relevant infection biology of each pathogen and the mechanistic rationale of each delivery platform. RNA sequencing (RNA-seq) generated high-quality datasets (mapping rate > 81.64%) with strong concordance to quantitative real-time PCR (qRT-PCR) validation (r = 0.83). Comparative transcriptomic analysis revealed distinct yet complementary immune signatures between tissues. Gill transcriptomes were enriched in phagosome, focal adhesion, extracellular matrix-receptor interaction (ECM-receptor interaction), and cytokine-cytokine receptor interaction pathways, accompanied by increased expression of major histocompatibility complex class I/II (MHC class I/II), mannose receptor, αVβ3 integrin, and calnexin, indicating innate activation, enhanced phagocytic capacity, epithelial barrier reinforcement, and adaptive immune coordination. Intestinal transcriptomes showed predominant enrichment of adaptive immune pathways, including the intestinal immune network for immunoglobulin (Ig) production, Forkhead box O (FoxO) signaling, and mitogen-activated protein kinase (MAPK) signaling, with increased expression of T-cell receptor (TCR), inducible T-cell co-stimulator ligand (ICOS-L), C-X-C chemokine receptor type 4 (CXCR4), and polymeric immunoglobulin receptor (pIgR), reflecting T and B cell coordination, lymphocyte trafficking, and mucosal immunoglobulin transport, alongside innate engagement through phagosome pathway enrichment. Shared upregulation of MHC class II, B-cell receptor (BCR) signaling, integrin alpha M (ITGAM), and immunoglobulin-associated components across both tissues suggests coordinated mucosal immune activation through a conserved immune module, warranting direct experimental validation. Collectively, these findings provide transcriptomic evidence that this vaccination strategy elicits an integrated, tissue-specialized immune response, advancing mechanistic understanding of gill and intestinal immunity in vaccine-induced protection of teleost fish.

Animals↗

PubMed2005

Innate immunity in experimental SIV infection and vaccination.

Innate immunity represents the first line of defence to pathogens besides the physical barrier and seems to play a role in protection against HIV/SIV infection and disease progression. High production of beta-chemokines and CD8+ T cell anti-viral factors in naive as well as in vaccinated macaques has been associated with complete or partial protection against SIV infection indicating that genetic or environmental factors may influence their production. This innate immunity may help in generating HIV/SIV-specific responses upon the first exposure to HIV/SIV. SIV subunit vaccines given by the targeted iliac lymph node route have been shown to induce an increased production of CD8+ T cell suppressor factors and beta-chemokines. Only a few vaccine studies have focused on enhancing the innate immune response against HIV/SIV. The use of unmethylated CpG motifs, HSP and GM-CSF as adjuvants in SIV vaccines has been shown to induce production of HIV/SIV-inhibiting cytokines and beta-chemokines, which seem to be important in modulating and steering the adaptive immune responses. HSP has also been shown to induce gammadelta+ T cells, which contribute to the innate immunity. More knowledge about the interplay between the innate and adaptive immune responses is important to develop new HIV/SIV vaccine strategies.

Animals↗

PubMed2005

Development of an adult-like cell-mediated immune response in calves after early vaccination with Mycobacterium bovis bacillus Calmette-Guérin.

Effects of neonatal vaccination on antigen-specific cellular and humoral immune responses of dairy calves have not been well described. The purpose of this study was to characterize the ontogeny of the adaptive immune response in calves sensitized to the attenuated strain of Mycobacterium bovis, bacillus Calmette-Guerín. Holstein bull calves were nonvaccinated (n = 6, vaccination controls) or vaccinated subcutaneously (n = 6) with bacillus Calmette-Guerín at 1 and 7 wk of age. Composition and functional capacities of blood mononuclear cell populations from calves were evaluated at 1 (prevaccination), 3, 6, 7, 8, 9, and 12 wk of age. Young adults (nulliparous heifers, n = 4) vaccinated in an identical manner were sampled concurrently to evaluate effects of animal maturity on the development of the adaptive immune response. Responses of nonvaccinated calves to recall antigen (Mycobacterium bovis purified protein derivative) ex vivo and in vivo (i.e., cutaneous delayed-type hypersensitivity) were minimal or nonexistent. Responses of cells from vaccinated calves and young adults to recall antigen, however, were evident as early as wk 2 after primary vaccination. Antigen-induced T cell subset proliferation, and secretion of interferon-gamma, nitric oxide, and tumor necrosis factor-alpha by cells from vaccinated calves were comparable to or greater than responses of vaccinated adults during the 11-wk study. Eleven weeks after primary vaccination, cutaneous responses of vaccinated calves and young adults to intradermal administration of antigen were pronounced and comparable, demonstrating the capacity of the bovine neonate to develop a vigorous cell-mediated immune response in vivo. Antibody responses (i.e., antibody concentrations in sera and in supernatants from antigen-stimulated cultures of blood mononuclear cells) of vaccinated calves, in contrast, were markedly lower than parallel responses of vaccinated adults. In conclusion, these results suggest that the bovine neonate can mount a vigorous, adult-like cell-mediated immune response when vaccinated at an early age.

Aging↗

PubMed2003

Pancreatic islet xenotransplantation: barriers and prospects.

Dramatic clinical advances indicate that pancreatic islet transplants can reliably restore euglycemia in insulin-dependent patients. However, clinical success actually highlights the pronounced deficiency of allogeneic pancreata available for islet isolation. This pressing issue has revitalized ongoing efforts to develop surrogate donor sources. Xenogeneic donors form a potential alternative tissue source because they can be generated in large numbers and are amenable to genetic engineering. However, there is less understanding of the innate and adaptive immune barriers to islet xenografts relative to those encountered by allografts. Presented evidence indicates that both innate and antigen-specific adaptive immune responses significantly contribute to islet xenograft rejection. Recent evidence suggests that the capacity to induce tolerance to islet xenografts may not differ markedly from strategies used to induce allograft tolerance.

Animals↗

PubMed2006

Cooperation between CD4+ and CD8+ T cells: when, where, and how.

Concepts of cell-cell interactions in adaptive immunity have alternated between the simple and the complex. The notion that one population of small, circulating lymphocytes is responsible for adaptive immunity was sequentially supplanted by the concept of separate T and B lymphocyte populations that cooperate to produce IgG antibody responses, by a three-cell model in which a myeloid APC initiates these cooperative lymphoid responses, by the recognition of T cell subsets, and by the idea that CD8+ T cell subset responses to graft antigens depend on CD4+ T cell subset activity. Simplicity was reintroduced with the revelation that CD8+ T cells can act independently of CD4+ T cells against acute viral infections. The pendulum has swung again toward complexity with recognition of the distinct and conjoint contributions of innate stimuli, APCs, NK and NKT cells, Tregs, and CD4+ helper T cells to CD8+ T cell behavior during acute and chronic infections or as memory cells. The renewed appreciation that multiple, sometimes rare cell types must communicate during cell-mediated immune responses has led to questions about how such interactions are orchestrated within organized lymphoid tissues. We review recent advances in deciphering the specific contribution of CD4+ T cells to physiologically useful CD8+ T cell responses, the signals involved in producing acute effectors versus long-lived memory cells, and the mechanisms underlying the cell-cell associations involved in delivery of such signals. We propose a model based on these new findings that may serve as a general paradigm for cellular interactions that occur in an inflamed lymph node during the initiation of immune responses.

Animals↗

PubMed2006

IL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production in human monocyte-derived dendritic cells.

Dendritic cells (DCs) play an important role in innate and adaptive immune responses. In addition to their phagocytic activity, DCs present foreign antigens to naïve T cells and regulate the development of adaptive immune responses. Upon contact with DCs, activated T cells produce large quantities of cytokines such as interferon-gamma (IFN-gamma) and interleukin (IL)-21, which have important immunoregulatory functions. Here, we have analyzed the effect of IL-21 and IFN-gamma on lipopolysaccharide (LPS)-induced maturation and cytokine production of human monocyte-derived DCs. IL-21 and IFN-gamma receptor genes were expressed in high levels in immature DCs. Pretreatment of immature DCs with IL-21 inhibited LPS-stimulated DC maturation and expression of CD86 and human leukocyte antigen class II (HLAII). IL-21 pretreatment also dramatically reduced LPS-stimulated production of tumor necrosis factor alpha, IL-12, CC chemokine ligand 5 (CCL5), and CXC chemokine ligand 10 (CXCL10) but not that of CXCL8. In contrast, IFN-gamma had a positive feedback effect on immature DCs, and it enhanced LPS-induced DC maturation and the production of cytokines. IL-21 weakly induced the expression Toll-like receptor 4 (TLR4) and translation initiation region (TIR) domain-containing adaptor protein (TIRAP) genes, whereas the expression of TIR domain-containing adaptor-inducing IFN-beta (TRIF), myeloid differentiation (MyD88) 88 factor, or TRIF-related adaptor molecule (TRAM) genes remained unchanged. However, IL-21 strongly stimulated the expression of suppressor of cytokine signaling (SOCS)-1 and SOCS-3 genes. SOCS are known to suppress DC functions and interfere with TLR4 signaling. Our results demonstrate that IL-21, a cytokine produced by activated T cells, can directly inhibit the activation and cytokine production of myeloid DCs, providing a negative feedback loop between DCs and T lymphocytes.

Cell Communication↗

PubMed2005

Mucosal adjuvants.

Induction of immune responses following oral immunization is frequently dependent upon the co-administration of appropriate adjuvants that can initiate and support the transition from innate to adaptive immunity. The three bacterial products with the greatest potential to function as mucosal adjuvants are the ADP-ribosylating enterotoxins (cholera toxin and the heat-labile enterotoxin of Escherichia coli), synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN), and monophosphoryl lipid A (MPL). The mechanism of adjuvanticity of the ADP-ribosylating enterotoxins is the subject of considerable debate. Our own view is that adjuvanticity is an outcome and not an event. It is likely that these molecules exert their adjuvant function by interacting with a variety of cell types, including epithelial cells, dendritic cells, macrophages, and possibly B- and T-lymphocytes. The adjuvant activities of CpG and MPL are due to several different effects they have on innate and adaptive immune responses and both MPL and CpG act through MyD88-dependent and -independent pathways. This presentation will summarize the probable mechanisms of action of these diverse mucosal adjuvants and discuss potential synergy between these molecules for use in conjunction with plant-derived vaccines.

Adenosine Diphosphate Ribose↗

PubMed2006

Regulation of murine dendritic cell immune responses by Helicobacter felis antigen.

Helicobacter infections are present in approximately 50% of humans, causing severe illnesses such as gastritis and malignancies. Dendritic cells (DC) are critical antigen-presenting cells which link innate and adaptive immune responses. The mechanism of dendritic cell regulation in Helicobacter-induced gastritis is poorly understood. These studies characterized DC isolated from the lamina propria of Helicobacter-infected mice and analyzed innate and adaptive immune responses elicited by Helicobacter antigen (Ag)-pulsed DC. The presence of DC was elevated in the gastric lamina propria infiltrate of infected mice in comparison with controls. After treatment with Helicobacter felis Ag, DC were polarized to secrete interleukin-6 as the dominant cytokine. In the presence of DC and Helicobacter Ag, responder allogeneic T cells in culture exhibited limited cell division. We suggest that the response of DC and T cells to Helicobacter Ag is critical to the chronic persistence of Helicobacter-induced gastritis.

Animals↗

PubMed2003

Transducing signals from antigen receptors to nuclear factor kappaB.

Signaling leading to the survival or apoptosis of immune system cells must be balanced to ensure the normal mounting and extinguishing of immune responses. One of the essential regulators of immune cell survival is the transcription factor nuclear factor kappaB (NF-kappaB). NF-kappaB is critical for the activation of T and B lymphocytes and is a central coordinator of innate and adaptive immunity. Pathogen recognition, whether mediated via the Toll-like receptors or via the antigen-specific T- and B-cell receptors, initiates the activation of distinct signal transduction pathways that activate NF-kappaB. Activation of NF-kappaB by these pathways is necessary for lymphocyte activation, expansion, and effector function in response to infection. In addition, recent work has shown that the aberrant activation of NF-kappaB by these pathways can contribute to the development of autoimmunity, chronic inflammation, or lymphoid malignancy. There is thus an urgent need to understand the exact molecular details of these signal transduction cascades so that we may develop novel therapeutics. This article will review the specific signal transduction pathways that mediate NF-kappaB activation in response to antigen receptor ligation in T and B lymphocytes. These newly defined pathways, which are essential for adaptive immune responses, are built around the key adapter protein, Bcl-10. Bcl-10 is known to participate in chromosomal translocations in human mucosa-associated lymphoid tissue lymphomas.

Animals↗

PubMed2004

The infecting dose of Chlamydia muridarum modulates the innate immune response and ascending infection.

Murine vaginal infection with the obligate intracellular bacterium Chlamydia muridarum is commonly used as a model for ascending Chlamydia infections of the human female genital tract. Gamma interferon-producing Th1 cells, in concert with other mononuclear infiltrates, primarily mediate antichlamydial immunity. However, many factors modify this response, including the bacterial load. To investigate the manner in which the inoculating dose of C. muridarum modulates a genital infection, we measured innate and adaptive cell numbers, CD4+ lymphocyte cytokine profile, chemokine expression, course of infection, and pathological sequelae in genital tracts of BALB/c mice infected with doses of C. muridarum ranging from 10(4) to 10(7) inclusion-forming units. We found that the influx of both innate and adaptive immune cells responded similarly in the lower genital tract (cervical-vaginal tissues) and upper genital tract (oviduct tissues) to increasing inoculating doses. However, cells expressing the innate markers Gr-1 and CD11c were affected to a greater degree by increasing dose than lymphocytes of the adaptive immune response (Th1, CD4+, CD8+, CD19+), resulting in a change in the balance of innate and adaptive cell numbers to favor innate cells at higher infecting doses. Surprisingly, we detected greater numbers of viable chlamydiae in the oviducts at lower inoculating doses, and the number of organisms appeared to directly correlate with hydrosalpinx formation after both primary infection and repeat infection. Taken together, these data suggest that innate immune cells contribute to control of ascending infection.

Animals↗

PubMed2001

Immunity in the mammary gland.

The ruminant mammary gland is an extremely important economic organ in that it provides a major nutrition source for a significant portion of the world's human population. The ruminant mammary gland is also responsible for providing protective immunity to neonates and for defending itself from invading pathogens. A wide array of humoral and cellular immune mechanisms are present in the mammary gland and actively participate in providing immunity to newborns and the mammary gland per se. The acute inflammatory response is essential in determining the outcome of intramammary challenge, and factors affecting innate and adaptive immunity in the context of mammary health are reviewed in detail. The ruminant mammary gland is also unique in that lymphocyte trafficking, which is essential to adaptive immunity, is shared with the peripheral immune system rather than the common mucosal immune system.

Animals↗