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Results for “Adaptive Immunity”

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At least 649 records · Page 36Linked to original sources

PubMed2005

Plasmacytoid dendritic cells and the regulation of immunoglobulin heavy chain class switching.

By substituting the heavy chain constant region of IgM and IgD with that of IgG, IgA or IgE, immunoglobulin class switching endows antibodies with novel effector functions that enhance the ability of the immune system to effectively clear invading pathogens. Plasmacytoid dendritic cells critically link innate immunity with adaptive immunity by producing massive amounts of type 1 IFN in response to viruses. We have recently found that type 1 IFN triggers class switching by inducing myeloid dendritic cells to upregulate the expression of BAFF and APRIL, two powerful B cell-activating molecules. In this paper, we propose that IFN-producing plasmacytoid dendritic cells modulate class switching by activating B cells through both T cell-dependent and T cell-independent pathways. A better understanding of these pathways may facilitate the development of novel antiviral vaccine strategies and aid in identifying new therapies for antibody-mediated autoimmune disorders, such as lupus.

Animals↗

PubMed2005

Immunity, inflammation, and allergy in the gut.

The gut immune system has the challenge of responding to pathogens while remaining relatively unresponsive to food antigens and the commensal microflora. In the developed world, this ability appears to be breaking down, with chronic inflammatory diseases of the gut commonplace in the apparent absence of overt infections. In both mouse and man, mutations in genes that control innate immune recognition, adaptive immunity, and epithelial permeability are all associated with gut inflammation. This suggests that perturbing homeostasis between gut antigens and host immunity represents a critical determinant in the development of gut inflammation and allergy.

Animals↗

PubMed2005

Differentiation, maturation, and survival of dendritic cells by osteopontin regulation.

Dendritic cells (DCs) are antigen-presenting cells with the ability to induce primary immune responses necessary in innate immunity and adaptive immunity. Osteopontin (OPN) is a secreted acidic phosphoprotein containing an arginine-glycine-aspartate sequence and has been suggested to play an important role in early cellular immune responses. The interaction between DCs and OPN has not been clarified. We hypothesized that there is an important interaction between DCs and OPN, which is an indispensable extracellular matrix component in early cellular immune responses. Human monocyte-derived DCs synthesized OPN especially during the differentiation from monocytes to immature DCs. By blocking of OPN with anti-OPN antibody, cultured DCs became smaller and expressed lower levels of costimulatory molecules and major histocompatibility complex class II antigens than untreated DCs. Furthermore, DCs treated with anti-OPN antibody easily underwent apoptosis. These results suggest that human DCs can produce OPN and that OPN may play a role in the differentiation, maturation, and survival of DCs by autocrine and/or paracrine pathways.

Apoptosis↗

PubMed2006

Cancer immunotherapy by interleukin-21: potential treatment strategies evaluated in a mathematical model.

The newly characterized interleukin (IL)-21 plays a central role in the transition from innate immunity to adaptive immunity and shows substantial tumor regression in mice. IL-21 is now developed as a cancer immunotherapeutic drug, but conditions for efficacious therapy, and the conflicting immunostimulatory and immunoinhibitory influence of the cytokine, are yet to be defined. We studied the effects of IL-21 on tumor eradication in a mathematical model focusing on natural killer (NK) cell-mediated and CD8+ T-cell-mediated lysis of tumor cells. Model parameters were estimated using results in tumor-bearing mice treated with IL-21 via cytokine gene therapy (CGT), hydrodynamics-based gene delivery (HGD), or standard interval dosing (SID). Our model accurately retrieved experimental growth dynamics in the nonimmunogenic B16 melanoma and the immunogenic MethA and MCA205 fibrosarcomas, showing a strong dependence of the NK-cell/CD8+ T-cell balance on tumor immunogenicity. Moreover, in melanoma, simulations of CGT-like dosing regimens, dynamically determined according to tumor mass changes, resulted in efficient disease elimination. In contrast, in fibrosarcoma, such a strategy was not superior to that of fixed dosing regimens, HGD or SID. Our model supports clinical use of IL-21 as a potent stimulator of cellular immunity against cancer, and suggests selecting the immunotherapy strategy according to tumor immunogenicity. Nonimmunogenic tumors, but not highly immunogenic tumors, should be controlled by IL-21 dosing, which depends on tumor mass at the time of administration. This method imitates, yet amplifies, the natural anticancer immune response rather than accelerates only one of the response arms in an unbalanced manner.

Animals↗

PubMed2005

Innate immunity influences long-term outcomes after human lung transplant.

RATIONALE: Lung transplantation is characterized by very high rates of acute and chronic allograft rejection. We hypothesize that activation of innate immunity augments adaptive immunity, leading to rejection after lung transplantation. In support of this idea, we have recently demonstrated that lung recipients heterozygous for either of two functional polymorphisms (Asp299Gly or Thr399Ile) in Toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness have decreased acute rejection over the first 6 months after transplant. OBJECTIVES: In the current analysis, we sought to extend our initial observations and investigate the effect of these TLR4 polymorphisms on post-transplant acute rejection beyond the first 6 months, bacterial infections, bronchiolitis obliterans syndrome, and survival. METHODS: Genotyping was performed on 170 lung transplant recipients. MEASUREMENTS AND MAIN RESULTS: Recipients heterozygous for either Asp299Gly or Thr399Ile had significantly reduced frequency (p = 0.02) and incidence of acute rejection (p = 0.04) sustained over 3 years after transplant, but no differences were observed in the overall onset of bronchiolitis obliterans syndrome. A trend, however, toward reduced onset of bronchiolitis obliterans syndrome grade 2 or 3 was observed in TLR4 heterozygotes. CONCLUSION: Our results demonstrate that activation of recipient innate immune responses through TLR4 has a significant and sustained effect on the development of acute lung rejection. Targeting innate immune signaling represents a promising area for future clinical studies in the prevention of lung allograft rejection.

Adult↗

PubMed2001

Role of T- and B-lymphocytes in pulmonary host defences.

Pulmonary infectious diseases cause significant morbidity and mortality in both industrialized and developing countries. Adaptive immune responses are required to defend the lung against pathogens that survive in normal macrophages and extracellular organisms that evade phagocytosis. Microbes initiate both innate immune responses and specific adaptive immune responses. Innate immune response molecules regulate T-lymphocyte differentiation. Activated T-lymphocytes provide cytokines, which activate macrophages and lytic signals that lyse infected antigen-presenting cells. Antibodies produced by plasma cells facilitate microbial clearance through diverse effector mechanisms including opsonization, complement fixation and antibody-dependent cytotoxicity. Lymphocytes determine the specificity of the immune response and orchestrate effector limbs of the immune response.

Animals↗

PubMed2006

Chemical and biological pollution contribute to the immunological profiles of free-ranging harbor seals.

Polychlorinated biphenyls and other persistent organic pollutants have been associated with immunotoxicity and outbreaks of (infectious) disease in marine mammals by rendering them vulnerable to infection by pathogens such as viruses and bacteria. In an immunotoxicological study of free-ranging harbor seals (Phoca vitulina), we obtained samples of blood and blubber from seal pups that were live-captured from two remote and two near-urban sites in British Columbia, Canada, and Washington state, USA. Using these samples, we quantified hematology, innate immune function, adaptive immune function, and polychlorinated biphenyl accumulation. While controlling for confounding factors (age, sex, and condition), univariate correlations between phagocytosis (r2 = 0.30, p = 0.002), respiratory burst (r2 =0.45, p= 0.000), T-lymphocyte function (r2 = 0.16, p = 0.028), lymphocyte signaling (r2 = 0.17, p = 0.025), and lymphocyte counts (r2 = 0.29, p = 0.002), and polychlorinated biphenyl concentrations suggested chemical-associated immunotoxicity. Principal component analysis of immunological endpoints provided additional evidence of immunotoxic effects in seals. However, principal component analysis also identified a noncontaminant-related factor by distinguishing between seals inhabiting urban versus remote sites, with results being consistent with increased pathogen exposure. Elevated fecal coliform concentrations in water, and observations of terrestrial spill-over pathogens in local seals, further support the notion of biological pollution at these sites. Although our study highlights the role that environmental contaminants might play in rendering marine mammal populations vulnerable to disease through immunotoxicity, it also suggests that biological pollution represents an emerging conservation concern.

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↗

PubMed2006

[Identification of an immunodominant antigen of Mycobacterium leprae and its application for the development of protective measures].

Host defense against Mycobacterium leprae (M. leprae) is chiefly conducted by cellular immunity. The adaptive immunity plays an important role, and T cells are activated through recognition of some immunodominant antigens of M. leprae. A search for an immunodominant antigen was carried out using human peripheral monocytes-derived dendritic cells and M. leprae-derived cell membrane fraction which is the most antigenic fraction of the bacteria, and Major Membrane Protein (MMP)-II was found as one of the immunodoninant antigens. The MMP-II highly stimulated both dendritic cells and macrophages to produce various cytokines. Further, MMP-II was recognized by T cells in vivo in patients infected with M. leprae. Then, we constructed a recombinant BCG secreting MMP-II. The recombinant BCG strongly stimulated both naive CD4+ and naive CD8+ T cells, and seemed to be a useful immunostimulatory agent.

Antigens, Bacterial↗

PubMedDate not supplied

Biological effect of OK-432 (picibanil) and possible application to dendritic cell therapy.

OK-432 (Picibanil), a streptococcal preparation with potent biological response modifying activities, was approved in Japan as an anticancer agent in 1975. In the ensuing 30 years, since then, a significant amount of data, including clinical as well as experimental studies, has been accumulated. OK-432 has been reported to induce various cytokines, activate immunological cells and thus augment anticancer immunity. Recently, the interrelation between innate immunity and adaptive immunity has become clear and it was reported that OK-432 acts, at least in part, via Toll-like receptor (TLR) 4-MD2 signaling pathway. In addition, dendritic cells (DCs) are considered to play a pivotal role in immunological response and it is reported that OK-432 induced maturation of DCs both in vitro and in vivo. These results suggest that OK-432 is a useful adjuvant in DC-based anticancer immunotherapy. Clinical studies of DC therapy with OK-432 are under way.

Animals↗

PubMed2004

[Cloning, expression and purification of the C-terminal section of murine heat shock protein gp96].

Heat shock protein gp96 is a glycoprotein which was found several years ago. Besides its function as a molecular chaperone, it is also reported to play important roles both in innate immunity and adaptive immunity. Gp96 can stimulate the maturation of antigen presenting cells (especially dendritic cells) and the secretion of cytokines. Gp96 and its associated peptides could stimulate peptide specific cytotoxic T lymphocyte reaction (CTL), which was very promising in the designing of anti-virus and anti-tumor vaccines. However the expression level of whole length gp96 was relatively low in E. coli and the purity of gp96 are not very suitable for further study. We successfully cloned the carboxy terminal fragment (560aa-751aa) of murine gp96 into the pGEX-6p-1 vector and expressed in BL21 strain. This fragment contains the peptide binding domain and the dimerization domain. After purification, the recombinant fusion protein was cleaved with the PreScission Protease and analyzed by Gelfiltration. The results show that this fragment may be related to the dimerization of gp96 and make an foundation for further investigations of the protein.

Animals↗

PubMed2006

Macrophage and dengue virus: friend or foe?

The cells of monocyte-macrophage (Mphi) lineage play important roles both in innate and adaptive immune responses. They are the first line of defence in body and their job is to phagocytose a foreign invader, the pathogen, digest it and remove it. Mphi help body in mounting the antigenspecific immune response by presenting the digested pathogen antigen in conjunction with major histocompatibility complex (MHC) class II molecules to recruit B and T lymphocytes response. Usually Mphi succeed in their job of eliminating most pathogens from the body but sometimes the pathogen strikes a "friendship" with them and starts using them for its benefit. A number of pathogens, including dengue virus (DV), subvert Mphi and use them for their replication, increasing the severity of damage to the body. This duality may be related to the fact that Mphi serve as efficient host cell for DV replication, in addition to being responsible for innate immunity and for initiating adaptive immune responses. This review gives a brief overview of the various roles of Mphi (enmity and friendship) during dengue virus infection.

Animals↗

PubMedDate not supplied

[New immunology--immunology of pattern recognition receptors].

Pattern recognition receptors (PRRs) have been found on all cells of the body--cells of the innate and adaptive immune systems, epithelial and endothelial cells, keratinocytes, etc. PRRs can recognize specific molecular structures of microorganisms as well as allergens and other substances. The interaction with ligands of foreign microorganisms activates PRRs, after which host cells start to produce cytokines to both specifically activate innate immunity and to control adaptive immune reactions. On the other hand, no immune response develops against microorganisms of the normal microflora. Practically, the development of all immune responses is controlled by PRRs. These responses start in epithelial cells, skin cells, and vascular epithelial cells, which meet alien first. The immune system uses these cells to control the composition of normal microflora. Accordingly, the definition of immune system functions should be complemented by the regulation of body's microflora in addition to the protection from alien and altered self.

Allergy and Immunology↗

PubMed1982

Stress, adaptation, and immunity: studies in humans.

The notion that some combination of excessive "stress" and inadequate coping may increase susceptibility to illness has long been part of our conventional wisdom. Yet, until recently, there have been few data to support this contention. During the past decade, the relationship between stress, adaptation, and human immunity has come under closer scrutiny. There is now considerable evidence that certain types of experimental and naturally-occurring stress are associated with alterations of human cellular immune function. Furthermore, these observed changes generally are immunosuppressive. However, the mediating mechanisms underlying this relationship remain poorly understood. Critical factors in the stress-adaptation-immunity relationship are: the duration and proximity of the stressor, the adaptive capacity of the individual, and the differential effects of certain stressors on immunologic components.

Adaptation, Psychological↗

PubMed2004

Age-associated decline in resistance to Babesia microti is genetically determined.

BACKGROUND: Although infection by the protozoan Babesia microti is rarely symptomatic in immunocompetent young people, healthy individuals aged >50 years may experience life-threatening disease. To determine the basis for this age relationship, we developed a mouse model of babesiosis using a novel clinical isolate of B. microti. METHODS: Mice were infected at 2, 6, 12, or 18 months. Parasitemia was monitored on Giemsa-stained blood smears or by flow cytometry. RESULTS: In DBA/2 mice, early and persistent parasitemias increased with age at infection. BALB/c and C57BL/6 mice were resistant, regardless of age, which indicates that allelic variation determines resistance to B. microti. Unlike immunocompetent mice, SCID mice, which retain an innate immune system but lack the lymphocytes needed for adaptive immunity, developed high and persistent levels of parasitemia that were markedly reduced by transfer of naive BALB/c or DBA/2 splenocytes. BALB/c cells reduced the persistent parasitemia to a greater extent than did age-matched DBA/2 cells. Of importance, there was an age-associated loss of protection by cells of both strains. CONCLUSION: The resistance to B. microti infection conferred by the adaptive immune system is genetically determined and associated with age. We postulate that there are age-related differences in the expression of alleles critical for adaptive immunity to B. microti.

Aging↗

PubMed2004

Cell-mediated immunity in poultry.

In avian species, adaptive immunity involves both humoral and cell-mediated immune (CMI) responses. Although humoral or antibody-mediated immune responses are particularly effective against extracellular antigens, CMI responses are specialized in the elimination of intracellular antigens; the latter include those that have entered cells via the endocytic pathway (exogenous antigens; e.g., phagocytosed bacteria) or were produced within the cell such as viral proteins and proteins resulting from neoplastic transformation of the cell (endogenous antigens). CMI responses, like most humoral immune responses, are tightly regulated and require "help" from T helper cells, specifically the type 1 T helper cells (Th1, hence, the name Th1 responses). Th1 cells are characterized by their production of cytokines such as interferon-gamma (IFN-gamma), tumor-necrosis factor-alpha (TNF-alpha), and interleukin-2 that drive CMI responses. The functional effectors of CMI responses are various immune cells including cytotoxic lymphocytes (cytotoxic T cells and natural killer cells) and macrophages. Cytotoxic lymphocytes and macrophages are specialized in the elimination of endogenous and exogenous antigens, respectively. In the past decade, substantial progress has been made in defining the role and regulation of avian CMI responses. Other advances have addressed strategies that strengthen this arm of adaptive immunity to optimize defense as well as protection against neoplastic diseases and nonneoplastic diseases caused by intracellular pathogens.

Animals↗

PubMed1997

Immune function.

To summarize, within the adaptive immune network, the CD4 T cell provides regulatory effects that play a central role in controlling the majority of immune functions and memory cells that enhance host protection. Many of the regulatory effects are mediated through the release of cytokines, a group of hormones that also promotes inflammation and replenishes hematopoietic elements. The CD8 T cell functions as a cytotoxic cell that is a crucial part of the host defense against intracellular pathogens such as viruses. The other major arm of the lymphoid network consists of B cells whose major function is the production of immunoglobulins that are crucial in host protection against encapsulated bacteria and other microbes. The role of the NK cell is less clear, but it appears to participate in host defenses against selected viruses and malignant cells. It also may be important in rejection reactions that are activated following tissue transplantation. The various lymphocyte types within the adaptive immune system are interdependent, as evidenced by the X-linked hyper-IgM syndrome in which a T-cell deficiency (CD40 ligand) manifests clinically as an antibody production problem.

B-Lymphocytes↗

PubMedDate not supplied

Molecular immunological approaches to biotherapy of human cancers--a review, hypothesis and implications.

The immune system of the human organism comprises the innate system cells and the adaptive immune cells. The former include the hematopoietic cells, mast cells, basophils, monocytes, dendritic cells (DCs) and macrophages, and the latter include CD4+ T cells, CD8+ T cells, T regulatory cells (Tr) and B cells. The innate system DCs are the major antigen-presenting cells to Th(o) CD4+ T cells in lymph nodes that polarize into T helper 1 (Th1) and T helper 2 (Th2) cells, which subsequently produce different cytokines. Polarized Th1 cells produce interleukin (IL)-2, IL-12 and interferon (IFN)-gamma, and polarized Th2 cells and the hematopoietic cells produce IL-4, IL-5, IL-6, IL-10 and IL-13. In healthy individuals there is a Th1/Th2 cytokine balance, but during microbial-induced inflammation the pathogens induce an overproduction of the Th2 cytokines that inhibit the adaptive immune response against the pathogen. A review of studies on the Th1/Th2 cytokine balance in humans harboring different tumor types revealed that tumor cells induce increased Th2 cytokine levels in patients' sera that can serve as indicators for the existence of tumors. In this review, studies which correlated the presence of increased Th2 cytokines with the presence of early tumors and tumor progression are discussed. It was suggested that early monitoring of human populations for elevated Th2 cytokines may be used to identify individuals at an early stage of tumor development. A hypothesis is presented which suggests that increased Th2 cytokine synthesis in cancer patients, with early and late tumors, may be treated with Th2 cytokine antagonists. This new approach to cancer treatment will be supplemented by co-treatment with CpG oligodeoxynucleotides(ODNs) which reactivate the adaptive antitumor immune response. Studies that provide information on the efficiency of CpG ODN treatment of tumors in mice revealed that tumor regression was achieved by inducing Toll-like receptor 9+ plasmacytoid dendritic cells (PDCs) to release large amounts of type I interferons (IFN alpha and beta), which inhibit Th2 cytokine synthesis by hematopoietic cells and CD4+ T cells and enhance Th1 cytokine synthesis and activation of the adaptive immunity. It is hypothesized that Th2 cytokine (IL-4 and IL-6) antagonists may be an effective treatment for cancer patients since cytokine antagonists inhibit the increased Th2 cytokines in patients. Such an approach may replace Th2 cytokine monoclonal antibodies, the current treatment for cancer patients. It is hypothesized that the effective treatment of cancer patients with Th2 cytokine antagonists, combined with CpG ODNs, will lead to the inhibition of Th2 cytokines and reacTivation of the Th1-induced antitumor adaptive immunity that will destroy tumor cells and cure cancer patients.

Humans↗