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Results for “Adaptive Immunity”

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At least 1,207 records · Page 67Linked to original sources

PubMed2003

Correction of defects responsible for impaired Qa-2 class Ib MHC expression on melanoma cells protects mice from tumor growth.

One of the principal mechanisms of tumor immune evasion is alteration of class I MHC expression. We have identified defects contributing to down-regulation of class I MHC expression in the widely studied murine B16 melanoma and its variants B16F1, B16F10, BL6-2, BL6-8 and B78H1. Transcription of the nonclassical class I MHC genes Q8 and Q9 (Qa-2 Ags) has been switched off in the entire panel of melanoma lines, suggesting that this event occurred early during tumor progression. B78H1, unlike B16F1 and B16F10 sublines, is also selectively devoid of TAP2 and low molecular weight protein 7 as well as classical class I MHC K(b) and D(b) transcripts. Cotransfection of B78H1 with TAP2 and class I H chain genes is sufficient to reconstitute surface expression of exogenously delivered class I MHC without concomitant re-expression of endogenous beta(2)-microglobulin-associated class I. The serological absence of endogenous class Ia and Ib at the surface of TAP2-negative as well as TAP2-transfected B78H1 makes this system a suitable model for studying the properties of isolated class I proteins in tumors. We used this system to demonstrate that B78H1 cells genetically manipulated to re-express Q9 Ag have reduced tumor potential in syngeneic B6 mice compared with TAP2-transfected parental melanoma. Both NK cells and CTLs appear to collaborate in restraining growth of Q9-positive tumors. The results implicate Qa-2 in antitumor responses and illustrate the utility of the B78H1 system for identifying in vivo interactions between class I MHC molecules of interest and immune cells of innate and/or adaptive immunity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Innate stimuli accentuate end-organ damage by nephrotoxic antibodies via Fc receptor and TLR stimulation and IL-1/TNF-alpha production.

Innate stimuli are well recognized as adjuvants of the systemic immune response. However, their role in driving end-organ disease is less well understood. Whereas the passive transfer of glomerular-targeting Abs alone elicited minimal renal disease, the concomitant delivery of innate stimuli triggered severe nephritis, characterized by proliferative glomerulonephritis with crescent formation, and tubulointerstitial disease. Specifically, stimulating TLR2, TLR3, TLR4, and TLR5 by using peptidoglycan, poly(I:C), LPS, and flagellin, respectively, all could facilitate anti-glomerular Ab-elicited nephritis. In this model, innate and immune triggers synergistically activated several cytokines and chemokines, including IL-1, IL-6, TNF-alpha, and MCP-1, some of which were demonstrated to be absolutely essential for the development of renal disease. Genetic studies revealed that, whereas the innate trigger is dependent on TLR/IL-1R-associated kinase-mediated signaling, the immune component was contingent on FcR-mediated signals. Importantly, infiltrating leukocytes as well as intrinsic glomerular cells may both serve to integrate these diverse signals. Extrapolating to spontaneous immune-mediated nephritis, although the adaptive immune system may be important in generating end-organ targeting Abs, the extent of damage inflicted by these Abs may be heavily dependent on cues from the innate immune system.

Adjuvants, Immunologic↗

PubMed1999

The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns.

The human liver contains significant numbers of T cells, NK cells, and lymphocytes that coexpress T and NK cell receptors. To evaluate their functional activities, we have compared the cytotoxic activities and cytokines produced by normal adult hepatic CD3+CD56- (T) cells, CD3-CD56+ (NK) cells, and CD3+CD56+ (natural T (NT)) cells. In cytotoxicity assays using immunomagnetic bead-purified NK cell, T cell, and NT cell subpopulations as effectors, fresh hepatic NK cells lysed K562 targets, while NT cells could be induced to do so by culturing with IL-2. Both NT and T cells were capable of redirected cytolysis of P815 cells using Abs to CD3. Flow cytometric analysis of cytokine production by fresh hepatic lymphocyte subsets activated by CD3 cross-linking or PMA and ionomycin stimulation indicated that NT cells and T cells could produce IFN-gamma, TNF-alpha, IL-2, and/or IL-4, but little or no IL-5, while NK cells produced IFN-gamma and/or TNF-alpha only. The majority of NT cells produced inflammatory (Th1) cytokines only; however, approximately 6% of all hepatic T cells, which included 5% of Valpha24 TCR-bearing NT cells and 2% of gammadeltaTCR+ cells, simultaneously produced IFN-gamma and IL-4. The existence of such large numbers of cytotoxic lymphocytes with multiple effector functions suggests that the liver is an important site of innate immune responses, early regulation of adaptive immunity, and possibly peripheral deletion of autologous cells.

Adult↗

PubMedDate not supplied

Localization and functions of SP-A and SP-D at mucosal surfaces.

Pulmonary surfactant protein A (SP-A) and D (SP-D), members of the collectin family, are implicated in innate host defense of the lung. Collectins consist of a collagen-like domain and a carbohydrate recognition domain. SP-A and SP-D recognize and interact with glycoconjugates on the surface of microorganisms. They protect the lung by interacting with a wide variety of potential pathogens, including viruses, bacteria, and fungi. This may result in enhanced killing and/or clearance by phagocytes. Although most extensively studied in the lung, both SP-A and SP-D, or proteins closely resembling SP-A and SP-D, are found in a number of other sites in the body and therefore may play a protective role at other sites than the lung. SP-A and SP-D protein and/or mRNA have been detected at various sites of the body: the respiratory tract, the gastrointestinal tract, the middle ear, and in the peritoneal cavity. The presence of SP-A and SP-D at these mucosal surfaces, in close contact with numerous potentially harmful microorganisms, supports a role for these "lung"-collectins in innate mucosal defense. SP-A and SP-D may be important molecules in a threefold innate defense, particularly in the neonatal period between maternally acquired immunity and a fully developed adaptive immune system; the time interval between first exposure to a pathogen and generation of specific antibodies; and states of impaired immune function.

Animals↗

PubMed2003

[Corticosteroids and inflammation].

Corticoids are molecules which the organism synthesizes to regulate a large number of immune and metabolic physiological mechanisms. The compounds used as therapeutic agents have at higher doses very useful anti-inflammatory and immunomodulatory properties. Corticoids have most original mechanisms of action which are essentially genomic (transcriptional) and characterized by activation (transactivation) or inhibition (transrepression) of numerous target genes. These molecules act in many cells involved in innate immunity (macrophages, granulocytes, mastocytes) and adaptive immunity (lymphocytes) but also in other cells (fibroblasts, epithelial and endothelial cells). The anti-inflammatory efficacy of corticoids may be explained by their inhibition of the synthesis of numerous cytokines, enzymes and mediators of inflammation or induction of cytokines and anti-inflammatory molecules (lipocortin). Corticoids also regulate cellular activation and survival processes (apoptosis), which explains their cytostatic efficacy in certain malignant hematological disorders.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Autoinflammatory syndromes.

The autoinflammatory disorders are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen specific T cells. These disorders are caused by primary dysfunction of the innate immune system, without evidence of adaptive immune dysregulation. Innate immune abnormalities include aberrant responses to pathogen associated molecular patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines (IL-1beta, TNF-alpha) or their receptors. The autoinflammatory diseases comprise both hereditary (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency, MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis, CRMO) and multifactorial (Crohn's and Behçet's diseases) disorders. Mutations responsible for FMF, TRAPS, CAPS, PAPA are in proteins involved in modulation of inflammation and apoptosis.

Autoimmune Diseases↗

PubMedDate not supplied

Implication of innate immunity in the pathogenesis of biliary atresia.

Biliary atresia (BA) is a complex disorder for which the etiology is still far from clear. Newborn infants that develop BA may carry certain genetic defects, resulting in susceptibility to uncertain pathogens with characteristic pathogen-associated molecular patterns (PAMPs). The pathogens with their characteristic PAMPs in turn lead to activation of the innate immune system by triggering pattern recognition receptors on the immune cells. Toll-like receptors (TLRs) are the most recognized pattern recognition receptors and TLR signaling is the telltale sign of activation of innate immunity. The activation of TLR and the innate immune system in BA is demonstrated by the up-regulation of TLR7 and by the association of promoter polymorphism of CD14 with BA. The antimicrobial peptide hepcidin and MxA, a protein downstream of TLR7 signaling, which is also known as a highly specific marker for type I IFN signaling, are also found highly expressed in the early stage of BA. This review examines the known components of innate immunity involved in BA and outlines the potential role of the innate immune system, in cooperation with adaptive immunity, in the pathogenesis of BA.

Animals↗

PubMed2006

Adipocytokines - novel link between inflammation and vascular function?

Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.

Adipocytes↗

PubMed2002

Neural immunity: Friend or foe?

The articles compiled in this special edition of Journal of NeuroVirology target a developing field of investigation seeking to uncover how the immune system affects both the pathogenic process and protection against the ravages of neurodegenerative processes. Whether caused by a microbe, trauma, toxic metabolite, autoimmunity, or part of a wide degenerative process, immune dysfunction commonly affects central nervous system (CNS) disease. All together, the work presented here proved to be a unique undertaking with contributing scientists outside the field of neurovirology. Indeed, multiple disciplines including molecular neuroscience, neuroimmunology, virology, cellular immunology, receptor pharmacology, neuronal electrophysiology, neurochemistry, clinical neurology, and development neurobiology were joined. The basis of this work rests with the hypothesis that brain mononuclear phagocytes (MP; perivascular and brain macrophages and microglia) act as inducers of disease by engaging the immune system to protect, defend, or induce neural injury. Indeed, it is the brain MP that act as scavengers killing microblial pathogens, regulate immune responses through antigen presentation and mobilization of adaptive immune activities, and affect the production of neurotrophic or toxic secretory factors that incite disease processes. For many years, these responses were thought to be reactive to ongoing disease mechanisms with little effects on disease itself, let alone repair. The works compiled in this issue demonstrate quite clearly this is no longer true. Immune responses cannot be directed only against a microbe but also against self-antigens that are expressed in damaged CNS, leading to innate neurotoxic or adaptive anti-self immunity that commonly follow viral infections. Importantly, therapeutic modalities may take advantage of CNS immune responses through vaccination generating neuroprotection. Together, these articles serve to bring together common neuroimmune links between highly divergent diseases (for example, Parkinson's and Alzheimer's disease and human immunodeficiency virus type-one dementia). In the end, I hope this work will serve as discussion points for future collaborations and began to break down the barriers of disease, enabling targeted research activities toward what we have in common.

Brain↗

PubMed1998

Neuroimmunoregulation and cancer (review).

It is certain that neuroimmune mechanisms play a role in host defence against cancer. However, this interaction is highly complex and many variations are possible according to the nature of the neoplasms involved. There are indications that adaptive immunity is present in a significant proportion of tumor bearing hosts, and this defence may be boosted by specially designed vaccines and cytokines. Natural immune mediators are also implicated in resistance against tumor development. Here we review the evidence suggesting that hormonal manipulation of the host can result in the elevation of immune defences against cancer. Such manipulation strengthens both the adaptive and natural immune defences of the host, both of which play significant roles. Natural defence mechanisms are boosted by cytokines and hormones during febrile reactions which are now known as the acute phase response. It is suggested that hormonal stimulation of immune mechanisms coupled with the usual immunostimulants already in use may be employed to good advantage for the combination immunotherapy of cancer. Modern molecular biology approaches permit the development of laboratory monitoring procedures which may be used for the prediction and follow-up of therapeutic success.

Acute-Phase Reaction↗

PubMed2006

The two faces of interleukin 10 in human infectious diseases.

Resolution of infections depends on the host's ability to mount a protective immune response. However, an exacerbated response to infections may result in deleterious lesions. Consequently, immunoregulatory mechanisms are needed to control immune response and prevent infection-associated lesions. Interleukin 10 may be a major regulator of innate and adaptive immunity in vitro and in animals, but its role in human infections is still unclear. Review of the published work reveals wide involvement of interleukin 10 in two major features of infectious diseases. On one hand, interleukin 10 prevents the development of immunopathological lesions that result from exacerbated protective immune response to acute and chronic infections. On the other hand, it is critically involved in persistence of bacteria and viruses by interfering with innate and adaptive protective immunity. Moreover, infections induce the expansion of interleukin-10-producing regulatory cells that are involved in protection against allergic diseases.

Bacterial Infections↗

PubMed2003

TNF receptor-associated factor 6 deficiency during hemopoiesis induces Th2-polarized inflammatory disease.

Toll-like receptors (TLR) initiate rapid innate immune responses by recognizing microbial products. These events in turn lead to the development of an efficient adaptive immune response through the up-regulation of a number of costimulatory molecules, including members of the TNF/TNFR superfamily, on the surface of an APC. TNFR-associated factor 6 (TRAF6) is a common signaling adapter used by members of both the TNFR and the TLR/IL-1R superfamilies, and as such plays a critical role in the development of immune responses. As TRAF6-deficient mice die prematurely, we generated chimeras reconstituted with TRAF6-deficient fetal liver cells to analyze functions of TRAF6 in vivo in the hemopoietic compartment. We found that TRAF6-deficient chimeras develop a progressive lethal inflammatory disease associated with massive organ infiltration and activation of CD4(+) T cells in a Th2-polarized phenotype, and a defect in IL-18 responsiveness. When recombination-activating gene 2(-/-) blastocysts were complemented with TRAF6-deficient embryonic stem cells, a marked elevation of activated CD4(+) T cells and progressive inflammatory disease were also observed. Moreover, T cell activation and lethal inflammation were not reversed in mixed chimeric mice generated from normal and TRAF6-deficient fetal liver cells. These results suggest that deletion of TRAF6 induces a dominant Th2-type polarized autoimmune response. Therefore, in addition to playing a critical role in innate and adaptive immunity, TRAF6 is likely to play a previously unrecognized role in the maintenance of self-tolerance.

Animals↗

PubMed2006

Expression of TOLL-like receptors (TLR) by bovine antigen-presenting cells-potential role in pathogen discrimination?

Invading pathogens are controlled by the innate and adaptive arms of the immune system. Adaptive immunity, mediated by B and T lymphocytes, recognises pathogens via high affinity receptors. However, the establishment of a primary adaptive immune response is not rapid enough to eradicate invading microorganisms as it involves cell proliferation, gene activation and protein synthesis. More rapid defence mechanisms are provided by innate immunity, which recognises invading pathogens by germ-line-encoded pattern recognition receptors. Recent evidence shows that this recognition can mainly be attributed to the family of TOLL-like receptors (TLR). Binding of pathogen-associated molecular patterns to TLR induces the production of reactive oxygen and nitrogen intermediates, pro-inflammatory cytokines, and up-regulates expression of co-stimulatory molecules, subsequently initiating the adaptive immunity. In this paper, we will discuss the current knowledge with regards to the TLR, and in particular the bovine family of TLR. In addition, we will show the expression of TLR mRNA in bovine antigen-presenting cell subsets, summarise the discovery and the critical roles of TLR2 in host defence against Mycobacteria, and provide evidence for a mycobacteria species-specific response of bovine macrophages.

Animals↗

PubMed2004

Immunomodulating agents.

Inflammation involves a universally recognized, although incompletely understood, cascade of molecular events orchestrated by lymphokines and other innate biochemicals of immunity. Repeated or extended contact with immunogenic agents results in adaptive immunity involving antigen-induced events that stimulate down-stream immune cells and result in expansion of the inflammatory cascade. When immunogenic stimulation persists or autoregulatory immune mechanisms go awry, however, adaptive immunologic events can result in immune-mediated processes detrimental to systemic or organ-specific homeostasis. Because of the complexities of immunologic events, the potential side effects of long-term corticosteroid therapy, and the focused spectrum of most conventional nonsteroidal anti-inflammatory agents (centered on arachidonic acid-related mechanisms), a variety of other chemotherapeutic immunosuppressive agents have assumed an increasingly prominent therapeutic role in veterinary ophthalmology in the management of chronic ocular inflammatory diseases. In addition, nonimmunosuppressive immunomodulating agents (ie, immuno-stimulants or immunorestoratives) may be used as adjunctive therapies in the management of ocular or visual system diseases.

Adjuvants, Immunologic↗

PubMed2000

Equine immunity to viruses.

The identification of some of the adaptive immune responses to infection with equine viruses has been the first step toward rational immunoprophylactic design. Sufficient knowledge of infection-induced immunity and informed estimates of the requirements for long-term immunity for EIV have now been obtained. Thus, the future for inactivated EIV vaccines is promising now that new adjuvants have been applied to induce cellular immunity and safe methods have been designed to stimulate virus-neutralizing (VN) antibody at mucosal surfaces. Adenoviruses induce circulating VN antibody, the presence of which appears to correlate with protection from reinfection. Therefore, the potential of vaccines to induce VN antibody and protect from challenge is an important next step with this virus. With persistent viruses such as EHV-1, antibody-mediated protection from infection can be achieved only at the site of initial infection, that is, the nasopharynx and upper respiratory tract. Systemic dissemination is very rapid and consequently VN antibody is unlikely to play a major role in prevention of disease once the initial infection event has occurred. Cellular immune responses, particularly CTLs, play a dominant role in protection and recovery and are important in immune surveillance and determination of the outcome of reactivation of latent virus. Therefore, the key to future EHV-1 vaccine design is to focus on stimulation of CTL responses, and this requires the successful presentation of vaccine-derived antigenic peptides to MHC class I molecules that are recognized by specific receptors on CTL. There is some evidence that stimulation of EHV-1-specific CTL precursors may correlate with immunity to this virus. By analogy with gamma herpesviruses in humans, CTL precursor frequency may also function as an immune correlate for EHV-2. Although EAV infection induces strong immunity in females and geldings, persistent infection of the genital tract is an important route of dissemination from stallions. Although inactivated vaccines induce strong immunity (which depends upon VN activity of serum antibody) to first infection, the immunologic control of persistent infection is currently poorly understood; however, analogy with other persistent viruses suggests that CTLs are also likely to play an important role in the control of persistent EAV infections.

Acute-Phase Proteins↗

PubMed2006

The changing immunological paradigm in coeliac disease.

When coeliac disease is referred to as an inflammatory disorder, this may detract from its true nature. Activation of innate and adaptive immunity takes place in the mucosal lesion, but the tissue reaction is not that of classical inflammation. In fact, coeliac disease contrasts strikingly with typical inflammatory bowel disorders such as ulcerative colitis and Crohn's disease. The coeliac lesion apparently reflects, in the main, immune-driven remodelling of mucosal architecture with only a minor inflammatory component - initially most likely resulting from innate signals. Complement split products might be one of several potential initial hits that lead to activation of lamina propria and epithelial cells with release of mediators such as interleukin-15. This cytokine appears to stimulate potentially pathogenic intraepithelial lymphocytes. In genetically susceptible individuals, such early innate events could turn into persistent pathogenic signalling with subsequent adaptive cellular and humoral immunopathology resulting in a chronic lesion. Nevertheless, mucosal homeostasis is surprisingly well preserved as signified by the remarkable dominance of plasma cells that produce dimeric immunoglobulin A as a basis for enhanced secretory immunity. This shows that the microvascular endothelium in the lesion largely maintains its 'gatekeeper' function for mucosal immune cells - in striking contrast to the 'promiscuous' situation in inflammatory bowel disease. Altogether, a two-signal model is emerging for the pathogenesis of coeliac disease - signal 1 generated by innate immunity and signal 2 by adaptive immunity. Hence, there is currently an increased focus on immune activation in the epithelial compartment rather than on changes in the microvasculature as a basis for classical inflammation.

Animals↗

PubMed2002

The immune response to infection with Treponema pallidum, the stealth pathogen.

Cutaneous immunobiology and spirochetal molecular biology have allowed investigators to propose a conceptual framework for the development of both the innate and adaptive immune response to Treponema pallidum infection. While some clinical manifestations can be attributed to humoral responses, most can be attributed to a combination of local innate and adaptive cellular immunity.

Antibody Formation↗

PubMed2005

Immune surveillance and anti-tumor immune responses: an anatomical perspective.

The development of adaptive immune responses against infectious agents relies on the initiation of antigen specific immune responses in secondary lymphoid organs and on the migration of effector cells at the site of infection. Similarly, the development of anti-tumor immunity depends on the recognition of tumor-derived antigens by specific lymphocytes in the context of the lymphoid tissues and on the re-localisation of the cells to the site of cell transformation. Here, we will review the preclinical studies, which have defined the spatial and temporal organisation of anti-tumor immunity, and discuss the implications of these findings in active immunotherapy.

Animals↗