Clinical & Experimental Immunology

Cover image for Vol. 187 Issue 3

Edited By: Mark Peakman and Leonie Taams

Impact Factor: 3.148

ISI Journal Citation Reports © Ranking: 2015: 63/151 (Immunology)

Online ISSN: 1365-2249

Featured

  • Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels

    Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels

    A conceptual natural killer (NK) model for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. Pregnenolone sulphate (PregS) is a potent steroid that activated transient receptor potential melastatin 3 ion channels (TRPM3) on NK cell subsets. PregS in combination with thapsigargin elevated cytoplasmic calcium and is suggested to phosphorylate extracellular-regulated kinase (ERK) 1/2 and polarization of secretory granules for degranulation in CD56dimCD16+ NK cells, resulting in target K562 cell death, whereas PregS-stimulated CD56brightCD16dim/– NK cells may activate p38 MAPK signalling pathways involved in the nuclear factor kappa B (NF-κβ) inflammatory immune response.

  • Herpes zoster and the search for an effective vaccine

    Herpes zoster and the search for an effective vaccine

    Varicella zoster virus (VZV) immune response during reactivation. When immune responses weaken, VZV reactivates by travelling anterograde towards nerve endings, replicates in keratinocytes and epithelial cells causing the formation of polykaryocytes, leading ultimately to a dermatomal rash. The local immune response in the ganglia is characterized by the infiltration of CD8, CD4, natural killer (NK) cells, macrophages and B cells. The immune response in the skin is characterized by CD4, CD8, NK cells and macrophages along with increased expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-6.

  • Expression of type III interferons (IFNλs) and their receptor in Sjögren's syndrome

    Expression of type III interferons (IFNλs) and their receptor in Sjögren's syndrome

    Representative double immunofluorescent staining for the common type III interferon (IFN) signalling receptor [IFN-λR1/interleukin (IL)−28Rα] and markers of inflammatory cells [plasmatocytoid dendritic cells (pDCs): CD303 and CD123, macrophages: CD68, T lymphocytes: CD3 and B lymphocytes: CD20] in a minor salivary gland (MSG) tissue from a Sjögren's syndrome (SS) patient. Co-localization is indicated with yellow arrows. Original magnification ×1000.

  • Porphyromonas gingivalis infection exacerbates the onset of rheumatoid arthritis in SKG mice

    Porphyromonas gingivalis infection exacerbates the onset of rheumatoid arthritis in SKG mice

    Osteoclast differentiation from bone marrow mononuclear cells (BMCs) of SKG mice. (a) After the separation of BMCs from each group of SKG mice using Histopaque 1083®, BMCs (2 × 105 cells/well) were cultured on 96-well plates in the presence of soluble nuclear factor kappa B ligand (sRANKL) (50 ng/ml) and macrophage colony-stimulating factor (M-CSF) (20 ng/ml) for 7 days. The number of osteoclasts with multiple nuclei (> 3) on 96-well plates was counted. The data summarized are the results obtained from three independent experiments (in each group of n = 5 mice). *Significantly higher number of osteoclasts by Student's t-test (*P < 0·05). (b) Representative tartrate-resistant acid phosphatase kit (TRAP)-stained images of multinuclear osteoclasts on 96-well plates on day 7. Original magnification ×100; scale bar, 30 µm.

  • The immunology of the vermiform appendix: a review of the literature

    The immunology of the vermiform appendix: a review of the literature

    Transverse section of a healthy adult appendix. 1, mesoappendix; 2, muscularis externa; 3, submucosa; 4, lymphoid follicle; 5, mucosa and 6, lumen.

  • Of the multiple mechanisms leading to type 1 diabetes, T cell receptor revision may play a prominent role (is type 1 diabetes more than a single disease?)

    Of the multiple mechanisms leading to type 1 diabetes, T cell receptor revision may play a prominent role (is type 1 diabetes more than a single disease?)

    Autoaggressive T cell development in the thymus. 1, Double-negative (DN) cells enter the thymus and recombination-activating gene (RAG) proteins become activated to rearrange T cell receptor (TCR) beta locus, cells express pre-TCR, RAGs become induced again to generate a mature TCR. 2, Developing cells progress to double-positive (DP) state. 3, DP cells interact with cortical epithelium to undergo positive selection in the thymic cortex. 4, Following TCR interaction with cortical thymic epithelial cells (cTEC), DP cells express CCR7 and CD69. 5, CCL19 is released from the medulla to attract DP cells based on CCR7 expression. 6, DP cells become single-positive for CD4 or CD8, interact with medullary thymic epithelial cells (mTEC) to undergo negative selection. Cells express CD62L. 7a, cells with high affinity, self-reactive TCRs are deleted; 7b, some cells undergo TCR editing to alter TCR V alpha expression; 7c, Self-reactive T cells may escape negative selection or be generated from faulty TCR editing. 8, SP cells with appropriate TCRs exit to the periphery following sphingosine-1-phosphate (S1P) concentration gradients.

  • Interleukin-9 and T helper type 9 cells in rheumatic diseases

    Interleukin‐9 and T helper type 9 cells in rheumatic diseases

    T helper type 9 (Th9) cells develop from naive T cells in the presence of transforming growth factor (TGF)-β, interleukin (IL)-4 and thymic stromal lymphopoietin (TSLP). Aberrant Th9 activation may cause the onset and progression of autoimmune and chronic inflammatory diseases such as asthma, rheumatoid and psoriatic arthritis, chronic gut inflammation, kidney diseases, systemic vasculitides and systemic sclerosis. MC = mast cells; Eo = eosinophils; Treg = regulatory T cells.

  • Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

    Cut to the chase: a review of CD26/dipeptidyl peptidase‐4's (DPP4) entanglement in the immune system

    Crystal structure of human dipeptidyl peptidase 4 (DPP4) and bovine adenosine deaminase (ADA) obtained from Protein Data Bank: 1W1I. (a) DPP4 crystal structure associated with bovine ADA at its glycosylation-rich region of the propeller domain. (b) Top view of propeller domain, showing ADA binding site at bladea 4 and 5 as well as ADA interactions with carbohydrates of N229. (c) Caveolin-1 binding site at aa 201–210 and Ser630.

  • MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset

    MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset

    Structure of the major histocompatibility complex class I chain-related gene A (MICA). (a) View of a ribbon representation of the crystal structure of MICA. Only the extracellular region is shown, which consists of two structural domains: α1α2 platform and α3. The α1α2 platform consists of four α-helices arranged on eight anti-parallel β-sheets. The α3 domain, a C-type immunoglobulin-like domain, is not in contact with the platform. Image from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) (www.rcsb.org) (ID 1B3J) . (b) Diagram of the transmembrane region and the cytoplasmic tail of MICA. Full-length MICA molecules (coded by MICA*A4, MICA*5, MICA*A6 and MICA*A9) are transmembrane (TM) proteins, whereas MICA*A5.1 attaches to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor and has no cytoplasmic tail. The sequence of amino acids of the TM region is shown in the lower box. The alleles differ in the number of trinucleotide GCT repetitions that code alanine (underlined); the frameshift in MICA*A5.1, due to a guanine insertion after the second GCT triplet, leads to a premature stop codon (black triangle).

  • From the bench to clinical practice: understanding the challenges and uncertainties in immunogenicity testing for biopharmaceuticals

    From the bench to clinical practice: understanding the challenges and uncertainties in immunogenicity testing for biopharmaceuticals

    Methods for the detection of neutralizing antibodies (NAb). A bioassay (a,b) models the drug's functional activity in an in-vitro test method. Cells expressing drug target ‘T’ are incubated with drug ‘D’. When the drug binds the cell-surface target it elicits a cellular response (such as cell proliferation, cell death, cytokine release or cyclic adenosine monophosphate (cAMP) production) which is measured by a subsequent method. (a) Non-NAb (Y-shaped grey symbol) engage drug but do not inhibit the binding of drug with its target, hence the cellular response is not inhibited. (b) NAb (Y-shaped red symbol) bind the drug's active site, blocking the interaction of drug and cell-surface target, thereby inhibiting the cellular response. The principle of a NAb immunoassay is shown in panels (c) and (d). Labelled drug-target ‘T’ is captured by platebound reagent drug ‘D’, generating an assay signal. (c) Non-NAb (Y-shaped grey symbol) are captured by platebound reagent drug, but the anti-drug antibodies (ADA) binding site distal from the drug's active site allows engagement of labelled target and generation of an immunoassay signal. (d) NAb (Y-shaped red symbol) bind platebound reagent drug and inhibit binding of labelled drug-target, reducing assay signal.

  • The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on vascular endothelial growth factor

    The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on vascular endothelial growth factor

    Foot blood flow monitored in vivo by laser Doppler perfusion imaging (LDPI) in untreated control arthritic, BoxA-treated and high-mobility group box 1 (HMGB1)-treated mice. Representative evaluation of an HMGB1-treated mice 7 (left) and 21 days (right) after arthritis induction. In colour-coded images, red indicates normal perfusion while yellow indicates reduced perfusion and blue indicates a marked reduction in blood flow in the hindlimb. The results are expressed as the ratio between the perfusion of the sum of the four limbs with that measured before the induction of arthritis. The blood flow of the arthritic joint is expressed as the ratio between perfusion of day 0 versus days 7, 14 and 21. *P < 0·05 versus control collagen antibody-induced arthritis (CAIA) mice. The number of vessels per field, obtained by evaluation of the CD31-positive cells, was increased significantly in HMGB1-treated mice with respect to control CAIA mice; n = 5 mice per group.

  • Collagen-induced arthritis increases inducible nitric oxide synthase not only in aorta but also in the cardiac and renal microcirculation of mice

    Collagen-induced arthritis increases inducible nitric oxide synthase not only in aorta but also in the cardiac and renal microcirculation of mice

    Increased inducible nitric oxide synthase (iNOS) immunolabelling in arthritic kidney medulla. (b) The collagen-induced arthritis (CIA) group presents increased iNOS immunolabelling in the interstitium (red arrows), compared to the control group (a). Counterstain: haematoxylin. Bars: 20 μm. (c) Densitometric analysis (arbitrary units, a.u.). Bars express mean ± standard deviation (n = 6; one-way analysis of variance (anova) followed by Bonferroni's post-test; *P < 0·01).

  • Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels
  • Herpes zoster and the search for an effective vaccine
  • Expression of type III interferons (IFNλs) and their receptor in Sjögren's syndrome
  • Porphyromonas gingivalis infection exacerbates the onset of rheumatoid arthritis in SKG mice
  • The immunology of the vermiform appendix: a review of the literature
  • Of the multiple mechanisms leading to type 1 diabetes, T cell receptor revision may play a prominent role (is type 1 diabetes more than a single disease?)
  • Interleukin‐9 and T helper type 9 cells in rheumatic diseases
  • Cut to the chase: a review of CD26/dipeptidyl peptidase‐4's (DPP4) entanglement in the immune system
  • MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset
  • From the bench to clinical practice: understanding the challenges and uncertainties in immunogenicity testing for biopharmaceuticals
  • The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on vascular endothelial growth factor
  • Collagen-induced arthritis increases inducible nitric oxide synthase not only in aorta but also in the cardiac and renal microcirculation of mice

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