Immunology
0019-2805
1365-2567
Anh Quốc
Cơ quản chủ quản: Wiley-Blackwell Publishing Ltd , WILEY
Lĩnh vực:
Immunology and AllergyImmunology
Các bài báo tiêu biểu
<b>Inhibition of inducible nitric oxide synthase expression by interleukin‐4 and interleukin‐13 in human lung epithelial cells</b> Nitric oxide produced by the inducible enzyme, nitric oxide synthase (iNOS), is implicated in immunological and inflammatory processes. We determined the effects of T‐helper (Th)2‐derived cytokines on the induction of iNOS from an epithelial A549 cell line and human airway epithelial cells stimulated by a mixture of interleukin‐1β (IL‐1β), interferon‐γ (IFN‐γ) and tumour necrosis factor‐α (TNF‐α). Interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13) but not interleukin‐10 (IL‐10) inhibited both iNOS mRNA expression and nitrite release in A549 cells. On human airway epithelial cells, IL‐4 and IL‐13 reduced iNOS mRNA expression. Dexamethasone also inhibited both iNOS expression and nitrite release. Th2 cytokines, IL‐4 and IL‐13, inhibit iNOS upregulation by Th1 cytokines, indicating an important reciprocal role of Th1 and Th2 T‐cell subsets on lung epithelial cells.
Tập 89 Số 3 - Trang 363-367 - 1996
Activation of mannan‐binding lectin‐associated serine proteases leads to generation of a fibrin clot Summary The lectin pathway of complement is activated upon binding of mannan‐binding lectin (MBL) or ficolins (FCNs) to their targets. Upon recognition of targets, the MBL‐and FCN‐associated serine proteases (MASPs) are activated, allowing them to generate the C3 convertase C4b2a. Recent findings indicate that the MASPs also activate components of the coagulation system. We have previously shown that MASP‐1 has thrombin‐like activity whereby it cleaves and activates fibrinogen and factor XIII. MASP‐2 has factor Xa‐like activity and activates prothrombin through cleavage to form thrombin. We now report that purified L‐FCN‐MASPs complexes, bound from serum to N‐ acetylcysteine‐Sepharose, or MBL‐MASPs complexes, bound to mannan‐agarose, generate clots when incubated with calcified plasma or purified fibrinogen and factor XIII. Plasmin digestion of the clot and analysis using anti‐D‐dimer antibodies revealed that the clot was made up of fibrin and was similar to that generated by thrombin in normal human plasma. Fibrinopeptides A and B (FPA and FPB, respectively) were released after fibrinogen cleavage by L‐FCN‐MASPs complexes captured on N‐ acetylcysteine‐Sepharose. Studies of inhibition of fibrinopeptide release indicated that the dominant pathway for clotting catalysed by the MASPs is via MASP‐2 and prothrombin activation, as hirudin, a thrombin inhibitor that does not inhibit MASP‐1 and MASP‐2, substantially inhibits fibrinopeptide release. In the light of their potent chemoattractant effects on neutrophil and fibroblast recruitment, the MASP‐mediated release of FPA and FPB may play a role in early immune activation. Additionally, MASP‐catalysed deposition and polymerization of fibrin on the surface of micro‐organisms may be protective by limiting the dissemination of infection.
Tập 129 Số 4 - Trang 482-495 - 2010
The early landscape of coronavirus disease 2019 vaccine development in the UK and rest of the world Summary Since the first World Health Organization notification on 31 December 2019, coronavirus disease 2019 (COVID‐19), the respiratory disease caused by the coronavirus severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has been responsible for over four million confirmed infections and almost 300 000 deaths worldwide. The pandemic has led to over half of the world's population living under lockdown conditions. To allow normal life to resume, public health interventions will be needed to prevent further waves of infections as lockdown measures are lifted. As one of the most effective countermeasures against infectious diseases, an efficacious vaccine is considered crucial to containing the COVID‐19 pandemic. Following the publication of the genome sequence of SARS‐CoV‐2, vaccine development has accelerated at an unprecedented pace across the world. Here we review the different platforms employed to develop vaccines, the standard timelines of development and how they can be condensed in a pandemic situation. We focus on vaccine development in the UK and vaccines that have entered clinical trials around the world.
Tập 160 Số 3 - Trang 223-232 - 2020
Facets of heat shock protein 70 show immunotherapeutic potential Summary Amongst the families of intracellular molecules that chaperone and assist with the trafficking of other proteins, notably during conditions of cellular stress, heat shock protein (hsp) 70 is one of the most studied. Although its name suggests that expression is exclusively induced during cellular hyperthermia, members of the hsp70 family of proteins can be constitutively expressed and/or induced by a range of other cellular insults. The ubiquitous presence of hsp70 in eukaryotic and prokaryotic cells, combined with its high degree of sequence homology and intrinsic immunogenicity, have prompted the suggestion that inappropriate immune reactivity to hsp70 might lead to pro‐inflammatory responses and the development of autoimmune disease. Indeed, hsp70 has been shown to be a potent activator of innate immunity and aberrant expression of hsp70 in certain organs promotes immunopathology. However, studies also suggest that hsp70 might have immunotherapeutic potential, as hsp70 purified from malignant and virally infected cells can transfer and deliver antigenic peptides to antigen‐presenting cells to elicit peptide‐specific immunity and, in contrast to its reported pro‐inflammatory effects, the administration of recombinant hsp70 can attenuate experimental autoimmune disease. This review focuses on the immunoregulatory capacity of hsp70 and its potential therapeutic value.
Tập 110 Số 1 - Trang 1-9 - 2003
Oral aspirin and ibuprofen increase cytokine‐induced synthesis of IL‐1β and of tumour necrosis factor‐α<i>ex vivo</i> We investigated the effect of oral aspirin and ibuprofen on the ex vivo synthesis of interleukin‐1α (IL‐1α), IL‐1β, IL‐2, IL‐6, tumour necrosis factor‐α (TNF) and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) by stimulated peripheral blood mononuclear cells (PBMC) from healthy volunteers. Seven volunteers took 325 mg of aspirin daily for 14 days. Three weeks after ending aspirin medication, ex vivo IL‐1β and TNF synthesis induced by exogenous IL‐1α was elevated threefold compared to the pre‐aspirin value (P = 0.01 and P = 0.005, respectively). Using lipopolysaccharide (LPS) as a stimulus, no influence of oral aspirin was observed. The increase in cytokine synthesis did not parallel decreased synthesis of prostaglandin E2 (PGE2 ). Seven weeks after discontinuation of aspirin, cytokine and PGE‐2 production returned to pre‐aspirin levels. Another seven volunteers took 200 mg of ibuprofen daily for 12 days. Again, there was no effect on LPS‐ or Staphylococcus epidermidis ‐induced cytokine synthesis. However, IL‐1α‐induced synthesis of IL‐1β was elevated to a mean individual increase of 538% (P < 0.001) and synthesis of TNF was elevated to 270% (P < 0.001) at the end of ibuprofen medication and 2 weeks after discontinuation of ibuprofen. There were parallel increases in PGE2 and both returned to their pre‐ibuprofen levels 5 weeks after stopping. Although inhibitors of cyclo‐oxygenase blunt PGE2 ‐mediated symptoms such as fever and pain, we conclude that short term use of either aspirin or ibuprofen results in a ‘rebound’ increase in cytokine‐induced cytokine synthesis that is not observed in LPS‐induced cytokines.
Tập 87 Số 2 - Trang 264-270 - 1996
Cancer immunoediting from immune surveillance to immune escape Summary Cancer immune surveillance is considered to be an important host protection process to inhibit carcinogenesis and to maintain cellular homeostasis. In the interaction of host and tumour cells, three essential phases have been proposed: elimination, equilibrium and escape, which are designated the ‘three E’s'. Several immune effector cells and secreted cytokines play a critical role in pursuing each process. Nascent transformed cells can initially be eliminated by an innate immune response such as by natural killer cells. During tumour progression, even though an adaptive immune response can be provoked by antigen‐specific T cells, immune selection produces tumour cell variants that lose major histocompatibility complex class I and II antigens and decreases amounts of tumour antigens in the equilibrium phase. Furthermore, tumour‐derived soluble factors facilitate the escape from immune attack, allowing progression and metastasis. In this review, the central roles of effector cells and cytokines in tumour immunity, and the escape mechanisms of tumour cells during tumour progression are discussed.
Tập 121 Số 1 - Trang 1-14 - 2007
Maternal–fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding Summary Allergen exclusion measures during pregnancy and lactation have been given consideration in studies of primary allergy prevention but complete avoidance of mother/neonatal allergen exposure has proven to be a difficult procedure. To evaluate a strategy to prevent allergen sensitization in early life in mice, we first established a neonatal model with ovalbumin sensitization through maternal allergen exposure during pregnancy or breastfeeding. The modulatory potential of preconception immunization was investigated on the neonatal development of subsequent allergic responses to maternal allergen exposure. Herein, we demonstrate that immunized mothers exposed to antigen during pregnancy or breastfeeding underwent intense vertical transmission of antibodies, including immunoglobulin G (IgG) in complex with ovalbumin and IgG1 antibody with anaphylactic function. It was further shown that maternal immunization efficiently decreased the passage of free antigens through breastfeeding and inhibited the enhanced IgE antibody response after postnatal antigen exposure. In addition, antenatal immunization decreased the antigen‐specific proliferative response of immunized neonates, in parallel with profound downmodulatory effects on both the activation and differentiation of T and B cells after a non‐specific stimulus and cytokine production. These findings showed that early life sensitization, subsequent to maternal allergen exposure during both the prenatal and postnatal periods, could be avoided by preventive vaccination of the mother.
Tập 122 Số 1 - Trang 107-115 - 2007
<scp>CD</scp>4<sup>+</sup> <scp>CD</scp>25<sup>−</sup> <scp>F</scp>ox<scp>P</scp>3<sup>+</sup> regulatory cells are the predominant responding regulatory <scp>T</scp> cells after human rotavirus infection or vaccination in gnotobiotic pigs Summary The distribution and dynamic changes of CD 4+ CD 25+ F oxP 3+ and CD 4+ CD 25− F oxP 3+ regulatory T (Treg) cells induced by human rotavirus (HRV ) infection and vaccination were examined in neonatal gnotobiotic pigs infected with virulent HRV (VirHRV ) or vaccinated with attenuated HRV (AttHRV ). Subsets of gnotobiotic pigs in the AttHRV and control groups were challenged with VirHRV at post‐inoculation day (PID ) 28. We demonstrated that VirHRV infection or AttHRV vaccination reduced frequencies and numbers of tissue‐residing Treg cells, and decreased the frequencies of interleukin‐10 (IL ‐10) and transforming growth factor‐β (TGF ‐β) producing CD 4+ CD 25− Treg cells in ileum, spleen and blood at PID 28. The frequencies of IL ‐10 and TGF ‐β producing CD 4+ CD 25− Treg cells in all sites at PID 28 were significantly inversely correlated with the protection rate against VirHRV ‐caused diarrhoea (r = −1, P < 0·0001). Hence, higher frequencies of functional CD 4+ CD 25− Treg cells can be an indicator for poorer protective immunity against rotavirus. Our results highlighted the importance of CD 4+ CD 25− Treg cells over CD 4+ CD 25+ Treg cells in rotavirus infection and immunity. AttHRV vaccination (induction of immune effector responses) reduced the expansion of CD 4+ CD 25− Treg cells in ileum seen in the challenged naive pigs during the acute phase of VirHRV infection and preserved normal levels of intestinal TGF ‐β producing Treg cells post‐challenge. The reduced suppressive effect of Treg cells in AttHRV ‐vaccinated pigs would unleash effector/memory T ‐cell activation upon challenge. Preserving TGF ‐β producing CD 4+ CD 25− Treg cells is important in maintaining homeostasis. Based on our findings, a model is proposed to depict the dynamic equilibrium course of Treg and effector T ‐cell responses after primary rotavirus infection/vaccination and challenge.
Tập 137 Số 2 - Trang 160-171 - 2012
The <i>CTLA‐4</i> gene polymorphisms are associated with CTLA‐4 protein expression levels in multiple sclerosis patients and with susceptibility to disease Summary Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) is an important molecule in the down‐regulation of T‐cell activation. A study was undertaken to evaluate the association of the CTLA‐4 gene polymorphisms −319C/T, +49A/G, (AT)n , CT60A/G and Jo31G/T with the levels of membrane CTLA‐4 (mCTLA‐4) and cytoplasmic CTLA‐4 (cCTLA‐4) in CD4+ T lymphocytes from patients with multiple sclerosis (MS) and with susceptibility to MS, and the course of the disease. It was found that the Jo31GG and CT60GG genotypes were associated with decreased mean fluorescence intensity (MFI) of total CTLA‐4 (mCTLA‐4 + cCTLA‐4) molecules in CD4+ T cells from both relapsing‐remitting (RR) and secondary progressive (SP) MS patients compared with others. Consequently, possessing the Jo31G allele and/or the CT60G allele were associated with susceptibility to MS. The percentages of cells expressing mCTLA‐4 and cCTLA‐4 in RR patients were higher in carriers of the alleles non‐predisposing to MS (namely CT60A and Jo31T), but the percentages of corresponding cells were unexpectedly significantly lower in SP patients than in RR patients. Increased risk of paresthesia and pyramidal signs as a first manifestation of disease, and earlier transition to the SP form in those patients, was also noted. It is hypothesized that the decreasing frequencies of cells expressing immunosuppressive mCTLA‐4 and cCTLA‐4 in carriers of alleles non‐predisposing to MS (i.e. CT60A and Jo31T) may lead to inadequate down‐regulation of ongoing T‐cell responses in these patients and, as a consequence, earlier progression of disease from the RR form to the SP form.
Tập 128 Số 1pt2 - 2009
Aging‐related Atg5 defect impairs neutrophil extracellular traps formation Summary Formation of neutrophil extracellular traps (NET s) is an important function of the innate immune system against infections. It has been proven that aging dysregulates immunity and impairs neutrophil function. However, the influence of aging on the ability to produce NET s has yet to be fully addressed. In this study, we tested the hypothesis that a lower level of autophagy in neutrophils from aged mice was responsible for the decrease in NET formation. We demonstrated that a broad range of Toll‐like receptor 2 (TLR 2) ligands could efficiently induce reactive oxygen species (ROS ) ‐dependent NET release in young mice, but not in aged ones. We further explored that the difference between young and aged mice in TLR 2 ligand‐induced NET osis is the result of an Atg5 defect and subsequent impaired autophagy. Furthermore, we found that lower autophagy capacity led to not only reduced NET formation, but also increased apoptosis. Our results suggest an important role of Atg5 and autophagy in maintaining the function of NET s formation in response to infection and in regulating neutrophil death. Targeting autophagy‐promoted NET s may present a therapeutic strategy to improve infection defence in an aged population.
Tập 151 Số 4 - Trang 417-432 - 2017