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Results for “Adaptive Immunity”

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At least 181 records · Page 10Linked to original sources

PubMed2005

Cdcs1, a major colitogenic locus in mice, regulates innate and adaptive immune response to enteric bacterial antigens.

BACKGROUND & AIMS: The absence of interleukin 10, a key cytokine in gut homeostasis, causes severe colitis in C3H/HeJBir but not C57BL/6J mice. The major modifier for colitis was mapped on chromosome 3 and designated cytokine deficiency-induced colitis susceptibility 1 (Cdcs1). We developed reciprocal Cdcs1 congenic stocks on both interleukin 10-deficient backgrounds to identify the susceptibility gene and its function. METHODS: C3H/HeJBir congenic for the C57BL/6J-derived Cdcs1 allele and reciprocal C57BL/6J congenic for the C3H/HeJBir allele were analyzed for colitis development. Parental strains were compared by electrophoretic mobility shift assay to assess the candidacy of nuclear factor-kappaB p50 in the Cdcs1 interval. Functional differences were observed in innate and adaptive immune responses of parental and congenic stocks after bacterial ligand exposure in vitro (cytokine release from bone marrow-derived macrophage and dendritic cells) and in vivo (serum cytokines and primed CD4+ T cell proliferation). RESULTS: Cdcs1 was positioned within a minimum 7-megabase interval containing nuclear factor-kappaB p50. C3H/HeJBir colitis was significantly diminished by the C57BL/6J genome in this interval. Conversely, colitis in C57BL/6J was significantly exacerbated by the reciprocal C3H/HeJBir genome. C3H/HeJBir macrophages constitutively expressed higher nuclear factor-kappaB p50. Functional assays showed that C3H/HeJBir showed reduced innate responsiveness both in vivo and in vitro to bacterial ligands but showed increased CD4 T-cell responses compared with C57BL/6J. This differential responsiveness was controlled by the respective allele at Cdcs1. CONCLUSIONS: The colitogenic Cdcs1 allele impairs innate immunity to bacterial products and in turn skews the adaptive immune response toward compensatory hyperresponsiveness and chronic intestinal inflammation.

Animals↗

PubMed2005

Regulation of arthritis by p53: critical role of adaptive immunity.

OBJECTIVE: The p53 tumor-suppressor protein is expressed in rheumatoid arthritis synovium, and loss of p53 function through somatic mutation can occur in longstanding disease. Previous studies demonstrated that p53 is protective in murine collagen-induced arthritis (CIA). To determine if adaptive immune responses or synovial effector functions are responsible for this effect, passive models of arthritis were studied in p53 wild-type and knockout mice. METHODS: Models of passive CIA, passive K/BxN serum transfer arthritis, and active CIA were induced in DBA/1 p53(-/-) or p53(+) mice. Hind paws were evaluated for histologic evidence of inflammation and joint destruction. Synovial interleukin-6 and matrix metalloproteinases 3 and 13 gene expression was analyzed by real-time quantitative polymerase chain reaction. To evaluate T cell function in p53(-/-) mice, draining lymph node (LN) cells from mice immunized with type II collagen (CII) were evaluated in vitro. RESULTS: Increased disease severity in p53(-/-) mice was confirmed in the standard CIA model. However, clinical arthritis, joint destruction, and synovial gene expression in the passive CIA and K/BxN serum transfer arthritis models were similar in p53(-/-) and p53(+) mice. To determine if the p53 effect was related to T cell function, LN cells from CII-immunized mice were isolated and stimulated with antigen in vitro. CII-stimulated T cell proliferation and interferon-gamma production were significantly higher in p53(-/-) mice. An independent assessment of Th1 function using the cutaneous delayed-type hypersensitivity model confirmed that p53(-/-) mice have enhanced T cell responses in vivo. CONCLUSION: Adaptive immune responses, rather than antibody-mediated responses, in p53(-/-) mice account for increased disease severity in the active CIA model.

Animals↗

PubMed2004

An adaptive immune optimization algorithm for energy minimization problems.

Based on the immune theory of biology, a novel evolutionary algorithm, adaptive immune optimization algorithm (AIOA), is proposed. In AIOA, density regulation and immune selection is adopted to control the individual diversity and the convergence adaptively. By an application of the algorithm to the optimization of test functions, it is shown that the algorithm is a highly efficient optimization method compared with other stochastic optimization methods. The algorithm was also applied to the optimization of Lennard-Jones clusters, and the results show that the method can find the optimal structure of N</=80 with a very high efficiency. The proposed algorithm may be a good tool for fast global optimization in chemical or biological molecular simulations.

Journal Article↗

PubMed2006

Complement and Toll-like receptors: key regulators of adaptive immune responses.

The innate immune system provides sophisticated defense mechanisms to protect complex macroorganisms from the attack of microorganisms. Among those, the complement system and Toll-like receptors are of paramount importance to discriminate between infectious non-self and non-infectious self and to provide critical danger signals instructing adaptive immune responses. Here, we will discuss recent advances in our understanding of the mechanisms underlying complement and TLR-mediated regulation of adaptive immunity. We will focus on the regulation of T cell immunity and discuss recent findings on the cross-talk between complement receptor and TLR signaling pathways. Such cross-talk is likely to affect the outcome of infections with intracellular pathogens, as well as the initiation and maintenance of aberrant immune responses leading to autoimmunity and atopy.

Animals↗

PubMed2005

Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses.

Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4(+) and CD8(+) T cells, increased the number of tumor Ag-specific CD8(+) T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-gamma producing CD8(+) T cells. Interestingly, AHCC treatment also showed increased cell number of NK and gammadelta T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.

Animals↗

PubMed2004

Memory in the innate and adaptive immune systems.

Specific memory is a hallmark of the vertebrate adaptive immune system. However, recent experiments indicate that specific memory might also exist in the innate immune systems of invertebrates. At present, the underlying mechanisms are unknown; yet such phenomenological evidence is relevant for understanding the principles and evolution of immune defence.

Animals↗

PubMed2003

GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro.

Infection remains the major complication of immunosuppressive therapy in organ transplantation. Therefore, reconstitution of the innate immunity against infections, without activation of the adaptive immune responses, to prevent graft rejection is a clinically desirable status in transplant recipients. We found that GM-CSF restored TNF mRNA and protein expression without inducing IL-2 production and T cell proliferation in glucocorticoid-immunosuppressed blood from either healthy donors or liver transplant patients. Gene array experiments indicated that GM-CSF selectively restored a variety of dexamethasone-suppressed, LPS-inducible genes relevant for innate immunity. A possible explanation for the lack of GM-CSF to restore T cell proliferation is its enhancement of the release of IL-1betaR antagonist, rather than of IL-1beta itself, since exogenously added IL-1beta induced an IL-2-independent Con A-stimulated proliferation of glucocorticoid-immunosuppressed lymphocytes. Finally, to test the in vivo relevance of our findings, we showed that GM-CSF restored the survival of dexamethasone- or cyclosporine A-immunosuppressed mice from an otherwise lethal infection with Salmonella typhimurium. In addition to this increased resistance to infection, GM-CSF did not induce graft rejection of a skin allotransplant in cyclosporine A-immunosuppressed mice. The selective restoration potential of GM-CSF suggests its therapeutic use in improving the resistance against infections upon organ transplantation.

Adjuvants, Immunologic↗

PubMed2005

IFN-gamma-induced immune adaptation of the proteasome system is an accelerated and transient response.

Peptide generation by the proteasome is rate-limiting in MHC class I-restricted antigen presentation in response to IFN-gamma. IFN-gamma-induced de novo formation of immunoproteasomes, therefore, essentially supports the rapid adjustment of the mammalian immune system. Here, we report that the molecular interplay between the proteasome maturation protein (POMP) and the proteasomal beta5i subunit low molecular weight protein 7 (LMP7) has a key position in this immune adaptive program. IFN-gamma-induced coincident biosynthesis of POMP and LMP7 and their direct interaction essentially accelerate immunoproteasome biogenesis compared with constitutive 20S proteasome assembly. The dynamics of this process is determined by rapid LMP7 activation and the immediate LMP7-dependent degradation of POMP. Silencing of POMP expression impairs recruitment of both beta5 subunits into the proteasome complex, resulting in decreased proteasome activity, reduced MHC class I surface expression, and induction of apoptosis. Furthermore, our data reveal that immunoproteasomes exhibit a considerably shortened half-life, compared with constitutive proteasomes. In consequence, our studies demonstrate that the cytokine-induced rapid immune adaptation of the proteasome system is a tightly regulated and transient response allowing cells to return rapidly to a normal situation once immunoproteasome function is no longer required.

Apoptosis↗

PubMed2004

Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5.

Mitogen-activated protein (MAP) kinases are essential regulators in immune responses, and their activities are modulated by kinases and phosphatases. MAP kinase phosphatase (MKP) is a family of dual-specificity phosphatases whose function is evolutionarily conserved. A number of mammalian MKPs have been identified so far, but their specific physiological functions in negative regulation of MAP kinases have not been genetically defined. Here we examine innate and adaptive immune responses in the absence of MKP5. JNK activity was selectively increased in Mkp5 (also known as Dusp10)-deficient mouse cells. Mkp5-deficient cells produced greatly enhanced levels of pro-inflammatory cytokines during innate immune responses and exhibited greater T-cell activation than their wild-type counterparts. However, Mkp5-deficient T cells proliferated poorly upon activation, which resulted in increased resistance to experimental autoimmune encephalomyelitis. By contrast, Mkp5-deficient CD4(+) and CD8(+) effector T cells produced significantly increased levels of cytokines compared with wild-type cells, which led to much more robust and rapidly fatal immune responses to secondary infection with lymphocytic choriomeningitis virus. Therefore, MKP5 has a principal function in both innate and adaptive immune responses, and represents a novel target for therapeutic intervention of immune diseases.

Animals↗

PubMed2002

The role of the innate and adaptive immune responses in Acanthamoeba keratitis.

Infections of the corneal surface are an important cause of blindness. Protozoal, viral, bacterial, and helminthic infections of the cornea account for up to 9 million cases of corneal blindness. Free-living amoebae of the genus Acanthamoeba produce a progressive infection of the cornea called Acanthamoeba keratitis. Disease is usually transmitted by Acanthamoeba trophozoites bound to soft contact lenses. Infection of the cornea is initiated when the parasite binds to the corneal epithelial surface. Recrudescence can occur and suggests that the adaptive immune response is not aroused by corneal Acanthamoeba infections. Systemic immunization with Acanthamoeba antigens elicits robust Th1 cell-mediated immunity and serum IgG antibody, yet fails to prevent the development of Acanthamoeba keratitis. However, immunization via mucosal surfaces induces anti-Acanthamoeba IgA antibodies in the tears and provides solid protection against the development of Acanthamoeba keratitis. Unlike other immune effector mechanisms that rely on cytolysis, inflammation, release of toxic molecules, or the induction of host cell death, the adaptive immune apparatus prevents Acanthamoeba infections of the cornea by simply preventing the attachment of the parasite to the epithelial surface. The beauty of this mechanism lies in its exquisite simplicity and efficacy.

Acanthamoeba↗

PubMed1997

Evidence for non-adaptive immune response in HIV infection.

Increased levels of soluble forms of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and E-selectin have been found in the sera of HIV-infected patients and have been associated with disease progression. The aim of the present study was to investigate whether this phenomenon reflects activation of the non-adaptive immune response in HIV infection. Fifty-one patients with HIV infection (42 men, nine women) were classified into two subgroups: those with HIV infection but without evidence of AIDS indicator conditions (HIV infected non-AIDS cases, n = 27) and those with AIDS (AIDS cases, n = 24). The activation of non-adaptive immune response was evaluated as the production of reactive oxygen species that cause lipid peroxidation, which was assessed by measuring thiobarbituric reactive substances (TBARS) using the thiobarbituric acid assay (TBA). Plasma levels of von Willebrand factor (vWF), measured by rocket immunoelectrophoresis, were used to show activation of endothelial cells even in the absence of any other causative agent, in these patients. TBARS levels in non-AIDS cases were significantly higher than in control subjects (n = 17) or AIDS cases (P < 0.001). The mean vWF levels were higher in AIDS cases than in non-AIDS cases or normal subjects (P < 0.05). TBARS levels remained significantly higher in non-AIDS cases after adjusting for age, CD4 T-cell and neutrophil counts, antiretroviral therapy and vWF plasma levels. The above findings indicate that in HIV infection, the virus per se is responsible for the increased oxidative stress that in turn activates various transduction pathways, may be leading to endothelial cell activation and shedding of adhesion molecules from the cell surface.

Adult↗

PubMed2005

A point of view: HIV-1/AIDS is an allergy but CpG ODN treatments may inhibit virus replication and reactivate the adaptive immunity--hypothesis and implications.

Reevaluation of the increase in the levels of IgE and IL-4 in sera of HIV-1 infected and AIDS patients led to the suggestion that AIDS resembles allergy. Studies on the properties of the viral shed gp120 revealed that it resemble environmental allergens in their ability to induce hematopoietic cells to release large amounts of Th2 cytokines, inhibitors of the patients adaptive immune response. Yet, induction of TLR9+ plasmacytoid DCs by CpG ODNs cause the release of type I interferons, inhibitors of HIV-1 replication and IL-4 release from hematopoietic cells. CpG ODN binding to TLR+ B cells inhibits IgE synthesis and reactivates the failing adaptive immunity. The possible use of CpG ODNs as treatment to patients is discussed.

AIDS Vaccines↗

PubMed2006

Regulations and roles of the interleukin-1 receptor associated kinases (IRAKs) in innate and adaptive immunity.

The interleukin-1 receptor associated kinases (IRAKs) are critically involved in the IL-1R/Toll-like receptor (TLR)-mediated signal transduction processes and therefore regulate cellular innate immune responses. Four IRAK members have been identified in the human genome (IRAK-1, 2, M, and 4), which seem to play distinct roles. Recent studies further suggest that some of the IRAK members may also participate in T cell and B cell signaling and regulate adaptive immunity. Given the critical and complex roles IRAK proteins play, it is not surprising that genetic variations in human IRAK genes have been found to be linked with various human inflammatory diseases. This review intends to summarize the recent advances regarding the biochemical regulations of various IRAK proteins and their cellular functions in mediating innate and adaptive immunity.

Animals↗

PubMed2005

Collectin surfactant protein D binds antibodies and interlinks innate and adaptive immune systems.

Innate immune collectins, such as surfactant protein D (SP-D), contain fibrillar collagen-like regions and globular carbohydrate-recognition domains (CRDs). SP-D recognizes carbohydrate arrays present on microbial surfaces via its CRDs, agglutinates microbes and enhances their phagocytosis. In contrast, adaptive immune proteins such as immunoglobulins (Igs) recognize pathogens via binding to specific antigens. Here we show that: SP-D binds various classes of immunoglobins, including IgG, IgM, IgE and secretory IgA, but not serum IgA; the globular domains of SP-D bind both the Fab and Fc domains of IgG; SP-D recognizes IgG via calcium-dependent protein-protein interactions, aggregates IgG-coated beads and enhances their phagocytosis by murine macrophage RAW 264.7 cells. Therefore, we propose that SP-D effectively interlinks innate and adaptive immune systems.

Animals↗

PubMed2005

TWEAK attenuates the transition from innate to adaptive immunity.

Innate immunity is the first line of defense against infection, protecting the host during the development of adaptive immunity and critically affecting the nature of the adaptive response. We show that, in contrast to tumor necrosis factor alpha (TNF-alpha), the related protein TWEAK attenuates the transition from innate to adaptive mechanisms. TWEAK-/- mice had overabundant natural killer (NK) cells and displayed hypersensitivity to bacterial endotoxin, with their innate immune cells producing excess interferon (IFN)-gamma and interleukin (IL)-12. TWEAK inhibited stimulation of the transcriptional activator STAT-1 and induced p65 nuclear factor (NF)-kappaB association with histone deacetylase 1, repressing cytokine production. TWEAK-/- mice developed oversized spleens with expanded memory and T helper 1 (TH1) subtype cells upon aging and mounted stronger innate and adaptive TH1-based responses against tumor challenge. Thus, TWEAK suppresses production of IFN-gamma and IL-12, curtailing the innate response and its transition to adaptive TH1 immunity.

Animals↗

PubMed2004

Maternal adaptive immunity influences the intestinal microflora of suckling mice.

The microflorae in the intestine of breast-fed infants are distinct from those that typically populate the intestine of formula-fed infants. Although the acquisition of passive immunity through breast-feeding may play a critical role in influencing the pattern of bacterial colonization of the gut, the precise mechanisms underlying the differences in the commensal microflorae of breast and formula-fed children have not been established. We hypothesized that the assemblage of commensal microflorae in suckling and weaned mice may be influenced by the maternal adaptive immune system. To test this hypothesis, we analyzed the intestinal microflorae of mice reared in the presence (wild-type) or absence of an intact maternal immune system (T- and B-cell deficient). Several types of bacteria (Lactobacillus, Enterococcus, Clostridium perfringens, Bifidobacterium, and Bacteroides) were isolated and enumerated from both the small and large intestine of 10-, 18-, 25- and 40- to 60-d old mice using selective media. The densities of bacteria were significantly lower in the small intestine of weaned mice that were reared by wild-type (WT) compared with immunodeficient (ID) dams. However, the microflorae were generally more abundant in the large intestine of suckling pups reared by WT compared with ID dams. Our results indicate that intestinal microflorae change throughout the suckling phase of development and that the maternal adaptive immune system influences the pattern and abundance of bacteria within the gut in an age- and site-specific manner.

Aging↗

PubMed2000

Evolution of adaptive immunity.

Antigen receptors and major histocompatibility molecules, key elements required for adaptive immunity, are first seen in jawed fish. So, how did they evolve and have they changed?

Animals↗

PubMed1999

Integrating innate and adaptive immunity in the whole animal.

The mammalian defense system can respond to a variety of threats, but this capability is not just a simple alarm system for triggering antigen-presenting cells and initiating cellular immunity. Instead, the body is an integrated system in which nearly every cell type can relay the alarm through the production of chemokines, which recruit specific inflammatory cells to the target tissues. This chemokine production is carefully regulated at several levels so that the kinetics and character of local tissue inflammation is tailored to the specific threat. First, the production of nuclear factor-kappa B-regulated chemokines can be modulated in non-bone marrow-derived cells through transcriptional repression mediated by RelB. RelB is also implicated in the differentiation of lymphoid dendritic cells, suggesting that this gene regulates the transition from acute inflammation to adaptive immunity. Second, tissue parenchymal cells, in their capacity as sentinel cells, are able to produce different patterns of chemokines in response to different alarm stimuli. Third, cells from different tissues also show distinct potentials for chemokine responses so that the non-specific damage from inflammation might be avoided in some cases. Finally, the differentiation of T-cell effectors allows for further regulation of local inflammation as their cytokines can also affect chemokine production. This integration of innate and adaptive immunity allows for both rapid responses and dynamic regulation of inflammation in vivo.

Adaptation, Physiological↗