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Results for “Adaptive Immunity”

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At least 1,135 records · Page 63Linked to original sources

PubMed1988

Temperature-mediated processes in teleost immunity: homeoviscous adaptation by channel catfish peripheral blood cells.

1. Channel catfish peripheral blood erythrocyte, thrombocyte, T cell and B cell membranes were assayed by fluorescence depolarization using the fluorescent probe 1,6-diphenyl-1,3,5 hexatriene (DPH) to determine the effects of in vivo temperature acclimation on membrane viscosity and the kinetics of homeoviscous adaptation. 2. Erythrocyte membranes did not undergo homeoviscous adaptation during the 8 week time period studied and were more rigid compared with those of the other cell types. 3. The kinetics of homeoviscous adaptation exhibited by membranes from T cells, B cells and thrombocytes differed: B cells required 1-3 weeks while T cells and thrombocytes each required 3-5 weeks. Membranes from T cells, B cells and thrombocytes from fish acclimated for relatively short times (less than or equal to 3 weeks) exhibited similar membrane fluidities. 4. T cells from channel catfish appeared not only to be sensitive to temperature but also to a factor(s) independent of temperature but correlated to long term in vivo acclimation, i.e. T cell membranes underwent additional decreases in membrane viscosity between 3 and 5 weeks. 5. In conclusion, it appears that low temperature-mediated immunosuppression of T cell functions in channel catfish is probably not due to an inherent non-adaptability or rigid nature of the T cell membranes.

Adaptation, Physiological↗

PubMed2004

Effects of cytokines and heat shock on defensin levels of cultured keratinocytes.

Burns have been associated with high levels of circulating pro-inflammatory cytokines which promote systemic inflammatory response syndrome (SIRS), immunosuppression and sepsis for which no effective treatment is currently available. Defensins, a family of cationic naturally occurring antimicrobial peptides, are considered important components of the innate immune system and enhance adaptive immunity. This study examines the effects of pro-inflammatory cytokines, interleukin-1beta (IL-1beta), gamma-interferon (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) on human beta-defensin-2 (HBD-2) levels in cultured keratinocytes. We also examined the effects of heat shock at 42 degrees C. The results demonstrate that only TNFalpha shows significant induction of HBD-2 but this induction was not sustained in the long-term. In addition, endogenous levels of defensin were significantly reduced by exposure to heat shock. The keratinocytes also responded to IL-1beta by becoming hypertrophic. These results indicate that stress-related, pro-inflammatory cytokines can induce keratinocytes to synthesize HBD-2, while heat shock appears to reduce its production. These experiments give us further insight into the role of natural antimicrobial peptides under conditions of stress.

Cell Size↗

PubMed2006

Mast cells: not only in allergy.

The past decade has confronted us with a striking abundance of novel findings regarding the roles of mast cells in immune responses in health and disease. Newly developed models and techniques have enabled clear-cut dissection of the mast cell contribution in these settings. We now understand that mast cells possess critical effector functions not only within the traditional context of allergic reactions. It is likely that mast cells played pivotal roles in primitive immune systems, yet these functions have been masked in the recent eras by newer immune functions, such as adaptive immunity. Conceivably, mast cells should be refocused on so as to obtain new insights about diverse pathologic conditions, ultimately leading to novel therapeutic approaches targeting these fascinating cells.

Animals↗

PubMed2006

Toll-like receptor function and signaling.

Mammals sense pathogen invasion through pattern-recognition receptors. A group of transmembrane proteins, Toll-like receptors (TLRs), play critical roles as pattern-recognition receptors. They are mainly expressed on antigen-presenting cells, such as macrophages or dendritic cells, and their signaling activates antigen-presenting cells to provoke innate immunity and to establish adaptive immunity. Each TLR has common effects, such as inflammatory cytokine induction or upregulation of costimulatory molecule expression, but also has its specific function, exemplified by type I IFN-inducing ability. These immunoadjuvant effects are not only critical in antimicrobial immunity but are also involved in manifestations of autoimmunity. Furthermore, some TLR agonists are now promising therapeutic tools for various immune disorders, including allergy. Therefore understanding molecular mechanisms on TLRs should be quite useful in the development of therapeutic maneuvers against allergy and autoimmune diseases.

Animals↗

PubMed2004

Observations on the proposed relationship between infection burden and early malignancy in developing countries (e.g., India).

Sastry and Parikh [Med. Hypotheses 60(4) (2003) 573] have recently sought an explanation for the fact that the occurrence of a particular cancer in populations in a developing country such as India takes place at a younger age (about one decade) than in populations in Western countries. They have hypothesized that a higher infectious burden in India gives rise to repeated cell divisions leading to early senescence of immune cells, and, thence their reduced ability for immune surveillance against cancer, resulting in earlier onset of cancer. The analysis presented here points out to some difficulties with this interpretation, both on empirical and theoretical grounds. The reduced surveillance ability, caused by higher infectious burden, of the immune cells postulated by Sastry and Parikh [loc. cit.] would also mean that populations in India should suffer higher incidence of cancer, as compared to people in Western countries; the empirical data show that, in fact, quite the opposite is true - in the present communication shows that for many common cancers, typical cities in India show the lowest incidence. Theoretically, it is postulated here that repeated heavy infections in India, in fact, challenge the immune system, particularly the adaptive immune system and create an immunological memory: this trains and strengthens the immune system against the future battles. Also it is shown that the shortening of the telomeric cap by repeated cell divisions caused by heavy infectious attacks, as argued by Sastry and Parikh [loc. cit.], is not the cause of earlier onset of cancers among Indians; in fact, when telomeric caps become shortened to a critical point, a danger signal is generated arresting the cell cycle - thus, it provides a fundamental mechanism for ordering the cell to cease proliferation. It is suggested that the root of occurrence of cancers at an earlier age in India perhaps lies in the accumulation of mutations at an earlier age among Indians who do develop cancers; the factors responsible for these accelerated mutations are not clear at the present time and need further investigation.

Age Distribution↗

PubMed2000

The role of interleukin 15 in mounting an immune response against microbial infections.

Interleukin (IL)-15 is a recently described cytokine that resembles IL-2 in its biological activities, stimulating natural killer cells, T cells and B cells to proliferate, secrete cytokines, and exhibit increased cytotoxicities or produce antibody. IL-15 also exerts unique functions such as stimulation of phagocytes, maintenance of mast cells and migration of activated/memory T cells. IL-15 is involved in protection against infections with a variety of microbes through not only activating innate immunity but also mounting adaptive immunity.

Animals↗

PubMed2002

Cytokines as a link between innate and adaptive antitumor immunity.

Recent studies indicate that cytokines produced by cells of the innate defense system play an essential role in influencing the immune response towards protective antitumor immunity. These cytokines might act as first 'danger signals' in alerting the immune system. By promoting the differentiation and activation of dendritic cells, antigen presentation and T-cell-mediated immune responses, these cytokines could be powerful natural adjuvants for the development of cancer vaccines. With regard to type I interferons - cytokines with a long history of clinical use - this new knowledge could be translated easily into novel strategies for the prevention and treatment of human malignancies.

Aging↗

PubMed2003

Breast milk and HIV-1: vector of transmission or vehicle of protection?

Transmission of HIV-1 to the infant through breastfeeding is a major cause of new paediatric HIV-1 infections worldwide. Although extended breastfeeding accounts for approximately 40% of infant HIV infections worldwide, most breastfed infants remain uninfected, despite prolonged and repeated exposure to HIV-1. Mechanisms associated with transmission of HIV-1 through breastfeeding and factors related to protection from such transmission remain poorly understood. Here we focus on the cellular origin of HIV in breast milk and on immune factors within the milk that may offer protection from transmission of HIV infection. The presence of innate immunity and induction of adaptive immunity against HIV is explored: in particular, specific antibodies, cellular responses, and their significance. The role of mucosal immune activation and epithelial integrity in HIV transmission is also addressed. We are of the opinion that advances in laboratory methods that study specific aspects of immunity will help open new areas of understanding of HIV transmission through breastfeeding and mechanisms of protection, and contribute to the development of novel prevention strategies.

Antibodies, Viral↗

PubMed2003

Toll-like receptors and intestinal defence: molecular basis and therapeutic implications.

Toll-like receptors (TLRs) play a principle role in distinct pathogen recognition and in the initiation of innate immune responses of the intestinal mucosa. Activated innate immunity interconnects downstream with adaptive immunity in complex feedback regulatory loops. Intestinal disease might result from inappropriate activation of the mucosal immune system driven by TLRs in response to normal luminal flora.

Dimerization↗

PubMed2002

Local synthesis of complement component C3 regulates acute renal transplant rejection.

Accumulating evidence suggests that innate immunity interacts with the adaptive immune system to identify potentially harmful antigens and eliminate them from the host. A central facet of innate immunity is complement, which for some time has been recognized as a contributor to inflammation in transplant rejection but without detailed analysis of its role in what is principally a T cell mediated process. Moreover, epithelial and vascular tissues at local sites of inflammation secrete complement components; however, the role of such local synthesis remains unclear. Here we show that the absence of locally synthesized complement component C3 is capable of modulating the rejection of renal allografts in vivo and regulating T-cell responses in vivo and in vitro. The results indicate that improved success in kidney transplantation could come from therapeutic manipulation of innate immunity in concert with T cell directed immunosuppression.

Acute Disease↗

PubMed2006

Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells.

Weak immunogenicity of chronic lymphocytic leukemia (CLL) cells may contribute to disease progression and inhibit effective immunotherapy. Accordingly, agents that enhance the immunogenicity of CLL cells may be useful in immunotherapeutic approaches to this disease. Since Toll-like receptors (TLRs) are major regulators of innate immunity and initiation of adaptive immunity, we studied the effects of viral pathogen associated molecular pattern agonists (that are recognized by TLRs) on the costimulatory phenotype and function of CLL cells. CLL cells (especially those with high endogenous expression of CD38) responded to TLR7-activating imidazoquinolines and guanosine analogs by increasing costimulatory molecule expression, producing inflammatory cytokines, and becoming more sensitive to killing by cytotoxic effectors. Additional activation of protein kinase C pathways increased the ability to stimulate T-cell proliferation, blocked phosphorylation of the transcription factor, signal transducer and activator of transcription (STAT)3, and resulted in the acquisition of a dendritic cell surface phenotype by TLR7-activated CLL cells. Normal B cells also responded to TLR7 activation by increasing costimulatory molecule expression and cytokine production. These findings suggest a potential role for TLR7 agonists in CLL immunotherapy.

Adult↗

PubMed2003

Immunotherapy of basal cell carcinoma: evolving approaches.

Nonmelanoma skin cancer (NMSC) is one of the most common types of cancer in the world. There is strong evidence that ultraviolet (UV) light plays a central role in the molecular pathogenesis of NMSC development. UV light causes DNA damage and loss of activity of tumor suppressor genes and overexpression of oncogenes and other genes related to enhanced growth and survival as well as tissue invasion. Also, UV light impairs the cutaneous immune response, especially Langerhans cell antigen-presenting function, resulting in immune tolerance to developing tumor cells. Standard treatments for NMSC include surgical excision, curettage and electrodessication, and Moh's micrographic surgery. Immunotherapy of NMSC has been attempted in the form of dinitrobenzene sensitization followed by topical application on the tumor, intralesional interferon injections, or perilesional interleukin-2. These treatments, although showing promise, have not been developed because of lower efficacy compared with surgical approaches, morbidity associated with treatments, as well as the expense of using recombinant cytokine treatments. The topical immune response modifier imiquimod is being developed as a novel local treatment for selected NMSC. Studies of the mechanism of action of imiquimod in NMSC indicate the presence of activated, natural killer cells (innate immunity), T-lymphocytes (adaptive immunity), antigen-presenting cells, and cytokines consistent with a delayed-type hypersensitivity reaction (Th1-lymphocyte cytokine pattern). This agent has been associated with a high response rate for the treatment of superficial basal cell carcinoma, with clearance rates ranging from 70% to 90% in a number of clinical trials. This novel immunotherapy represents a new, nonsurgical treatment option in the care of patients with NMSC.

Aminoquinolines↗

PubMed2005

The role of gut-associated lymphoid tissues and mucosal defence.

The newborn infant leaves a germ-free intrauterine environment to enter a contaminated extrauterine world and must have adequate intestinal defences to prevent the expression of clinical gastrointestinal disease states. Although the intestinal mucosal immune system is fully developed after a full-term birth, the actual protective function of the gut requires the microbial stimulation of initial bacterial colonization. Breast milk contains prebiotic oligosaccharides, like inulin-type fructans, which are not digested in the small intestine but enter the colon as intact large carbohydrates that are then fermented by the resident bacteria to produce SCFA. The nature of this fermentation and the consequent pH of the intestinal contents dictate proliferation of specific resident bacteria. For example, breast milk-fed infants with prebiotics present in breast milk produce an increased proliferation of bifidobacteria and lactobacilli (probiotics), whereas formula-fed infants produce more enterococci and enterobacteria. Probiotics, stimulated by prebiotic fermentation, are important to the development and sustainment of intestinal defences. For example, probiotics can stimulate the synthesis and secretion of polymeric IgA, the antibody that coats and protects mucosal surfaces against harmful bacterial invasion. In addition, appropriate colonization with probiotics helps to produce a balanced T helper cell response (Th1=Th2=Th3/Tr1) and prevent an imbalance (Th1>Th2 or Th2>Th1) contributing in part to clinical disease (Th2 imbalance contributes to atopic disease and Th1 imbalance contributes to Crohn's disease and Helicobacter pylori-induced gastritis). Furthermore, a series of pattern recognition receptors, toll-like receptors on gut lymphoid and epithelial cells that interact with bacterial molecular patterns (e.g. endotoxin (lipopolysaccharide), flagellin, etc.), help modulate intestinal innate immunity and an appropriate adaptive immune response. Animal and clinical studies have shown that inulin-type fructans will stimulate an increase in probiotics (commensal bacteria) and these bacteria have been shown to modulate the development and persistence of appropriate mucosal immune responses. However, additional studies are needed to show that prebiotics can directly or indirectly stimulate intestinal host defences. If this can be demonstrated, then prebiotics can be used as a dietary supplement to stimulate a balanced and an appropriately effective mucosal immune system in newborns and infants.

Animals↗

PubMed2000

Natural killer T cell activation inhibits hepatitis B virus replication in vivo.

We have previously reported that hepatitis B virus (HBV)-specific CD8(+) cytotoxic T lymphocytes and CD4(+) helper T lymphocytes can inhibit HBV replication in the liver of HBV transgenic mice by secreting interferon (IFN)-gamma when they recognize viral antigen. To determine whether an activated innate immune system can also inhibit HBV replication, in this study we activated natural killer T (NKT) cells in the liver of HBV transgenic mice by a single injection of alpha-galactosylceramide (alpha-GalCer), a glycolipid antigen presented to Valpha14(+)NK1.1(+) T cells by the nonclassical major histocompatibility complex class I-like molecule CD1d. Within 24 h of alpha-GalCer injection, IFN-gamma and IFN-alpha/beta were detected in the liver of HBV transgenic mice and HBV replication was abolished. Both of these events were temporally associated with the rapid disappearance of NKT cells from the liver, presumably reflecting activation-induced cell death, and by the recruitment of activated NK cells into the organ. In addition, prior antibody-mediated depletion of CD4(+) and CD8(+) T cells from the mice did not diminish the ability of alpha-GalCer to trigger the disappearance of HBV from the liver, indicating that conventional T cells were not downstream mediators of this effect. Finally, the antiviral effect of alpha-GalCer was inhibited in mice that are genetically deficient for either IFN-gamma or the IFN-alpha/beta receptor, indicating that most of the antiviral activity of alpha-GalCer is mediated by these cytokines. Based on these results, we conclude that alpha-GalCer inhibits HBV replication by directly activating NKT cells and by secondarily activating NK cells to secrete antiviral cytokines in the liver. In view of these findings, we suggest that, if activated, the innate immune response, like the adaptive immune response, has the potential to control viral replication during natural HBV infection. In addition, the data suggest that therapeutic activation of NKT cells may represent a new strategy for the treatment of chronic HBV infection.

Animals↗

PubMed2000

A novel PCR-based technique using expressed sequence tags and gene homology for murine genetic mapping: localization of the complement genes.

The complement system is a cascade of serum proteins and receptors which forms a vital arm of innate immunity and enhances the adaptive immune response. This work establishes the chromosomal localization of four key genes of the murine complement system. Mapping was performed using a novel and rapid PCR restriction length polymorphism method which was developed to exploit the murine expressed sequence tag (EST) database. This technique circumvents the laborious cDNA or genomic cloning steps of other mapping methods by relying on EST data and the prediction of exon-intron boundaries. This method can be easily applied to the genes of other systems, ranging from the interests of the individual researcher to large-scale gene localization projects. Here the complement system, probably one of the most well-characterized areas of immunology, was used as a model system. It was shown that the C3a receptor C1r and C1s genes form an unexpected complement gene cluster towards the telomeric end of chromosome 6. The second mannose binding lectin-associated serine protease gene was mapped to the telomeric end of chromosome 4, which is distinct from other complement-activating serine proteases. These results provide new insights into the evolution of this group of proteins.

Animals↗

PubMed2005

The role of toll-like receptors in the pathogenesis and treatment of dermatological disease.

Toll-like receptors (TLR) are crucial players in the innate immune response to microbial invaders. These receptors are expressed on immune cells, such as monocytes, macrophages, dendritic cells, and granulocytes. Importantly, TLR are not only expressed by peripheral blood cells, but their expression has been demonstrated in airway epithelium and skin, important sites of host-pathogen interaction. Host cells expressing TLR are capable of recognizing conserved pathogen-associated molecular patterns, such as lipopolysaccharide and CpG DNA, and their activation triggers signaling pathways that result in the expression of immune response genes and cytokine production. As TLR are instrumental in both launching innate immune responses and influencing adaptive immunity, regulation of TLR expression at sites of disease such as in leprosy, acne, and psoriasis may be important in the pathophysiology of these diseases. Furthermore, since TLR are vital players in infectious and inflammatory diseases, they have been identified as potential therapeutic targets. Indeed, synthetic TLR agonists such as imiquimod have already established utility in treating viral pathogens and skin cancers. In the future, it seems possible there may also be drugs capable of blocking TLR activation and thus TLR-dependent inflammatory responses, providing new treatment options for inflammatory diseases.

Gene Expression Regulation↗

PubMed2007

Translational mini-review series on Toll-like receptors: recent advances in understanding the role of Toll-like receptors in anti-viral immunity.

(TLRs) respond to pathogens to initiate the innate immune response and direct adaptive immunity, and evidence to date suggests that they have a role in the detection of viruses. Many viral macromolecules have been shown to activate anti-viral signalling pathways via TLRs, leading to the induction of cytokines and interferons, while viruses also have means of not only evading detection by TLRs, but also of subverting these receptors for their own purposes. This review discusses the role of TLRs in the context of other known viral detection systems, and examines some of the often surprising results from studies using mice deficient in TLRs and their adaptors, in an attempt to unravel the particular contribution of TLRs to anti-viral immunity.

Animals↗

PubMed2006

Antimicrobial peptide LL-37 internalized by immature human dendritic cells alters their phenotype.

The human cathelicidin LL-37 has been shown to be involved in the barrier function of the innate immunity, being released from specific cells upon challenge and exerting immunomodulatory effects. We here demonstrate that LL-37 affects immature dendritic cells, derived from human peripheral blood monocytes (MDDC). LL-37 is internalized by MDDC with subsequent localization primarily in the cytoplasmic compartment. However, LL-37 could also be detected in the nuclei of MDDC, suggesting that LL-37 may be transported into the nucleus. The uptake of LL-37 is dose, time and energy dependent, indicating that the observed internalization process involves an endocytic pathway. Incubation of immature MDDC with LL-37 caused phenotypic changes, characterized by an increased expression of the antigen-presenting molecule HLA-DR, and the costimulatory molecule CD86. Taken together, these findings suggest that LL-37 released upon triggering of the innate immunity, may affect cellular adaptive immunity through an interaction with immature dendritic cells.

Amino Acid Sequence↗