Sample records for circulating immune complexes

  1. Circulating Immune Complexes among Diabetic Children

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    George Nicoloff


    Full Text Available Insulin dependent diabetes mellitus (IDDM is an autoimmune disease associated with the presence of different types of autoantibodies. The presence of these antibodies and the corresponding antigens in the circulation leads to the formation of circulating immune complexes (CIC. CIC are known to persist in the blood for long periods of time. Such CIC following deposition in the small blood vessels have the potential to lead to microangiopathy with debilitating clinical consequences. The aim of our pilot study was to investigate whether a correlation exists between CIC and the development of microvascular complications in diabetic children. Isolation of a new glycoprotein complement inhibition factor (CIF from the parasitic plant Cuscuta europea seed, which appears to bind specifically to complement component C3 has provided an unique tool for the measurement of immune complexes by means of ELISA-type techniques (CIF-ELISA. We studied the levels of CIC (IgG, IgM and IgA in 58 diabetic children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years, 29 of them had vascular complications (group 1 and the other 29 were without vascular complications (group 2. As controls, we studied sera samples from 21 healthy children (mean age 13.54±4.03 years. Sera from the diabetic patients showed statistically significant higher levels of CIC IgG ( p=0.03 than sera from the control group. In sera from group 1 values of CIC IgG showed statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045; p=0.011 Sera from 59% of the patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from 17/26 (65% were positive for CIC IgG, 8/26 (31% for CIC IgM and 2/26 (8% for CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005 and microalbuminuria (r=0.42, p=0.033. CIC IgA correlated with age (r=0.44, p=0.03. CIC IgM correlated with the duration of diabetes (r=0.63, p=0.02. These

  2. Specific circulating immune complexes in acute chagas' disease

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    Ricardo Corral


    Full Text Available The presence of circulating immune complexes formed by IgM and IgG (CIC-IgM and CIC-IgG was investigated, using antigen-specific enzyme-immunoassays (ELISA, in 30 patients with acute Chagas' disease who showed parasitemia and inoculation chagoma. Control population consisted of patients with chronic T. cruzi infection (30, acute toxoplasmosis 10, leishmaniasis (8, rheumatoid arthritis (3 and healthy individuals with negative serology for Chagas* disease (30. Acute chagasic patients were 100% CIC-IgG and 96.66% CIC-IgM positive whereas immunofluorescence tests yielded 90% and 86.66% of positivity for specific IgG and IgM antibodies, respectively. Chronic patients were 68% CIC-IgG and 0% CIC-IgM positive. The 30 negative and the 21 cross-reaction controls proved negative for ELISA (CIC-IgM and CIC-IgG. The high sensitivity of ELISA assays would allow early immunologic diagnosis, as well as prompt treatment, of acute T. cruzi infection, thus eliminating the problem of the false-positive and false-negative results which affects traditional methods for detection of circulating antibodies.

  3. [Circulating immuns complexes and infections endocarditis. 64 cases (author's transl)]. (United States)

    Herreman, G; Godeau, P; Cabane, J; Acar, J F; Digeon, M; Bach, J F


    An immunological study, with examination for circulating immune complexes (CIC) by precipitation by polyethylene-glycol (PEG) and by fixation of labelled C1q, was carried out in 64 patients with infectious endocarditis (IE). One or more complementary studies during the course of the illness were possible in 23. CIC were found in 84 p. 100 of cases (66 p. 100 of acute IE and 89 p. 100 of subacute IE), during the active phase of the disease. High levels of PEG precipitate were correlated with typical cutaneous signs (including Osler's nodes), with the presence of cryoglobulins. With effective antibiotic treatment, the level of PEG precipitate (17 patients) returned to normal within one month, in parallel with a fall in rheumatoid factor and in cryoglobulins. By contrast, ineffective treatment was invariably reflected (6 patients) by a rise in levels of PEG precipitate. The estimation of CIC using the PEG technique during IE would already appear to be a value aid in cases of difficult diagnosis, and a research area worthy of further exploration within the context of IE.

  4. [Immunologic study of subacute infectious endocarditis through the search for circulating immune complexes. Preliminary results apropos of 13 cases]. (United States)

    Herreman, G; Godeau, P; Cabane, J; Digeon, M; Laver, M; Bach, J F


    The detection of circulating immune complexes by precipitation by polyethylene glycol represents a valuable technique of study in sub-acute bacterial endocarditis. In a series of 13 patients, this measurement was carried out, confirming the quasi-constant presence of circulating immune complexes in active S.B.E. This might be of diagnostic value in forms with negative blood culture and, further, make it possible, subsequently, to find the antigen responsible by dissociation of the circulating immune complexes.

  5. Flow cytometric determination of circulating immune complexes with the indirect granulocyte phagocytosis test

    NARCIS (Netherlands)

    Terstappen, L.W.M.M.; Grooth, de B.G.; Nolten, G.M.J.; Napel, ten C.H.H.; Berkel, van W.; Greve, J.


    A method for the determination of circulating immune complexes (CIC) was adapted for flow cytometric analysis. Human granulocytes were used to phagocytose IgG-bearing CIC of serum from systemic lupus erythematosus (SLE) patients. A method for labeling the phagocytosed CIC with FITC-conjugated anti-h

  6. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H


    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

  7. Status of circulating immune complexes, IL8 titers and cryoglobulins in patients with dengue infection. (United States)

    Patra, Goutam; Ghosh, Manab; Modak, Dolanchampa; Bandopadhyay, Bhaswati; Saha, Bibhuti; Mukhopadhyay, Sumi


    Dengue, a serious viral infection caused by the mosquito vector, Aedes aegyptii, affects about 390 million people annually from more than 125 countries across the globe. However, until now, there is no reliable clinical or laboratory indicator to accurately predict the development of dengue severity. Here, we explored critical pathophysiological determinants like IL8, circulating immune complex (CIC) and cryoglobulin in dengue-infected patients for identification of novel dengue severity biomarker(s). Totally, 100 clinically suspected dengue cases were tested by NS1 ELISA and MAC ELISA for dengue virus aetiology. For control, 49 healthy volunteers were included. Blood profiling (complete hemogram and liver function test) of patient population were done using automated cell counter and standard auto analyzer based biochemical analysis. Serum CIC was quantified by PEG precipitation. Serum cryoglobulins were estimated by Folin assay. Levels of serum IL-8 were assessed by standard sandwich ELISA kits. Patient CIC were further characterized by SDS Gel electrophoresis. Forty per cent of the cases tested positive, of which 11 patients had severe clinical manifestation. The mean ±SEM of cryoglobulin concentration for DHF, DF, and HC were 1.30 ± 0.31, 0.59 ± 0.08 and 0.143 ± 0.009 μg/μl, respectively. Thus, DHF and DF patients have shown 9- and 2.2-fold increase in cryoglobulin levels; and 18- and 5-fold increased CIC, respectively compared to HC patients. The mean ±SEM of CIC-PEG index for DHF, DF and HC were 491 ± 41.22, 146 ± 14.19 and 27.98 ± 2.56, respectively. Raised levels of IL8 titers were also found in all 11 DHF patients. Peak levels of CIC, cryoglobulin and IL8 titers were associated with thrombocytopenia. SDS PAGE analysis of CIC from DHF revealed the presence of at least six protein bands that were not observed in samples from DF and HC. Prediction efficacy of IL8, CIC and cryoglobulin for DHF was determined using the receiver operator characteristic

  8. Circulating immune complexes in patients with usual interstitial pulmonary fibrosis: partial characterization and relationship with Thermoactinomyces vulgaris. (United States)

    Cocchiara, R; Giallongo, A; Amoroso, S; Spina, G; Stancampiano, R; Geraci, D


    Sixty-six sera were analysed by solid-phase conglutinin binding assay, to detect the levels of circulating immune complexes (CIC), and by enzyme-linked immunosorbent assay (ELISA) to show a correlation with antibodies to Thermoactinomyces vulgaris. Sixty per cent of patients with usual interstitial pulmonary fibrosis (UIP), were positive for CIC; and T. vulgaris antibodies were detected in 60% of the same patients. In comparison, there was a low frequency of positive results in bronchitis patients (5% for CIC and 35% for T. vulgaris), and in normal blood donors (0% for CIC and 30% for T. vulgaris). Furthermore 31% of patients with lung cancer were found positive for CIC, but not for T. vulgaris. Immune complexes purified on Protein A-Sepharose and by sucrose density gradient from patients with UIP, showed a sedimentation coefficient higher than 19 S. The purified material was found to contain IgG and IgM as antibodies. Binding of immune complexes, purified by sedimentation on sucrose gradient, to conglutinin was inhibited by the presence of T. vulgaris antigen; thus suggesting that this antigen might be present in the complexes. Images Figure 7 PMID:7319561

  9. Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglobulin A in patients with Sjögren's syndrome

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    Hadži-Mihailović Miloš


    Full Text Available Introduction. Sjögren's syndrome (SS is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. Objective The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC and immunoglobulin G (IgG, and salivary proteins (SP and salivary immunoglobulin A (sIgA in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR and the duration of disease. Methods. The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and sIgA was separated from the whole saliva using the method of immune chromatography. Results. The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of sIgA and IgG were increased with statistical significance. Conclusion The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.

  10. Circulating immune complexes of Hodgkin's disease contain an antigen that is present in Hodgkin and Reed-Sternberg cells. (United States)

    Bepler, G; Zhen, Q Y; Havemann, K


    Circulating immune complexes (CIC), isolated from the serum of a patient with Hodgkin's disease (HD) and from control serum (CS) of healthy adults, were used to generate heterologous antisera in rabbits. The antiserum directed against CIC from HD (AS-HD) and the antiserum directed against CIC from CS (AS-CS) were used to identify immunoglobulins, complement factors and alpha2-macroglobulin as immune complex components. After adsorbing both antisera with normal human sera, we found that the adsorbed AS-HD was immunoreactive with radio-labelled CIC from HD serum but not with radiolabelled CIC from CS. Sera of patients with different diseases and sera of healthy adults were assessed for the occurrence of this Hodgkin immune complex-associated antigen (HIC-Ag). The HIC-Ag was present in 37% (12/33) of sera from patients with HD, 8% (8/101) of sera from patients with nonmalignant diseases, and 0% (0/6) of sera from healthy adults. This antigen was equally distributed among HD patients with and without symptoms, but its occurrence correlated with an advanced clinical stage of the disease. Using the adsorbed AS-HD in the immunoperoxidase technique, we identified the HIC-Ag as a cytoplasmic antigen in Hodgkin and Reed-Sternberg cells; whereas, the adsorbed AS-CS did not reveal any staining. These data indicate the presence of an HIC-Ag in the sera of patients with HD and suggest that the adsorbed AS-HD might be useful for isolation and characterization of this antigen for future use as a tumour marker.

  11. Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Brandslund, I;


    Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related...


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    Kovalenko T.I.


    Full Text Available Under physiological conditions a formation and a presence of the CEC in liquids is one of the manifestations of the immune response to receipt of antigens and an important factor, which provides immunity. Circulating immune complexes act as agents involved in the regulation of immune response and maintaining communication between the immune system and other regulatory systems of the body and direction to his defense. The intensity of the formation of the CEC may vary under the influence of infectious antigens and immune preparations. Material and methods. Material for the experiment were white male rats 3 months of age ("young" weighing 100 -140gr. (n = 40 and 22-month ("old" weighing 200 -240 g. (n = 40. And the first (n=10 and second (n=10 groups of rats served as controls. Third (n=15 and fourth (n=15 group of animals was injected intraperitoneal daily agar culture of Pseudomonas aeruginosa № 27835 ATCC (injected with 1.5 ml suspension of bacteria, which contained 109 CFU/ml. Fifth (n=15 and sixth (n=15 groups of animals were injected intraperitoneally daily agar culture of Escherichia coli number 25592, ATCC (injected with 1.5 ml of bacteria suspension which contain 109 CFU/ml. Control animals were taken from the experiment by decapitation 3rd day – n=20. Control and infected animals were taken from the experiment by decapitation at 3rd day - n=27, 5th day – n=27 and 7th day – n=26. In the second phase of the experiment Ia (n = 6 and IIa (n = 6 were the control group of rats following administration of the experimental composite preparation consisting amino acids, nucleotides, enzymes, vitamins (MF. In two age groups of animals with inflammation induced by E. coli suspension treated with MF 20 mсl 3- month rats (IIIa group n = 6 and 40 mсl 22-month rats (IVa group n = 6. Ib (n = 6 and IIb (n = 6 were the control group of rats after the injection of comparison, containing mannitol and natural antioxidant betakaroten (PO. In two age

  13. Circulating Immune Complexes and trace elements (Copper, Iron and Selenium as markers in oral precancer and cancer : a randomised, controlled clinical trial

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    Karjodkar Freny R


    Full Text Available Abstract Aim To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium in serum of patients with oral submucous fibrosis (OSMF, oral leukoplakia (L, and oral squamous cell carcinoma (SCC, analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. Methods Circulating immune complexes (CIC were estimated using 37.5% Polyethylene Glycol 6000(PEG serum precipitation. Serum estimation of copper (Cu, Iron (Fe and selenium (Se was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. Results The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. Conclusion The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment.

  14. IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities. (United States)

    Procaccia, S; Lazzarin, A; Colucci, A; Gasparini, A; Forcellini, P; Lanzanova, D; Foppa, C U; Novati, R; Zanussi, C


    To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells. PMID:3608224

  15. Detection of microbial antigenic components of circulating immune complexes in HIV patients:Involvement in CD4+ T lymphocyte count depletion

    Institute of Scientific and Technical Information of China (English)

    Ezeani Michael Chukwudi; Okafor UU; Onyenekwe CC; Wachukwu CK; Anyiam DCD; Meludu SC; Ukibe RN; Ifeanyichukwu M; Onochie A; Anahalu I


    Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades ofCD4 T lymphocyte counts inHIV sero positive and sero-negative participants.Methods: Polyethelene glycol(PEG-600) and buffering methods of precipitation and dissociation of immune complexes was used to generate immune solution from sera of100 HIV sero-positive and100 HIV sero-negative participants. These were categorized into 3 grades based onCD4 count:> 500 cell/mm3,200-499 cell/mm3 and<200 cell/mm3. The immune solutions were assayed using membrane based immunoassay and antibody titration, along side its unprocessed serum for detection of various microbial antigens and or antibodies. CD4 T cell counts were estimated using Patec Cyflow SL-3Germany.Results: Antigenic component of immune complexes of various infectious agents was detected in99 and70 HIV sero-positive andHIV sero-negative participants, respectively. In group A, there were10 HIV positive participants, including4 (40.0%)had circulating immune complexes(CICs) due toSalmonella species only;1(10.0%) due toSalmonella-Plasmodium falciparum (P. falciparum),Salmonella-P. falciparum-HCV andP. falciparum antigens, respectively. In group B,45(45.4%) HIVsero-positive participants withCICs hadCD4 T lymphocyte count between200-499 cells/mm3. Out of these,20(44.4%) hadCICs due to Salmonella species only; 9(20%) due toSalmonella-P. falciparum. In groupC, there were44(44.4%) HIVsero-positive participants, including3(6.8%) due toSalmonella species only;24(54.4%) due toSalmonella-P. falciparum;2(4.5%) due toP. falciparum only.Conclusions:InHIV sero-positive participants, presence of heterogeneity of Salmonella species-P. falciparum antigens was highly incriminated inCD4 count depletion but not homogeneity of malaria parasites antigens. Malaria parasites antigens only were incriminated inCD4+ count depletion amongstHIV sero-negative participants. Before taking any decision on the management ofHIV-1

  16. Omental implantation of BOECs in hemophilia dogs results in circulating FVIII antigen and a complex immune response. (United States)

    Ozelo, Margareth C; Vidal, Barbara; Brown, Christine; Notley, Colleen; Hegadorn, Carol; Webster, Sandra; Harpell, Lori; Ahlin, James; Winterborn, Andrew; Handforth, Janine; Arruda, Valder R; Hough, Christine; Lillicrap, David


    Ex vivo gene therapy strategies avoid systemic delivery of viruses thereby mitigating the risk of vector-associated immunogenicity. Previously, we delivered autologous factor VIII (FVIII)-expressing blood outgrowth endothelial cells (BOECs) to hemophilia A mice and showed that these cells remained sequestered within the implanted matrix and provided therapeutic levels of FVIII. Prior to translating this strategy into the canine (c) model of hemophilia A, we increased cFVIII transgene expression by at least 100-fold with the use of the elongation factor 1 alpha (EF1α) promoter and a strong endothelial enhancer element. BOECs isolated from hemophilia A dogs transduced with this lentiviral vector express levels of cFVIII ranging between 1.0 and 1.5 U/mL per 10(6) cells over 24 hours. Autologous BOECs have been implanted into the omentum of 2 normal and 3 hemophilia A dogs. These implanted cells formed new vessels in the omentum. All 3 hemophilia A dogs treated with FVIII-expressing autologous BOECs developed anti-FVIII immunoglobulin G2 antibodies, but in only 2 of the dogs were these antibodies inhibitory. FVIII antigen levels >40% in the absence of FVIII coagulant function were detected in the circulation for up to a year after a single gene therapy treatment, indicating prolonged cellular viability and synthesis of FVIII.

  17. [Regulation of innate immunity during xenogenic changes in blood circulation]. (United States)

    Shevchenko, V S


    Calcium-dependent innate immune response with participation of the superfamily of immunoglobulins to several intra- and extracorporal xenobiotics were studied at 216 recipients during synthetic cardiac valves implantation or veins transplantation in coronary arteries. It was shown that immediate immune response to xenobiotics was manifested by generation of the antitissue anodical autoprecipitin with specificity to the surface cell membrane component. This reaction initiated and regulated the subsequent dynamics of the two different fibrinogen autoimmune complexes formation, resulting in development of the immunogenic damages of blood circulation. Correction of these rapid innate immune responses is important for prevention and normalisation of the xenogenic damages of blood circulation during trans- and implantation on the heart impaired with endocarditis or aterosclerosis.

  18. Abnormal kappa:lambda light chain ratio in circulating immune complexes as a marker for B cell activity in juvenile idiopathic arthritis. (United States)

    Low, J M; Chauhan, A K; Moore, T L


    Patients with juvenile idiopathic arthritis (JIA) have been shown to have elevated levels of circulating immune complexes (CICs) which correlated with disease activity. Our aim was to assess B cell activity by measuring the amount of and the kappa:lambda chain immunoglobulin light (L) chain ratio in CICs from JIA patients and to determine potential evidence for either an antigen-driven response or B-cell receptor editing. We used an enzyme-linked immunosorbent assay to measure kappa and lambda chains present in the CICs from the sera of patients with JIA. Statistical analysis was performed using Pearson's correlation, one-way ANOVA and Bonferroni post hoc analysis. Sera from 44 JIA patients were examined for the concentration of L chains in CICs. Healthy controls had a kappa:lambda chain ratio of 1.2:1, whereas this ratio was reversed among JIA subgroups with RF-positive polyarthritis (1:1.2), RF-negative polyarthritis (1:1.3), oligoarthritis (1:2.3) and systemic-onset arthritis (1:2.5). In addition, overall lambda chain selection was not significantly associated with a particular immunoglobulin heavy (H) chain and occurred with all immunoglobulin isotypes. We showed preferential selection of lambda chains contributing to the formation of potentially pathogenic CICs from JIA patients, of all onset types compared to healthy controls, in an H chain-independent manner. The reversal of kappa:lambda chain ratio within the JIA CICs and association with all immunoglobulin isotypes demonstrated the potential for L chain editing. Furthermore, we conclude that a reversal of the normal kappa:lambda chain ratio in JIA CICs may be used as a marker for increased B-cell activity.

  19. Rubella-specific immune complexes after congenital infection and vaccination. (United States)

    Coyle, P K; Wolinsky, J S; Buimovici-Klein, E; Moucha, R; Cooper, L Z


    Circulating immune complexes which contained rubella-specific immunoglobulins were detected in 21 out of 63 subjects with congenital rubella and in 39 out of 65 subjects vaccinated with attenuated rubella virus, but in none of 43 subjects susceptible to rubella or 87 subjects with remote naturally acquired immunity to rubella. The presence or level of circulating immune complexes and the presence of rubella-specific complexes did not correlate with conventional serum rubella hemagglutination inhibition antibody titers. In the group with congenital infection, the presence of specific complexes many years after birth was associated with late-emerging clinical problems involving several organ systems. In vaccinates, the presence of specific complexes was associated with a higher incidence of side reactions. Two-thirds of the vaccinates and all of those revaccinated showed specific immune complexes as late as 8 months after immunization. PMID:7085069

  20. Circulating Immune Complexes of IgA Bound to Beta 2 Glycoprotein are Strongly Associated with the Occurrence of Acute Thrombotic Events (United States)

    Martínez-Flores, José A.; Serrano, Manuel; Pérez, Dolores; de la Cámara A, Gómez; Lora, David; Morillas, Luis; Ayala, Rosa; Paz-Artal, Estela; Morales, José M.


    Aim: Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis and/or gestational morbidity in patients with antiphospholipid autoantibodies (aPL). Over recent years, IgA anti-beta2-glycoprotein I (B2GPI) antibodies (IgA aB2GPI) have reached similar clinical relevance as IgG or IgM isotypes. We recently described the presence of immune complexes of IgA bounded to B2GPI (B2A-CIC) in the blood of patients with antecedents of APS symptomalology. However, B2A-CIC's clinical associations with thrombotic events (TEV) have not been described yet. Methods: A total of 145 individuals who were isolate positive for IgA aB2GPI were studied: 50 controls without any APS antecedent, 22 patients with recent TEV (Group-1), and 73 patients with antecedents of old TEV (Group-2). Results: Mean B2A-CIC levels and prevalence in Group-1 were 29.6 ± 4.1 AU and 81.8%, respectively, and were significantly higher than those of Group-2 and controls (p < 0.001). In a multivariable analysis, positivity of B2A-CIC was an independent variable for acute thrombosis with a 22.7 odd ratio (confidence interval 5.1 –101.6, 95%, p < 0.001). Levels of B2A-CIC dropped significantly two months after the TEV. B2A-CIC positive patients had lower platelet levels than B2A-CIC-negative patients (p < 0.001) and more prevalence of thrombocytopenia (p < 0.019). Group-1 had no significant differences in C3 and C4 levels compared with other groups. Conclusion: B2A-CIC is strongly associated with acute TEV. Patients who did not develop thrombosis and were B2A-CIC positive had lower platelet levels, which suggest a hypercoagulable state. This mechanism is unrelated to complement-fixing aPL. B2A-CIC could potentially select IgA aB2GPI-positive patients at risk of developing a thrombotic event. PMID:27063992

  1. Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis (United States)

    Ahmetspahic, Diana; Ruck, Tobias; Schulte-Mecklenbeck, Andreas; Schwarte, Kathrin; Jörgens, Silke; Scheu, Stefanie; Windhagen, Susanne; Graefe, Bettina; Melzer, Nico; Klotz, Luisa; Arolt, Volker; Wiendl, Heinz; Meuth, Sven G.


    Objective: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. Methods: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)–23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined. Results: In comparison to CD4+ T lymphocytes, myeloid and lymphoid innate cell subsets of patients with MS expressed significantly lower amounts of CD52 on their cell surface. Six months after CD52 depletion, numbers of circulating plasmacytoid dendritic cells (DCs) and conventional DCs were reduced compared to baseline. GM-CSF and IL-23 production in DCs remained unchanged. Within the ILC compartment, the subset of CD56bright NK cells specifically expanded under alemtuzumab treatment, but their cytolytic activity did not change. Conclusions: Our findings demonstrate that 6 months after alemtuzumab treatment, specific DC subsets are reduced, while CD56bright NK cells expanded in patients with MS. Thus, alemtuzumab specifically restricts the DC compartment and expands the CD56bright NK cell subset with potential immunoregulatory properties in MS. We suggest that remodeling of the innate immune compartment may promote long-term efficacy of alemtuzumab and preserve immunocompetence in patients with MS. PMID:27766281

  2. "Immune Complexes in Juvenile Idiopathic Arthritis"

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    Terry Lynn Moore


    Full Text Available Abstract for invited review in Molecular Mechanisms of Immune Complex Pathophysiology thematic issue to be published in Frontiers in Immunology. Immune Complexes(ICin Juvenile Idiopathic Arthritis (JIA Terry L. Moore, MD, FAAP, FACR, MACR Professor of Internal Medicine,Pediatrics, and Molecular Biology and Immunology Director of Adult and Pediatric Rheumatology Saint Louis University School of Medicine Saint Louis, Missouri 631`04,USA Juvenile idiopathic arthritis (JIA reflects a group of clinically heterogeneous, autoimmune disorders in children characterized by chronic arthritis and hallmarked by elevated levels of circulating immune complexes (CICs and associated complement activation by-products in their sera. ICs have been detected in patients’ sera with JIA utilizing a variety of methods, including the anti-human IgM affinity column,C1q solid phase assay, polyethylene glycol precipitation, Staphylococcal Protein A separation method, anti-C1q/C3 affinity columns, and FcγRIII affinity method. As many as 75% of JIA patients have had IC detected in their sera. The CIC proteome in JIA patients has been examined to elucidate disease-associated proteins that are expressed in active disease. Evaluation of these IC s have shown the presence of multiple peptide fragments by SDS-PAGE and 2-DE. Subsequently, all isotypes of rheumatoid factor (RF, isotypes of anti-cyclic citrullinated (CCP peptide antibodies, IgG, C1q, C4, C3, and the membrane attack complex (MAC were detected in these IC. Complement activation and levels of IC correlate with disease activity in JIA, indicating their role in the pathophysiology of the disease. This review will summarize the existing literature and discuss the role of possible protein modification that participates in the generation of immune response. We will address the possible role of these events in the development of ectopic germinal centers that become the secondary site of plasma cell development in JIA. We

  3. Similar levels of immune complexes in cases of multiple sclerosis and their unaffected relatives. (United States)

    Haile, R W; Karavodin, L M; Visscher, B R; Detels, R; Valdiviezo, N L


    To investigate the possible effect of the hypothetical multiple sclerosis susceptibility (MSS) gene on circulating immune complexes, we employed a sensitive assay to test for the presence of immune complexes in sera of MS patients and unaffected relatives classified by the presence/absence of HLA-defined markers for the MSS gene. We found no significant differences between cases and relatives. The results suggest that elevated immune complex levels in MS patients' sera reported by others may not be unique to MS cases, but may represent instead a familial phenomenon. We also report a possible association between the A3 + B7 haplotype and increased immune complexes.

  4. The effects of ageing on the immune response to Schistosoma haematobium and hookworm by measuring circulating immune complexes, C3, IgG, IgA and IgM levels in residents of Omi dam area of Kogi State, Nigeria. (United States)

    Oyeyinka, G O; Awogun, I A; Akande, T M; Awarun, J A; Arinola, O G; Salimonu, L S


    In this study, the effects of infestation (with Schistosoma haematobium or hookworm) during host ageing on the serum levels of circulating immune complexes (CIC), C3, IgG, IgA and IgM were examined in residents of Omi dam area of Kogi state, Nigeria. S. haematobium-infested and hookworm-infested individuals showed no significant alteration in the levels of CIC, C3, IgG, IgA and IgM in comparison with controls. These levels were the same in infested subjects and controls even when the patients were pooled. Infested old people had the same concentrations of serum CIC, C3 IgG and IgM in comparison with infested young people but IgA levels were higher in the aged group (t=2.100; P0.20) was observed in the overall population of infested subjects; and infestation in old age did not alter CIC, C3, IgG, IgA and IgM levels in comparison with uninfested young people. For the uninfested, IgG, IgA and IgM values were similar in the aged and the young but the levels of CIC were higher (t=2.156; P0.10) in the aged. The results of this study suggest that the elevated CIC levels found in old people is age-related; and that the contribution of parasitic infestation to these raised levels is uncertain.

  5. Constant illumination reduces circulating melatonin and impairs immune function in the cricket Teleogryllus commodus

    Directory of Open Access Journals (Sweden)

    Joanna Durrant


    Full Text Available Exposure to constant light has a range of negative effects on behaviour and physiology, including reduced immune function in both vertebrates and invertebrates. It is proposed that the associated suppression of melatonin (a ubiquitous hormone and powerful antioxidant in response to the presence of light at night could be an underlying mechanistic link driving the changes to immune function. Here, we investigated the relationship between constant illumination, melatonin and immune function, using a model invertebrate species, the Australian black field cricket, Teleogryllus commodus. Crickets were reared under either a 12 h light: 12 h dark regimen or a constant 24 h light regimen. Circulating melatonin concentration and immune function (haemocyte concentration, lytic activity and phenoloxidase (PO activity were assessed in individual adult crickets through the analysis of haemolymph. Constant illumination reduced melatonin and had a negative impact on haemocyte concentrations and lytic activity, but its effect on PO activity was less apparent. Our data provide the first evidence, to our knowledge, of a link between exposure to constant illumination and variation in haemocyte concentration in an invertebrate model, while also highlighting the potential complexity of the immune response following exposure to constant illumination. This study provides insight into the possible negative effect of artificial night-time lighting on the physiology of invertebrates, but whether lower and potentially more ecologically relevant levels of light at night produce comparable results, as has been reported in several vertebrate taxa, remains to be tested.

  6. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status [Abstract (United States)

    The circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a H...

  7. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status. (United States)

    Circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a HoBi-...

  8. Circulant conference matrices for new complex Hadamard matrices


    Dita, Petre


    The circulant real and complex matrices are used to find new real and complex conference matrices. With them we construct Sylvester inverse orthogonal matrices by doubling the size of inverse complex conference matrices. When the free parameters take values on the unit circle the inverse orthogonal matrices transform into complex Hadamard matrices. The method is used for $n=6$ conference matrices and in this way we find new parametrisations of Hadamard matrices for dimension $ n=12$.

  9. Antigen cross-presentation of immune complexes. (United States)

    Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda


    The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α(+) DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8(+) T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8(-) DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets.


    Institute of Scientific and Technical Information of China (English)

    刘祖崇; 张定风; 潘澄清; 郑美贞; 贾小平; 齐珍元; 刘玲


    本文采用亲和层析法纯化的肝细胞膜特异性脂蛋白(LSP)制备抗血清并提取IgG.用ELISA间接法测定乙型肝炎94例患者血清的LSP特异性复合物(ICLSP)并同时测定乙型肝炎表面系统免疫复合物(ICHBS)及C3补体含量.发现血液中ICLSP,含量以重型肝炎和慢性活动性肝炎组中为高,在此类患者中工ICLSP的阳性检出率高于ICHBS的阳性率.在ICLSP阳性病例中多伴有C3补体的消耗,ICLSP可能是引向重型肝炎肝持续损害原因之一,ICLSP的形成可能是继发于肝组织损伤,LSP渗入血液内的结果.%The anti-LSP-IgG was prepared from tbe rabbit antiserum against LSP which was isolated from human embryo liver and purified with the affinity chromatography technique. By means of the ELISA detecting system and the anti-LSP-IgG as the coated antigen,the cirenlatJng immune complex ICnsP was studied in the 94 patiens with variouS types of viral hepatitis B.The content of ICLSP was increased in the serum of fulminant and ehronic active hepatitis,and the percentage ef positive ICLSP was found higher than those of positive ICHBs. We also found that the complement fraction 3 was consumed in the ICLsP positive oases.It seems that IQLSp plays an important role in elieiting the protracted deterioration in fulminant hepatitis and subaeut liver necrosis.Perhaps the ICLSP may be resulted from the liver tissue damage from which the LSP penetrating into the blood.

  11. The pathogenesis of arthritis in Lyme disease: humoral immune responses and the role of intra-articular immune complexes. (United States)

    Hardin, J. A.; Steere, A. C.; Malawista, S. E.


    We studied 78 patients with Lyme disease to determine how immune complexes and autoantibodies are related to the development of chronic Lyme arthritis. Circulating C1q binding material was found in nearly all patients at onset of erythema chronicum migrans, the skin lesion that marks the onset of infection with the causative spirochete. In patients with only subsequent arthritis this material tended to localize to joints where it gradually increased in concentrations with greater duration of joint inflammation. In joints, its concentration correlated positively with the number of synovial fluid polymorphonuclear leukocytes. Despite the prolonged presence of putative immune complexes, rheumatoid factors could not be demonstrated. These observations suggest that phlogistic immune complexes based on spirochete antigens form locally within joints during chronic Lyme arthritis. PMID:6334939

  12. Is the immune network a complex network?

    CERN Document Server

    Souza-e-Silva, Hallan


    Some years ago a cellular automata model was proposed to describe the evolution of the immune repertoire of B cells and antibodies based on Jerne's immune network theory and shape-space formalism. Here we investigate if the networks generated by this model in the different regimes can be classified as complex networks. We have found that in the chaotic regime the network has random characteristics with large, constant values of clustering coefficients, while in the ordered phase, the degree distribution of the network is exponential and the clustering coefficient exhibits power law behavior. In the transition region we observed a mixed behavior (random-like and exponential) of the degree distribution as opposed to the scale-free behavior reported for other biological networks. Randomness and low connectivity in the active sites allow for rapid changes in the connectivity distribution of the immune network in order to include and/or discard information and generate a dynamic memory. However it is the availabil...

  13. Epidemic spreading with immunization rate on complex networks

    CERN Document Server

    Tanimoto, Shinji


    We investigate the spread of diseases, computer viruses or information on complex networks and also immunization strategies to prevent or control the spread. When an entire population cannot be immunized and the effect of immunization is not perfect, we need the targeted immunization with immunization rate. Under such a circumstance we calculate epidemic thresholds for the SIR and SIS epidemic models. It is shown that, in scale-free networks, the targeted immunization is effective only if the immunization rate is equal to one. We analyze here epidemic spreading on directed complex networks, but similar results are also valid for undirected ones.

  14. Transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure.

    Directory of Open Access Journals (Sweden)

    Shikha Malhotra

    Full Text Available Lassa virus (LASV is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs of non-human primates (NHP following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1β and IL23α, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response.

  15. Transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure. (United States)

    Malhotra, Shikha; Yen, Judy Y; Honko, Anna N; Garamszegi, Sara; Caballero, Ignacio S; Johnson, Joshua C; Mucker, Eric M; Trefry, John C; Hensley, Lisa E; Connor, John H


    Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1β and IL23α, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response.

  16. Enhanced in vivo protein synthesis in circulating immune cells of ICU patients. (United States)

    Januszkiewicz, Anna; Klaude, Maria; Loré, Karin; Andersson, Jan; Ringdén, Olle; Rooyackers, Olav; Wernerman, Jan


    Insufficient function of the immune system contributes to a poor prognosis in intensive care unit (ICU) patients. However, the immune system function is not easily monitored and evaluated. In vivo protein synthesis determination in immune competent cells offers a possibility to quantify immunological activation. The aim of this descriptive study was to determine the in vivo fractional protein synthesis rate (FSR) in immune cells of ICU patients during the initial phase of the critical illness. Patients (n = 20) on ventilator treatment in the general ICU were studied during their first week of ICU stay. FSR was determined in circulating T lymphocytes, mononuclear cells, the whole population of blood leukocytes, and in stationary immune cells of palatine tonsils during a 90-min period by a flooding technique. Healthy, adult subjects (n = 11), scheduled for elective ear, nose, and throat surgery served as a control group. The FSR in leukocytes and mononuclear cells of ICU patients was higher compared with the control group. In contrast, the FSR of circulating T lymphocytes and of tonsillar cells was not different from that in the healthy subjects. In summary, the ICU patients showed a distinct polarization of metabolic responses during the initial phase of the critical illness. The in vivo rate of protein synthesis was high in the circulating mononuclear cells and leukocytes, reflecting enhanced metabolic activity in these cell populations. Determination of the in vivo protein synthesis rate may be used as a tool to obtain additional information on activation of the immune system.

  17. Differential expression of functional Fc-receptors and additional immune complex receptors on mouse kidney cells. (United States)

    Suwanichkul, Adisak; Wenderfer, Scott E


    The precise mechanisms by which circulating immune complexes accumulate in the kidney to form deposits in glomerulonephritis are not well understood. In particular, the role of resident cells within glomeruli of the kidney has been widely debated. Immune complexes have been shown to bind one glomerular cell type (mesangial cells) leading to functional responses such as pro-inflammatory cytokine production. To further assess the presence of functional immunoreceptors on resident glomerular cells, cultured mouse renal epithelial, endothelial, and mesangial cells were treated with heat-aggregated mouse IgG or preformed murine immune complexes. Mesangial and renal endothelial cells were found to bind IgG complexes, whereas glomerular epithelial cell binding was minimal. A blocking antibody for Fc-gamma receptors reduced binding to mesangial cells but not renal endothelial cells, suggesting differential immunoreceptor utilization. RT-PCR and immunostaining based screening of cultured renal endothelial cells showed limited low-level expression of known Fc-receptors and Ig binding proteins. The interaction between mesangial cells and renal endothelial cells and immune complexes resulted in distinct, cell-specific patterns of chemokine and cytokine production. This novel pathway involving renal endothelial cells likely contributes to the predilection of circulating immune complex accumulation within the kidney and to the inflammatory responses that drive kidney injury.

  18. The immune theory of psychiatric diseases : a key role for activated microglia and circulating monocytes

    NARCIS (Netherlands)

    Beumer, Wouter; Gibney, Sinead M.; Drexhage, Roosmarijn C.; Pont-Lezica, Lorena; Doorduin, Janine; Klein, Hans C.; Steiner, Johann; Connor, Thomas J.; Harkin, Andrew; Versnel, Marjan A.; Drexhage, Hemmo A.


    This review describes a key role for mononuclear phagocytes in the pathogenesis of major psychiatric disorders. There is accumulating evidence for activation of microglia (histopathology and PET scans) and circulating monocytes (enhanced gene expression of immune genes, an overproduction of monocyte

  19. The immune theory of psychiatric diseases: A key role for activated microglia and circulating monocytes

    NARCIS (Netherlands)

    W. Beumer (Wouter); S.M. Gibney (Sinead); R.C. Drexhage (Roos); L. Pont-Lezica (Lorena); J. Doorduin (Janine); H.C. Klein (Hans); J. Steiner (Johann); L. Connor; A. Harkin (Andrew); M.A. Versnel (Marjan); H.A. Drexhage (Hemmo)


    textabstractThis review describes a key role for mononuclear phagocytes in the pathogenesis of major psychiatric disorders. There is accumulating evidence for activation of microglia (histopathology and PET scans) and circulating monocytes (enhanced gene expression of immune genes, an overproduction

  20. Immune surveillance by rhinovirus-specific circulating CD4+ and CD8+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    John W Steinke

    Full Text Available It is difficult to experimentally infect volunteers with RV strains to which the subject demonstrates serological immunity. However, in RV challenges, viral clearance begins before de novo adaptive immune responses would develop. We speculated that adaptive immunity to RV reflects heterologous immunity by effector memory cells.DCs were generated from monocytes using GM-CSF and IL-4 and RV39 loading accomplished with a dose of ∼ 350 TCID50/10(5 cells. RV-induced maturation was established as modulation of MHC class II, CD80, CD83, and CD86. Circulating RV targeting CD4 and CD8 T cells were investigated as induction of RV-specific proliferation (CFSE-dilution.Maturation of DC by RV was confirmed as upregulation of MHC Class II (83.3 ± 5.0% to 87.8 ± 4.1%, CD80 (39.4 ± 7.2% to 47.6 ± 7.7% and CD86 (78.4 ± 4.7% to 84.1 ± 3.4%. Both CD4 and CD8 memory T cells were recognized in the circulation of healthy subjects.RV drives DC maturation and results in their ability to present RV antigens to both T helper and cytotoxic lymphocytes. Both CD4 and CD8 cells capable of recognizing RV-associated antigens are present in the circulation of healthy subjects where they are presumably involved in immune surveillance and explain the rapid recruitment of an adaptive immune response during RV infection.

  1. Investigation of fine and complex vortex circulation structures

    Institute of Scientific and Technical Information of China (English)


    The formation and evolution of fine and complicated vortex circulation structures were investigated using a two-dimensional quasi-geostrophic barotropic model simulation.We find that the highly localized asymmetric and complex configuration of energy transfer flux between large-and small-scale components is caused by the nonlinear interaction between a large-scale vortex with an initial axi-symmetric flow and four beta meso-scale vortices.The complex structure is characterized by a fine pattern,which contains seven closed systems with spatial scales of less than 100 km,embedded in a positive flux wave train and a negative wave train,respectively.The average wind speed decreased with time in the positive flux region,but was nearly unchanged in the negative flux region.This pattern reveals the evolutionary asymmetry and localization of wind speed of the major vortex.The track of the major vortex center has a trend toward the center of the negative flux center,indicating that there is a certain relation between the complex structure of the energy transfer flux and the motion of the major vortex center.These results imply that the formation and evolution of the fine and complex structure should be attributed to the nonlinear interaction between the vortices at different spatial scales.

  2. Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration. (United States)

    Lechner, Judith; Chen, Mei; Hogg, Ruth E; Toth, Levente; Silvestri, Giuliana; Chakravarthy, Usha; Xu, Heping


    Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b(+) cells and CD16(hi)HLA-DR(-) neutrophils were significantly increased (P = 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4(+) T-cells was reduced in nAMD patients without subretinal fibrosis (P = 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b(+) cells and neutrophils are associated with nAMD and that reduced levels of CD4(+) T-cells are associated with the absence of subretinal fibrosis in nAMD.

  3. The complexity of Drosophila innate immunity

    Directory of Open Access Journals (Sweden)

    A Reumer


    Full Text Available Metazoans rely on efficient mechanisms to oppose infections caused by pathogens. The immediate and first-line defense mechanism(s in metazoans, referred to as the innate immune system, is initiated upon recognition of microbial intruders by germline encoded receptors and is executed by a set of rapid effector mechanisms. Adaptive immunity is restricted to vertebrate species and it is controlled and assisted by the innate immune system.Interestingly, most of the basic signaling cascades that regulate the primeval innate defense mechanism(s have been well conserved during evolution, for instance between humans and the fruit fly, Drosophila melanogaster. Being devoid of adaptive signaling and effector systems, Drosophila has become an established model system for studying pristine innate immune cascades and reactions. In general, an immune response is evoked when microorganisms pass the fruit fly’s physical barriers (e.g., cuticle, epithelial lining of gut and trachea, and it is mainly executed in the hemolymph, the equivalent of the mammalian blood. Innate immunity in the fruit fly consists of a phenoloxidase (PO response, a cellular response (hemocytes, an antiviral response, and the NF-κB dependent production of antimicrobial peptides referred to as the humoral response. The JAK/STAT and Jun kinase signaling cascades are also implicated in the defence against pathogens.

  4. An improved acquaintance immunization strategy for complex network. (United States)

    Chen, Li; Wang, Dongyi


    The acquaintance immunization strategy is a common strategy to suppress epidemic on complex network which achieves a seemingly perfect balance between cost and effectiveness compared with other canonical immunization strategies. However, the acquaintance immunization strategy fails to take the time-varying factor and local information of nodes into consideration, which limits its effectiveness in some specific network topology. Our improved immunization strategy is based on a new mathematical model Network Structure Index (NSI), which digs deep to measure the connection property and surrounding influence of a node's neighbor nodes to better determine the importance of nodes during immunization. Both mathematical derivation and the simulation program tested on various network topology support our idea that this improved acquaintance immunization strategy protects more nodes from infection and immunizes important nodes more efficiently than the original strategies. As to say, our strategy has more adaptability and achieves a more reasonable balanced point between cost and effectiveness.

  5. Urinary excretion of the C5b-9 membrane attack complex of complement is a marker of immune disease activity in autologous immune complex nephritis. (United States)

    Pruchno, C J; Burns, M M; Schulze, M; Johnson, R J; Baker, P J; Alpers, C E; Couser, W G


    The urinary excretion of the C5b-9 membrane attack complex of complement correlates with glomerular deposition of antibody in the passive Heymann nephritis (PHN) model of membranous nephropathy (MN). To determine if this parameter can be correlated with antibody deposition in a model of MN induced by an autologous mechanism and thus more analogous to human MN, the relationship of urinary C5b-9 to ongoing glomerular immune complex formation late in autologous immune complex nephritis (AICN) was studied. Based on urinary C5b-9, the animals were divided into two groups at 12 weeks after induction of AICN, those with persistently high urinary C5b-9 excretion and those in whom urinary excretion of C5b-9 returned to undetectable levels. While all rats developed glomerular deposition of rat IgG and significant proteinuria, high C5b-9 excretors had greater proteinuria and prolonged positive staining for glomerular C3. When normal syngeneic kidneys were transplanted into rats (n = 3) from each group, only those with persistent C5b-9 excretion developed subepithelial immune deposits of rat IgG in the transplanted kidney. As in the PHN model of MN, proteinuria was dissociated widely from urinary C5b-9 excretion, glomerular C3 staining, and evidence of circulating antibody. Thus these findings demonstrate that urinary excretion of C5b-9 serves as an index of on-going immunologic disease activity in the AICN model of MN, while proteinuria does not.

  6. The complexity, function and applications of RNA in circulation

    Directory of Open Access Journals (Sweden)

    Alton eEtheridge


    Full Text Available Blood carries a wide array of biomolecules, including nutrients, hormones and molecules that are secreted by cells for specific biological functions. The recent finding of stable RNA of both endogenous and exogenous origin in the circulation raises a number of questions and opens a broad, new field: exploring the origins, functions and applications of these extracellular RNA molecules. These findings raise many important questions, including: what are the mechanisms of export and cellular uptake, what is the nature and source of their stability, what molecules do they interact with in the blood, and what are the possible biological functions of the circulating RNA. This review summarizes some key recent developments in circulating RNA research and discusses some of the open questions in the field.

  7. Crystallization and Structure Determination of Superantigens and Immune Receptor Complexes. (United States)

    Rödström, Karin E J; Lindkvist-Petersson, Karin


    Structure determination of superantigens and the complexes they form with immune receptors have over the years provided insight in their modes of action. This technique requires growing large and highly ordered crystals of the superantigen or receptor-superantigen complex, followed by exposure to X-ray radiation and data collection. Here, we describe methods for crystallizing superantigens and superantigen-receptor complexes using the vapor diffusion technique, how the crystals may be optimized, and lastly data collection and structure determination.

  8. Immune Complex Glomerulonephritis in Patients with Hepatitis C

    Directory of Open Access Journals (Sweden)

    Stokes Michael


    Full Text Available Hepatitis C virus (HCV may have a pathogenic role in several forms of immune complex glomerulonephritis (ICGN, including cryoglobulinemic membrano-proliferative glomerulonephritis (MPGN and membranous nephropathy. HCV infection may also be related indirectly (e.g. secondary to HCV-related liver disease or coincidentally to glomerulonephritis. These include cases of fibrillary/immunotactoid glomerulopathy, MPGN arising in allografts, allograft glomerulopathy, rapidly progressive glomerulo-nephritis, focal and segmental glomerulosclerosis, and ICGN arising in individuals co-infected with human immunodeficiency virus (HIV. This review summarizes the clinical and pathologic features of HCV-associated glomerular disease, particularly immune complex glomerulonephritis, and discusses possible pathogenic mechanisms.

  9. Measles surveillance in Taiwan, 2012-2014: Changing epidemiology, immune response, and circulating genotypes. (United States)

    Cheng, Wen-Yueh; Wang, Hsiao-Chi; Wu, Ho-Sheng; Liu, Ming-Tsan


    In Taiwan, although the coverage rate of two doses of measles-containing vaccine has been maintained at over 95% since 2001, measles outbreaks occurred in 2002, 2009, and 2011. The present study reports that 43 cases were confirmed by laboratory testing in Taiwan in 2012-2014 and that adults have emerged as one of groups susceptible to measles virus (MV) infection, who may have discrepant humoral immune reactions--indicated by the level of IgM and IgG antibodies compared to a naïve, susceptible measles case. Thirty-seven of 43 cases confirmed by RT-PCR were further characterized by genotyping. In Taiwan, genotype H1 was the major strain in circulation prior to 2010, while D9 was the most frequently detected MV genotype between 2010 and 2011. The genotyping data collected between 2012 and 2014 revealed that H1 rebounded in 2012 after an absence in 2011 and was imported from China and Vietnam. In 2014, genotype B3 first appeared in Taiwan following import from the Philippines and became the most frequently detected strain. Genotype D8, linked to importation from various countries, including India, Indonesia, Thailand, and Vietnam, showed sequence divergence. D9 was imported from Malaysia in 2014. The MV genotypes detected in Taiwan reflected the genotypes of circulating endemic measles strains in neighboring countries. A significant rise in the number of measles cases and in measles with genotypes imported from surrounding countries indicated that measles resurged in Asia in 2014.

  10. The hemodynamics of human septic shock relate to circulating innate immunity factors. (United States)

    Hartemink, Koen J; Groeneveld, A B Johan


    The role of innate immunity, e.g., complement activation and cytokine release in the hemodynamic alterations in the course of human septic shock is largely unknown. We prospectively studied 14 consecutive septic shock patients with a pulmonary artery catheter in place. For 3 days after admission, hemodynamic variables and plasma levels of C3a, a product of complement activation, and interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) were measured 6-hourly. Doses of vasoactive drugs were recorded. Of the 14 patients, 8 died in the ICU. Patients had a hyperdynamic circulation with tachycardia, mild hypotension, increased cardiac index, peripheral vasodilation and myocardial depression. C3a, IL-6 and TNF-α plasma levels were supranormal in 123 of 138 (89%), 132 of 138 (96%) and 83 of 111 (75%) measurements, respectively. Independently of blood culture results, treatment with vasoactive drugs and outcome, mean arterial blood pressure and systemic vascular resistance index were lower when IL-6 levels were higher and left ventricular function was less depressed when C3a levels were higher in the course of septic shock. The TNF-α levels did not invariably relate to peripheral vascular and myocardial function parameters. Our serial observations suggest that, in human septic shock, peripheral vasodilation is most strongly and independently, of all inflammatory factors, associated with IL-6 release, whereas complement activation partly offsets the myocardial depression of the syndrome. Innate immunity factors may thus differ in their contribution to the course of hemodynamic abnormalities of septic shock.

  11. Reduced complement-mediated immune complex solubilizing capacity and the presence of incompletely solubilized immune complexes in SLE sera

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, I; Jensenius, J C


    Reduced complement-mediated solubilization (CMS) of pre-formed immune complexes (IC) was demonstrated in sera from 11 out of 12 SLE patients. The presence of incompletely solubilized endogeneous IC in SLE sera was indicated by the following findings: (1) When IC positive SLE sera with reduced CMS...

  12. Receptor-like kinase complexes in plant innate immunity

    DEFF Research Database (Denmark)

    Greeff, Michael Christiaan; Roux, Milena Edna; Mundy, John;


    , the aforementioned RLKs activate generic immune responses termed pattern-triggered immunity (PTI). RLKs can form complexes with other family members and engage a variety of intracellular signaling components and regulatory pathways upon stimulation. This review focuses on interesting new data about how......Receptor-like kinases (RLKs) are surface localized, transmembrane receptors comprising a large family of well-studied kinases. RLKs signal through their transmembrane and juxtamembrane domains with the aid of various interacting partners and downstream components. The N-terminal extracellular...

  13. Immunogenicity to Biotherapeutics – the role of Anti-drug Immune complexes

    Directory of Open Access Journals (Sweden)

    Murli eKrishna


    Full Text Available AbstractBiologic molecules are increasingly becoming a part of the therapeutics portfolio that has been either recently approved for marketing or those that are in the pipeline of several biotech and pharmaceutical companies. This is largely based on their ability to be highly specific relative to small molecules. However by virtue of being a large protein, and having a complex structure with structural variability arising from production using recombinant gene technology in cell lines, such therapeutics run the risk of being recognized as foreign by a host immune system. Given the range of immune mediated adverse effects that have been documented to biologic drugs thus far, including infusion reactions, and the evolving therapeutic platforms in the pipeline that engineer different functional modules in a biotherapeutic, it is critical to understand the interplay of the adaptive and innate immune responses, the pathophysiology of immunogenicity to biologic drugs in instances where there have been immune mediated adverse clinical sequelae and address technical approaches for their laboratory evaluation. The current paradigm in immunogenicity evaluation has a tiered approach to the detection and characterization of anti-drug antibodies (ADAs elicited in vivo to a biotherapeutic; alongside with the structural, biophysical and molecular information of the therapeutic, these analytical assessments form the core of the immunogenicity risk assessment. However many of the immune mediated adverse effects attributed to ADAs require the formation of a drug/ADA immune complex intermediate (ICs that can have a variety of downstream effects. This review will focus on the activation of potential immunopathological pathways arising as a consequence of circulating as well as cell surface bound drug bearing-ICs, risk factors that are either intrinsic to the therapeutic molecule or to the host which might predispose to IC mediated effects, and review the recent

  14. Myeloid-derived suppressor cells (MDSC) facilitate distant metastasis of malignancies by shielding circulating tumor cells (CTC) from immune surveillance. (United States)

    Liu, Qiaofei; Liao, Quan; Zhao, Yupei


    The mechanisms of distant metastasis of malignancies largely remain unknown. Circulating tumor cells (CTC) derived from the primary cancer initiate distant metastasis by entering and traversing the bloodstream. Current methods to detect CTC are based on the notion that CTC do not express the common leukocyte antigen CD45. However, these methods neglect the fact that CTC can directly adhere to platelets and immune cells and therefore appear to be CD45-positive. The potential effects of interactions between CTC and adhesive immune cells have been largely overlooked, despite the fact that most CTC are killed by immune effector cells and only those that evade immune surveillance result in clonal expansion and metastatic lesions. It is crucial to define the characteristics that allow a select CTC population to escape immune surveillance; particularly, it must be determined whether interactions between CTC and adhesive immune cells provide a protective effect on CTC survival. If interactions between CTC and adhesive immune cells offer a selective advantage to those CTC cells, the next consideration is which characteristics of a CTC-immune cell population allow sufficient protection to facilitate immune evasion. Myeloid-derived suppressor cells (MDSC) are a large heterogeneous population of immature myeloid cells that accumulate during cancer progression to induce extensively systemic and local immunosuppression, a phenomenon that has been demonstrated to facilitate cancer distant metastasis. We hypothesize, therefore, that CTC populations interacting with adhesive immune cells will have different biological behavior than CTC populations alone. Further, we hypothesize that CTC can create a defensive shield consisting of adhesive MDSC, which allows evasion of immune surveillance and therefore facilitates distant metastatic lesions. This possibility highlights the importance of direct interactions between CTC and adhesive immune cells and suggests the potential target that

  15. Circulating Biomarkers of Immune Activation, Oxidative Stress and Inflammation Characterize Severe Canine Visceral Leishmaniasis (United States)

    Solcà, Manuela S.; Andrade, Bruno B.; Abbehusen, Melissa Moura Costa; Teixeira, Clarissa R.; Khouri, Ricardo; Valenzuela, Jesus G.; Kamhawi, Shaden; Bozza, Patrícia Torres; Fraga, Deborah Bittencourt Mothé; Borges, Valeria Matos; Veras, Patrícia Sampaio Tavares; Brodskyn, Claudia Ida


    Clinical manifestations in canine visceral leishmaniasis (CVL) have not been clearly associated with immunological status or disease progression. We simultaneously assessed biomarkers of inflammation, immune activation, oxidative stress, and anti-sand fly saliva IgG concentrations in dog sera with different clinical manifestations to characterize a biosignature associated with CVL severity. In a cross-sectional exploratory study, a random population of 70 dogs from an endemic area in Brazil was classified according to CVL clinical severity and parasitological evaluation. A panel of biomarkers and anti–sand fly saliva IgG were measured in canine sera. Assessment of protein expression of profile biomarkers identified a distinct biosignature that could cluster separately animal groups with different clinical scores. Increasing severity scores were associated with a gradual decrease of LTB4 and PGE2, and a gradual increase in CXCL1 and CCL2. Discriminant analyses revealed that combined assessment of LTB4, PGE2 and CXCL1 was able to distinguish dogs with different clinical scores. Dogs with the highest clinical score values also exhibited high parasite loads and higher concentrations of anti-saliva antibodies. Our findings suggest CVL clinical severity is tightly associated with a distinct inflammatory profile hallmarked by a differential expression of circulating eicosanoids and chemokines. PMID:27595802

  16. Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis

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    Lohit Garg


    Full Text Available Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.

  17. Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis. (United States)

    Garg, Lohit; Gupta, Sagar; Swami, Abhishek; Zhang, Ping


    Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.

  18. Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice.

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    Thomas R Welch

    Full Text Available BACKGROUND: The role of circulating complement in host defense and immune disease is well established. Although a number of cells and tissues are capable of synthesizing complement components locally, the importance of such local synthesis in immune disease has been difficult to establish. METHODOLOGY/PRINCIPAL FINDINGS: We used bone marrow transplantation (BMT between C3 knockout (C3KO and wild type (WT mice to construct animals that were discordant for systemic (hepatic and local (monocytic C3 synthetic capacity. An immune complex glomerulonephritis (GN was then induced using intraperitoneal injections of horse spleen apoferritin (HSA with a lipopolysaccharide (LPS adjuvant. All HSA/LPS animals developed a proliferative GN with glomerular infiltration by monocytes. By sensitive ELISA, monocyte C3 synthesis could be detected in C3KO animals transplanted with WT bone marrow cells. Despite this, there were no significant differences among groups of mice in measures of clinical (proteinuria, renal function or histologic (glomerular cellularity, crescents disease severity. CONCLUSIONS/SIGNIFICANCE: In this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.

  19. [The participation of neutrophilic mechanisms in the pathogenesis of chronic elevated blood immune complexes]. (United States)

    Bidiuk, M M; Chop'iak, V V; Liubinets', L A; Pavlovich, S I; Nykytiuk, H P; Porokhovs'ka, Z S


    For reproduction of chronic hyperimmunocomplexemia model the classic Cochrane C. G., 1973 elaboration was used. The circulating immune complexes (CIC) were identified by precipitation methods, and fixated--by immunofluorescent in endothelium reproduction of aorta, and their clearance organs--liver and spleen. The estimation of neutrophil status was carried out according to rosette-forming neutrophils ability--by latex, zimosane, mieloperoxidasa, NST tests. The growth of large and middle CIC in vessel bed was estimated, their fixation in aorta bifurcation, and also on liver and spleen calls, but their intensivity is less, comparing to aorta endothelium. The neutrophil status was characterised by O-neutrophils growth, strengthening of capturing macrophages function, considerable activation of fermentative polynuclear systems, although reserve possibilities in them grew in less degree. Morphologic investigations allow to speak mediatingly about neutrophils participation in endotheliocytes damage, and also about their ability to secure the mononuclear cells further participation in damaging of aorta walls and partially of liver and spleen.

  20. Clearing the complexity: immune complexes and their treatment in lupus nephritis

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    Catherine Toong


    Full Text Available Catherine Toong1, Stephen Adelstein1, Tri Giang Phan21Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; 2Immunology Program, Garvan Institute of Medical Research and St. Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, AustraliaAbstract: Systemic lupus erythematosus (SLE is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.Keywords: immune complex, systemic lupus erythematosus, nephritis, therapy

  1. Significance of Lipid-Derived Reactive Aldehyde-Specific Immune Complexes in Systemic Lupus Erythematosus (United States)

    Wang, Gangduo; Pierangeli, Silvia S.; Willis, Rohan; Gonzalez, Emilio B.; Petri, Michelle; Khan, M. Firoze


    Even though systemic lupus erythematosus (SLE) is associated with high morbidity and mortality rates among young and middle-aged women, the molecular mechanisms of disease pathogenesis are not fully understood. Previous studies from our laboratory suggested an association between oxidative stress and SLE disease activity (SLEDAI). To further assess the role of reactive oxygen species (ROS) in SLE, we examined the contribution of lipid-derived reactive aldehydes (LDRAs)-specific immune complexes in SLE. Sera from 60 SLE patients with varying SLEDAI and 32 age- and gender- matched healthy controls were analyzed for oxidative stress and related markers. Patients were divided into two groups based on their SLEDAI scores (<6 and ≥ 6). Both SLEDAI groups showed higher serum 4-hydroxynonenal (HNE)-/malondialdehyde (MDA)-protein adducts and their specific immune complexes (HNE-/MDA-specific ICs) together with IL-17 than the controls, but the levels were significantly greater in the high SLEDAI (≥ 6) group. Moreover, the serum levels of anti-oxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase (CAT) were significantly reduced in both patient groups compared to controls. Remarkably, for the first time, our data show that increased HNE-/MDA-specific ICs are positively associated with SLEDAI and elevated circulating immune complexes (CICs), suggesting a possible causal relationship among oxidative stress, LDRA-specific ICs and the development of SLE. Our findings, apart from providing firm support to an association between oxidative stress and SLE, also suggest that these oxidative stress markers, especially the HNE-/MDA-specific ICs, may be useful in evaluating the prognosis of SLE as well as in elucidating the mechanisms of disease pathogenesis. PMID:27749917

  2. Receptor-like kinase complexes in plant innate immunity.

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    Christiaan eGreeff


    Full Text Available Receptor-like kinases (RLKs are surface localized, transmembrane receptors comprising a large family of well-studied kinases. RLKs signal through their transmembrane and juxtamembrane domains with the aid of various interacting partners and downstream components. The N-terminal extracellular domain defines ligand specificity, and RLK families are sub-classed according to this domain. The most studied of these subfamilies include those with 1 leucine rich repeat (LRR domains, 2 LysM domains (LYM and 3 the Catharanthus roseus RLK1-like (CrRLK1L domain. These proteins recognize distinct ligands of microbial origin or ligands derived from intracellular protein/carbohydrate signals. For example, the pattern recognition receptor (PRR AtFLS2 recognizes flg22 from flagellin, and the PRR AtEFR recognizes elf18 from elongation factor (EF-Tu. Upon binding of their cognate ligands, the aforementioned RLKs activate generic immune responses termed pattern triggered immunity (PTI. RLKs can form complexes with other family members and engage a variety of intracellular signaling components and regulatory pathways upon stimulation. This review focuses on interesting new data about how these receptors form protein complexes to exert their function.

  3. A circulating complex between ASAT and IgG in serum in an apparently healthy woman. (United States)

    Fex, G; Berntorp, K


    An elevated level of serum aspartate aminotransferase (ASAT) activity in a subjectively healthy woman was shown to be due to circulating ASAT:IgG complexes. The complexes were demonstrated by taking advantage of the specific interaction between protein A and IgG. Thus, greater than 90% of the patient's ASAT activity in serum could be bound to protein A-Sepharose demonstrating that nearly all the patient's serum ASAT was complexed to IgG. The ASAT-binding capacity of patient serum was calculated as approximately 850 micrograms ASAT/l which corresponds to about 0.01% of patient's IgG.

  4. Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients. (United States)

    Riva, E; Maggi, F; Abbruzzese, F; Bellomi, F; Giannelli, G; Picardi, A; Scagnolari, C; Folgori, A; Spada, E; Piccolella, E; Dianzani, F; Antonelli, G


    In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

  5. Congenic mice: cutting tools for complex immune disorders. (United States)

    Rogner, Ute C; Avner, Philip


    Autoimmune diseases are, in general, under complex genetic control and subject to strong interactions between genetics and the environment. Greater knowledge of the underlying genetics will provide immunologists with a framework for study of the immune dysregulation that occurs in such diseases. Ascertaining the number of genes that are involved and their characterization have, however, proven to be difficult. Improved methods of genetic analysis and the availability of a draft sequence of the complete mouse genome have markedly improved the outlook for such research, and they have emphasized the advantages of mice as a model system. In this review, we provide an overview of the genetic analysis of autoimmune diseases and of the crucial role of congenic and consomic mouse strains in such research.

  6. Pathogenic role of modified LDL antibodies and immune complexes in atherosclerosis. (United States)

    Lopes-Virella, Maria F; Virella, Gabriel


    There is strong evidence supporting a key role of the adaptive immune response in atherosclerosis, given that both activated Th cells producing predominantly interferon-γ and oxidized LDL (oxLDL) and the corresponding antibodies have been isolated from atheromatous plaques. Studies carried out using immune complexes (IC) prepared with human LDL and rabbit antibodies have demonstrated proatherogenic and pro-inflammatory properties, mostly dependent on the engagement of Fcγ receptors Ⅰ and Ⅱ in macrophages and macrophage-like cell lines. Following the development of a methodology for isolating modified LDL (mLDL) antibodies from serum and isolated IC, it was confirmed that antibodies reacting with oxLDL and advanced glycation end product-modified LDL are predominantly IgG of subtypes 1 and 3 and that mLDL IC prepared with human reagents possesses pro-inflammatory and proatherogenic properties. In previous studies, LDL separated from isolated IC has been analyzed for its modifications, and the reactivity of antibodies isolated from the same IC with different LDL modifications has been tested. Recently, we obtained strong evidence suggesting that the effects of mLDL IC on phagocytic cells are modulated by the composition of the mLDL. Clinical studies have shown that the level of mLDL in circulating IC is a strong predictor of cardiovascular disease (CVD) and, in diabetic patients, other significant complications, such as nephropathy and retinopathy. In conclusion, there is convincing ex vivo and clinical data supporting the hypothesis that, in humans, the humoral immune response to mLDL is pathogenic rather than protective.

  7. Immune Defenses of the Invasive Apple Snail Pomacea canaliculata (Caenogastropoda, Ampullariidae: Phagocytic Hemocytes in the Circulation and the Kidney.

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    Juan A Cueto

    hyalinocytes participate in the storage and circulation of this compound. Injection of microorganisms in the foot results in phagocytosis by hemocytes in the islets, and the different phagosomes formed are similar to those in circulating hyalinocytes. Dispersed hemocytes were obtained after kidney collagenase digestion and cell sorting, and they were able to phagocytize fluorescent beads. A role for the kidney as an immune barrier is proposed for this snail.

  8. [Strain-specific antibodies as an indicator of the circulation of wild poliomyelitis viruses and their role in the formation of collective immunity in the population]. (United States)

    Seĭbil', V B; Malyshkina, L P; Lavrova, I K; Efimova, V F


    Essential differences in the intensity of collective immunity to poliomyelitis in the donors of Moscow and Kaluga were established. To find out the nature of high characteristics of collective immunity to poliovirus, types 1 and 2, in the donors of Kaluga, strain-specific antibodies to wild and vaccine polioviruses were studied. In a considerable number of donors strain-specific antibodies to poliovirus, types 1 and 2, were detected. This made it possible to presume a sufficiently wide circulation of these viruses among the population of the city in the middle of the 20th century and, as a consequence, high level of collective immunity appeared. Strain-specific antibodies to poliovirus of type 3 were rarely detected. This made it possible to suggest that the circulation of viruses of this type among the population was limited. Immunity to viruses of this type was due only to immunization. For this reason the characteristics of collective immunity in the donors of Moscow and Kaluga coincided. The detection of strain-specific antibodies to poliomyelitis virus allowed to retrospectively form the opinion of the spread and time of the circulation of wild poliomyelitis viruses in the population.

  9. Ethnic disparities in routine immunization coverage: a reason for persistent poliovirus circulation in Karachi, Pakistan? (United States)

    Siddiqui, Nida Tariq; Owais, Aatekah; Agha, Ajmal; Karim, Mehtab S; Zaidi, Anita K M


    Karachi is the only mega city in the world with persistent poliovirus transmission. We determined routine childhood immunization rates in Karachi and identified predictors of vaccine completion. A population-based cross-sectional survey was conducted in Karachi between August and September 2008. Data on demographics, socioeconomic, and DTP3 vaccination status in children 12 to 23 months old were collected. Logistic regression was used to identify predictors of vaccination completion. Overall, 1401 participants were approached; 1391 consented to participate. Of these, 1038 (75%) were completely vaccinated. Punjabi families had the highest DTP3 coverage (82%), followed by Urdu-speaking families (79%). Pashtun (67%) and Bengali (48%) families had the lowest vaccine coverage. Children of mothers with ≥ 12 years of schooling (OR = 25.4; 95% CI = 5.7-113.1) were most likely to be vaccinated. A quarter of study participants were unvaccinated. Targeted strategies for boosting DTP3 rates in communities with low immunization coverage are essential for polio eradication in Karachi.

  10. Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab.

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    Ahmad A Tarhini

    Full Text Available We evaluated neoadjuvant ipilimumab in patients with surgically operable regionally advanced melanoma in order to define markers of activity in the blood and tumor as assessed at baseline (before ipilimumab and early on-treatment. Patients were treated with ipilimumab (10 mg/kg intravenously every 3 weeks ×2 doses bracketing surgery. Tumor and blood biospecimens were obtained at baseline and at surgery. Flow cytometry and immunohistochemistry for select biomarkers were performed. Thirty five patients were enrolled; IIIB (3; N2b, IIIC (32; N2c, N3, IV (2. Worst toxicities included Grade 3 diarrhea/colitis (5; 14%, hepatitis (2; 6%, rash (1; 3%, elevated lipase (3; 9%. Median follow up was 18 months: among 33 evaluable patients, median progression free survival (PFS was 11 months, 95% CI (6.2-19.2. There was a significant decrease in circulating myeloid derived suppressor cells (MDSC. Greater decrease in circulating monocyte gate MDSC Lin1-/HLA-DR-/CD33⁺/CD11b⁺ was associated with improved PFS (p = 0.03. There was a significant increase in circulating regulatory T cells (Treg; CD4⁺CD25hi⁺Foxp3⁺ that, unexpectedly, was associated with improved PFS (HR = 0.57; p = 0.034. Baseline evidence of fully activated type I CD4⁺ and CD8⁺ antigen-specific T cell immunity against cancer-testis (NY-ESO-1 and melanocytic lineage (MART-1, gp100 antigens was detected and was significantly potentiated after ipilimumab. In tumor, there was a significant increase in CD8⁺ T cells after ipilimumab (p = 0.02. Ipilimumab induced increased tumor infiltration by fully activated (CD69⁺ CD3⁺/CD4⁺ and CD3⁺/CD8⁺ T cells with evidence of induction/potentiation of memory T cells (CD45RO⁺. The change in Treg observed within the tumor showed an inverse relationship with clinical benefit and greater decrease in tumor MDSC subset Lin1-/HLA-DR-/CD33⁺/CD11b⁺ was associated with improved PFS at one year. Neoadjuvant evaluation revealed a

  11. Gut microbiota, immunity and disease: a complex relationship

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    Michele M Kosiewicz


    Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gut microbiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

  12. [Hepon, promoter of local immunity in the complex therapy of dysfunctional microflora in bowel disorders]. (United States)

    Parfenov, A I; Ruchkina, I N


    The promoter of local immunity Heponum contributes to the restoration of eubiosis and normalization of showings of the immune status in patients with post-infection IBS. It is recommended to include Heponum in the complex therapy of chronic bowels diseases with the purpose of the restoration of normal microbiocenosis.

  13. Global efficiency of local immunization on complex networks

    CERN Document Server

    Hébert-Dufresne, Laurent; Young, Jean-Gabriel; Dubé, Louis J


    Epidemics occur in all shapes and forms: infections propagating in our sparse sexual networks, information spreading through our much denser social interactions, or viruses circulating on the Internet. With the advent of large databases and efficient analysis algorithms, these processes can be better predicted and controlled. In this study, we use different characteristics of network organization to identify the influential spreaders in networks of diverse nature. We propose a local measure of node influence based on the network's community structure which is easily estimated in real systems and frequently outperforms the usual measure of a node's importance. More importantly, through an extensive study spanning 17 empirical networks and 2 epidemic models, we formulate a readily applicable approach which proves efficient even though different networks and different diseases require different strategies.This research is expected to guide efforts regarding public health policies, computer network security and t...

  14. Assessment of serum copper, iron and immune complexes in potentially malignant disorders and oral cancer

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    Ritu TIWARI

    Full Text Available Abstract Potentially malignant disorders (PMDs of oral cavity and oral cancer remain a cause of serious concern despite intensive research and development. Diet and immunity have been identified to play a crucial role as modifying factors in these diseases. Our study intended to explore this relationship by estimating and comparing the serum levels of copper, iron and circulating immune complexes (CICs in patients diagnosed with PMDs and oral cancer and normal healthy individuals. In this study, 40 histopathologically diagnosed cases of PMDs and oral cancer were included along with 30 healthy controls and 5 ml of venous blood was drawn using venipuncture. Serum estimation of copper, iron and CIC then followed using the colorimetric and spectrophotometric methods. The data obtained was subjected to statistical analysis using one way ANOVA and Pearson’s Product-Moment Correlation Test. The mean serum copper level was measured as 138.98 ± 10.13µg/100ml in the PMD group and 141.99 ± 21.44 µg/100ml in the oral cancer as compared to 105.5 + 18.81µ/100ml in the controls. The mean serum CIC levels was highest in the oral cancer (9.65 ± 0.16OD470 followed by the PMD group (0.18 + 0.21 OD470 and least in the control group (0.048 ± 0.02OD470. Whereas, the serum levels of iron showed a significant decrease in the PMD group (110.9 ± 10.54 µg/100ml and the oral cancer group (114.29 ± 25.83 µg/100ml as compared with the control group (136.85 ± 14.48 µg/100ml. There was no positive correlation obtained between the three groups with respect to the chosen parameters indicating that the variables were independent of each other. It can be thus be ascertained that trace elements like copper and iron as well as humoral responses (CICs have a close relationship with PMDs and oral cancers.

  15. Immune complex modulation by plasma proteins. With special reference to the complement system and autoimmune diseases

    DEFF Research Database (Denmark)

    Baatrup, G


    The complement (C) system consists of two activation pathways, the classical and the alternative, which may both be activated by immune complexes (IC). C activation products become attached to the IC during activation leading to profound changes in the properties of the complexes. The common term...

  16. The simple neuroendocrine-immune regulatory network in oyster Crassostrea gigas mediates complex functions (United States)

    Liu, Zhaoqun; Wang, Lingling; Zhou, Zhi; Sun, Ying; Wang, Mengqiang; Wang, Hao; Hou, Zhanhui; Gao, Dahai; Gao, Qiang; Song, Linsheng


    The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of the host. In the present study, the bioinformatical analysis of the transcriptomic data from oyster Crassostrea gigas and further biological validation revealed that oyster TNF (CgTNF-1 CGI_10018786) could activate the transcription factors NF-κB and HSF (heat shock transcription factor) through MAPK signaling pathway, and then regulate apoptosis, redox reaction, neuro-regulation and protein folding in oyster haemocytes. The activated immune cells then released neurotransmitters including acetylcholine, norepinephrine and [Met5]-enkephalin to regulate the immune response by arising the expression of three TNF (CGI_10005109, CGI_10005110 and CGI_10006440) and translocating two NF-κB (Cgp65, CGI_10018142 and CgRel, CGI_10021567) between the cytoplasm and nuclei of haemocytes. Neurotransmitters exhibited the immunomodulation effects by influencing apoptosis and phagocytosis of oyster haemocytes. Acetylcholine and norepinephrine could down-regulate the immune response, while [Met5]-enkephalin up-regulate the immune response. These results suggested that the simple neuroendocrine-immune regulatory network in oyster might be activated by oyster TNF and then regulate the immune response by virtue of neurotransmitters, cytokines and transcription factors.

  17. Complex mean circulation over the inner shelf south of Martha's Vineyard revealed by observations and a high-resolution model (United States)

    Ganju, Neil K.; Lentz, Steven J.; Kirincich, Anthony R.; Farrar, J. Thomas


    Inner-shelf circulation is governed by the interaction between tides, baroclinic forcing, winds, waves, and frictional losses; the mean circulation ultimately governs exchange between the coast and ocean. In some cases, oscillatory tidal currents interact with bathymetric features to generate a tidally rectified flow. Recent observational and modeling efforts in an overlapping domain centered on the Martha's Vineyard Coastal Observatory (MVCO) provided an opportunity to investigate the spatial and temporal complexity of circulation on the inner shelf. ADCP and surface radar observations revealed a mean circulation pattern that was highly variable in the alongshore and cross-shore directions. Nested modeling incrementally improved representation of the mean circulation as grid resolution increased and indicated tidal rectification as the generation mechanism of a counter-clockwise gyre near the MVCO. The loss of model skill with decreasing resolution is attributed to insufficient representation of the bathymetric gradients (Δh/h), which is important for representing nonlinear interactions between currents and bathymetry. The modeled momentum balance was characterized by large spatial variability of the pressure gradient and horizontal advection terms over short distances, suggesting that observed inner-shelf momentum balances may be confounded. Given the available observational and modeling data, this work defines the spatially variable mean circulation and its formation mechanism—tidal rectification—and illustrates the importance of model resolution for resolving circulation and constituent exchange near the coast. The results of this study have implications for future observational and modeling studies near the MVCO and other inner-shelf locations with alongshore bathymetric variability.

  18. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H;


    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...

  19. Characterization of an old complex circulating recombinant form, CRF27_cpx, originating from the Democratic Republic of Congo (DRC) and circulating in France. (United States)

    Vidal, Nicole; Frange, Pierre; Chaix, Marie-Laure; Mulanga, Claire; Lepira, François; Bazepeo, Samuel Edidi; Goujard, Cecile; Meyer, Laurence; Rouzioux, Christine; Delaporte, Eric; Peeters, Martine


    Full-length genomes were characterized for two samples, 02CD-LBR024 from the Democratic Republic of Congo (DRC) and 04FR-CD-KZS from France, that formed a separate subcluster with a previously characterized env subtype E isolate from DRC with a recombinant structure different from CRF01-AE. Since the three viruses are clearly epidemiologically unlinked and share the same complex recombinant structure, they represent a circulating recombinant form, designated as CRF27-cpx. The recombination pattern involves six different HIV-1 subtypes (A, E, G, H, J, and K) and a small unclassified fragment. The genetic distances are relatively high, indicating that CRF27-cpx evolved over a long time. Their prevalence is low (0.75%) and remained stable over time in the DRC. The existence of the 04FR.CD.KZS virus, in a patient who recently seroconverted in France, confirmed that these strains now circulate outside the DRC. Continuous monitoring of HIV-1 strains thus remains important to allow early identification of the introduction of new variants.

  20. Receptor-like kinase complexes in plant innate immunity

    DEFF Research Database (Denmark)

    Greeff, Michael Christiaan; Roux, Milena Edna; Mundy, John;


    domain defines ligand specificity, and RLK families are sub-classed according to this domain. The most studied of these subfamilies include those with (1) leucine-rich repeat (LRR) domains, (2) LysM domains (LYM), and (3) the Catharanthus roseus RLK1-like (CrRLK1L) domain. These proteins recognize...... distinct ligands of microbial origin or ligands derived from intracellular protein/carbohydrate signals. For example, the pattern-recognition receptor (PRR) AtFLS2 recognizes flg22 from flagellin, and the PRR AtEFR recognizes elf18 from elongation factor (EF-Tu). Upon binding of their cognate ligands...... these receptors form protein complexes to exert their function....

  1. Embracing Complexity beyond Systems Medicine: A New Approach to Chronic Immune Disorders (United States)

    te Velde, Anje A.; Bezema, Tjitske; van Kampen, Antoine H. C.; Kraneveld, Aletta D.; 't Hart, Bert A.; van Middendorp, Henriët; Hack, Erik C.; van Montfrans, Joris M.; Belzer, Clara; Jans-Beken, Lilian; Pieters, Raymond H.; Knipping, Karen; Huber, Machteld; Boots, Annemieke M. H.; Garssen, Johan; Radstake, Tim R.; Evers, Andrea W. M.; Prakken, Berent J.; Joosten, Irma


    In order to combat chronic immune disorders (CIDs), it is an absolute necessity to understand the bigger picture, one that goes beyond insights at a one-disease, molecular, cellular, and static level. To unravel this bigger picture we advocate an integral, cross-disciplinary approach capable of embracing the complexity of the field. This paper discusses the current knowledge on common pathways in CIDs including general psychosocial and lifestyle factors associated with immune functioning. We demonstrate the lack of more in-depth psychosocial and lifestyle factors in current research cohorts and most importantly the need for an all-encompassing analysis of these factors. The second part of the paper discusses the challenges of understanding immune system dynamics and effectively integrating all key perspectives on immune functioning, including the patient’s perspective itself. This paper suggests the use of techniques from complex systems science in describing and simulating healthy or deviating behavior of the immune system in its biopsychosocial surroundings. The patient’s perspective data are suggested to be generated by using specific narrative techniques. We conclude that to gain more insight into the behavior of the whole system and to acquire new ways of combatting CIDs, we need to construct and apply new techniques in the field of computational and complexity science, to an even wider variety of dynamic data than used in today’s systems medicine. PMID:28018353

  2. Canine Distemper Virus (CDV) immune-stimulating complexes (iscoms), but not measles virus iscoms, protect dogs against CDV infection.

    NARCIS (Netherlands)

    P. de Vries (Petra); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)


    textabstractThe potential of immune-stimulating complexes (iscoms), a novel form of antigenic presentation, for the induction of protective immunity against morbillivirus infection was shown by immunizing dogs with canine distemper virus (CDV) iscoms, which contained the fusion (F) protein and a min

  3. Molecular Components of the Sporothrix schenckii Complex that Induce Immune Response. (United States)

    Alba-Fierro, Carlos A; Pérez-Torres, Armando; Toriello, Conchita; Romo-Lozano, Yolanda; López-Romero, Everardo; Ruiz-Baca, Estela


    Sporotrichosis is a fungal disease caused by the Sporothrix schenckii complex that includes species such as S. brasiliensis, S. schenckii sensu stricto, S. globosa, S. luriei, S. mexicana, and S. pallida, which exhibit different potentially antigenic molecular components. The immune response of susceptible hosts to control infection and disease caused by these fungi has been little studied. Besides, the fungus-host interaction induces the activation of different types of immune response. This mini-review analyzes and discusses existing reports on the identification and functional characterization of molecules from species of the S. schenckii complex with clinical relevance, and the mechanisms that mediate the type and magnitude of the immune response in experimental models in vivo and in vitro. This knowledge is expected to contribute to the development of protective and therapeutic strategies against sporotrichosis and other mycoses.

  4. Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: Involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes

    NARCIS (Netherlands)

    Claassen, I.J.T.M.; Osterhaus, A.D.M.E.; Claassen, E.


    Several mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system. However, until

  5. Complement fixation by solid phase immune complexes. Reduced capacity in SLE sera

    DEFF Research Database (Denmark)

    Baatrup, G; Jonsson, H; Sjöholm, A


    We describe an ELISA for assessment of complement function based on the capacity of serum to support fixation of complement components to solid phase immune complexes (IC). Microplates were coated with aggregated bovine serum albumin (BSA) followed by rabbit anti-BSA IgG. The solid phase IC were ...

  6. Serum and plasma fibronectin binds to complement reacted immune complexes primarily via Clq

    DEFF Research Database (Denmark)

    Baatrup, G; Svehag, S E


    The binding of fibronectin to human Clq, C3b, and complement-reacted immune complexes (IC) was investigated by enzyme-linked immunosorbent assays. Microplates were coated with BSA followed by incubation with rabbit-anti-BSA IgG or F(ab')2 fragments of rabbit anti-BSA. Incubation of the solid phas...

  7. [Serum immune complexes and cardiopulmonary bypass. A review of thirty-four cases (author's transl)]. (United States)

    Herreman, G; Poisson-Lespassailles, C; Puech, H; Vanetti, A; Delaunay, L; Yvart, J; Fermé, I


    The immunologic status of patients undergoing cardiopulmonary bypass as investigated. Rheumatoid factor, cryoglobulinemia and serum immune complexes were looked for. Studies were performed before the operation and eight or fifteen days later. From the results, it is concluded that the immunologic changes that occur in the immediate postoperative period cannot be interpreted because of the profound modifications resulting from cardiopulmonary bypass.

  8. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P;


    injury. In the current study, we sought to determine whether endogenous IL-10 is playing a regulatory role in the lung inflammatory response. On the basis of lung mRNA and ELISA measurements, IL-10 induction was found during development of inflammation in the IgG immune complex model of lung injury...

  9. Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E;


    Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease g...

  10. Circulating blood leukocyte gene expression profiles: Effects of the Ames dwarf mutation on pathways related to immunity and inflammation


    Dhahbi, Joseph; Li, Xichen; Tran, Tim; Masternak, Michal M.; Bartke, Andrzej


    Aging is associated with a decline of immune competence and an increase in markers of inflammation. There is considerable evidence that inflammatory processes play a role in aging and the determination of lifespan. Hypopituitary Ames dwarf mice have extended longevity and exhibit many symptoms of delayed aging, although various aspects of immune function are suppressed in the mutants. In the present study, the expression of genes related to immunity and inflammation was compared in peripheral...

  11. Treatment of symptomatic complex posterior circulation cerebral artery stenosis with balloon-mounted stents: technique feasibility and outcome

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bin; Li, Gui-lin; Wang, Ren-zhi [Chinese Academy of Medical Science and Peking Union Medical College, Department of Neurosurgery, Peking Union Medical College Hospital, Beijing (China); Miao, Zhong-rong; Ji, Xun-min; Jiao, Li-qun; Ling, Feng [Capital University of Medical Science, Department of Neurosurgery, XuanWu Hospital, Beijing (China); Hua, Yang [Capital University of Medical Science, Department of Vascular Ultrasonography, XuanWu Hospital, Beijing (China)


    This study aimed to retrospectively analyze a series of patients with complex posterior circulation stenosis who underwent stent-assisted angioplasty to evaluate the feasibility of the procedure and summarize the experience with regard to complications. A total of 16 consecutive patients with 27 complex posterior circulation artery stenoses refractory to medical therapy were enrolled. Technical success rate, periprocedural complication, and long-term follow-up result were evaluated. The study population included 16 patients with 27 lesions. A total of 36 stents were successfully implanted. The technical success rate was 100%, and the overall periprocedural complication rate was 12.5% (2/16). During a median of 25.5 months of follow-up, three patients presented recurrent transient ischemic attacks, which were confirmed had restenosis more than 50% by control angiography or transcranial Doppler. Stent-assisted angioplasty is a feasible treatment method for complex posterior circulation artery stenosis. However, it appears to be associated with a relatively high periprocedural complication rate. Therefore, strict periprocedural management to reduce mortality and morbidity is needed. (orig.)

  12. The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization. (United States)

    Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z


    We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

  13. Simplicity belies a complex system: a response to the minimal model of immunity of Langman and Cohn. (United States)

    Efroni, Sol; Cohen, Irun R


    Langman and Cohn have written a paper entitled "If the immune repertoire evolved to be large, random, and somatically generated, then em leader " This paper uses reductionist logic to prove that the minimal model of immunity proposed by Langman and Cohn is the only reasonable description of the workings of the immune system. Here we analyze the logic behind this model and show that the complexity of the real immune system contradicts the teachings of Langman and Cohn.

  14. Decimeter waves in complex treatment of patients with cerebral blood circulation insufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Strelkova, N.I.

    Decimeter waves (DMW) were introduced into the therapeutic armamentarium relatively recently. The effect of DMW on the CNS was studied in the Division of Neurology at the Central Scientific Research Institute of Resort Science and Physiotherapy for a number of years on four groups of patients: (A) Parkinson's Disease Group, (B) patients with sequelae of open and closed craniocerebral injuries, (C) cerebral stroke patients basically of the ischemic type and (D) patients with transitory cerebral circulation disorders. The experience gained showed that the use of DMW improved cerebral circulation and aided in development of collateral circulation. It was found that in cases of tremor Parkinsonism and in epilepsy, DMW therapy should be applied to the collarbone area. Application of DMW in early stages of injury needs further study. Obviously, a single therapeutic intervention cannot provide complete recovery; a combined treatment must be applied, advisably under conditions of a resort spa. 11 references.

  15. Structure of immune stimulating complex matrices and immune stimulating complexes in suspension determined by small-angle X-ray scattering

    DEFF Research Database (Denmark)

    Pedersen, J.S.; Oliveira, C.L.P.; Hübschmann, Henriette Baun;


    Immune stimulating complex (ISCOM) particles consisting of a mixture of Quil-A, cholesterol, and phospholipids were structurally characterized by small-angle x-ray scattering (SAXS). The ISCOM particles are perforated vesicles of very well-defined structures. We developed and implemented a novel...... (to our knowledge) modeling method based on Monte Carlo simulation integrations to describe the SAXS data. This approach is similar to the traditional modeling of SAXS data, in which a structure is assumed, the scattering intensity is calculated, and structural parameters are optimized by weighted...

  16. An RLP23-SOBIR1-BAK1 complex mediates NLP-triggered immunity. (United States)

    Albert, Isabell; Böhm, Hannah; Albert, Markus; Feiler, Christina E; Imkampe, Julia; Wallmeroth, Niklas; Brancato, Caterina; Raaymakers, Tom M; Oome, Stan; Zhang, Heqiao; Krol, Elzbieta; Grefen, Christopher; Gust, Andrea A; Chai, Jijie; Hedrich, Rainer; Van den Ackerveken, Guido; Nürnberger, Thorsten


    Plants and animals employ innate immune systems to cope with microbial infection. Pattern-triggered immunity relies on the recognition of microbe-derived patterns by pattern recognition receptors (PRRs). Necrosis and ethylene-inducing peptide 1-like proteins (NLPs) constitute plant immunogenic patterns that are unique, as these proteins are produced by multiple prokaryotic (bacterial) and eukaryotic (fungal, oomycete) species. Here we show that the leucine-rich repeat receptor protein (LRR-RP) RLP23 binds in vivo to a conserved 20-amino-acid fragment found in most NLPs (nlp20), thereby mediating immune activation in Arabidopsis thaliana. RLP23 forms a constitutive, ligand-independent complex with the LRR receptor kinase (LRR-RK) SOBIR1 (Suppressor of Brassinosteroid insensitive 1 (BRI1)-associated kinase (BAK1)-interacting receptor kinase 1), and recruits a second LRR-RK, BAK1, into a tripartite complex upon ligand binding. Stable, ectopic expression of RLP23 in potato (Solanum tuberosum) confers nlp20 pattern recognition and enhanced immunity to destructive oomycete and fungal plant pathogens, such as Phytophthora infestans and Sclerotinia sclerotiorum. PRRs that recognize widespread microbial patterns might be particularly suited for engineering immunity in crop plants.

  17. Characterization of DNA antigens from immune complexes deposited in the skin of patients with systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    曾凡钦; 尹若菲; 谭国珍; 郭庆; 许德清


    Background Skin lesions are common manifestations in systemic lupus erythematosus (SLE). It is still unknown what the definite pathogenesis of skin involvement was and whether DNA participated in it. Our study was designed to explore the pathogenetic role and nature of nuclear antigen (DNA) deposited in the skin lesions of patients with SLE.Methods Thirty skin samples from patients with SLE and 2 normal skin samples were studied. Extracellular DNA was evaluated by indirect immunofluorescence methods. The deposited immune complexes were extracted by cryoprecipitation, and DNA was then isolated with phenol and chloroform. DNA fragment sizes were detected by agarose gel electrophoresis. Finally, 8 different probes were used to analyze the origin of these DNA molecules using Dot hybridization.Results Extracellular DNA staining was found only in skin lesions, mainly those located in the basement membrane zone, vascular wall, and hair follicle wall. Normal skin and non-lesion SLE skin showed no fluorescence at locations outside the nuclei. There were no differences in the rate and intensity of extracellular DNA staining when comparing active phase to remission phase patients. No relationship was found between extracellular DNA and circulating anti-dsDNA antibodies. Deposited DNA fragments clustered into four bands of somewhat discrete sizes: 20 000 bp, 1300 bp, 800-900 bp, 100-200 bp. Small sized fragments (100-200 bp) were positively correlated with disease activity (P<0.05, r=0.407). Dot hybridization showed significant homology of the various extracellular DNA fragments examined with human genomic DNA, but not with DNA from the microorganisms and viruses we examined. There were also homologies between DNA samples from different individuals.Conclusions DNA and its immune complexes may contribute to the pathogenesis of skin lesions in SLE. These DNA molecules range in size from 100 bp to 20 kb and may be endogenous in origin.

  18. Massively parallel RNA sequencing identifies a complex immune gene repertoire in the lophotrochozoan Mytilus edulis.

    Directory of Open Access Journals (Sweden)

    Eva E R Philipp

    Full Text Available The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus.

  19. One Problem, Many Solutions : Simple Statistical Approaches Help Unravel the Complexity of the Immune System in an Ecological Context

    NARCIS (Netherlands)

    Buehler, Deborah M.; Versteegh, Maaike A.; Matson, Kevin D.; Tieleman, Irene


    The immune system is a complex collection of interrelated and overlapping solutions to the problem of disease. To deal with this complexity, researchers have devised multiple ways to measure immune function and to analyze the resulting data. In this way both organisms and researchers employ many tac

  20. A new trick for an ancient drug: quinine dissociates antiphospholipid immune complexes. (United States)

    Bezati, E; Wu, X-X; Quinn, A S; Taatjes, D J; Rand, J H


    Quinine, a quinoline derivative, is an ancient antipyretic drug with antimalarial properties that has been phased out by more effective synthetic candidates. In previous studies we discovered that hydroxychloroquine (HCQ), a synthetic antimalarial with structural similarities to quinine, reduced the binding of antiphospholipid (aPL) immune complexes to phospholipid bilayers. We performed ellipsometry and atomic force microscopy (AFM) studies to measure the effect of quinine on dissociation of anti-β2-glycoprotein I (anti-β2GPI) immune complexes. We found that quinine desorbed pre-formed β2GPI-aPL immunoglobulin (Ig)G complexes from phospholipid bilayers at significantly lower molar concentrations than HCQ. Quinine also inhibited the formation of immune complexes with a higher efficacy than HCQ at equivalent drug concentrations of 0.2 mg/ml (0.192 ± 0.025 µg/cm(2) for quinine vs. 0.352 ± 0.014 µg/cm(2) for HCQ, p quinine disintegrated immune complexes bound to planar phospholipid layers. The desorptive and inhibitory effects of the old drug, quinine, toward β2GPI-aPL IgG complexes and β2GPI were significantly more pronounced compared to the synthetic antimalarial, HCQ. The results suggest that the quinoline core of the molecule is a critical domain for this activity and that side chains may further modulate this effect. The results also indicate that there may yet be room for considering new activities of very old drugs in devising clinical trials on potential non-anticoagulant treatments for antiphospholipid syndrome (APS).

  1. A complex immune response in halo nevi correlates with immune reactivity on infiltrated melanocytes, adjacent hair follicles and blood vessels

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Introduction: A clinical “halo nevus” is a benign melanocytic-neoplasm, often exhibiting spontaneous involution. A characteristic clinical feature is depigmentation of the surrounding skin, and a centripetal progression of the tumor regression phenomenon. Case Report: An 18 year old male consulted the dermatologist for changes in color of an asymptomatic mole. Materials and Methods: A clinical evaluation was performed, and skin biopsies were obtained for hematoxylin and eosin (H&E review, and for immunohistochemical (IHC studies including CD3, CD4, CD8, CD20, CD68, CD99, myeloid/histiocyte antigen, S-100, PNL2 and SOX-10. Results: A neoplastic process was identified on H&E examination, located along the dermal/epidermal junction and within the dermis. The neoplasm was composed of nests, cords and strands of benign melanocytes, with infiltrating lymphocytes. IHC staining demonstrated a strong pattern of positivity with all of the IHC antibodies within, infiltrating and surrounding the primary neoplastic process. In addition, evidence of the primary tumor immune response was noted around surrounding blood vessels and hair follicles, and on adjacent epidermal melanocytes. Conclusions: In the present study, we demonstrate by histopathologic and immunologic evidence that lymphocytes are primarily responsible for halo nevus tumor regression. Moreover, the immune response involves not only CD8 positive T lymphocytes, but a larger spectrum of B and T lineage lymphocytes. Thus, the immunologic foundations of halo nevus regression are likely of greater complexity than previously determined..

  2. Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses

    Directory of Open Access Journals (Sweden)

    Alejandra Urrutia


    Full Text Available Systems approaches for the study of immune signaling pathways have been traditionally based on purified cells or cultured lines. However, in vivo responses involve the coordinated action of multiple cell types, which interact to establish an inflammatory microenvironment. We employed standardized whole-blood stimulation systems to test the hypothesis that responses to Toll-like receptor ligands or whole microbes can be defined by the transcriptional signatures of key cytokines. We found 44 genes, identified using Support Vector Machine learning, that captured the diversity of complex innate immune responses with improved segregation between distinct stimuli. Furthermore, we used donor variability to identify shared inter-cellular pathways and trace cytokine loops involved in gene expression. This provides strategies for dimension reduction of large datasets and deconvolution of innate immune responses applicable for characterizing immunomodulatory molecules. Moreover, we provide an interactive R-Shiny application with healthy donor reference values for induced inflammatory genes.

  3. Immunity

    Institute of Scientific and Technical Information of China (English)


    920630 Effects of the spleen on immunestate of patients with gastric cancer.QIUDengbo (仇登波), et al. Dept General Surg,Union Hosp, Tongji Med Univ, Wuhan, 430022.Natl Med J China 1992; 72(6): 334-337. For analysing the effects of the spleen on im-mune state of gastric cancer patients.T-lym-

  4. Application of fluorescent monocytes for probing immune complexes on antigen microarrays.

    Directory of Open Access Journals (Sweden)

    Zoltán Szittner

    Full Text Available Microarrayed antigens are used for identifying serum antibodies with given specificities and for generating binding profiles. Antibodies bind to these arrayed antigens forming immune complexes and are conventionally identified by secondary labelled antibodies.In the body immune complexes are identified by bone marrow derived phagocytic cells, such as monocytes. In our work we were looking into the possibility of replacing secondary antibodies with monocytoid cells for the generation of antibody profiles. Using the human monocytoid cell line U937, which expresses cell surface receptors for immune complex components, we show that cell adhesion is completely dependent on the interaction of IgG heavy chains and Fcγ receptors, and this recognition is susceptible to differences between heavy chain structures and their glycosylation. We also report data on a possible application of this system in autoimmune diagnostics.Compared to secondary antibodies, fluorescent monocytesas biosensors are superior in reflecting biological functions of microarray-bound antibodies and represent an easy and robust alternative for profiling interactions between serum proteins and antigens.

  5. Application of fluorescent monocytes for probing immune complexes on antigen microarrays. (United States)

    Szittner, Zoltán; Papp, Krisztián; Sándor, Noémi; Bajtay, Zsuzsa; Prechl, József


    Microarrayed antigens are used for identifying serum antibodies with given specificities and for generating binding profiles. Antibodies bind to these arrayed antigens forming immune complexes and are conventionally identified by secondary labelled antibodies.In the body immune complexes are identified by bone marrow derived phagocytic cells, such as monocytes. In our work we were looking into the possibility of replacing secondary antibodies with monocytoid cells for the generation of antibody profiles. Using the human monocytoid cell line U937, which expresses cell surface receptors for immune complex components, we show that cell adhesion is completely dependent on the interaction of IgG heavy chains and Fcγ receptors, and this recognition is susceptible to differences between heavy chain structures and their glycosylation. We also report data on a possible application of this system in autoimmune diagnostics.Compared to secondary antibodies, fluorescent monocytesas biosensors are superior in reflecting biological functions of microarray-bound antibodies and represent an easy and robust alternative for profiling interactions between serum proteins and antigens.

  6. Increased C1q binding immune complexes in Felty's syndrome: comparison with uncomplicated rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Hurd, E.R.; Chubick, A.; Jasin, H.E.; Ziff, M.


    Sera from patients with Felty's syndrome (FS) and rheumatoid arthritis (RA) were examined for the presence of circulating immune complexes (IC) by using the 125I-C1q binding and monoclonal rheumatoid factor (mRF) techniques. Of 15 patients with FS, 9 (60%) had high 125I-C1q binding as compared to 3 of 26 RA patients (12%). The average C1q binding was significantly higher in the FS patients than in the RA patients without FS. C1q binding in both FS and RA patients was significantly higher than a group of 90 normal controls. In addition, serum C4 levels were significantly lower in the FS patients than in the RA patients. In contrast to these findings, IC levels in FS and RA patients were very similar when measured by the mRF technique. These studies indicate that FS patients have higher levels of complement-fixing IC in their sera than RA patients without FS. These findings raise the possibility that the complement-fixing IC found in these patients may play a role in the pathogenesis of neutropenia of FS.

  7. Fallen angels or risen apes? A tale of the intricate complexities of imbalanced immune responses in the pathogenesis and progression of immune-mediated and viral cancers

    Directory of Open Access Journals (Sweden)

    Beatrice Omusiro Ondondo


    Full Text Available Excessive immune responses directed against foreign pathogens, self-antigens or commensal microflora can cause cancer establishment and progression if the execution of tight immuno-regulatory mechanisms fails. On the other hand, induction of potent tumour antigen-specific immune responses together with stimulation of the innate immune system is a pre-requisite for effective antitumour immunity, and if suppressed by the strong immuno-regulatory mechanisms can lead to cancer progression. Therefore, it is crucial that the inevitable co-existence of these fundamental, yet conflicting roles of immune-regulatory cells is carefully streamlined as imbalances can be detrimental to the host. Infection with chronic persistent viruses is characterised by severe immune dysfunction resulting in T cell exhaustion and sometimes deletion of antigen-specific T cells. More often this is due to increased immuno-regulatory processes which are triggered to down-regulate immune responses and limit immunopathology. However, such heightened levels of immune disruption cause a concomitant loss of tumour immune-surveillance and create a permissive microenvironment for cancer establishment and progression, as demonstrated by increased incidences of cancer in immunosuppressed hosts. Paradoxically, while some cancers arise as a consequence of increased immuno-regulatory mechanisms that inhibit protective immune responses and impinge on tumour surveillance, other cancers arise due to impaired immuno-regulatory mechanisms and failure to limit pathogenic inflammatory responses. This intricate complexity, where immuno-regulatory cells can be beneficial in certain immune settings but detrimental in other settings underscores the need for carefully formulated interventions to equilibrate the balance between immuno-stimulatory and immuno-regulatory processes.

  8. Cenozoic Circulation History of the North Atlantic Ocean From Seismic Stratigraphy of the Newfoundland Ridge Drift Complex (United States)

    Boyle, P. R.; Romans, B.; Norris, R. D.; Tucholke, B. E.; Swift, S. A.; Sexton, P. F.


    In the North Atlantic Ocean, contour-following bottom currents have eroded regional unconformities and deposited contourite drifts that exceed two km in thickness and extend for 100s of km. The character of deep-water masses that are conveyed through ocean basins by such currents influence global heat transfer and ocean-atmosphere partitioning of CO2. The Newfoundland Ridge Drift Complex lies directly under the modern Deep Western Boundary Current southeast of Newfoundland, close to the site of overturning in the northwest Atlantic Ocean and at the intersection of the warm Gulf Stream and cool Labrador surface currents. To the south are regions of the western North Atlantic basin that are influenced by southern- as well as northern-sourced bottom waters. Here, we document the evolution of North Atlantic deep-water circulation by seismic-stratigraphic analysis of the long-lived and areally extensive Newfoundland Ridge Drift Complex. IODP Expedition 342 boreholes provide age control on seismic units, allowing sedimentation patterns to be placed in a temporal framework. We find three major phases of sedimentation: pre-contourite drift (~115-50 Ma), active contourite drift (~50-2.6 Ma), and late-contourite drift (~2.6-0 Ma). Bottom-current-controlled deposition of terrigenous-rich sediment began at ~50 Ma, which correlates to the onset of a long-term global cooling trend. A further change in deep circulation near the Eocene-Oligocene transition (~30 Ma) is indicated by more focused drift sedimentation with greatly increased accumulation rates and stratal architecture dominated by mud waves. At ~2.6 Ma to present the axis of drift accumulation shifted markedly towards shallower water depths, corresponding with the onset of Northern Hemisphere ice sheets. We discuss how these reorganizations of deep circulation correlate with results of other North Atlantic seismic stratigraphic studies to the north and south.

  9. Ternary WD40 repeat-containing protein complexes: evolution, composition and roles in plant immunity

    Directory of Open Access Journals (Sweden)

    Jimi C. Miller


    Full Text Available Plants, like mammals, rely on their innate immune system to perceive and discriminate among the majority of their microbial pathogens. Unlike mammals, plants respond to this molecular dialogue by unleashing a complex chemical arsenal of defense metabolites to resist or evade pathogen infection. In basal or non-host resistance, plants utilize signal transduction pathways to detect non-self, damaged-self and altered-self-associated molecular patterns and translate these danger signals into largely inducible chemical defenses. The WD40 repeat (WDR-containing proteins Gβ and TTG1 are constituents of two independent ternary protein complexes functioning at opposite ends of a plant immune signaling pathway. Gβ and TTG1 are also encoded by single-copy genes that are ubiquitous in higher plants, implying the limited diversity and functional conservation of their respective complexes. In this review, we summarize what is currently known about the evolutionary history of these WDR-containing ternary complexes, their repertoire and combinatorial interactions, and their downstream effectors and pathways in plant defense.

  10. MPO-ANCA associated crescentic glomerulonephritis with numerous immune complexes: case report

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    Morizane Ryuji


    Full Text Available Abstract Background Antineutrophil cytoplasmic antibody (ANCA-associated crescentic glomerulonephritis (CGN is a major cause of rapidly progressive glomerulonephritis (RPGN. ANCA-associated CGN is generally classified into pauci-immune RPGN, in which there are few or no immune complexes. Case Presentation A 78-year-old man presented with RPGN after a 7-year course of chronic proteinuria and hematuria with stable renal function. A blood examination showed a high titer of myeloperoxidase (MPO-ANCA. A renal biopsy showed crescentic glomerulonephritis with abundant subepithelial, intramenbranous and subendothelial deposits by electron microscopy, leading to the diagnosis of ANCA-associated CGN superimposed on type 3 membranoproliferative glomerulonephritis (MPGN. Conclusions This case is unique in that type 3 MPGN and MPO-ANCA-associated CGN coexisted, and no similar case has been reported to date. Because ANCA-associated CGN has a predilection for elderly individuals and primary type 3 MPGN is rarely seen in this age group, coincidental existence appears less likely. This case may confer valuable information regarding the link between immune complex and ANCA-associated CGN.

  11. Scrapie affects the maturation cycle and immune complex trapping by follicular dendritic cells in mice.

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    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrP(d accumulations in the brain and lymphoreticular system (LRS. Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrP(d accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs and tingible body macrophages (TBMs. Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrP(d plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrP(d accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrP(d. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrP(d accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function.

  12. Immune-Complexed Adenovirus Induce AIM2-Mediated Pyroptosis in Human Dendritic Cells (United States)

    Eichholz, Karsten; Bru, Thierry; Tran, Thi Thu Phuong; Fernandes, Paulo; Mennechet, Franck J. D.; Manel, Nicolas; Alves, Paula; Perreau, Matthieu


    Human adenoviruses (HAdVs) are nonenveloped proteinaceous particles containing a linear double-stranded DNA genome. HAdVs cause a spectrum of pathologies in all populations regardless of health standards. Following repeat exposure to multiple HAdV types, we develop robust and long-lived humoral and cellular immune responses that provide life-long protection from de novo infections and persistent HAdV. How HAdVs, anti-HAdV antibodies and antigen presenting cells (APCs) interact to influence infection is still incompletely understood. In our study, we used physical, pharmacological, biochemical, fluorescence and electron microscopy, molecular and cell biology approaches to dissect the impact of immune-complexed HAdV (IC-HAdV) on human monocyte-derived dendritic cells (MoDCs). We show that IC-HAdV generate stabilized complexes of ~200 nm that are efficiently internalized by, and aggregate in, MoDCs. By comparing IC-HAdV, IC-empty capsid, IC-Ad2ts1 (a HAdV-C2 impaired in endosomal escape due to a mutation that impacts protease encapsidation) and IC-AdL40Q (a HAdV-C5 impaired in endosomal escape due to a mutation in protein VI), we demonstrate that protein VI-dependent endosomal escape is required for the HAdV genome to engage the DNA pattern recognition receptor AIM2 (absent in melanoma 2). AIM2 engagement induces pyroptotic MoDC death via ASC (apoptosis-associated speck protein containing a caspase activation/recruitment domain) aggregation, inflammasome formation, caspase 1 activation, and IL-1β and gasdermin D (GSDMD) cleavage. Our study provides mechanistic insight into how humoral immunity initiates an innate immune response to HAdV-C5 in human professional APCs. PMID:27636895

  13. Sustained immune complex-mediated reduction in CD16 expression after vaccination regulates NK cell function

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    Martin R Goodier


    Full Text Available Cross-linking of FcγRIII (CD16 by immune complexes induces antibody dependent cellular cytotoxicity (ADCC by natural killer (NK cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, down-regulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal influenza vaccination. CD16 downregulation persisted for at least 12 weeks after vaccination and was associated with robust enhancement of influenza-specific plasma antibodies after intramuscular (but not intranasal vaccination. This effect could be emulated in vitro by co-culture of NK cells with influenza antigen and immune serum and, consistent with the sustained effects after vaccination, only very limited recovery of CD16 expression was observed during long term in vitro culture of immune complex-treated cells. CD16 downregulation was most marked among normally CD16high CD57+ NK cells, irrespective of NKG2C expression, and was strongly positively associated with degranulation (surface CD107a expression. CD16 downregulation was partially reversed by inhibition of ADAM17 matrix metalloprotease, leading to a sustained increase in both CD107a and CD25(IL-2R expression. Both the degranulation and CD25 responses of CD57+ NK cells were uniquely dependent on TIV-specific IgG. These data support a role for CD16 in early activation of NK cells after vaccination and for CD16 down regulation as a means to modulate NK cell responses and maintain immune homeostasis of both antibody and T cell-dependent pathways.

  14. Genome complexity in the coelacanth is reflected in its adaptive immune system. (United States)

    Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T


    We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

  15. Genome complexity in the coelacanth is reflected in its adaptive immune system (United States)

    Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W.; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T.


    We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

  16. Design of Complex Systems to Achieve Passive Safety: Natural Circulation Cooling of Liquid Salt Pebble Bed Reactors (United States)

    Scarlat, Raluca Olga

    This dissertation treats system design, modeling of transient system response, and characterization of individual phenomena and demonstrates a framework for integration of these three activities early in the design process of a complex engineered system. A system analysis framework for prioritization of experiments, modeling, and development of detailed design is proposed. Two fundamental topics in thermal-hydraulics are discussed, which illustrate the integration of modeling and experimentation with nuclear reactor design and safety analysis: thermal-hydraulic modeling of heat generating pebble bed cores, and scaled experiments for natural circulation heat removal with Boussinesq liquids. The case studies used in this dissertation are derived from the design and safety analysis of a pebble bed fluoride salt cooled high temperature nuclear reactor (PB-FHR), currently under development in the United States at the university and national laboratories level. In the context of the phenomena identification and ranking table (PIRT) methodology, new tools and approaches are proposed and demonstrated here, which are specifically relevant to technology in the early stages of development, and to analysis of passive safety features. A system decomposition approach is proposed. Definition of system functional requirements complements identification and compilation of the current knowledge base for the behavior of the system. Two new graphical tools are developed for ranking of phenomena importance: a phenomena ranking map, and a phenomena identification and ranking matrix (PIRM). The functional requirements established through this methodology were used for the design and optimization of the reactor core, and for the transient analysis and design of the passive natural circulation driven decay heat removal system for the PB-FHR. A numerical modeling approach for heat-generating porous media, with multi-dimensional fluid flow is presented. The application of this modeling

  17. Characterisation and immune responses to meningococcal recombinant porin complexes incorporated into liposomes. (United States)

    Sánchez, Sandra; Abel, Ana; Marzoa, Juan; Gorringe, Andrew; Criado, Teresa; Ferreirós, Carlos M


    We have analysed the structure of meningococcal outer membrane complexes and found that the main complexes are formed by different combinations of PorA and/or PorB molecules, associated to other proteins such as RmpM. In view of the growing knowledge of the importance of conformational epitopes in the immune responses to many pathogens, our aim in this study was to analyse the interactions of PorA and PorB by reconstitution of both recombinant porins into liposomes and determine the relevance of these interactions for the immune response. Recombinant PorA and PorB incorporated into liposomes associate forming complexes that are homomeric when only one of the porins is present, but heteromeric when both neisserial porins are present, mimicking those found previously in native outer membrane vesicles (OMVs). Association of PorA and PorB to form heterocomplexes modifies the immunogenicity of at least PorB, allowing the production of antibodies that recognise conformational epitopes, and produces new epitopes that react with a 50 kDa outer membrane protein not yet identified.

  18. Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex.

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    Katherine Belov


    Full Text Available The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used the Monodelphis domestica (gray short-tailed opossum sequence to construct the first map of a marsupial major histocompatibility complex (MHC. The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral "immune supercomplex" that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes.

  19. Interleukin-33 primes mast cells for activation by IgG immune complexes.

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    Shinjiro Kaieda

    Full Text Available Mast cells (MCs are heterogeneous cells whose phenotype is modulated by signals received from the local microenvironment. Recent studies have identified the mesenchymal-derived cytokine IL-33 as a potent direct activator of MCs, as well as regulator of their effector phenotype, and have implicated this activity in the ability of mast cells to contribute to murine experimental arthritis. We explored the hypothesis that IL-33 enables participation of synovial MCs in murine K/BxN arthritis by promoting their activation by IgG immune complexes. Compared to wild-type (WT control mice, transgenic animals lacking the IL-33 receptor ST2 exhibited impaired MC-dependent immune complex-induced vascular permeability (flare and attenuated K/BxN arthritis. Whereas participation of MCs in this model is mediated by the activating IgG receptor FcγRIII, we pre-incubated bone marrow-derived MCs with IL-33 and found not only direct induction of cytokine release but also a marked increase in FcγRIII-driven production of critical arthritogenic mediators including IL-1β and CXCL2. This "priming" effect was associated with mRNA accumulation rather than altered expression of Fcγ receptors, could be mimicked by co-culture of WT but not ST2(-/- MCs with synovial fibroblasts, and was blocked by antibodies against IL-33. In turn, WT but not ST2(-/- MCs augmented fibroblast expression of IL-33, forming a positive feedback circuit. Together, these findings confirm a novel role for IL-33 as an amplifier of IgG immune complex-mediated inflammation and identify a potential MC-fibroblast amplification loop dependent on IL-33 and ST2.

  20. Immunogenicity of Isogenic IgG in Aggregates and Immune Complexes (United States)

    St. Clair, J. Benjamin; Detanico, Thiago; Aviszus, Katja; Kirchenbaum, Greg A.; Christie, Merry; Carpenter, John F.


    A paradox in monoclonal antibody (mAb) therapy is that despite the well-documented tolerogenic properties of deaggregated IgG, most therapeutic IgG mAb induce anti-mAb responses. To analyze CD4 T cell reactions against IgG in various physical states, we developed an adoptive transfer model using CD4+ T cells specific for a Vκ region-derived peptide in the hapten-specific IgG mAb 36–71. We found that heat-aggregated or immune complexes (IC) of mAb 36–71 elicited anti-idiotypic (anti-Id) antibodies, while the deaggregated form was tolerogenic. All 3 forms of mAb 36–71 induced proliferation of cognate CD4+ T cells, but the aggregated and immune complex forms drove more division cycles and induced T follicular helper cells (TFH) development more effectively than did the deaggregated form. These responses occurred despite no adjuvant and no or only trace levels of endotoxin in the preparations. Physical analyses revealed large differences in micron- and nanometer-sized particles between the aggregated and IC forms. These differences may be functionally relevant, as CD4+ T cell proliferation to aggregated, but not IC mAb 36–71, was nearly ablated upon peritoneal injection of B cell-depleting antibody. Our results imply that, in addition to denatured aggregates, immune complexes formed in vivo between therapeutic mAb and their intended targets can be immunogenic. PMID:28114383

  1. Neutrophil Recruitment by Tumor Necrosis Factor from Mast Cells in Immune Complex Peritonitis (United States)

    Zhang, Yan; Ramos, Bernard F.; Jakschik, Barbara A.


    During generalized immune complex-induced inflammation of the peritoneal cavity, two peaks of tumor necrosis factor (TNF) were observed in the peritoneal exudate of normal mice. In mast cell-deficient mice, the first peak was undetected, and the second peak of TNF and neutrophil influx were significantly reduced. Antibody to TNF significantly inhibited neutrophil infiltration in normal but not in mast cell-deficient mice. Mast cell repletion of the latter normalized TNF, neutrophil mobilization, and the effect of the antibody to TNF. Thus, in vivo, mast cells produce the TNF that augments neutrophil emigration.

  2. A standardized method for quantitating the complement-mediated immune complex solubilizing capacity of human serum

    DEFF Research Database (Denmark)

    Baatrup, G; Peterson, I; Svehag, S E;


    A standardized radioassay for measuring the complement-mediated immune complex solubilizing capacity (CMSC) and the initial kinetics of the solubilization (IKS) reaction is described. The total complement (C)-mediated solubilizing capacity was determined after incubation of diluted serum and 125I......-BSA-anti-BSA. Percentage C-mediated solubilization (CMS) was measured after centrifugation by determining the distribution of radioactivity. The dependency of CMSC upon factors such as serum dilution and buffer system used, amount of IC added to serum, serum storage conditions and centrifugation conditions...


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    Belyuchenko I. S.


    Full Text Available Complex compost includes all elements of the periodic table and is valuable due to the complexity of its system. Among the elements forming a chemical composition of the complex compost we can identify two most important, which are distinguishing a specific character of the interaction with each other and defining the basic processes to ensure vegetation of living system - nitrogen and carbon. Nitrogen determines the rate of energy and connects with living forms of organic matter; it is included as the part of protein and is a major element in determining the productivity of ecosystems. At the cycle of carbon its organic forms and carbon dioxide take a part, presenting the main factors of the processes of respiration and photosynthesis

  4. Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study (United States)

    Wu, Wei; Zheng, Ya-li; Tian, Li-ping; Lai, Jian-bo; Hu, Chan-chan; Zhang, Peng; Chen, Jing-kai; Hu, Jian-bo; Huang, Man-li; Wei, Ning; Xu, Wei-juan; Zhou, Wei-hua; Lu, Shao-jia; Lu, Jing; Qi, Hong-li; Wang, Dan-dan; Zhou, Xiao-yi; Duan, Jin-feng; Xu, Yi; Hu, Shao-hua


    This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders. PMID:28074937

  5. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes (United States)

    Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.


    Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

  6. The Guaymas Basin hiking guide to hydrothermal mounds, chimneys and microbial mats: complex seafloor expressions of subsurface hydrothermal circulation

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    Andreas eTeske


    Full Text Available The hydrothermal mats, mounds and chimneys of the southern Guaymas Basin are the surface expression of complex subsurface hydrothermal circulation patterns. In this overview we document the most frequently visited features of this hydrothermal area with photographs, temperature measurements, and selected geochemical data; many of these distinct habitats await characterization of their microbial communities and activities. Microprofiler deployments on microbial mats and hydrothermal sediments show their steep geochemical and thermal gradients at millimeter-scale vertical resolution. Mapping these hydrothermal features and sampling locations within the southern Guaymas Basin suggest linkages to underlying shallow sills and heatflow gradients. Recognizing the inherent spatial limitations of much current Guaymas Basin sampling calls for a wider survey of the entire spreading region.

  7. CRISPR-based immune systems of the Sulfolobales: complexity and diversity

    DEFF Research Database (Denmark)

    Garrett, Roger Antony; Shah, Shiraz Ali; Vestergaard, Gisle Alberg


    CRISPR (cluster of regularly interspaced palindromic repeats)/Cas and CRISPR/Cmr systems of Sulfolobus, targeting DNA and RNA respectively of invading viruses or plasmids are complex and diverse. We address their classification and functional diversity, and the wide sequence diversity of RAMP...... (repeat-associated mysterious protein)-motif containing proteins encoded in Cmr modules. Factors influencing maintenance of partially impaired CRISPR-based systems are discussed. The capacity for whole CRISPR transcripts to be generated despite the uptake of transcription signals within spacer sequences...... is considered. Targeting of protospacer regions of invading elements by Cas protein-crRNA (CRISPR RNA) complexes exhibit relatively low sequence stringency, but the integrity of protospacer-associated motifs appears to be important. Different mechanisms for circumventing or inactivating the immune systems...

  8. Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

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    Shinji Uemoto


    Full Text Available To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference and its graphical form (scatter plot. In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication.

  9. Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia (ITP)

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Ghanima, Waleed; Nielsen, Claus H;


    with TPO-RAs (median age 50 years (inter-quartile range; IQR 20-69), median platelet counts 24 × 10(9)/L (IQR 15-47 × 10(9)/L), 28 females) and 16 healthy controls (nine females, median age 37 years, IQR 22-51 years) were collected before and during treatment, and analyzed for a panel of cytokines......BACKGROUND: Thrombopoietin-receptor-agonists (TPO-RAs) increase platelet production in Immune Thrombocytopenia (ITP) by stimulating Mpl. The effect of TPO-RAs on inflammatory cytokine production in ITP patients has not been well investigated. METHODS: Plasma samples from 48 ITP patients treated...... and chemokines by enzyme-linked immunosorbent assay and immuno-bead-based multiplex assay. RESULTS: Elevated levels of C-X-C motif chemokine 10 (CXCL10; p treatment...

  10. Spatio-temporal regulation of Hsp90-ligand complex leads to immune activation.

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    Yasuaki eTamura


    Full Text Available Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We found that an Hsp90-cancer antigen peptide complex was efficiently cross-presented by human monocyte-derived dendritic cells and induced peptide-specific cytotoxic T lymphocytes. Furthermore, we observed that the internalized Hsp90-peptide complex was strictly sorted to the Rab5+, EEA1+ static early endosome and the Hsp90-chaperoned peptide was processed and bound to MHC class I molecules through a endosome-recycling pathway. We also found that extracellular Hsp90 complexed with CpG-A or self-DNA stimulates production of a large amount of IFN-α from pDCs via static early endosome targeting. Thus, extracellular Hsp90 can target the antigen or nucleic acid to a static early endosome by spatio-temporal regulation. Moreover, we showed that Hsp90 associates with and delivers TLR7/9 from the ER to early endosomes for ligand recognition. Hsp90 inhibitor, geldanamycin derivative inhibited the Hsp90 association with TLR7/9, resulting in inhibition IFN-α production, leading to improvement of SLE symptoms. Interstingly, we observed that serum Hsp90 is clearly increased in patients with active SLE compared with that in patients with inactive disease. Serum Hsp90 detected in SLE patients binds to self-DNA and/or anti-DNA Ab, thus leading to stimulation of pDCs to produce IFN-α. Thus, Hsp90 plays a crucial role in the pathogenesis of SLE and that an Hsp90 inhibitor will therefore provide a new therapeutic approach to SLE and other nucleic acid-related autoimmune diseases. We will discuss how spatio-temporal regulation of Hsp90-ligand complexes within antigen-presenting cells affects the innate immunity and adaptive immunity.

  11. Complex structure of type VI peptidoglycan muramidase effector and a cognate immunity protein

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tianyu [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Ding, Jinjing; Zhang, Ying; Wang, Da-Cheng, E-mail: [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Liu, Wei, E-mail: [The Third Military Medical University, Chongqing 400038 (China); Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)


    The structure of the Tse3–Tsi3 complex associated with the bacterial type VI secretion system of P. aeruginosa has been solved and refined at 1.9 Å resolution. The structural basis of the recognition of the muramidase effector and its inactivation by its cognate immunity protein is revealed. The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1–Tsi1 has been structurally characterized. Here, the structure of the Tse3–Tsi3 complex is reported at 1.9 Å resolution. The results reveal that Tse3 contains a C-terminal catalytic domain that adopts a soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites were surprisingly observed close to the catalytic Glu residue. The electrostatic properties of the substrate-binding groove are also distinctive from those of known structures with a similar fold. All of these features imply that a unique catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3 comprises a single domain showing a β-sandwich architecture that is reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into the groove of Tse3 and completely occlude its active site, which forms the structural basis of Tse3 inactivation. This work is the first crystallographic report describing the three-dimensional structure of the Tse3–Tsi3 effector–immunity pair.

  12. Phagocytosis of IgA Immune Complexes by Human U937 Cells

    Institute of Scientific and Technical Information of China (English)

    郭彩云; 崔薇; 张伟


    In order to study FcαR Ⅰ mediated phagocytosis ot lgA immune complexes by U937 cells, antigen 8.9NIP/BSA was labeled with FITC and reacted with anti-NIP IgA or anti-NIP IgG antibody to form immune complexes (ICs). They were then incubated with phorbol 12-myristate B-acetate (PMA) stimulated U937 cells. The phagocytosed ICs were quantified by flow cytometry. The results was that the expression of FcαR Ⅰ on U937 cells was higher than that of FcγR Ⅰ , FcyR Ⅱ and FcγR Ⅲ. After stimulation by PMA, expression of FcαR Ⅰ on U937 cells was markedly upregulated and the phagocytosis of IgA ICs was enhanced. FcαR Ⅰ mediated specific IgA phagocytosis was stronger than FcγR Ⅰ and FcγR Ⅱ mediated IgG phagocytosis. Complement receptors, CR1 and CR3, enhanced U937 cell phagocytosis of IgA ICs. It concludes that FcγR Ⅰ mediated strong phagocytosis of IgA ICs.

  13. Modeling the Paranagua Estuarine Complex, Brazil: tidal circulation and cotidal charts

    Directory of Open Access Journals (Sweden)

    Ricardo de Camargo


    Full Text Available The tidal circulation in Paranagua Bay (Parana State, Southern Brazil was studied based on the Princeton Ocean Model. The model domain covered the near shore region and the estuarine area, with about 1 km grid resolution in cross-shore and along-shore directions. Homogeneous and diagnostic distributions for temperature and salinity were used and 12 tidal constituents were considered to specify the elevations at the open boundaries. Tidal analysis of 29-days time series of elevations and currents for each grid point generated corange and cophase lines as well as the correspondent axes of the current ellipses for each constituent. These computed values reproduced well the observed amplifications and phase lags of surface elevations and currents. Residual flows show the formation of tidal eddies, related to coastal geometry and bottom topography.A circulação de maré na Baía de Paranaguá (Estado do Paraná, sul do Brasil foi estudada através do Princeton Ocean Model. O domino do modelo abrange a região costeira adjacente e a área estuarina, com resolução de aproximadamente I km nas direções perpendicular e paralela à costa. Distribuições homogêneas e diagnosticas para temperatura e salinidade foram usadas e 12 constituintes de maré especificaram as elevações de superfície nos contornos abertos. Análises de maré de séries temporais de 29 dias de elevações e correntes para cada ponto de grade geraram linhas cotidais de amplitude e de fase, assim como elipses de correntes, para cada constituinte. Os valores obtidos pelo modelo reproduziram satisfatoriamente as amplificações e defasagens observadas nas elevações e correntes de superfície. Fluxos residuais mostram a formação de vórtices de maré, relacionados com a geometria da costa e a topografia do fundo.

  14. Complex interactions between diapirs and 4-D subduction driven mantle wedge circulation. (United States)

    Sylvia, R. T.; Kincaid, C. R.


    Analogue laboratory experiments generate 4-D flow of mantle wedge fluid and capture the evolution of buoyant mesoscale diapirs. The mantle is modeled with viscous glucose syrup with an Arrhenius type temperature dependent viscosity. To characterize diapir evolution we experiment with a variety of fluids injected from multiple point sources. Diapirs interact with kinematically induced flow fields forced by subducting plate motions replicating a range of styles observed in dynamic subduction models (e.g., rollback, steepening, gaps). Data is collected using high definition timelapse photography and quantified using image velocimetry techniques. While many studies assume direct vertical connections between the volcanic arc and the deeper mantle source region, our experiments demonstrate the difficulty of creating near vertical conduits. Results highlight extreme curvature of diapir rise paths. Trench-normal deflection occurs as diapirs are advected downward away from the trench before ascending into wedge apex directed return flow. Trench parallel deflections up to 75% of trench length are seen in all cases, exacerbated by complex geometry and rollback motion. Interdiapir interaction is also important; upwellings with similar trajectory coalesce and rapidly accelerate. Moreover, we observe a new mode of interaction whereby recycled diapir material is drawn down along the slab surface and then initiates rapid fluid migration updip along the slab-wedge interface. Variability in trajectory and residence time leads to complex petrologic inferences. Material from disparate source regions can surface at the same location, mix in the wedge, or become fully entrained in creeping flow adding heterogeneity to the mantle. Active diapirism or any other vertical fluid flux mechanism employing rheological weakening lowers viscosity in the recycling mantle wedge affecting both solid and fluid flow characteristics. Many interesting and insightful results have been presented based

  15. Antibodies against a class II HLA-peptide complex raised by active immunization of mice with antigen mimicking peptides

    DEFF Research Database (Denmark)

    Dam-Tuxen, R; Riise, Erik Skjold


    , have been found in the peripheral blood of MS patients. These autoreactive T cells are believed to play a role in the pathogenesis of MS. In this article, antibodies against the HLA complex DR2b (DRA1*0101/DRB1*1501) in complex with the MBP-derived peptide MBP(85-99) have been generated by immunization...

  16. Protein-carbohydrate complex reveals circulating metastatic cells in a microfluidic assay

    KAUST Repository

    Simone, Giuseppina


    Advances in carbohydrate sequencing technologies reveal the tremendous complexity of the glycome and the role that glycomics might have to bring insight into the biological functions. Carbohydrate-protein interactions, in particular, are known to be crucial to most mammalian physiological processes as mediators of cell adhesion and metastasis, signal transducers, and organizers of protein interactions. An assay is developed here to mimic the multivalency of biological complexes that selectively and sensitively detect carbohydrate-protein interactions. The binding of β-galactosides and galectin-3 - a protein that is correlated to the progress of tumor and metastasis - is examined. The efficiency of the assay is related to the expression of the receptor while anchoring to the interaction\\'s strength. Comparative binding experiments reveal molecular binding preferences. This study establishes that the assay is robust to isolate metastatic cells from colon affected patients and paves the way to personalized medicine. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Combined surgical and endovascular approach to treat a complex aortic coarctation without extracorporeal circulation. (United States)

    Carrel, Thierry P; Berdat, Pascal A; Baumgartner, Iris; Dinkel, Hans-Peter; Schmidli, Jürg


    Various therapeutic approaches have been proposed to treat complex coarctation of the aorta (eg, recoarctation, which requires repetitive interventions, or coarctation with a hypoplastic aortic arch). Resection followed by end-to-end anastomosis or by graft interposition is technically demanding and exposes the patient to considerable perioperative risks. Cardiopulmonary bypass and deep hypothermic circulatory arrest may be necessary to control the distal aortic arch. The role of stent technology in treating this type of lesion has not yet been defined. We present a 21-year-old woman with a recurrent coarctation of the aorta associated with a hypoplastic aortic arch and a pseudoaneurysm of the proximal descending aorta. She had undergone 4 previous interventions. Treatment consisted of a combined surgical and endovascular approach without cardiopulmonary bypass and included extraanatomic aortic bypass, partial debranching of the supraaortic vessels, and stent-graft insertion to exclude the aneurysm.

  18. First insights into circulating Mycobacterium tuberculosis complex lineages and drug resistance in Guinea. (United States)

    Ejo, Mebrat; Gehre, Florian; Barry, Mamadou Dian; Sow, Oumou; Bah, Nene Mamata; Camara, Mory; Bah, Boubacar; Uwizeye, Cecile; Nduwamahoro, Elie; Fissette, Kristina; De Rijk, Pim; Merle, Corinne; Olliaro, Piero; Burgos, Marcos; Lienhardt, Christian; Rigouts, Leen; de Jong, Bouke C


    In this study we assessed first-line anti-tuberculosis drug resistance and the genotypic distribution of Mycobacterium tuberculosis complex (MTBC) isolates that had been collected from consecutive new tuberculosis patients enrolled in two clinical trials conducted in Guinea between 2005 and 2010. Among the total 359 MTBC strains that were analyzed in this study, 22.8% were resistant to at least one of the first line anti-tuberculosis drugs, including 2.5% multidrug resistance and 17.5% isoniazid resistance, with or without other drugs. In addition, further characterization of isolates from a subset of the two trials (n = 184) revealed a total of 80 different spoligotype patterns, 29 "orphan" and 51 shared patterns. We identified the six major MTBC lineages of human relevance, with predominance of the Euro-American lineage. In total, 132 (71.7%) of the strains were genotypically clustered, and further analysis (using the DESTUS model) suggesting significantly faster spread of LAM10_CAM family (p = 0.00016). In conclusion, our findings provide a first insight into drug resistance and the population structure of the MTBC in Guinea, with relevance for public health scientists in tuberculosis control programs.

  19. Immune complex formation and in situ B-cell clonal expansion in human cerebral cavernous malformations. (United States)

    Shi, Changbin; Shenkar, Robert; Kinloch, Andrew; Henderson, Scott G; Shaaya, Mark; Chong, Anita S; Clark, Marcus R; Awad, Issam A


    Cerebral cavernous malformations (CCMs) represent clusters of dilated vascular channels, predisposing to hemorrhagic stroke and seizures. They are associated with defective blood brain barrier, hemorrhages of different ages and a robust inflammatory cell infiltrate. We report for the first time evidence of co-localized IgG and complement membrane attack complexes in CCM lesions. CD4(+) and CD8(+) T-cells are aggregated with CD20(+) B-cells. And IgG repertoire analyses demonstrate in situ B-cell clonal expansion and antigen-driven affinity maturation in CCMs. These results suggest an organ-intrinsic adaptive immune response in CCMs that should be further characterized as a potential therapeutic target.

  20. The etiology of childhood immune thrombocytopenic purpura: how complex is it? (United States)

    Chanock, Stephen


    Recent developments in genomics and basic immunology have provided a new set of tools for investigation into the etiology and treatment of childhood immune thrombocytopenia purpura (ITP). The genomic revolution is generating a catalog of germ-line common genetic variants, some of which could influence the susceptibility or outcome of ITP. Similarly, in vitro analyses and animal models have been employed to probe the basic alterations underlying ITP. The emergence of a more refined understanding of complex diseases such as ITP has important implications for prevention, therapy, and follow-up. The relative contribution of the genetic component and its interaction with the strong environmental stimulus, such as an acute, antecedent viral infection, remains to be determined.

  1. Regulation of plant innate immunity by three proteins in a complex conserved across the plant and animal kingdoms. (United States)

    Palma, Kristoffer; Zhao, Qingguo; Cheng, Yu Ti; Bi, Dongling; Monaghan, Jacqueline; Cheng, Wei; Zhang, Yuelin; Li, Xin


    Innate immunity against pathogen infection is an evolutionarily conserved process among multicellular organisms. Arabidopsis SNC1 encodes a Resistance protein that combines attributes of multiple mammalian pattern recognition receptors. Utilizing snc1 as an autoimmune model, we identified a discrete protein complex containing at least three members--MOS4 (Modifier Of snc1, 4), AtCDC5, and PRL1 (Pleiotropic Regulatory Locus 1)--that are all essential for plant innate immunity. AtCDC5 has DNA-binding activity, suggesting that this complex probably regulates defense responses through transcriptional control. Since the complex components along with their interactions are highly conserved from fission yeast to Arabidopsis and human, they may also have a yet-to-be-identified function in mammalian innate immunity.

  2. Enzyme-linked immunosorbent assays using immune complexes for the diagnosis of tuberculosis. (United States)

    Pereira Arias-Bouda, Lenka M; Kuijper, Sjoukje; van Deutekom, Henk; van Gijlswijk, Rob; Pekel, Inge; Jansen, Henk M; Kolk, Arend H J


    The serodiagnosis of tuberculosis has long been the subject of investigation, but we still lack a test with widespread clinical utility. The poor sensitivity and specificity of commercial assays precludes their use as the sole means of diagnosis. All of these assays use mycobacterial antigens adsorbed onto a surface. Little attention has been paid to changes in antigen conformation that may occur as a result of passive coating of these antigens to solid supports like polystyrene. Such changes may cause technical artifacts resulting in false-positive (FP) and false-negative (FN) reactions. We have developed two different enzyme-linked immunosorbent assay (ELISA) systems, in which human serum antibodies and target antigens of Mycobacterium tuberculosis are able to associate and dissociate freely in solution to form immune complexes. In one ELISA, rabbit antibodies against M. tuberculosis, passively coated in the ELISA wells, capture the immune complexes (ICs). In the other ELISA, the ICs are detected by these same rabbit antibodies but are first captured by passively coated goat anti-rabbit IgG. We have compared these two ELISA systems with an ELISA using M. tuberculosis antigens passively adsorbed to the solid polystyrene surface of the plate. We studied sera from 81 patients with tuberculosis and 47 healthy subjects. The differences between tuberculosis (TB) patients and healthy subjects were statistically significant in all three of our ELISA systems. However, the ELISA systems using soluble M. tuberculosis antigens distinguished better between TB patients and healthy subjects than the ELISA using surface-adsorbed M. tuberculosis antigens. We suggest that in the latter ELISA, passive adsorption of the target antigens induces conformational change, generating altered epitopes that are recognized by antibodies present in the serum from even healthy people. These altered conformational epitopes are recognized by antibodies that were originally evoked by antigens

  3. The effects of colloidal bismuth tartrate on colitis induced by immune-complex in rabbits

    Institute of Scientific and Technical Information of China (English)

    Li Zheng; Shu Xian Wang; Zhen Qiang Gao


    AIM To observe the therapeutic effect of colloidal bismuth tartrate in an animal colitis model.METHODS Immune-complex colitis was induced in groups of rabbits by formalin, and two hours later0.85 mL heat-aggregated rabbit IgG was given intravenously through the ear cannula. Animals wereintracolonically treated with colloidal bismuth tartrate (BITNAL), and its effect was compared withsulfasalazine (SASP), indomethacin (IND) and bifidobiogen (BIFG). Animals were killed, the mucosalappearance was scored (0-4), and tissue saved for histological studies, the number of neutrophils present ininflamed colonic tissue was quantitated by the myeloperoxidase (MPO) activity assay, the production oflipoxygenase and cyclo-oxygenase products was monitored and eicosanoid production were assayed byincubation colonic specimens and the media for prostaglandin E2(PGE2), leukotriene (LTB4), thromboxaneB2(TXPe) were examined by radiommunoassay.RESULTS Immune-complex colitis was induced by formalin and IgG, colonic damage persisted for at least1 wk by macrography. Histologically, the inflammatory response included mucosal and submucosalinfiltration by polymorphonuclear leukocytes, macrophages, lymphocytes and fibroblasts, the macroscopic,persent 2 wk after IgG, was correlated with greatly increased PGE2, LTB4 and TXB2 compared with levels incontrols. Treatment with BITNAL (500 mg/kg) resulted in a lowered inflammation index, lowered MPOactivity and inhibited the increased formation of PGF-2, LTB4 and TXB2 by the inflamed colon, and IND(500 mg/kg) markedly inhibited prostanoid formation in both inflamed and control colon but did not reducetissue damage, SASP (500 mg/kg) also inhibited the formation of PGE2, LTB4 and TXB2 but the effectswere less marked. BIFG (400 mg/kg) did not significantly reduce the colonic injury and the media sythesizedby the rabbit colon.CONCLUSION BITAL provides better therapeutic effects in experimental colitis than anti-inflammatorydrug IND or SASP.

  4. Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies. (United States)

    Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C


    Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normalVGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy.

  5. Big Roles of Small Kinases:The Complex Functions of Receptor-Like Cytoplasmic Kinases in Plant Immunity and Development

    Institute of Scientific and Technical Information of China (English)

    Wenwei Lin; Xiyu Ma; Libo Shan; Ping He


    Plants have evolved a large number of receptor-like cytoplasmic kinases (RLCKs) that often functionally and physically associate with receptor-like kinases (RLKs) to modulate plant growth, development and immune responses. Without any apparent extracellular domain, RLCKs relay intracellular signaling often via RLK complex-mediated transphosphorylation events. Recent advances have suggested essential roles of diverse RLCKs in concert with RLKs in regulating various cellular and physiological responses. We summarize here the complex roles of RLCKs in mediating plant immune responses and growth regulation, and discuss specific and overlapping functions of RLCKs in transducing diverse signaling pathways.

  6. Cas1–Cas2 complex formation mediates spacer acquisition during CRISPR–Cas adaptive immunity


    Nuñez, James K.; Kranzusch, Philip J.; Noeske, Jonas; Wright, Addison V.; Davies, Christopher W; Doudna, Jennifer A.


    The initial stage of CRISPR–Cas immunity involves the acquisition of foreign DNA spacer segments into the host genomic CRISPR locus. The nucleases Cas1 and Cas2 are the only proteins conserved amongst all CRISPR–Cas systems, yet the molecular functions of these proteins during immunity are unknown. Here we show that Cas1 and Cas2 from Escherichia coli form a stable complex that is essential for spacer acquisition and determine the 2.3-Å resolution crystal structure of the Cas1–Cas2 complex. M...

  7. Structure of insoluble immune complexes as studied by spectroturbidimetry and dynamic light scattering (United States)

    Khlebtsov, Boris N.; Burygin, Gennadii L.; Matora, Larisa Y.; Shchyogolev, Sergei Y.; Khlebtsov, Nikolai G.


    We describe two variants of a method for determining the average composition of insoluble immune complex particles (IICP). The first variant is based on measuring the specific turbidity (the turbidity per unit mass concentration of the dispersed substance) and the average size of IICP determined from dynamic light scattering (DLS). In the second variant, the wavelength exponent (i.e., the slope of the logarithmic turbidity spectrum) is used in combination with specific turbidity measurements. Both variants allow the average biopolymer volume fraction to be determined in terms of the average refractive index of IICP. The method is exemplified by two experimental antigen+antibody systems: (i) lipopolysaccharide-protein complex (LPPC) of Azospirillum brasilense Sp245+rabbit anti-LPPC; and (ii) human IgG (hIgG)+sheep anti-hIgG. Our measurements by the two methods for both types of systems gave, on the average, the same result: the volume fraction of the IICP biopolymers is about 30%; accordingly, the volume fraction of buffer solvent is 70%.

  8. Toll-Like Receptor-Dependent Immune Complex Activation of B Cells and Dendritic Cells. (United States)

    Moody, Krishna L; Uccellini, Melissa B; Avalos, Ana M; Marshak-Rothstein, Ann; Viglianti, Gregory A


    High titers of autoantibodies reactive with DNA/RNA molecular complexes are characteristic of autoimmune disorders such as systemic lupus erythematosus (SLE). In vitro and in vivo studies have implicated the endosomal Toll-like receptor 9 (TLR9) and Toll-like receptor 7 (TLR7) in the activation of the corresponding autoantibody producing B cells. Importantly, TLR9/TLR7-deficiency results in the inability of autoreactive B cells to proliferate in response to DNA/RNA-associated autoantigens in vitro, and in marked changes in the autoantibody repertoire of autoimmune-prone mice. Uptake of DNA/RNA-associated autoantigen immune complexes (ICs) also leads to activation of dendritic cells (DCs) through TLR9 and TLR7. The initial studies from our lab involved ICs formed by a mixture of autoantibodies and cell debris released from dying cells in culture. To better understand the nature of the mammalian ligands that can effectively activate TLR7 and TLR9, we have developed a methodology for preparing ICs containing defined DNA fragments that recapitulate the immunostimulatory activity of the previous "black box" ICs. As the endosomal TLR7 and TLR9 function optimally from intracellular acidic compartments, we developed a facile methodology to monitor the trafficking of defined DNA ICs by flow cytometry and confocal microscopy. These reagents reveal an important role for nucleic acid sequence, even when the ligand is mammalian DNA and will help illuminate the role of IC trafficking in the response.

  9. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    LENUS (Irish Health Repository)

    Bergin, David A


    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  10. Neuronal Fc gamma receptor I as a novel mediator for IgG immune complex-induced peripheral sensitization

    Institute of Scientific and Technical Information of China (English)

    Lintao Qu


    Chronic pain often accompanies immune-related diseases with an elevated level of IgG immune complex (IgG-IC) in the serum and/or the affected tissues though the underlying mechanisms are largely unknown. Fc gamma receptors (FcγRs), known as the receptors for the Fc domain of immunoglobulin G (IgG), are typically expressed on immune cells. A general consensus is that the activation of FcγRs by IgG-IC in such immune cells induces the release of proinflammatory cytokines from the immune cells, which may contribute to the IgG-IC-mediated peripheral sensitization. In addition to the immune cells, recent studies have revealed that FcγRI, but not FcγRII and FcγRIII, is also expressed in a subpopulation of primary sensory neurons. Moreover, IgG-IC directly excites the primary sensory neurons through neuronal FcγRI. These findings indicate that neuronal FcγRI provides a novel direct linkage between immunoglobulin and primary sensory neurons, which may be a novel target for the treatment of pain in the immune-related disorders. In this review, we summarize the expression pattern, functions, and the associated cellular signaling of FcγRs in the primary sensory neurons.

  11. Allergen-containing immune complexes used for immunotherapy of allergic asthma. Preparation of complexes and evaluation of their clinical performance in guinea pigs

    DEFF Research Database (Denmark)

    Poulsen, L K; Lundberg, L; Søndergaard, I


    Guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes between antigen and specific IgG) IT were compared with placebo. The bronchial...

  12. Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: possible implication for TLR4-signalling and chronic immune activation. (United States)

    Trøseid, Marius; Lind, Andreas; Nowak, Piotr; Barqasho, Babilonia; Heger, Bernt; Lygren, Idar; Pedersen, Karin K; Kanda, Tatsuo; Funaoka, Hiroyuki; Damås, Jan K; Kvale, Dag


    Progressive HIV infection is characterized by profound enterocyte damage, microbial translocation and chronic immune activation. We aimed to test whether High Mobility Group Box protein 1(HMGB1), a marker of cell death, alone, or in combination with LPS, might contribute to HIV-associated immune activation and progression. Altogether, 29 untreated HIV-infected individuals, 25 inflammatory bowel disease (IBD) patients and 30 controls were included. HIV-infected patients had lower plasma LPS levels than IBD patients, but higher levels of soluble CD14 and Myeloid Differentiation (MD) 2, which interacts with TLR4 to initiate LPS-signalling. Furthermore, plasma levels of HMGB1 and MD2 were correlated directly within the HIV-infected cohort (r = 0.89, P < 0.001) and the IBD-cohort (r = 0.85, P < 0.001), implying HMGB1 signalling through the MD2/TLR4-pathway. HMGB1 and LPS, although not inter-correlated, were both moderately (r = 0.4) correlated with CD38 density on CD8+ T cells in HIV progressors. The highest levels of CD38 density and MD2 were found in progressors with plasma levels of both LPS and HMGB1 above the fiftieth percentile. Our results could imply that, in some patients, immune activation is triggered by microbial translocation, in some by cell death and in some by HMGB1 in complex with bacterial products through activation of the MD2/TLR4-pathway.

  13. Increase in frequencies of circulating Th-17 cells correlates with microbial translocation, immune activation and exhaustion in HIV-1 infected patients with poor CD4 T-cell reconstitution. (United States)

    Valiathan, Ranjini; Asthana, Deshratn


    We analyzed the association of circulating Th-17 cells (cTh-17) with immune activation (IA), immune exhaustion (IE) and regulatory T-cells (T-regs) in 20 human immunodeficiency virus-1 (HIV-1) infected patients with impaired restoration of CD4 T-cell counts despite prolonged suppression of plasma viremia (discordant) and compared it with 20 HIV-1 infected patients showing good immunologic and virologic responses (concordant) following highly active antiretroviral therapy (HAART). Discordant HIV-1 infected patients showed significantly higher frequencies of cTh-17 cells compared to concordant patients and healthy controls after PMA+Ionomicin stimulation. Discordant patients also showed higher CD4 T-cell immune activation (HLA-DR+CD38+) than concordant patients which directly correlated with microbial translocation. Additionally, CD4 T-cells of discordant patients showed higher frequencies of CD4 T-cells expressing multiple immune exhaustion markers (Tim3+PD-1+) which correlated with immune activation indicating that combined analysis of inhibitory molecules along with PD-1 might be a better predictor for immune exhaustion of CD4 T-cells. Increased cTh-17 cell frequency correlated inversely with CD4 T-cell percentages and absolute counts and directly with CD4 T-cell immune activation and T-reg frequencies. Persistent CD4 T-cell immune activation might favor differentiation of activated CD4 T-cells toward cTh-17 phenotype in discordant patients. Discordant patients had significantly lower baseline CD4 T-cell counts and higher viral load at the initiation of HAART and higher immune activation and immune exhaustion after being on HAART for long time indicating that these factors might be associated with an increase in cTh-17 cell frequency, thus, increasing the risk of disease progression despite virologic control.

  14. Hepatitis B virus surface antigen (HBsAg and antibody (anti-HBs forming immune complexes in fulminant hepatitis

    Directory of Open Access Journals (Sweden)

    Soares Manoel C.P.


    Full Text Available This paper reports an unusual pattern of serological HBV markers and the presence of HBsAg/anti-HBs immune complexes in serum samples from two patients with fulminant hepatitis from the Brazilian Western Amazon Basin. The diagnosis was made by both serologic tests and demonstration of antigen/antibody complexes by transmission electron microscopy. Concurrent Delta virus superinfection is also discussed.

  15. Antigen transfer from exosomes to dendritic cells as an explanation for the immune enhancement seen by IgE immune complexes.

    Directory of Open Access Journals (Sweden)

    Rebecca K Martin

    Full Text Available IgE antigen complexes induce increased specific T cell proliferation and increased specific IgG production. Immediately after immunization, CD23(+ B cells capture IgE antigen complexes, transport them to the spleen where, via unknown mechanisms, dendritic cells capture the antigen and present it to T cells. CD23, the low affinity IgE receptor, binds IgE antigen complexes and internalizes them. In this study, we show that these complexes are processed onto B-cell derived exosomes (bexosomes in a CD23 dependent manner. The bexosomes carry CD23, IgE and MHC II and stimulate antigen specific T-cell proliferation in vitro. When IgE antigen complex stimulated bexosomes are incubated with dendritic cells, dendritic cells induce specific T-cell proliferation in vivo, similar to IgE antigen complexes. This suggests that bexosomes can provide the essential transfer mechanism for IgE antigen complexes from B cells to dendritic cells.

  16. Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune Responses

    Directory of Open Access Journals (Sweden)

    Catalina Burbano


    Full Text Available Microparticles (MPs are induced during apoptosis, cell activation, and even “spontaneous” release. Initially MPs were considered to be inert cellular products with no biological function. However, an extensive research and functional characterization have shown that the molecular composition and the effects of MPs depend upon the cellular background and the mechanism inducing them. They possess a wide spectrum of biological effects on intercellular communication by transferring different molecules able to modulate other cells. MPs interact with their target cells through different mechanisms: membrane fusion, macropinocytosis, and receptor-mediated endocytosis. However, when MPs remain in the extracellular milieu, they undergo modifications such as citrullination, glycosylation, and partial proteolysis, among others, becoming a source of neoantigens. In rheumatoid arthritis (RA and systemic lupus erythematosus (SLE, reports indicated elevated levels of MPs with different composition, content, and effects compared with those isolated from healthy individuals. MPs can also form immune complexes amplifying the proinflammatory response and tissue damage. Their early detection and characterization could facilitate an appropriate diagnosis optimizing the pharmacological strategies, in different diseases including cancer, infection, and autoimmunity. This review focuses on the current knowledge about MPs and their involvement in the immunopathogenesis of SLE and RA.

  17. Frustrated phagocytosis on micro-patterned immune complexes to characterize lysosome movements in live macrophages.

    Directory of Open Access Journals (Sweden)

    Arnaud M. Labrousse


    Full Text Available Lysosome mobilization is a key cellular process in phagocytes for bactericidal activities and trans-matrix migration. The molecular mechanisms that regulate lysosome mobilization are still poorly known. Lysosomes are hard to track as they move towards phagosomes throughout the cell volume. In order to anticipate cell regions where lysosomes are recruited to, human and RAW264.7 macrophages were seeded on surfaces that were micro-patterned with immune complexes (ICs as 4 µm-side squares. Distances between IC patterns were adapted to optimize cell spreading in order to constrain lysosome movements mostly in 2 dimensions. Fc receptors triggered local frustrated phagocytosis, frustrated phagosomes appeared as rings of F-actin dots around the IC patterns as early as 5 minutes after cells made contact with the substratum. Frustrated phagosomes recruited actin-associated proteins (vinculin, paxillin and gelsolin. The fusion of lysosomes with frustrated phagosomes was shown by the release of beta-hexosaminidase and the recruitment of Lamp-1 to frustrated phagosomes. Lysosomes of RAW264.7 macrophages were labeled with cathepsinD-mCherry to visualize their movements towards frustrated phagosomes. Lysosomes saltatory movements were markedly slowed down compared to cells layered on non-opsonized patterns. In addition, the linearity of the trajectories and the frequency and duration of contacts of lysosomes with frustrated phagosomes were measured.¬¬¬¬¬¬¬¬ Using PP2 we showed that instant velocity, pauses and frequency of lysosome/phagosome contacts were at least in part dependent on Src tyrosine kinases. This experimental set-up is the first step towards deciphering molecular mechanisms which are involved in lysosome movements in the cytoplasm (directionality, docking and fusion using RNA interference, pharmacological inhibition or mutant expression.

  18. Non-immunoglobulin A mesangial immune complex glomerulonephritis in kidney transplants. (United States)

    Giannico, Giovanna A; Arnold, Shanna; Langone, Anthony; Schaefer, Heidi; Helderman, J Harold; Shaffer, David; Fogo, Agnes B


    We have observed a predominantly mesangial non-immunoglobulin A immune complex mesangial glomerulopathy (MG) in renal transplants with mesangial deposits by immunofluorescence and electron microscopy. Clinicopathological features of 28 patients with MG were analyzed and compared with 28 transplant controls, matched for age, sex, ethnicity, donor type, estimated glomerular filtration rate, and interval from transplant to biopsy. Indications for biopsy in the MG group were allograft dysfunction in 64%, allograft dysfunction/proteinuria in 29%, and proteinuria in 7%. Biopsy indications in controls were allograft dysfunction (61%), allograft dysfunction/proteinuria (18%), proteinuria (14%), and delayed graft function (7%). Most MG cases had mild mesangial hypercellularity with endocapillary proliferation in 2 and crescents in 2 without fibrinoid necrosis. Immunoglobulin M-dominant deposits were present in 83%, and immunoglobulin G was dominant in 17% with mesangial deposits in 93% of cases by electron microscopy. Compared with controls, MG had higher Banff interstitial inflammation score (i) (P = .036) and was associated with concurrent acute T-cell-mediated rejection (P = .023), but not with acute or chronic antibody-mediated rejection. MG patients and controls had similar prevalence of polyomavirus nephropathy and Epstein-Barr virus infection. At follow-up, most MG patients had stable estimated glomerular filtration rate with no or stable proteinuria. Disease-specific graft survival was not different in MG versus controls. We conclude that, in view of the apparent self-limited nature of this lesion, additional treatment may not be required in these patients. Awareness of this lesion may thus spare patients unwarranted further intervention.

  19. Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcγR Cooperation and Is Dependent on CARD9 (United States)

    Rhoads, Jillian P.; Lukens, John R.; Wilhelm, Ashley J.; Moore, Jared L.; Mendez-Fernandez, Yanice; Kanneganti, Thirumala-Devi


    Oxidized low-density lipoprotein (oxLDL) is known to activate inflammatory responses in a variety of cells, especially macrophages and dendritic cells. Interestingly, much of the oxLDL in circulation is complexed to Abs, and these resulting immune complexes (ICs) are a prominent feature of chronic inflammatory disease, such as atherosclerosis, type-2 diabetes, systemic lupus erythematosus, and rheumatoid arthritis. Levels of oxLDL ICs often correlate with disease severity, and studies demonstrated that oxLDL ICs elicit potent inflammatory responses in macrophages. In this article, we show that bone marrow–derived dendritic cells (BMDCs) incubated with oxLDL ICs for 24 h secrete significantly more IL-1β compared with BMDCs treated with free oxLDL, whereas there was no difference in levels of TNF-α or IL-6. Treatment of BMDCs with oxLDL ICs increased expression of inflammasome-related genes Il1a, Il1b, and Nlrp3, and pretreatment with a caspase 1 inhibitor decreased IL-1β secretion in response to oxLDL ICs. This inflammasome priming was due to oxLDL IC signaling via multiple receptors, because inhibition of CD36, TLR4, and FcγR significantly decreased IL-1β secretion in response to oxLDL ICs. Signaling through these receptors converged on the adaptor protein CARD9, a component of the CARD9–Bcl10–MALT1 signalosome complex involved in NF-κB translocation. Finally, oxLDL IC–mediated IL-1β production resulted in increased Th17 polarization and cytokine secretion. Collectively, these data demonstrate that oxLDL ICs induce inflammasome activation through a separate and more robust mechanism than oxLDL alone and that these ICs may be immunomodulatory in chronic disease and not just biomarkers of severity. PMID:28130494

  20. Emerging complexity and new roles for the RIG-I-like receptors in innate antiviral immunity

    Institute of Scientific and Technical Information of China (English)

    John; S.Errett; Michael; Gale; Jr.


    Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors(RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns(PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger downstream signaling cascades that induce innate immunity that controls viral replication and spread. Products of RLR signaling also serve to modulate the adaptive immune response to infection. Recent studies have additionally connected RLRs to signaling cascades that impart inflammatory and apoptotic responses to virus infection. Viral evasion of RLR signaling supports viral outgrowth and pathogenesis, including the onset of viral-associated cancer.

  1. Granulocyte-macrophage stimulating factor (GM-CSF increases circulating dendritic cells but does not abrogate suppression of adaptive cellular immunity in patients with metastatic colorectal cancer receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Martinez Micaela


    Full Text Available Abstract Background Advanced cancer and chemotherapy are both associated with immune system suppression. We initiated a clinical trial in patients receiving chemotherapy for metastatic colorectal cancer to determine if administration of GM-CSF in this setting was immunostimulatory. Methods Between June, 2003 and January, 2007, 20 patients were enrolled in a clinical trial (NCT00257322 in which they received 500 ug GM-CSF daily for 4 days starting 24 hours after each chemotherapy cycle. There were no toxicities or adverse events reported. Blood was obtained before chemotherapy/GM-CSF administration and 24 hours following the final dose of GM-CSF and evaluated for circulating dendritic cells and adaptive immune cellular subsets by flow cytometry. Peripheral blood mononuclear cell (PBMC expression of γ-interferon and T-bet transcription factor (Tbx21 by quantitative real-time PCR was performed as a measure of Th1 adaptive cellular immunity. Pre- and post-treatment (i.e., chemotherapy and GM-CSF samples were evaluable for 16 patients, ranging from 1 to 5 cycles (median 3 cycles, 6 biologic sample time points. Dendritic cells were defined as lineage (- and MHC class II high (+. Results 73% of patients had significant increases in circulating dendritic cells of ~3x for the overall group (5.8% to 13.6%, p = 0.02 and ~5x excluding non-responders (3.2% to 14.5%, p Tbx21 levels declined by 75% following each chemotherapy cycle despite administration of GM-CSF (p = 0.02. PBMC γ-interferon expression, however was unchanged. Conclusions This clinical trial confirms the suppressive effects of chemotherapy on Th1 cellular immunity in patients with metastatic colorectal cancer but demonstrates that mid-cycle administration of GM-CSF can significantly increase the proportion of circulating dendritic cells. As the role of dendritic cells in anti-tumor immunity becomes better defined, GM-CSF administration may provide a non-toxic intervention to augment this arm

  2. Prf immune complexes of tomato are oligomeric and contain multiple Pto-like kinases that diversify effector recognition. (United States)

    Gutierrez, Jose R; Balmuth, Alexi L; Ntoukakis, Vardis; Mucyn, Tatiana S; Gimenez-Ibanez, Selena; Jones, Alexandra M E; Rathjen, John P


    Cytoplasmic recognition of pathogen virulence effectors by plant NB-LRR proteins leads to strong induction of defence responses termed effector triggered immunity (ETI). In tomato, a protein complex containing the NB-LRR protein Prf and the protein kinase Pto confers recognition of the Pseudomonas syringae effectors AvrPto and AvrPtoB. Although structurally unrelated, AvrPto and AvrPtoB interact with similar residues in the Pto catalytic cleft to activate ETI via an unknown mechanism. Here we show that the Prf complex is oligomeric, containing at least two molecules of Prf. Within the complex, Prf can associate with Pto or one of several Pto family members including Fen, Pth2, Pth3, or Pth5. The dimerization surface for Prf is the novel N-terminal domain, which also coordinates an intramolecular interaction with the remainder of the molecule, and binds Pto kinase or a family member. Thus, association of two Prf N-terminal domains brings the associated kinases into close promixity. Tomato lines containing Prf complexed with Pth proteins but not Pto possessed greater immunity against P. syringae than tomatoes lacking Prf. This demonstrates that incorporation of non-Pto kinases into the Prf complex extends the number of effector proteins that can be recognized.

  3. Alternative Pathway Dysregulation and the Conundrum of Complement Activation by IgG4 Immune Complexes in Membranous Nephropathy (United States)

    Borza, Dorin-Bogdan


    Membranous nephropathy (MN), a major cause of nephrotic syndrome, is a non-inflammatory immune kidney disease mediated by IgG antibodies that form glomerular subepithelial immune complexes. In primary MN, autoantibodies target proteins expressed on the podocyte surface, often phospholipase A2 receptor (PLA2R1). Pathology is driven by complement activation, leading to podocyte injury and proteinuria. This article overviews the mechanisms of complement activation and regulation in MN, addressing the paradox that anti-PLA2R1 and other antibodies causing primary MN are predominantly (but not exclusively) IgG4, an IgG subclass that does not fix complement. Besides immune complexes, alterations of the glomerular basement membrane (GBM) in MN may lead to impaired regulation of the alternative pathway (AP). The AP amplifies complement activation on surfaces insufficiently protected by complement regulatory proteins. Whereas podocytes are protected by cell-bound regulators, the GBM must recruit plasma factor H, which inhibits the AP on host surfaces carrying certain polyanions, such as heparan sulfate (HS) chains. Because HS chains present in the normal GBM are lost in MN, we posit that the local complement regulation by factor H may be impaired as a result. Thus, the loss of GBM HS in MN creates a micro-environment that promotes local amplification of complement activation, which in turn may be initiated via the classical or lectin pathways by subsets of IgG in immune complexes. A detailed understanding of the mechanisms of complement activation and dysregulation in MN is important for designing more effective therapies. PMID:27199983

  4. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses (United States)

    Mittelbrunn, María; Molina, Ana; Escribese, María M.; Yáñez-Mó, María; Escudero, Ester; Ursa, Ángeles; Tejedor, Reyes; Mampaso, Francisco; Sánchez-Madrid, Francisco


    The integrin 41 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes. However, the behavior of 41 during the formation of the immune synapse is currently unknown. Here, we show that 41 is recruited to both human and murine antigen-dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular activation complex. However, when conjugates are formed in the presence of anti-4 antibodies, VLA-4 colocalizes with the CD3- chain at the center of the synapse. In addition, antibody engagement of 4 integrin promotes polarization toward a T helper 1 (Th1) response in human in vitro models of CD4+ T cell differentiation and naïve T cell priming by dendritic cells. The in vivo administration of anti-4 integrin antibodies also induces an immune deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown Norway rats. These data reveal a regulatory role of 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions.

  5. Fetal Circulation (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Fetal Circulation Updated:Oct 18,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  6. Platelet immune complex interaction in pathogenesis of Kawasaki disease and childhood polyarteritis.


    Levin, M; Holland, P C; Nokes, T J; Novelli, V; Mola, M; Levinsky, R J; Dillon, M J; Barratt, T M; Marshall, W C


    The role of platelets in the pathogenesis of vasculitis and the formation of coronary artery aneurysms was studied in 19 children with Kawasaki disease and five with polyarteritis. All patients with Kawasaki disease developed thrombocytosis in the third week of illness. The peak platelet count was significantly correlated (p less than 0.005) with the subsequent development of coronary artery aneurysms. The rise in platelet count was associated with the appearance in the circulation of a facto...

  7. Antiepithelial autoantibodies associated with the feline eosinophilic granuloma complex. (United States)

    Gelberg, H B; Lewis, R M; Felsburg, P J; Smith, C A


    A retrospective study of banked sera from 19 cats with the eosinophilic granuloma complex revealed that 68% of affected cats had circulating antibodies to components of normal cat epithelium. Seemingly, the eosinophilic granuloma complex of cats may be an autoimmune disease; however, epidermal damage caused by the eosinophilic granuloma complex may release altered self-antigens to which the cat's immune system responds.

  8. Diminished ability of erythrocytes from patients with systemic lupus erythematosus to limit opsonized immune complex deposition on leukocytes and activation of granulocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Rasmussen, J M; Voss, A


    To compare the ability of normal erythrocytes and erythrocytes from systemic lupus erythematosus (SLE) patients to bind immune complexes (IC), thereby inhibiting IC deposition on polymorphonuclear leukocytes (PMN) and the consequent induction of a PMN respiratory burst (RB)....

  9. RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions

    NARCIS (Netherlands)

    Wiedenheft, Blake; van Duijn, Esther; Bultema, Jelle; Waghmare, Sakharam; Zhou, Kaihong; Barendregt, Arjan; Westphal, Wiebke; Heck, Albert; Boekema, Egbert; Dickman, Mark; Doudna, Jennifer A.


    Prokaryotes have evolved multiple versions of an RNA-guided adaptive immune system that targets foreign nucleic acids. In each case, transcripts derived from clustered regularly interspaced short palindromic repeats (CRISPRs) are thought to selectively target invading phage and plasmids in a sequenc

  10. Immune complex detection by immunofluorescence on polymorphonuclear leucocytes : an experimental and clinicopathological study

    NARCIS (Netherlands)

    J.W. Steffelaar (Jan Willem)


    textabstractDiseases, which are the result of immune reactions associated with tissue damage may be caused by several mechanisms. The immunologic mechanisms resulting in tissue damage have been categorized in 4 types (Gell and Coombs, 1968). 1. the anaphylactic type, mediated by IgE type of antibodi

  11. The attachment of serum- and plasma-derived C3 to solid-phase immune aggregates and its relation to complement-mediated solubilization of immune complexes

    DEFF Research Database (Denmark)

    Baatrup, G; Svehag, S E; Jensenius, J C


    The interaction between immune aggregates and complement (C) was investigated. Solid-phase immune aggregates were prepared by coating microwells with heat-aggregated bovine serum albumin (BSA) followed by rabbit anti-BSA antibody. The immune aggregates were reacted with human serum or citrated pl...

  12. Interactions of opsonized immune complexes with whole blood cells: binding to erythrocytes restricts complex uptake by leucocyte populations

    DEFF Research Database (Denmark)

    Nielsen, C H; Svehag, S E; Marquart, H V;


    The binding of opsonized, fluorescein-labelled bovine serum albumin (BSA)/rabbit anti-BSA complexes (IC) to washed human whole blood cells and isolated leucocytes in the presence of autologous serum was investigated by flow cytometry. In the presence of erythrocytes (E), the IC-binding to granulo......The binding of opsonized, fluorescein-labelled bovine serum albumin (BSA)/rabbit anti-BSA complexes (IC) to washed human whole blood cells and isolated leucocytes in the presence of autologous serum was investigated by flow cytometry. In the presence of erythrocytes (E), the IC...

  13. A role for the RNA pol II–associated PAF complex in AID-induced immune diversification (United States)

    Willmann, Katharina L.; Milosevic, Sara; Pauklin, Siim; Schmitz, Kerstin-Maike; Rangam, Gopinath; Simon, Maria T.; Maslen, Sarah; Skehel, Mark; Robert, Isabelle; Heyer, Vincent; Schiavo, Ebe; Reina-San-Martin, Bernardo


    Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions. PMID:23008333

  14. Effects of syndyphalin-33 on feed intake and circulating measures of growth hormone, cortisol, and immune cell populations in the recently-weaned pig (United States)

    The synthetic met-enkephalin syndyphalin-33 (SD-33) increases feed intake in sheep and transiently increases circulating growth hormone (GH) concentrations in sheep, rats, and pigs. Two experiments were performed to evaluate the effects of SD-33 on recently-weaned pigs. In a preliminary experiment, ...

  15. IgA Nephropathy and Henoch-Schoenlein Purpura Nephritis: Aberrant Glycosylation of IgA1, Formation of IgA1-Containing Immune Complexes, and Activation of Mesangial Cells

    DEFF Research Database (Denmark)

    Novak, J.; Moldoveanu, Z.; Renfrow, M.B.;


    IgA1 in the circulation and glomerular deposits of patients with IgA nephropathy (IgAN) is aberrantly glycosylated; the hinge-region O-linked glycans are galactose-deficient. The circulating IgA1 of patients with Henoch-Schoenlein purpura nephritis (HSPN) has a similar defect. This aberrancy...... at specific sites. We sought to define the aberrant glycosylation of a galactose-deficient IgA1 myeloma protein and analyze the formation of the immune complexes and their biological activities. Supplementation of serum or cord-blood serum with this IgA1 protein resulted in formation of new IgA1 complexes...... determined the O-glycosylation sites in the hinge region of the IgA1 myeloma protein and IgA1 proteins from sera of IgAN patients. The IgA1 myeloma protein had galactose-deficient sites at residues 228 and/or 230 and 232. These sites reacted with IgG specific to galactose-deficient IgA1. IgA1 from the Ig...

  16. Complex multicellular systems and immune competition: new paradigms looking for a mathematical theory. (United States)

    Bellomo, Nicola; Forni, Guido


    This chapter deals with the modeling and simulation of large systems of interacting entities whose microscopic state includes not only geometrical and mechanical variables (typically position and velocity), but also biological functions or specific activities. The main issue looks at the development of a biological mathematical theory for multicellular systems. The first part is devoted to the derivation of mathematical structures to be properly used to model a variety of biological phenomena with special focus on immune competition. Then, some specific applications are proposed referring to the competition between neoplastic and immune cells. Finally, the last part is devoted to research perspectives towards the objective of developing a mathematical-biological theory. A critique is presented of what has already been achieved towards the above target and what is still missing with special focus on multiscale systems.

  17. Helper T-cell heterogeneity: a complex developmental issue in the immune system

    Institute of Scientific and Technical Information of China (English)

    Chen Dong


    After activation by antigen-presenting cells, naive, antigen-specific CD4+ T cells differentiate into effector T cells. Two decades ago, Coffman and Mosman first discovered the heterogeneity of effector T cells, which were named as Th 1 or Th2 cells.1 Th 1 and Th2 cells are differentially induced and are involved in immunity against intracellular and extracellular pathogens, respectively, as well as immunopathologies such as autoimmunity and allergy.

  18. The molecular evolution of four anti-malarial immune genes in the Anopheles gambiae species complex


    Simard Frederic; Antonio-Nkondjio Christophe; Awono-Ambene Parfait H; Marshall Jonathon C; Slotman Michel A; Parmakelis Aristeidis; Caccone Adalgisa; Powell Jeffrey R


    Abstract Background If the insect innate immune system is to be used as a potential blocking step in transmission of malaria, then it will require targeting one or a few genes with highest relevance and ease of manipulation. The problem is to identify and manipulate those of most importance to malaria infection without the risk of decreasing the mosquito's ability to stave off infections by microbes in general. Molecular evolution methodologies and concepts can help identify such genes. Withi...

  19. Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse. (United States)

    Finetti, Francesca; Paccani, Silvia Rossi; Riparbelli, Maria Giovanna; Giacomello, Emiliana; Perinetti, Giuseppe; Pazour, Gregory J; Rosenbaum, Joel L; Baldari, Cosima T


    Most eukaryotic cells have a primary cilium which functions as a sensory organelle. Cilia are assembled by intraflagellar transport (IFT), a process mediated by multimeric IFT particles and molecular motors. Here we show that lymphoid and myeloid cells, which lack primary cilia, express IFT proteins. IFT20, an IFT component essential for ciliary assembly, was found to colocalize with both the microtubule organizing centre (MTOC) and Golgi and post-Golgi compartments in T-lymphocytes. In antigen-specific conjugates, IFT20 translocated to the immune synapse. IFT20 knockdown resulted in impaired T-cell receptor/CD3 (TCR/CD3) clustering and signalling at the immune synapse, due to defective polarized recycling. Moreover, IFT20 was required for the inducible assembly of a complex with other IFT components (IFT57 and IFT88) and the TCR. The results identify IFT20 as a new regulator of immune synapse assembly in T cells and provide the first evidence to implicate IFT in membrane trafficking in cells lacking primary cilia, thereby introducing a new perspective on IFT function beyond its role in ciliogenesis.

  20. Elitism-based immune genetic algorithm and its application to optimization of complex multi-modal functions

    Institute of Scientific and Technical Information of China (English)


    A novel immune genetic algorithm with the elitist selection and elitist crossover was proposed,which is called the immune genetic algorithm with the elitism (IGAE).In IGAE,the new methods for computing antibody similarity,expected reproduction probability,and clonal selection probability were given.IGAE has three features.The first is that the similarities of two antibodies in structure and quality are all defined in the form of percentage,which helps to describe the similarity of two antibodies more accurately and to reduce the computational burden effectively.The second is that with the elitist selection and elitist crossover strategy IGAE is able to find the globally optimal solution of a given problem.The third is that the formula of expected reproduction probability of antibody can be adjusted through a parameter β,which helps to balance the population diversity and the convergence speed of IGAE so that IGAE can find the globally optimal solution of a given problem more rapidly.Two different complex multi-modal functions were selected to test the validity of IGAE.The experimental results show that IGAE can find the globally maximum/minimum values of the two functions rapidly.The experimental results also confirm that IGAE is of better performance in convergence speed,solution variation behavior,and computational efficiency compared with the canonical genetic algorithm with the elitism and the immune genetic algorithm with the information entropy and elitism.

  1. Dynamics of the Atlantic meridional overturning circulation and Southern Ocean in an ocean model of intermediate complexity (United States)

    McCreary, Julian P.; Furue, Ryo; Schloesser, Fabian; Burkhardt, Theodore W.; Nonaka, Masami


    A steady-state, variable-density, 2-layer, ocean model (VLOM) is used to investigate basic dynamics of the Atlantic meridional overturning circulation and Southern Ocean. The domain consists of idealized (rectangular) representations of the Atlantic, Southern, and Pacific Oceans. The model equations represent the depth-averaged, layer-1 response (except for one solution in which they represent the depth-integrated flow over both layers). To allow for overturning, water can cross the bottom of layer 1 at the velocity we =wd +wm +wn , the three parts representing: interior diffusion wd that increases the layer-1 thickness h throughout the basin, mixed-layer entrainment wm that ensures h is never less than a minimum value hm , and diapycnal (cooling) processes external to the basin wn that adjust h to hn . For most solutions, horizontal mixing has the form of Rayleigh damping with coefficient ν , which we interpret to result from baroclinic instability through the closure, V∗ = - (ν /f2) ∇P , where ∇P = ∇(1/2 g‧h2) is the depth-integrated pressure gradient, g‧ is the reduced-gravity coefficient, and ν is a mixing coefficient; with this interpretation, the layer-1 flow corresponds to the sum of the Eulerian-mean and eddy-mean (V∗) transport/widths, that is, the "residual" circulation. Finally, layer-1 temperature cools polewards in response to a surface heat flux Q, and the cooling can be strong enough in the Southern Ocean for g‧ = 0 south of a latitude y0 , in which case layer 1 vanishes and the model reduces to a single layer 2. Solutions are obtained both numerically and analytically. The analytic approach splits fields into interior and boundary-layer parts, from which a coupled set of integral constraints can be derived. The set allows properties of the circulation (upwelling-driven transport out of the Southern Ocean M , downwelling transport in the North Atlantic, transport of the Antarctic Circumpolar Current) and stratification (Atlantic

  2. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase. (United States)

    Zhi, Huiying; Dai, Jing; Liu, Junling; Zhu, Jieqing; Newman, Debra K; Gao, Cunji; Newman, Peter J


    IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  3. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase.

    Directory of Open Access Journals (Sweden)

    Huiying Zhi

    Full Text Available IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  4. Extensive changes in innate immune gene expression in obese Göttingen minipigs do not lead to changes in concentrations of circulating cytokines and acute phase proteins

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Moesgaard, S. G.;


    The usefulness of Göttingen minipigs as models for obesity and obesity-related pathologies is well established. The low-grade inflammation associated with obesity involves a range of innate immune factors; however, to our knowledge, the impact of obesity on innate immune factor expression has...... between adipose tissues and a decreased tissue-specific expression of cytokines and chemokines. In contrast to obese humans, no changes in serum concentrations of haptoglobin, C-reactive protein, serum amyloid A, tumor necrosis factor-α and interleukin 6 were found in obese Göttingen minipigs....... not been studied in Göttingen minipigs. Therefore, we studied the expression of innate immune genes in liver and adipose tissues as well as serum concentrations of cytokines and acute phase proteins in obese vs. lean Göttingen minipigs. In the liver, of 35 investigated genes, the expression of nine...

  5. Arabidopsis SENESCENCE-ASSOCIATED GENE101 stabilizes and signals within an ENHANCED DISEASE SUSCEPTIBILITY1 complex in plant innate immunity. (United States)

    Feys, Bart J; Wiermer, Marcel; Bhat, Riyaz A; Moisan, Lisa J; Medina-Escobar, Nieves; Neu, Christina; Cabral, Adriana; Parker, Jane E


    Plant innate immunity against invasive biotrophic pathogens depends on the intracellular defense regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). We show here that Arabidopsis thaliana EDS1 interacts in vivo with another protein, SENESCENCE-ASSOCIATED GENE101 (SAG101), discovered through a proteomic approach to identify new EDS1 pathway components. Together with PHYTOALEXIN-DEFICIENT4 (PAD4), a known EDS1 interactor, SAG101 contributes intrinsic and indispensable signaling activity to EDS1-dependent resistance. The combined activities of SAG101 and PAD4 are necessary for programmed cell death triggered by the Toll-Interleukin-1 Receptor type of nucleotide binding/leucine-rich repeat immune receptor in response to avirulent pathogen isolates and in restricting the growth of normally virulent pathogens. We further demonstrate by a combination of cell fractionation, coimmunoprecipitation, and fluorescence resonance energy transfer experiments the existence of an EDS1-SAG101 complex inside the nucleus that is molecularly and spatially distinct from EDS1-PAD4 associations in the nucleus and cytoplasm. By contrast, EDS1 homomeric interactions were detected in the cytoplasm but not inside the nucleus. These data, combined with evidence for coregulation between individual EDS1 complexes, suggest that dynamic interactions of EDS1 and its signaling partners in multiple cell compartments are important for plant defense signal relay.

  6. Enhanced antitumor immunity of nanoliposome-encapsulated heat shock protein 70 peptide complex derived from dendritic tumor fusion cells. (United States)

    Zhang, Yunfei; Luo, Wen; Wang, Yucai; Chen, Jun; Liu, Yunyan; Zhang, Yong


    Tumor-derived heat shock proteins peptide complex (HSP.PC-Tu) has been regarded as a promising antitumor agent. However, inadequate immunogenicity and low bioavailability limit the clinical uses of this agent. In a previous study, we first produced an improved HSP70.PC-based vaccine purified from dendritic cell (DC)-tumor fusion cells (HSP70.PC-Fc) which had increased immunogenicity due to enhanced antigenic tumor peptides compared to HSP70.PC-Tu. In order to increase the bioavailability of HSP70.PC-Fc, the peptide complex was encapsulated with nanoliposomes (NL-HSP70.PC-Fc) in this study. After encapsulation, the tumor immunogenicity was observed using various assays. It was demonstrated that the NL-HSP70.PC-Fc has acceptable stability. The in vivo antitumor immune response was increased with regard to T-cell activation, CTL response and tumor therapy efficiency compared to that of HSP70.PC-Fc. In addition, it was shown that DC maturation was improved by NL-HSP70.PC-Fc, which added to the antitumor immunity. The results obtained for NL-HSP70.PC-Fc, which improved immunogenicity and increases the bioavailability of HSP70.PC, may represent superior heat shock proteins (HSPs)-based tumor vaccines. Such vaccines deserve further investigation and may provide a preclinical rationale to translate findings into early phase trials for patients with breast tumors.

  7. Moderate alcohol consumption alters both leucocyte gene expression profiles and circulating proteins related to immune response and lipid metabolism in men

    NARCIS (Netherlands)

    Joosten, M.M.; Erk, van M.J.; Pellis, E.P.M.; Witkamp, R.F.; Hendriks, H.F.J.


    Moderate alcohol consumption has various effects on immune and inflammatory processes, which could accumulatively modulate chronic disease risk. So far, no comprehensive, integrative profiling has been performed to investigate the effects of longer-term alcohol consumption. Therefore, we studied the

  8. Immune cell activation from multivalent interactions with liquid-crystalline polycation-DNA complexes (United States)

    Schmidt, Nathan; Jin, Fan; Lande, Roberto; Curk, Tine; Xian, Wujing; Frasca, Loredana; Dobnikar, Jure; Frenkel, Daan; Gilliet, Michel; Wong, Gerard


    Microbial DNA can trigger type I interferon (IFN) production in plasmacytoid cells (pDCs) by binding to endosomal toll-like receptor 9 (TLR9). TLR9 in pDCs do not normally respond to self-DNA, but in certain autoimmune diseases self-DNA can complex with the polycationic antimicrobial peptide LL37 into condensed structures which allow DNA to access endosomal compartments and stimulate TLR9 in pDCs. We use x-ray studies and cell measurements of IFN secretion by pDCs to show that a broad range of polycation-DNA complexes stimulate pDCs and elucidate the criterion for high IFN production. Furthermore, we show via experiments and computer simulations that the distinguishing factor for why certain complexes activate pDCs while others do not is the self-assembled structure of the liquid-crystalline polycation-DNA complex.

  9. Role of Circulating Lymphocytes in Patients with Sepsis

    Directory of Open Access Journals (Sweden)

    Raul de Pablo


    Full Text Available Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

  10. [Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment]. (United States)

    Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I


    Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

  11. Visualization of Complex Biological Systems: An Immune Response Model Using OpenGL (United States)

    Burns, John; Ruskin, Heather J.; Perrin, Dimitri; Walsh, John

    In this paper we present an update on our novel visualization technologies based on cellular immune interaction from both large-scale spatial and temporal perspectives. We do so with a primary motive: to present a visually and behaviourally realistic environment to the community of experimental biologists and physicians such that their knowledge and expertise may be more readily integrated into the model creation and calibration process. Visualization aids understanding as we rely on visual perception to make crucial decisions. For example, with our initial model, we can visualize the dynamics of an idealized lymphatic compartment, with antigen presenting cells (APC) and cytotoxic T lymphocyte (CTL) cells. The visualization technology presented here offers the researcher the ability to start, pause, zoom-in, zoom-out and navigate in 3-dimensions through an idealised lymphatic compartment.

  12. Nearshore circulation

    NARCIS (Netherlands)

    Battjes, J.A.; Sobey, R.J.; Stive, M.J.F.


    Shelf circulation is driven primarily by wind- and tide-induced forces. It is laterally only weakly constrained so that the geostrophic (Coriolis) acceleration is manifest in the response. Nearshore circulation on the other hand is dominated by wave-induced forces associated with shallow-water. wave

  13. Selective modulation of follicle-stimulating hormone signaling pathways with enhancing equine chorionic gonadotropin/antibody immune complexes. (United States)

    Wehbi, Vanessa; Decourtye, Jérémy; Piketty, Vincent; Durand, Guillaume; Reiter, Eric; Maurel, Marie-Christine


    The injection of equine chorionic gonadotropin (eCG) in dairy goats induces the production of anti-eCG antibodies (Abs) in some females. We have previously shown that Abs negatively modulate the LH and FSH-like bioactivities of eCG, in most cases, compromising fertility in treated females. Surprisingly, we found out that some anti-eCG Abs improved fertility and prolificity of the treated females, in vivo. These Abs, when complexed with eCG, enhanced LH and FSH ability to induce steroidogenesis on specific target cells, in vitro. In the present study, we analyzed the impact of three eCG/anti-eCG Ab-enhancing complexes on two transduction mechanisms triggered by the FSH receptor: guanine nucleotide-binding protein alphaS-subunit/cAMP/protein kinase A (PKA) and beta-arrestin-dependent pathways, respectively. In all cases, significant enhancing effects were observed on ERK phosphorylation compared with eCG alone. However, cAMP production and PKA activation induced by eCG could be differently modulated by Abs. By using a pharmacological inhibitor of PKA and small interfering RNA-mediated knock-down of endogenous beta-arrestin 1 and 2, we demonstrated that signaling bias was induced and was clearly dependent on the complexed Ab. Together, our data show that eCG/anti-eCG Ab-enhancing complexes can differentially modulate cAMP/PKA and beta-arrestin pathways as a function of the complexed Ab. We hypothesize that enhancing Abs may change the eCG conformation, the immune complex acquiring new "biased" pharmacological properties ultimately leading to the physiological effects observed in vivo. The modulation of ligand pharmacological properties by Abs opens promising research avenues towards the optimization of glycoprotein hormone biological activities and, more generally, the development of new therapeutics.

  14. Mycobacterium tuberculosis PE25/PPE41 protein complex induces activation and maturation of dendritic cells and drives Th2-biased immune responses. (United States)

    Chen, Wei; Bao, Yige; Chen, Xuerong; Burton, Jeremy; Gong, Xueli; Gu, Dongqing; Mi, Youjun; Bao, Lang


    Mycobacterium tuberculosis evades innate host immune responses by parasitizing macrophages and causes significant morbidity and mortality around the world. A mycobacterial antigen that can activate dendritic cells (DCs) and elicit effective host innate immune responses will be vital to the development of an effective TB vaccine. The M. tuberculosis genes PE25/PPE41 encode proteins which have been associated with evasion of the host immune response. We constructed a PE25/PPE41 complex gene via splicing by overlapping extension and expressed it successfully in E. coli. We investigated whether this protein complex could interact with DCs to induce effective host immune responses. The PE25/PPE41 protein complex induced maturation of isolated mouse DCs in vitro, increasing expression of cell surface markers (CD80, CD86 and MHC-II), thereby promoting Th2 polarization via secretion of pro-inflammatory cytokines IL-4 and IL-10. In addition, PE25/PPE41 protein complex-activated DCs induced proliferation of mouse CD4(+) and CD8(+) T cells, and a strong humoral response in immunized mice. The sera of five TB patients were also highly reactive to this antigen. These findings suggest that interaction of the PE25/PPE41 protein complex with DCs may be of great immunological significance.

  15. Circulating Extracellular microRNA in Systemic Autoimmunity

    DEFF Research Database (Denmark)

    Heegaard, Niels H. H.; Carlsen, Anting Liu; Skovgaard, Kerstin


    MicroRNAs (miRNAs) are differentially regulated in healthy, activated, inflamed, neoplastic, or otherwise pathological cells and tissues. While their main functions are executed intracellularly, many miRNAs can reproducibly be detected extracellularly in plasma and serum. This circulating......, extracellular miRNA is protected against degradation by complexation with carrier proteins and/or by being enclosed in subcellular membrane vesicles. This, together with their tissue- and disease-specific expression, has fuelled the interest in using circulating microRNA profiles as harbingers of disease, i.......e., as diagnostic analytes and as clues to dysregulated pathways in disease. Many studies show that inflammation and immune dysregulation, e.g., in autoimmune diseases, are associated with distinct miRNA expression changes in targeted tissues and in innate and adaptive immunity cells such as lymphocytes, natural...

  16. Immobilized surfactant-nanotube complexes support selectin-mediated capture of viable circulating tumor cells in the absence of capture antibodies. (United States)

    Mitchell, Michael J; Castellanos, Carlos A; King, Michael R


    The metastatic spread of tumor cells from the primary site to anatomically distant organs leads to a poor patient prognosis. Increasing evidence has linked adhesive interactions between circulating tumor cells (CTCs) and endothelial cells to metastatic dissemination. Microscale biomimetic flow devices hold promise as a diagnostic tool to isolate CTCs and develop metastatic therapies, utilizing E-selectin (ES) to trigger the initial rolling adhesion of tumor cells under flow. To trigger firm adhesion and capture under flow, such devices also typically require antibodies against biomarkers thought to be expressed on CTCs. This approach is challenged by the fact that CTCs are now known to exhibit heterogeneous expression of conventional biomarkers. Here, we describe surfactant-nanotube complexes to enhance ES-mediated capture and isolation of tumor cells without the use of capture antibodies. While the majority of tumor cells exhibited weaker rolling adhesion on halloysite nanotubes (HNT) coated with ES, HNT functionalization with the sodium dodecanoate (NaL) surfactant induced a switch to firm cellular adhesion under flow. Conversely, surfactant-nanotube complexes significantly reduced the number of primary human leukocytes captured via ES-mediated adhesion under flow. The switch in tumor cell adhesion was exploited to capture and isolate tumor cells in the absence of EpCAM antibodies, commonly utilized as the gold standard for CTC isolation. Additionally, HNT-NaL complexes were shown to capture tumor cells with low to negligible EpCAM expression, that are not efficiently captured using conventional approaches.

  17. Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment. (United States)

    Phillips, Dennis R; Clark, Kevin D


    The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms.

  18. Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment (United States)

    Phillips, Dennis R.


    The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms. PMID:28199361

  19. Patients with inflammatory arthritic diseases harbor elevated serum and synovial fluid levels of free and immune-complexed glucose-6-phosphate isomerase (G6PI)

    DEFF Research Database (Denmark)

    Schaller, Monica; Stohl, William; Benoit, Vivian


    in the sera of most immune-based inflammatory arthritis patients are elevated and may reflect ongoing inflammation and cell destruction. The high serum levels of enzymatically inactive forms of G6PI in RA relative to those in other arthritic diseases are partially due to G6PI-containing immune complexes...... arthritides, serum and SF obtained concomitantly from 91 clinically well-defined arthritis patients were assessed in a blinded manner for G6PI enzymatic assay and for G6PI protein concentration by ELISA. Sera and SF from patients with immune-based inflammatory arthritis contained significantly higher levels...

  20. Design of Complex Systems to Achieve Passive Safety: Natural Circulation Cooling of Liquid Salt Pebble Bed Reactors


    Scarlat, Raluca Olga


    This dissertation treats system design, modeling of transient system response, and characterization of individual phenomena and demonstrates a framework for integration of these three activities early in the design process of a complex engineered system. A system analysis framework for prioritization of experiments, modeling, and development of detailed design is proposed. Two fundamental topics in thermal-hydraulics are discussed, which illustrate the integration of modeling and experimentat...

  1. Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity (United States)

    Zhang, Jing; Rouillon, Christophe; Kerou, Melina; Reeks, Judith; Brugger, Kim; Graham, Shirley; Reimann, Julia; Cannone, Giuseppe; Liu, Huanting; Albers, Sonja-Verena; Naismith, James H; Spagnolo, Laura; White, Malcolm F


    Summary The prokaryotic Clusters of Regularly Interspaced Palindromic Repeats (CRISPR) system utilizes genomically-encoded CRISPR RNA (crRNA), derived from invading viruses and incorporated into ribonucleoprotein complexes with CRISPR-associated (CAS) proteins, to target and degrade viral DNA or RNA on subsequent infection. RNA is targeted by the CMR complex. In Sulfolobus solfataricus, this complex is composed of seven CAS protein subunits (Cmr1-7) and carries a diverse “payload” of targeting crRNA. The crystal structure of Cmr7 and low resolution structure of the complex are presented. S. solfataricus CMR cleaves RNA targets in an endonucleolytic reaction at UA dinucleotides. This activity is dependent on the 8-nucleotide repeat-derived 5′ sequence in the crRNA, but not on the presence of a proto-spacer associated motif (PAM) in the target. Both target and guide RNAs can be cleaved, although a single molecule of guide RNA can support the degradation of multiple targets. PMID:22227115

  2. Post-transplant immune complex nephritis in a patient with systemic lupus erythematosus associated with ANCA vasculitis. (United States)

    Sanchez, Carlos; Rebolledo, Alejandra; Gahona, Junior; Rojas, Mauricio; Jiménez, Raquel; Bojórquez, Aurora


    Nearly 20% of SLE corresponds to the pediatric population, and 75% of them have kidney involvement representing an important etiology of chronic kidney disease. A correlation between SLE and ANCA-associated vasculitis has been identified as an overlapping syndrome. Kidney allograft recurrence is rare in SLE when disease control is achieved and with nowadays immunosuppression treatment. Histologic transformation is unusual, especially when there are negative serologic markers and no immune complex deposition reported in native kidneys. A 17-year-old female with crescentic glomerulonephritis, p-ANCA-positive antibodies with pauci-immune pattern in kidney biopsy develops end-stage renal disease requiring hemodialysis. Deceased donor kidney transplant was performed receiving triple immunosuppression thereafter. Thirteen months later serum creatinine rises without evidence of infection, urinary obstruction, or clinical and serologic disease relapse. Allograft biopsy reports mesangial proliferation and "full-house" immunofluorescence. The role of ANCA in SLE physiopathology is controversial, and its relation with lupus nephritis is also discordant. ANCA could represent an important factor in the heterogeneity of systemic lupus erythematosus and lupus nephritis.

  3. The Structure of the Toxin and Type Six Secretion System Substrate Tse2 in Complex with Its Immunity Protein. (United States)

    Robb, Craig S; Robb, Melissa; Nano, Francis E; Boraston, Alisdair B


    Tse2 is a cytoactive toxin secreted by a type six secretion apparatus of Pseudomonas aeruginosa. The Tse2 toxin naturally attacks a target in the cytoplasm of bacterial cells, and can cause toxicity if artificially introduced into eukaryotic cells. The X-ray crystal structure of the complex of Tse2 and its cognate immunity protein Tsi2 revealed a heterotetrameric structure with an extensive binding interface. Structural identity was found between Tse2 and NAD-dependent enzymes, especially ADP-ribosylating toxins, which facilitated the identification of the Tse2 active site and revealed it to be occluded upon binding the inhibitor Tsi2. The structural identity shared with NAD-dependent enzymes, including conserved catalytic residues, suggests that the mechanism of Tse2 toxicity may be NAD dependent.

  4. Diagnosis of human immunodeficiency virus type 1 infection in infants by immune complex dissociation p24 assay. (United States)

    Paul, M O; Toedter, G; Hofheinz, D; Tetali, S; Pelton, S; Marecki, M; Brena, A; Abrams, E J; Landesman, S; Pahwa, S


    Using immune complex dissociation (ICD), we retrospectively examined serum and plasma of 206 infants aged 0 to 4 months who were perinatally exposed to human immunodeficiency virus (HIV). All samples were analyzed in a blinded manner. Infection status was determined based on the results of HIV culture and Centers for Disease Control and Prevention classification. The overall diagnostic sensitivity of the assay was 59% (93 samples, 73 infants), and specificity was 100% (160 samples, 133 infants). When the samples were analyzed according to age, sensitivity was highest at age 1 to 2 months (17 of 21 infants, 81%). Sensitivities at other ages were 53% at 80% at 1 to 2 months of age and 100% specificity, as evaluated, up to 4 months of age.

  5. The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies

    Energy Technology Data Exchange (ETDEWEB)

    Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.; Ivanova, N.; Francino, P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland,A.; Detter, J.C.; Land, M.; Richardson, P.M.; Yu, X.J.; Walker, D.H.; McBride, J.W.; Kyrpides, N.C.


    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, a-proteobacterium is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, and 17 putative pseudogenes, and a substantial proportion of non-coding sequence (27 percent). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences, and a unique serine-threonine bias associated with the potential for O-glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly G:C tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Proteins associated with pathogen-host interactions were identified including a small group of proteins (12) with tandem repeats and another with eukaryotic-like ankyrin domains (7).

  6. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease. (United States)

    Cornell, Lynn D; Chicano, Sonia L; Deshpande, Vikram; Collins, A Bernard; Selig, Martin K; Lauwers, Gregory Y; Barisoni, Laura; Colvin, Robert B


    Autoimmune pancreatitis (AIP) is a mass-forming chronic fibroinflammatory condition centered on the pancreatobiliary system and characterized by predominant immunoglobulin G4 (IgG4)-positive plasma cells. Recent reports have brought to light the multiorgan involvement of this disease. We describe a series of 5 cases of tubulointerstitial nephritis (TIN) associated with AIP and characterize the clinical, pathologic, ultrastructural, and immunopathologic features of TIN. The specimens consisted of 4 biopsies and 1 nephrectomy. The average patient age was 64 years (range 45 to 78) and the male to female ratio was 4:1. All had histologic and/or clinical and radiographic evidence of AIP, mass-forming sclerosing cholangitis, or both. The clinical impression in 4 patients was a renal mass or vasculitis. Two patients had renal insufficiency. Histologic preparations revealed a dense tubulointerstitial lymphoplasmacytic infiltrate. Eosinophils were often numerous. Tubulitis and tubular injury were present, along with tubular atrophy with focally thickened tubular basement membranes (TBMs). The histologic appearance ranged from a cellular, inflammatory pattern without tubular atrophy to a striking expansive interstitial fibrosis with tubular destruction. The nephrectomy specimen demonstrated a masslike nodular pattern of inflammation with normal renal tissue elsewhere. Glomeruli were uninvolved. By immunohistochemistry or immunofluorescence, numerous plasma cells in the infiltrate were positive for IgG4. TBM granular IgG deposits, predominantly of the IgG4 subclass, were detected in 4 of 5 cases by either immunofluorescence or immunohistochemistry. By electron microscopy, corresponding amorphous electron-dense deposits were present in the TBM in these cases. This type of TIN, typically characterized by a masslike lesion consisting of a lymphoplasmacytic infiltrate with eosinophils and prominent IgG4-positive plasma cells and immune-complex deposits in the TBM, may be part of

  7. Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake. (United States)

    Willcocks, Lisa C; Lyons, Paul A; Clatworthy, Menna R; Robinson, James I; Yang, Wanling; Newland, Stephen A; Plagnol, Vincent; McGovern, Naomi N; Condliffe, Alison M; Chilvers, Edwin R; Adu, Dwomoa; Jolly, Elaine C; Watts, Richard; Lau, Yu Lung; Morgan, Ann W; Nash, Gerard; Smith, Kenneth G C


    Copy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcgammaRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcgammaRIIIb-deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcgammaRIIIb. Reduced FcgammaRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility.

  8. The immunity of the ICMS (Circulation Tax) on interstate operations involving natural gas; Da imunidade do ICMS (Imposto sobre Circulacao de Mercadorias e Servicos) em operacoes interestaduais envolvendo gas natural

    Energy Technology Data Exchange (ETDEWEB)

    Yvy, Maytta A.S.; Galvao, Katia C.P.; Mendonca, Fabiano A.S. [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Faculdade de Direito


    The Federal Constitution of Brazil, in the article 155, para. 2nd, X, b, determines that there will not be Circulation Taxs (ICMS) over operations that destinates to other States petroleum, including lubricants, liquid and gaseous fuels of him derived. It establishes, therefore, hypothesis of tributary immunity. However, the interpretation of this rule in the juridical scenery is rounded by doubts. There are two possible interpretations: or the natural gas is included in this hypothesis of tributary immunity, considering it is a derived gaseous fuel of the petroleum or, in the other hand, it is not included in the hypothesis, since it is not admitted as a petroleum product. Using not juridical interpretative elements and using constitutional principles and interpretative rules, the conclusion is that the natural gas doesn't integrate the normative hypothesis, in view that the opposite comprehension would surpass the meaning of the norm in exam, falling in inconstitutionality. However, having in mind the convenience of enlarging the natural gas participation in the national energy head office, the possibility of granting tributary discharge through exemption of ICMS over operations between States involving natural gas is open. (author)

  9. Circulating Biomarkers of Immune Activation Distinguish Viral Suppression from Nonsuppression in HAART-Treated Patients with Advanced HIV-1 Subtype C Infection

    Directory of Open Access Journals (Sweden)

    Glen Malherbe


    Full Text Available Few studies have examined immune activation profiles in patients with advanced HIV-1 subtype C infection or assessed their potential to predict responsiveness to HAART. BioPlex, ELISA, and nephelometric procedures were used to measure plasma levels of inflammatory biomarkers in HIV-1 subtype C-infected patients sampled before and after 6 months of successful HAART (n=20; in patients failing HAART (n=30; and in uninfected controls (n=8. Prior to HAART, CXCL9, CXCL10, β2M, sTNF-R1, TGF-β1, IFN-γ, IL-6, TNF, and sCD14 were significantly elevated in HIV-1-infected patients compared to controls (P<0.01. All of these markers, with the exception of sTNF-R1, were also elevated in patients failing HAART (P<0.05. The persistently elevated levels of CXCL9, CXCL10, and β2M in patients failing therapy in the setting of a marked reduction in these markers in patients on successful HAART suggest that they may be useful not only to monitor immune activation during HAART, but also to distinguish between good and poor responders. In the case of sCD14 and TGF-β1, the levels of these biomarkers remained persistently elevated despite HAART-induced virological suppression, a finding that is consistent with ongoing monocyte-macrophage activation, underscoring a potential role for adjuvant anti-inflammatory therapy.

  10. Cation-anionicpalladium Complexes- New Types of Antitumor, Immune Response-modulating and Radioprotective Agents

    Institute of Scientific and Technical Information of China (English)



    Here we report results of our investigations of new class of bioactive palladium compounds (AHn)m[PdC14],which were discovered as a result of systematic study of correlations between composition,structure and bioactivity of different types of platinum metals coordination compounds.For the first time we demonstrated in vivoa possibility of development of palladium compounds,which exceed cisplatin in antitumor activity and do not show immunosuppressive effects,and palladium compounds with immunostimulating and radioprotective activities.Combinations of cytostatic agents or radiation with palladium complexes lead to significant synergism of their activities and high therapeutic efficiency exceeded an efficiency of their separated use.

  11. Inferring selection in the Anopheles gambiae species complex: an example from immune-related serine protease inhibitors

    Directory of Open Access Journals (Sweden)

    Little Tom J


    Full Text Available Abstract Background Mosquitoes of the Anopheles gambiae species complex are the primary vectors of human malaria in sub-Saharan Africa. Many host genes have been shown to affect Plasmodium development in the mosquito, and so are expected to engage in an evolutionary arms race with the pathogen. However, there is little conclusive evidence that any of these mosquito genes evolve rapidly, or show other signatures of adaptive evolution. Methods Three serine protease inhibitors have previously been identified as candidate immune system genes mediating mosquito-Plasmodium interaction, and serine protease inhibitors have been identified as hot-spots of adaptive evolution in other taxa. Population-genetic tests for selection, including a recent multi-gene extension of the McDonald-Kreitman test, were applied to 16 serine protease inhibitors and 16 other genes sampled from the An. gambiae species complex in both East and West Africa. Results Serine protease inhibitors were found to show a marginally significant trend towards higher levels of amino acid diversity than other genes, and display extensive genetic structuring associated with the 2La chromosomal inversion. However, although serpins are candidate targets for strong parasite-mediated selection, no evidence was found for rapid adaptive evolution in these genes. Conclusion It is well known that phylogenetic and population history in the An. gambiae complex can present special problems for the application of standard population-genetic tests for selection, and this may explain the failure of this study to detect selection acting on serine protease inhibitors. The pitfalls of uncritically applying these tests in this species complex are highlighted, and the future prospects for detecting selection acting on the An. gambiae genome are discussed.

  12. Constraints on the Lost City Hydrothermal System from borehole thermal data; 3-D models of heat flow and hydrothermal circulation in an oceanic core complex. (United States)

    Titarenko, S.; McCaig, A. M.


    A perennial problem in near-ridge hydrothermal circulation is that the only directly measurable data to test models is often vent fluid temperature. Surface heat flow measurements may be available but without the underlying thermal structure it is not known if they are transient and affected by local hydrothermal flow, or conductive. The Atlantis Massif oceanic core complex at 30 °N on the mid-Atlantic Ridge, offers a unique opportunity to better constrain hydrothermal circulation models. The temperature profile in gabbroic rocks of IODP Hole 1309D was measured in IODPExpedition 340T, and found to be near-conductive, but with a slight inflexion at ~750 mbsf indicating downward advection of fluid above that level. The lack of deep convection is especially remarkable given that the long-lived Lost City Hydrothermal Field (LCHF) is located only 5km to the south. We have modelled hydrothermal circulation in the Massif using Comsol Multiphysics, comparing 2-D and 3-D topographic models and using temperature-dependent conductivity to give the best estimate of heatflow into the Massif. We can constrain maximum permeability in gabbro below 750 mbsf to 5e-17 m2. The thermal gradient in the upper part of the borehole can be matched with a permeability of 3e-14 m2 in a 750 m thick layer parallel to the surface of the massif, with upflow occurring in areas of high topography and downflow at the location of the borehole. However in 3-D the precise flow pattern is quite model dependent, and the thermal structure can be matched either by downflow centred on the borehole at lower permeability or centred a few hundred metres from the borehole at higher permeability. The borehole gradient is compatible with the longevity (>120 kyr) and outflow temperature (40-90 °C) of the LCHF either with a deep more permeable (1e-14 m2 to 1e-15 m2) domain beneath the vent site in 2-D or a permeable fault slot 500 to 1000m wide and parallel to the transform fault in 3-D. In both cases topography

  13. High Titers of Circulating Maternal Antibodies Suppress Effector and Memory B-Cell Responses Induced by an Attenuated Rotavirus Priming and Rotavirus-Like Particle-Immunostimulating Complex Boosting Vaccine Regimen (United States)

    Nguyen, Trang V.; Yuan, Lijuan; Azevedo, Marli S. P.; Jeong, Kwang-il; Gonzalez, Ana M.; Iosef, Cristiana; Lovgren-Bengtsson, Karin; Morein, Bror; Lewis, Peggy; Saif, Linda J.


    We investigated maternal antibody (MatAb) effects on protection and immune responses to rotavirus vaccines. Gnotobiotic pigs were injected intraperitoneally at birth with pooled serum from sows hyperimmunized with human rotavirus (HRV); control pigs received no sow serum. Pigs with or without MatAbs received either sequential attenuated HRV (AttHRV) oral priming and intranasal boosting with VP2/VP6 virus-like particle (VLP)-immunostimulating complex (ISCOM) (AttHRV/VLP) or intranasal VLP-ISCOM prime/boost (VLP) vaccines at 3 to 5 days of age. Subsets of pigs were challenged at 28 or 42 days postinoculation with virulent Wa HRV to assess protection. Isotype-specific antibody-secreting cell (ASC) responses to HRV were quantitated by enzyme-linked immunospot assay to measure effector and memory B-cell responses in intestinal and systemic lymphoid tissues pre- and/or postchallenge. Protection rates against HRV challenge (contributed by active immunity and passive circulating MatAbs) were consistently (but not significantly) lower in the MatAb-AttHRV/VLP groups than in the corresponding groups without MatAbs. Intestinal B-cell responses in the MatAb-AttHRV/VLP group were most suppressed with significantly reduced or no intestinal immunoglobulin A (IgA) and IgG effector and memory B-cell responses or antibody titers pre- and postchallenge. This suppression was not alleviated but was enhanced after extending vaccination/challenge from 28 to 42 days. In pigs vaccinated with nonreplicating VLP alone that failed to induce protection, MatAb effects differed, with intestinal and systemic IgG ASCs and prechallenge memory B cells suppressed but the low intestinal IgA and IgM ASC responses unaffected. Thus, we demonstrate that MatAbs differentially affect both replicating and nonreplicating HRV vaccines and suggest mechanisms of MatAb interference. This information should facilitate vaccine design to overcome MatAb suppression. PMID:16603615


    Directory of Open Access Journals (Sweden)

    V. N. Zorina


    Full Text Available Abstract. We investigated effects of combined oral contraceptives (COC containing low- and microdoses of estrogenic components upon serum levels of macroglobulin family proteins (alpha-2-macroglobulin, α2-MG, and pregnancy-associated alpha-2-glycoprotein, α2-PAG, their immune complexes with IgG, as well as concentrations of some cytokines (IL-1β, IL-6, TNFα, IFNγ. It was shown that cytokine levels did not differ with control, whereas α2-MG concentrations showed a time-dependent decrease in a group of women taking COC with microdoses of estrogens, and α2-PAG levels increased tenfold, independent on dosage and time of COC application. Meanwhile, contents of PAG-IgG complexes exhibits a gradual decrease, along with increase in MG-IgG. Considering PAG as a marker of normal and malignant proliferation, we suggest, that the levels of α2-PAG may be useful in monitoring of women taking COC, in order to predict high risk of pathological  proliferation  by  evaluation  of  individuals with  elevated  α2-PAG  levels.  (Med.  Immunol.,  2011, vol. 13, N 6, pp 635-638 

  15. CRISPR-Cas Adaptive Immune Systems of the Sulfolobales: Unravelling Their Complexity and Diversity

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    Roger A. Garrett


    Full Text Available The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive structural and functional diversity. They carry large and multiple CRISPR loci and often multiple copies of diverse Type I and Type III interference modules as well as more homogeneous adaptation modules. These acidothermophilic organisms have recently provided seminal insights into both the adaptation process, the diverse modes of interference, and their modes of regulation. The functions of the adaptation and interference modules tend to be loosely coupled and the stringency of the crRNA-DNA sequence matching during DNA interference is relatively low, in contrast to some more streamlined CRISPR-Cas systems of bacteria. Despite this, there is evidence for a complex and differential regulation of expression of the diverse functional modules in response to viral infection. Recent work also supports critical roles for non-core Cas proteins, especially during Type III-directed interference, and this is consistent with these proteins tending to coevolve with core Cas proteins. Various novel aspects of CRISPR-Cas systems of the Sulfolobales are considered including an alternative spacer acquisition mechanism, reversible spacer acquisition, the formation and significance of antisense CRISPR RNAs, and a novel mechanism for avoidance of CRISPR-Cas defense. Finally, questions regarding the basis for the complexity, diversity, and apparent redundancy, of the intracellular CRISPR-Cas systems are discussed.

  16. Characteristic expression of major histocompatibility complex and immune privilege genes in human pluripotent stem cells and their derivatives. (United States)

    Chen, Hsin-Fu; Yu, Chun-Ying; Chen, Mei-Jou; Chou, Shiu-Huey; Chiang, Ming-Shan; Chou, Wen-Hsi; Ko, Bor-Sheng; Huang, Hsiang-Po; Kuo, Hung-Chih; Ho, Hong-Nerng


    Pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), have been regarded as useful sources for cell-based transplantation therapy. However, immunogenicity of the cells remains the major determinant for successful clinical application. We report the examination of several hESC lines (NTU1 and H9), hiPSC lines, and their derivatives (including stem cell-derived hepatocytes) for the expression of major histocompatibility complex (MHC), natural killer (NK) cell receptor (NKp30, NKp44, NKp46) ligand, immune-related genes, human leukocyte antigen (HLA) haplotyping, and the effects in functional mixed lymphocyte reaction (MLR). Flow cytometry showed lower levels (percentages and fluorescence intensities) of MHC class I (MHC-I) molecules, β2-microglobulin, and HLA-E in undifferentiated stem cells. The levels were increased after cotreatment with interferon-γ and/or in vitro differentiation. Antigen-presenting cell markers (CD11c, CD80, and CD86) and MHC-II (HLA-DP, -DQ, and -DR) remained low throughout the treatments. Recognition of stem cells/derivatives by NK lysis receptors were lower or absent. Activation of responder lymphocytes was significantly lower by undifferentiated stem cells than by allogeneic lymphocytes in MLR, but differentiated NTU1 hESCs induced a cell number-dependent lymphocyte proliferation comparable with that by allogeneic lymphocytes. Interestingly, activation of lymphocytes by differentiated hiPSCs or H9 cells became blunted at higher cell numbers. Real-time reverse transcriptase PCR (RT-PCR) showed significant differential expression of immune privilege genes (TGF-β2, Arginase 2, Indole 1, GATA3, POMC, VIP, CALCA, CALCB, IL-1RN, CD95L, CR1L, Serpine 1, HMOX1, IL6, LGALS3, HEBP1, THBS1, CD59, and LGALS1) in pluripotent stem cells/derivatives when compared to somatic cells. It was concluded that pluripotent stem cells/derivatives are predicted to be immunogenic, though evidence suggests

  17. A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes (United States)

    Sulaiman, Azad A.; Zolnierczyk, Katarzyna; Japa, Ornampai; Owen, Jonathan P.; Maddison, Ben C.; Hodgkinson, Jane E.; Gough, Kevin C.


    effector response targeting juvenile parasites which we demonstrate extends to an abrogation of the ADCC response. Thus suggesting that FhTLM is a stage specific evasion molecule that utilises host cytokine receptors. These findings are the first to clearly demonstrate the interaction of a helminth cytokine with a host receptor complex resulting in immune modifications that facilitate the non-protective chronic immune response which is characteristic of F. hepatica infection. PMID:27806135

  18. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S


    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...... an inverse correlation between anti-dsDNA antibodies and the DNA concentration in the circulation in both murine and human serum samples. High titer of anti-DNA antibodies in human sera correlated with reduced levels of circulating chromatin, and in lupus prone mice with deposition within glomeruli....... The inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect...

  19. Impact of Universal Hepatitis B Vaccination on Prevalence, Infection-Associated Morbidity and Mortality, and Circulation of Immune Escape Variants in Russia (United States)

    Klushkina, Vitalina V.; Kyuregyan, Karen K.; Kozhanova, Tatiana V.; Popova, Oksana E.; Dubrovina, Polina G.; Isaeva, Olga V.; Gordeychuk, Ilya V.; Mikhailov, Mikhail I.


    Vaccination of newborns against hepatitis B (HB) was introduced in Russia in 1998. Since then the incidence of acute HB has rapidly declined. However, prevalence of chronic HB remains stable. The aim of this study was to estimate the effect of vaccination on HBV-associated morbidity, and to assess the prevalence of HBV immune escape variants after 10 years of vaccination. Methods 6,217 sera samples collected from volunteers in six epidemiologically different regions of Russia were tested for serological and molecular markers of HBV infection. A mathematical model developed by the U.S. Centers for Disease Control and Prevention was used to estimate the effect of vaccination and birth dose coverage on the incidence of HB and adverse outcomes of infection. Results Prevalence of HBsAg in the study population varied from 1.2% to 8.2%; anti-HBc detection rates were 13.0–46.2%. HBsAg detection rates in epidemiologically significant cohorts were 0.6–10.5% in women of childbearing age; 0–2.4% in children ≤5 years old; 1.9–8.1% in adults ≥30 years old. Mathematical modeling demonstrated that the current 96.1–99.6% level of birth dose coverage increased the effectiveness of vaccination 10–21 times compared to 50% and 0% birth dose coverage scenarios. HBV DNA was detected in 63 sera samples. The frequency of amino acid substitutions in HBsAg was 38% (24/63). Only in 3% (2/63) the mutations were within the a-determinant of HBsAg (M133T and G145S, one case each). None of the identified mutations eluded HBsAg detection, since all these samples tested positive for HBsAg by commercial ELISA. Conclusion Despite a significant decline in acute HB incidence after the introduction of universal vaccination, many undiagnosed potential sources of infection remain. Low prevalence of HBV immune escape variants is a favorable predictor of vaccine effectiveness in the future. PMID:27280884

  20. Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte death and matrix-metalloproteinase-mediated cartilage matrix degradation despite enhanced joint inflammation.

    NARCIS (Netherlands)

    Nabbe, K.C.A.M.; Lent, P.L.E.M. van; Holthuysen, A.E.M.; Sloetjes, A.W.; Koch, A.E.; Radstake, T.R.D.J.; Berg, W.B. van den


    During immune-complex-mediated arthritis (ICA), severe cartilage destruction is mediated by Fcgamma receptors (FcgammaRs) (mainly FcgammaRI), cytokines (e.g. IL-1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2) cytokine abundantly found in synovial fluid of patients with

  1. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    Directory of Open Access Journals (Sweden)

    Shunying Jin

    Full Text Available Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC deposition-induced acute lung injury (ALI. Components of gamma amino butyric acid (GABA signaling, including GABA B receptor 2 (GABABR2, GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP, in the bronchoalveolar lavage fluid (BALF. Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting

  2. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators. (United States)

    Jin, Shunying; Merchant, Michael L; Ritzenthaler, Jeffrey D; McLeish, Kenneth R; Lederer, Eleanor D; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T; Lentsch, Alex B; Roman, Jesse; Klein, Jon B; Rane, Madhavi J


    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a

  3. The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following different administration routes. (United States)

    Ge, Wei; Hu, Pei-Zhen; Huang, Yang; Wang, Xiao-Ming; Zhang, Xiu-Min; Sun, Yu-Jing; Li, Zeng-Shan; Si, Shao-Yan; Sui, Yan-Fang


    Our previous study showed that nanoemulsion-encapsulated MAGE1-HSP70/SEA (MHS) complex protein vaccine elicited MAGE-1 specific immune response and antitumor effects against MAGE-1-expressing tumor and nanoemulsion is a useful vehicle with possible important implications for cancer biotherapy. The purpose of this study was to compare the immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70 and SEA as NE(MHS) vaccine following different administration routes and to find out the new and effective immune routes. Nanoemulsion vaccine was prepared using magnetic ultrasound methods. C57BL/6 mice were immunized with NE(MHS) via po., i.v., s.c. or i.p., besides mice s.c. injected with PBS or NE(-) as control. The cellular immunocompetence was detected by ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were also examined. The results showed that the immune responses against MAGE-1 expressing murine tumors elicited by NE(MHS) via 4 different routes were approximately similar and were all stronger than that elicited by PBS or NE(-), suggesting that this novel nanoemulsion carrier can exert potent antitumor immunity against antigens encapsulated in it. Especially, the present results indicated that nanoemulsion vaccine adapted to administration via different routes including peroral, and may have broader applications in the future.

  4. Generation of a CRISPR database for Yersinia pseudotuberculosis complex and role of CRISPR-based immunity in conjugation. (United States)

    Koskela, Katja A; Mattinen, Laura; Kalin-Mänttäri, Laura; Vergnaud, Gilles; Gorgé, Olivier; Nikkari, Simo; Skurnik, Mikael


    The clustered regularly interspaced short palindromic repeat - CRISPR-associated genes (CRISPR-Cas) system is used by bacteria and archaea against invading conjugative plasmids or bacteriophages. Central to this immunity system are genomic CRISPR loci that contain fragments of invading DNA. These are maintained as spacers in the CRISPR loci between direct repeats and the spacer composition in any bacterium reflects its evolutionary history. We analysed the CRISPR locus sequences of 335 Yersinia pseudotuberculosis complex strains. Altogether 1902 different spacer sequences were identified and these were used to generate a database for the spacer sequences. Only ∼10% of the spacer sequences found matching sequences. In addition, surprisingly few spacers were shared by Yersinia pestis and Y. pseudotuberculosis strains. Interestingly, 32 different protospacers were present in the conjugative plasmid pYptb32953. The corresponding spacers were identified from 35 different Y. pseudotuberculosis strains indicating that these strains had encountered pYptb32953 earlier. In conjugation experiments, pYptb32953-specific spacers generally prevented conjugation with spacer-positive and spacer-free strains. However, some strains with one to four spacers were invaded by pYptb32953 and some spacer-free strains were fully resistant. Also some spacer-positive strains were intermediate resistant to conjugation. This suggests that one or more other defence systems are determining conjugation efficiency independent of the CRISPR-Cas system.

  5. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient (United States)

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine


    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

  6. Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex-mediated inflammation in mice. (United States)

    Gros, Angèle; Syvannarath, Varouna; Lamrani, Lamia; Ollivier, Véronique; Loyau, Stéphane; Goerge, Tobias; Nieswandt, Bernhard; Jandrot-Perrus, Martine; Ho-Tin-Noé, Benoît


    Platelets protect vascular integrity during inflammation. Recent evidence suggests that this action is independent of thrombus formation and requires the engagement of glycoprotein VI (GPVI), but it remains unclear how platelets prevent inflammatory bleeding. We investigated whether platelets and GPVI act primarily by preventing detrimental effects of neutrophils using models of immune complex (IC)-mediated inflammation in mice immunodepleted in platelets and/or neutrophils or deficient in GPVI. Depletion of neutrophils prevented bleeding in thrombocytopenic and GPVI(-/-) mice during IC-mediated dermatitis. GPVI deficiency did not modify neutrophil recruitment, which was reduced by thrombocytopenia. Neutrophil cytotoxic activities were reduced in thrombocytopenic and GPVI(-/-) mice during IC-mediated inflammation. Intravital microscopy revealed that in this setting, intravascular binding sites for platelets were exposed by neutrophils, and GPVI supported the recruitment of individual platelets to these spots. Furthermore, the platelet secretory response accompanying IC-mediated inflammation was partly mediated by GPVI, and blocking of GPVI signaling impaired the vasculoprotective action of platelets. Together, our results show that GPVI plays a dual role in inflammation by enhancing neutrophil-damaging activities while supporting the activation and hemostatic adhesion of single platelets to neutrophil-induced vascular breaches.

  7. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Tracey Salter


    Full Text Available Hepatitis B virus (HBV presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

  8. Complement fixing hepatitis B core antigen immune complexes in the liver of patients with HBs antigen positive chronic disease. (United States)

    Rizzetto, M; Bonino, F; Crivelli, O; Canese, M G; Verme, G


    One hundred and fifty-two biopsies from serologically HBsAg positive and negative patients with liver disease were studied in immunofluorescence: for the presence of the surface (HBs) and the core (HBc) antigenic determinants foeterminants of the hepatitis B virus, of immunoglobulins and complement (C) deposits, and for the capacity to fix human C. Circumstantial evidence is presented suggesting that HBc immune-complexes are a relevant feature in the establishment and progression of chronic HBSAg liver disease. C fixation by liver cells was shown in all HBC positive patients with chronic hepatitis; an active form was present in every case, except two with a persistent hepatitis, an inverse ratio of HBc to C binding fluorescence being noted between active chronic hepatitis and cirrhotic patients. HBc without C fixation was observed in only three patients in the incubation phase of infectious hepatitis. IgG deposits were often found in HBc containing, C fixing nuclei. No C binding or IgG deposits were observed in acute self-limited type B hepatitis, in serologically positive patients with normal liver or minimal histological lesions, with and without HBs cytoplasmic fluorescence in their biopsy, or in serologically negative individuals. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1001973

  9. Flavonols modulate the effector functions of healthy individuals' immune complex-stimulated neutrophils: a therapeutic perspective for rheumatoid arthritis. (United States)

    Santos, Everton O L; Kabeya, Luciana M; Figueiredo-Rinhel, Andréa S G; Marchi, Larissa F; Andrade, Micássio F; Piatesi, Fabiana; Paoliello-Paschoalato, Adriana B; Azzolini, Ana Elisa C S; Lucisano-Valim, Yara M


    Rheumatoid arthritis (RA) patients usually exhibit immune complex (IC) deposition and increased neutrophil activation in the joint. In this study, we assessed how four flavonols (galangin, kaempferol, quercetin, and myricetin) modulate the effector functions of healthy individuals' and active RA patients' IC-stimulated neutrophils. We measured superoxide anion and total reactive oxygen species production using lucigenin (CL-luc)- and luminol (CL-lum)-enhanced chemiluminescence assays, respectively. Galangin, kaempferol, and quercetin inhibited CL-lum to the same degree (mean IC50=2.5 μM). At 2.5 μM, quercetin and galangin suppressed nearly 65% CL-lum of active RA patients' neutrophils. Quercetin inhibited CL-luc the most effectively (IC50=1.71±0.36 μM). The four flavonols diminished myeloperoxidase activity, but they did not decrease NADPH oxidase activity, phagocytosis, microbial killing, or cell viability of neutrophils. The ability of the flavonols to scavenge hypochlorous acid and chloramines, but not H2O2, depended on the hydroxylation degree of the flavonol B-ring. Therefore, at physiologically relevant concentrations, the flavonols partially inhibited the oxidative metabolism of IC-stimulated neutrophils without affecting the other investigated effector functions. Using these compounds to modulate IC-mediated neutrophil activation is a promising safe therapeutic strategy to control inflammation in active RA patients.

  10. Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Satoko Arai


    Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

  11. Chylous Ascites in a Patient with HIV/AIDS: A Late Complication of Mycobacterium avium Complex-Immune Reconstitution Inflammatory Syndrome

    Directory of Open Access Journals (Sweden)

    Imam H. Shaik


    Full Text Available Chylous ascites is very rare in HIV/AIDS and its association with Mycobacterium avium complex-immune reconstitution inflammatory syndrome (MAC-IRIS has been rarely reported. Here, we report a case of a young African-American male who developed chylous ascites as a late sequela to immune reconstitution inflammatory syndrome while on treatment for MAC. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV RNA level should be monitored for development of IRIS. Although the long term prognosis is poor, early diagnosis and treatment help to improve quality of life.

  12. M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement

    DEFF Research Database (Denmark)

    Frederiksen, Pernille Dorthea; Thiel, Steffen; Larsen, Claus Bindslev;


    Ficolins play a role in the innate immune defence as pathogen-associated molecular pattern recognition molecules. Three ficolins are found in humans: H-ficolin, L-ficolin and M-ficolin. L-ficolin and H-ficolin circulate in blood in complexes with mannan-binding lectin-associated serine proteases...

  13. Immune System and Disorders (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...


    Directory of Open Access Journals (Sweden)

    M. V. Chepeleva


    Full Text Available Purpose: To Study immune status in patients with coxarthrosis consequent to treatment of congenital hip dysplasia and Perthes' disease as well as to determine additional variables indicating arthrosis progression.Materials and methods: The authors analyzed results of preoperative immune examination of 13 male patients aged 11,4±0,7 years (10-13 with coxarthrosis of type I-II developed consequently to treatment of hip dysplasia and Perthes' disease. Based on obtained anatomical and functional outcomes the authors divided the patients into two groups. First group included 8 patients with postoperative improvement of joint function and absence of disease progression. Second group (5 patients was featured by functional deterioration and arthrosis advancing.Results: Patients of the second group demonstrated statistically significant elevation in certain parameters of humoral (circulating immune complex and cellular immunity (CD3+HLA-DR (%, CD3+HLA-DR (109/l as well as interleukin-6.Conclusion: Obtained results have proven that initial immune parameters (IL-6, circulating immune complex, lymphocytes with activation markers can be used as additional variables for decision making in regard to option and advisability of reconstructive joint preserving procedures in patients with coxarthrosis consequent to treatment of hip dysplasia and Perthes' disease.

  15. Immune Cells in Blood Recognize Tumors (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  16. VanderLaan Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Hongyan Pan


    Full Text Available Circulant matrices have become a satisfactory tools in control methods for modern complex systems. In the paper, VanderLaan circulant type matrices are presented, which include VanderLaan circulant, left circulant, and g-circulant matrices. The nonsingularity of these special matrices is discussed by the surprising properties of VanderLaan numbers. The exact determinants of VanderLaan circulant type matrices are given by structuring transformation matrices, determinants of well-known tridiagonal matrices, and tridiagonal-like matrices. The explicit inverse matrices of these special matrices are obtained by structuring transformation matrices, inverses of known tridiagonal matrices, and quasi-tridiagonal matrices. Three kinds of norms and lower bound for the spread of VanderLaan circulant and left circulant matrix are given separately. And we gain the spectral norm of VanderLaan g-circulant matrix.

  17. Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10.

    Directory of Open Access Journals (Sweden)

    Carmen A Ambarus

    Full Text Available BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-γ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs. Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MΦ(IL-4. In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2. The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10.

  18. Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Warner, R L


    The C-X-C chemokines of the IL-8 family possess potent chemotactic activity for neutrophils, but their in vivo role in inflammatory responses is not well understood. In the IgG immune complex-induced model of acute lung inflammatory injury in the rat we have evaluated the roles of two rat...... chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... by 125I-labeled albumin leakage from the pulmonary vasculature) and reduced neutrophil accumulation in the lung (as determined by myeloperoxidase (MPO content) and neutrophil counts in bronchoalveolar lavage (BAL) fluids); however, no change in TNF-alpha levels in BAL fluids was found. Chemotactic...

  19. Solubilization of immune complexes in complement factor deficient sera and the influence of temperature, ionic strength and divalent cations on the solubilization reaction

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Svehag, Svend-Erik;


    The complement-mediated solubilization (CMS) of immune complexes (IC) and the initial kinetics (IKS) of this reaction in human sera depleted of or deficient in C2, C3, C8, factors B, P and I were investigated. Sera depleted of B or P and those lacking native C3 or factor I showed virtually no CMS...... by a radioassay and kinetic data for the binding of C3b to preformed immune complexes. The CMS capacity reached maximum at 39-41 degrees C and at an ionic strength of approximately 0.20 mu. Selective chelation of Mg2+ completely abolished the CMS of IC. Maximal CMS was observed at Mg2+ concentration of about 2m...

  20. Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya (United States)


    Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya Walter Otieno1,2, Benson BA Estambale1...anemia. Children with sickle cell trait (HbAS) are less predisposed to getting severe manifestations of malaria. We carried out a study to determine the...2012 to 00-00-2012 4. TITLE AND SUBTITLE Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P

  1. SWR1 Chromatin-Remodeling Complex Subunits and H2A.Z Have Non-overlapping Functions in Immunity and Gene Regulation in Arabidopsis. (United States)

    Berriri, Souha; Gangappa, Sreeramaiah N; Kumar, S Vinod


    Incorporation of the histone variant H2A.Z into nucleosomes by the SWR1 chromatin remodeling complex is a critical step in eukaryotic gene regulation. In Arabidopsis, SWR1c and H2A.Z have been shown to control gene expression underlying development and environmental responses. Although they have been implicated in defense, the specific roles of the complex subunits and H2A.Z in immunity are not well understood. In this study, we analyzed the roles of the SWR1c subunits, PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1 (PIE1), ACTIN-RELATED PROTEIN6 (ARP6), and SWR1 COMPLEX 6 (SWC6), as well as H2A.Z, in defense and gene regulation. We found that SWR1c components play different roles in resistance to different pathogens. Loss of PIE1 and SWC6 function as well as depletion of H2A.Z led to reduced basal resistance, while loss of ARP6 fucntion resulted in enhanced resistance. We found that mutations in PIE1 and SWC6 resulted in impaired effector-triggered immunity. Mutation in SWR1c components and H2A.Z also resulted in compromised jasmonic acid/ethylene-mediated immunity. Genome-wide expression analyses similarly reveal distinct roles for H2A.Z and SWR1c components in gene regulation, and suggest a potential role for PIE1 in the regulation of the cross talk between defense signaling pathways. Our data show that although they are part of the same complex, Arabidopsis SWR1c components could have non-redundant functions in plant immunity and gene regulation.

  2. Immune complexes in scabies. In vitro study of the serum C1q fixation in the presence of mite and unparasited human scale extracts. (United States)

    Van Neste, D; Salmon, J


    The in vitro addition of mice or human unparasited scale extracts to the serum of 8 patients with scabies and 5 healthy controls did not significantly modify the fixation of 125I-C1q as compared to control tubes (serum with physiological saline). These results suggest that antigens or substances derived from the scabies mite are not involved in the immune complexes present in the serum of the parasited patients.

  3. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S;


    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known....... Serum samples from autoimmune (NZBxNZW)F1 mice, healthy BALB/c mice, patients with SLE, RA and normal healthy individuals were analyzed for presence and amount of circulating anti-dsDNA antibodies and nucleosomal DNA. Here we use a quantitative PCR to measure circulating DNA in sera. We demonstrate...

  4. Complex interplay of body condition, life history, and prevailing environment shapes immune defenses of garter snakes in the wild. (United States)

    Palacios, Maria G; Cunnick, Joan E; Bronikowski, Anne M


    The immunocompetence "pace-of-life" hypothesis proposes that fast-living organisms should invest more in innate immune defenses and less in adaptive defenses compared to slow-living ones. We found some support for this hypothesis in two life-history ecotypes of the snake Thamnophis elegans; fast-living individuals show higher levels of innate immunity compared to slow-living ones. Here, we optimized a lymphocyte proliferation assay to assess the complementary prediction that slow-living snakes should in turn show stronger adaptive defenses. We also assessed the "environmental" hypothesis that predicts that slow-living snakes should show lower levels of immune defenses (both innate and adaptive) given the harsher environment they live in. Proliferation of B- and T-lymphocytes of free-living individuals was on average higher in fast-living than slow-living snakes, opposing the pace-of-life hypothesis and supporting the environmental hypothesis. Bactericidal capacity of plasma, an index of innate immunity, did not differ between fast-living and slow-living snakes in this study, contrasting the previously documented pattern and highlighting the importance of annual environmental conditions as determinants of immune profiles of free-living animals. Our results do not negate a link between life history and immunity, as indicated by ecotype-specific relationships between lymphocyte proliferation and body condition, but suggest more subtle nuances than those currently proposed.

  5. Down regulation of the TCR complex CD3 ζ-chain on CD3+ T cells: a potential mechanism for helminth mediated immune modulation

    Directory of Open Access Journals (Sweden)

    Laura Jane Appleby


    Full Text Available The CD3ζ forms part of the T cell receptor (TCR where it plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways leading to T cell effector functions. Down regulation of CD3ζ leads to impairment of immune responses including reduced cell proliferation and cytokine production. In experimental models helminth parasites have been shown to modulate immune responses directed against them and unrelated antigens, so called bystander antigens, but there is a lack of studies validating these observations in humans. This study focused on investigated the relationship between expression levels of the TCR CD3ζ chain with lymphocyte cell proliferation during human infection with the helminth parasite, Schistosoma haematobium which causes uro-genital schistosomiasis. Using flow cytometry, peripheral blood mononuclear cells (PBMCs from individuals naturally exposed to S. haematobium in rural Zimbabwe were phenotyped, and expression levels of CD3ζ on T cells were related to intensity of infection. In this population, parasite infection intensity was inversely related to CD3ζ expression levels (p<0.05, consistent with down-regulation of CD3ζ expression during helminth infection. Furthermore, PBMC proliferation was positively related to expression levels of CD3ζ (p<0.05 after allowing for confounding variables (host age, sex, infection level. CD3ζ expression levels had a differing relationship between immune correlates of susceptibility and immunity, measured by antibody responses, indicating a complex relationship between immune activation status and immunity. The relationships between the CD3ζ chain of the TCR and schistosome infection, PBMC proliferation and schistosome-specific antibody responses have not previously been reported, and these results may indicate a mechanism for the impaired T cell proliferative responses observed during human schistosome infection.

  6. Allergen-containing immune complexes used for immunotherapy of allergic asthma. II. IgE and IgG immune response during and after hyposensitization of sensitized guinea pigs

    DEFF Research Database (Denmark)

    Poulsen, L K; Lundberg, L; Søndergaard, I


    In a previous study guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes prepared from antigen and specific IgG) IT was compared...... with placebo. In the present study methods were evaluated for determination of the allergen-specific IgE and IgG. IgE was determined by the passive cutaneous anaphylactic test (PCA) and the variability of this test on different strains of the recipient guinea pig was investigated. The same strain as used...

  7. Simvastatin Efficiently Lowers Small LDL-IgG Immune Complex Levels: A Therapeutic Quality beyond the Lipid-Lowering Effect.

    Directory of Open Access Journals (Sweden)

    Gerd Hörl

    Full Text Available We investigated a polyethylene glycol non-precipitable low-density lipoprotein (LDL subfraction targeted by IgG and the influence of statin therapy on plasma levels of these small LDL-IgG-immune complexes (LDL-IgG-IC. LDL-subfractions were isolated from 6 atherosclerotic subjects and 3 healthy individuals utilizing iodixanol density gradient ultracentrifugation. Cholesterol, apoB and malondialdehyde (MDA levels were determined in each fraction by enzymatic testing, dissociation-enhanced lanthanide fluorescence immunoassay and high-performance liquid chromatography, respectively. The levels of LDL-IgG-IC were quantified densitometrically following lipid electrophoresis, particle size distribution was assessed with dynamic light scattering and size exclusion chromatography. The influence of simvastatin (40 mg/day for three months on small LDL-IgG-IC levels and their distribution among LDL-subfractions (salt gradient separation were investigated in 11 patients with confirmed coronary artery disease (CAD. We demonstrate that the investigated LDL-IgG-IC are small particles present in atherosclerotic patients and healthy subjects. In vitro assembly of LDL-IgG-IC resulted in particle density shifts indicating a composition of one single molecule of IgG per LDL particle. Normalization on cholesterol levels revealed MDA values twice as high for LDL-subfractions rich in small LDL-IgG-IC if compared to dominant LDL-subfractions. Reactivity of affinity purified small LDL-IgG-IC to monoclonal antibody OB/04 indicates a high degree of modified apoB and oxidative modification. Simvastatin therapy studied in the CAD patients significantly lowered LDL levels and to an even higher extent, small LDL-IgG-IC levels without affecting their distribution. In conclusion simvastatin lowers levels of small LDL-IgG-IC more effectively than LDL-cholesterol and LDL-apoB levels in atherosclerotic patients. This antiatherogenic effect may additionally contribute to the known

  8. Comparison of the breadth and complexity of bovine viral diarrhea (BVDV) populations circulating in 34 persistently infected cattle generated in one outbreak. (United States)

    Ridpath, J F; Bayles, D O; Neill, J D; Falkenberg, S M; Bauermann, F V; Holler, L; Braun, L J; Young, D B; Kane, S E; Chase, C C L


    Exposure to bovine viral diarrhea viruses (BVDV) results in acute and persistent infections. Persistent infections result from in utero exposure during the first trimester of gestation. Clinical presentation, in persistently infected cattle (PI), is highly variable. The reasons for this variation is largely unknown. The BVDV circulating in PI exist as quasispecies (swarms of individual viruses). An outbreak resulting in 34 PI cattle presented an opportunity to compare a large number of PI׳s. Methods were developed to compare the circulating viral populations within PI animals. It was found that PI animals generated in the same outbreak carry circulating viral populations that differ widely in size and diversity. Further, it was demonstrated that variation in PI viral populations could be used as a quantifiable phenotype. This observation makes it possible to test the correlation of this phenotype to other phenotypes such as growth rate, congenital defects, viral shed and cytokine expression.

  9. Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications

    Directory of Open Access Journals (Sweden)

    Robert J. Greenstein


    Conclusions: We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases.

  10. 免疫复合物型增效乙型肝炎疫苗的稳定性%Stability of immune complex as enhanced hepatitis B vaccine

    Institute of Scientific and Technical Information of China (English)

    张昀; 何亚丽; 孙进文; 陈国明; 张德有; 周根喜


    Objective To study the stability of immune complex as enhanced hepatitis B (HB) vaccine. Methods Immune complex as enhanced HB vaccine was stored at 37℃ for 6 weeks (accelerated stability test) and at 2~8℃ for 30 months (long term stability test) respectively,and subjected to overall control tests,of which the potency (ED50) in mice was compared with that of routine recombinant HB (yeast) vaccine. Results All the quality indexes of immune complex as enhanced HB vaccine after storage at 37℃ for 6 weeks and at 2 ~ 8℃ for 30 months met the relevant temporary requirements. Compared with those of routine HB vaccine,the ED50 values of the immune complex in mice at various time points were low,of which the increasing rate was slow. The DE50 values of immune complex,except those after storage at 37℃ for 2 and 4 weeks,showed significant difference from those of routine HB vaccine (P< 0. 05). Conclusion Immune complex as enhanced HB (HB) vaccine showed high stability as compared with routine HB vaccine,of which the potency in mice was superior to that of routine HB vaccine. It provided an experimental basis for determination of validity period of immune complex as enhanced HB vaccine.%目的 探讨免疫复合物型增效乙型肝炎疫苗的稳定性.方法 将复合物型增效乙型肝炎疫苗分别于37℃保存6周(加速稳定性试验),2~8℃保存30个月(长期稳定性试验),进行各项质量指标检测,并比较其小鼠效力(ED50值)与常规重组乙型肝炎疫苗(酵母)的差异.结果 经37℃保存6周,2~8℃保存30个月后,免疫复合物型增效乙型肝炎疫苗各项质量指标均符合其暂定规程质量标准;小鼠效力(ED50值)不同时间点检测结果均低于常规乙肝疫苗,且升高趋势慢于常规乙肝疫苗,除37℃保存2周和4周外,其余差异均具有统计学意义(P<0.05).结论 免疫复合物型增效乙型肝炎疫苗稳定性良好;其小鼠效力(ED50值)优于常规乙肝疫苗,且比常规乙

  11. Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster. (United States)

    Verma, Puja; Tapadia, Madhu G


    In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. Here we provide evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. We show that early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. We also show that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected.

  12. Circulation economics

    DEFF Research Database (Denmark)

    Ingebrigtsen, Stig; Jakobsen, Ove


    Purpose - This paper is an attempt to advance the critical discussion regarding environmental and societal responsibility in economics and business. Design/methodology/approach - The paper presents and discusses as a holistic, organic perspective enabling innovative solutions to challenges...... concerning the responsible and efficient use of natural resources and the constructive interplay with culture. To reach the goal of sustainable development, the paper argues that it is necessary to make changes in several dimensions in mainstream economics. This change of perspective is called a turn towards...... presupposes a perspective integrating economic, natural and cultural values. Third, to organize the interplay between all stakeholders we introduce an arena for communicative cooperation. Originality/value - The paper concludes that circulation economics presupposes a change in paradigm, from a mechanistic...

  13. Inefficient binding of IgM immune complexes to erythrocyte C3b-C4b receptors (CR1) and weak incorporation of C3b-iC3b into the complexes

    DEFF Research Database (Denmark)

    Kávai, M; Rasmussen, J M; Baatrup, G


    The binding of soluble complement-reacted IgM immune complexes (IC) to erythrocyte (E) C3b-C4b receptors (CR1) and the incorporation of C3b-iC3b into solid phase IgM-IC was investigated. The optimal binding of liquid phase IgM-IC to E-CR1 was obtained with IC formed at moderate antibody excess, b...

  14. Structures of the Ultra-High-Affinity Protein-Protein Complexes of Pyocins S2 and AP41 and Their Cognate Immunity Proteins from Pseudomonas aeruginosa. (United States)

    Joshi, Amar; Grinter, Rhys; Josts, Inokentijs; Chen, Sabrina; Wojdyla, Justyna A; Lowe, Edward D; Kaminska, Renata; Sharp, Connor; McCaughey, Laura; Roszak, Aleksander W; Cogdell, Richard J; Byron, Olwyn; Walker, Daniel; Kleanthous, Colin


    How ultra-high-affinity protein-protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase-Im interaction is a model system for the study of high-affinity protein-protein interactions. However, despite the fact that closely related colicin-like bacteriocins are widely produced by Gram-negative bacteria, this interaction has only been studied using colicins from Escherichia coli. In this work, we present the first crystal structures of two pyocin DNase-Im complexes from Pseudomonas aeruginosa, pyocin S2 DNase-ImS2 and pyocin AP41 DNase-ImAP41. These structures represent divergent DNase-Im subfamilies and are important in extending our understanding of protein-protein interactions for this important class of high-affinity protein complex. A key finding of this work is that mutations within the immunity protein binding energy hotspot, helix III, are tolerated by complementary substitutions at the DNase-Immunity protein binding interface. Im helix III is strictly conserved in colicins where an Asp forms polar interactions with the DNase backbone. ImAP41 contains an Asp-to-Gly substitution in helix III and our structures show the role of a co-evolved substitution where Pro in DNase loop 4 occupies the volume vacated and removes the unfulfilled hydrogen bond. We observe the co-evolved mutations in other DNase-Immunity pairs that appear to underpin the split of this family into two distinct groups.

  15. Structures of the Ultra-High-Affinity Protein–Protein Complexes of Pyocins S2 and AP41 and Their Cognate Immunity Proteins from Pseudomonas aeruginosa (United States)

    Joshi, Amar; Grinter, Rhys; Josts, Inokentijs; Chen, Sabrina; Wojdyla, Justyna A.; Lowe, Edward D.; Kaminska, Renata; Sharp, Connor; McCaughey, Laura; Roszak, Aleksander W.; Cogdell, Richard J.; Byron, Olwyn; Walker, Daniel; Kleanthous, Colin


    How ultra-high-affinity protein–protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase–Im interaction is a model system for the study of high-affinity protein–protein interactions. However, despite the fact that closely related colicin-like bacteriocins are widely produced by Gram-negative bacteria, this interaction has only been studied using colicins from Escherichia coli. In this work, we present the first crystal structures of two pyocin DNase–Im complexes from Pseudomonas aeruginosa, pyocin S2 DNase–ImS2 and pyocin AP41 DNase–ImAP41. These structures represent divergent DNase–Im subfamilies and are important in extending our understanding of protein–protein interactions for this important class of high-affinity protein complex. A key finding of this work is that mutations within the immunity protein binding energy hotspot, helix III, are tolerated by complementary substitutions at the DNase–Immunity protein binding interface. Im helix III is strictly conserved in colicins where an Asp forms polar interactions with the DNase backbone. ImAP41 contains an Asp-to-Gly substitution in helix III and our structures show the role of a co-evolved substitution where Pro in DNase loop 4 occupies the volume vacated and removes the unfulfilled hydrogen bond. We observe the co-evolved mutations in other DNase–Immunity pairs that appear to underpin the split of this family into two distinct groups. PMID:26215615

  16. Induction of immune responses in mice by vaccination with Liposome-entrapped DNA complexes encoding Toxoplasma gondii SAG1 and ROP1 genes

    Institute of Scientific and Technical Information of China (English)

    陈海峰; 陈观今; 郑焕钦; 郭红


    Objective To evaluate the immune responses induced by experimental DNA construct encoding Toxoplasma gondii (T.gondii) surface antigen1 (SAG1) and rhoptry protein 1 (ROP1) in mice as a hybrid gene. Methods Truncated SAG1 and ROP1 DNA fragments were amplified using polymerase chain reaction (PCR) and inserted into pEGFP-N3 vector to construct recombinant plasmid pSAG1-ROP1. NIH3T3 mammalian cells were transiently transfected with the DNA construct. Female BALB/c mice were given three intramuscular injections of 10 μg plasmid DNA entrapped in liposome. Four weeks after the final booster injection, blood samples were collected and subjected to enzyme-linked immuno sorbent assay (ELISA) to investigate humoral and cell-mediated immune responses. Reversal transcript-polymerase chain reaction (RT-PCR) was used to evaluate the transcription of inoculated DNA-liposome complex in the injected site. Dot-blot hybridization was employed in order to detect whether or not the injected DNA was incorporated into the genomic DNA of the immunized mice.Results Green fluorescence was observed in pSAG1-ROP1-transfected cells. Western blot analysis showed antibody recognition of the expressed SAG1-ROP1 was between 58 kDa and 75 kDa. No expression was observed in blank control plasmid-transfected cells. The sera of immunized mice exhibited antibodies to T.gondii tachyzoites and primarily interferon-γ and interlukin-2. RT-PCR showed that the duration of transcribed inoculated liposome entrapped DNA in the injected muscular tissue was at least ten days post the first injection. Dot-blot hybridization revealed that the presence of foreign DNA in the splenocytes and peripheral blood leukocytes was transient and that no foreign DNA had inserted into the genomic DNA of mice immunized with pSAG1-ROP1. Conclusions Immunization with a liposome-encapsulated DNA construct encoding the T.gondii SAG1 and ROP1 can induce humoral and cell-mediated immune responses.

  17. Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus. (United States)

    Moi, Meng Ling; Ami, Yasushi; Shirai, Kenji; Lim, Chang-Kweng; Suzaki, Yuriko; Saito, Yuka; Kitaura, Kazutaka; Saijo, Masayuki; Suzuki, Ryuji; Kurane, Ichiro; Takasaki, Tomohiko


    Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells.

  18. Characterization of NF-κB Reporter U937 Cells and Their Application for the Detection of Inflammatory Immune-Complexes.

    Directory of Open Access Journals (Sweden)

    Csilla Kecse-Nagy

    Full Text Available Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies belonging to distinct immunoglobulin classes and subclasses but not the net biological effect of the combination of these antibodies. We set out to develop a biosensor that is suitable for the detection and characterization of antigen specific serum antibodies. We genetically modified the monocytoid U937 cell line carrying Fc receptors with a plasmid encoding NF-κB promoter-driven GFP. This clone, U937-NF-κB, was characterized with respect to FcR expression and response to solid-phase immunoglobulins. Human IgG3, IgG4 and IgG1 induced GFP production in a time- and dose-dependent manner, in this order of efficacy, while IgG2 triggered no activation at the concentrations tested. IgA elicited no response alone but showed significant synergism with IgG3 and IgG4. We confirmed the importance of activation via FcγRI by direct stimulation with monoclonal antibody and by competition assays. We used citrullinated peptides and serum from rheumatoid arthritis patients to generate immune complexes and to study the activation of U937-NF-κB, observing again a synergistic effect between IgG and IgA. Our results show that immunoglobulins have distinct pro-inflammatory potential, and that U937-NF-κB is suitable for the estimation of biological effects of immune-complexes, offering insight into monocyte activation and pathogenesis of antibody mediated diseases.

  19. Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton


    B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto......'s thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture...

  20. ELISA for evaluating the incorporation of plasma derived complement split-products C3b/iC3b into solid-phase immune complexes

    DEFF Research Database (Denmark)

    Zimmermann-Nielsen, E; Svehag, S E; Thorlacius-Ussing, O;


    An ELISA that measures plasma derived complement (C) split-products C3b/iC3b deposited on solid-phase immune complexes during C activation is described. Plates are coated with BSA, anti-BSA and plasma is added. Deposited C3b/iC3b is then detected by biotinylated anti-C3c-antibodies, avidin......) or classical pathway (CP) with regard to age or gender was demonstrated. The total coefficient of variation was systemic lupus erythematosus (SLE). There was a weak correlation between...

  1. [The effect of adaptation to the periodic action of hypoxia on the indices of the immunity system and on the course of allergic diseases]. (United States)

    Meerson, F Z; Frolov, B A; Volianik, M N; Boev, V M; Bannikov, V K; Smoliagin, A I; Tverdokhleb, V P; Afonina, S N; Livshits, N M; Frolova, M A


    The authors studied the effect of adaptation to periodical exposure to hypoxia on the organism's immune status and the values of neurohumoral regulation in children with bronchial asthma and adults suffering from allergic dermatoses and autoimmune thyroiditis. It was found that adaptation facilitated normalization of humoral values of immunity in allergic and autoimmune disorders (the content of serum immunoglobulins increased while the level of circulating immune complexes reduced) and was attended by a stable therapeutic effect. The revealed changes of the immune values occurred in increase of the reserve potency of the hypothalamo-hypophyseal-adrenal and sympathoadrenal systems and reduction of the blood histamine level.

  2. Two Complex, Adenovirus-Based Vaccines That Together Induce Immune Responses to All Four Dengue Virus Serotypes▿


    Holman, David H.; Wang, Danher; Raviprakash, Kanakatte; Raja, Nicholas U.; LUO, MIN; Zhang, Jianghui; Porter, Kevin R.; Dong, John Y.


    Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirement...

  3. The molecular evolution of four anti-malarial immune genes in the Anopheles gambiae species complex - art. no. 79


    Parmakelis, A.; Slotman, M. A.; Marshall, J. C.; Awono Ambene, P. H.; Antonio Nkondjio, C.; Simard, Frédéric; Caccone, A; Powell, J. R.


    Background: If the insect innate immune system is to be used as a potential blocking step in transmission of malaria, then it will require targeting one or a few genes with highest relevance and ease of manipulation. The problem is to identify and manipulate those of most importance to malaria infection without the risk of decreasing the mosquito's ability to stave off infections by microbes in general. Molecular evolution methodologies and concepts can help identify such genes. Within the se...

  4. Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

    DEFF Research Database (Denmark)

    Fismen, S; Hedberg, A; Fenton, K A;


    (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i...

  5. Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone) increases antibody response, cellular immunity, and antigenically drifted protection. (United States)

    Lay, Marla; Callejo, Bernadette; Chang, Stella; Hong, David K; Lewis, David B; Carroll, Timothy D; Matzinger, Shannon; Fritts, Linda; Miller, Christopher J; Warner, John F; Liang, Lily; Fairman, Jeffery


    Safe and effective adjuvants for influenza vaccines that could increase both the levels of neutralizing antibody, including against drifted viral subtypes, and T-cell immunity would be a major advance in vaccine design. The JVRS-100 adjuvant, consisting of DOTIM/cholesterol cationic liposome-DNA complexes, is particularly promising for vaccines that require induction of high levels of antibody and T-cell immunity, including CD8(+) cytotoxic T lymphocytes (CTL). Inclusion of protein antigens with JVRS-100 results in the induction of enhanced humoral and cell-mediated (i.e., CD4(+) and CD8(+) T cells) immune responses. The JVRS-100 adjuvant combined with a split trivalent influenza vaccine (Fluzone-sanofi pasteur) elicited increased antibody and T-cell responses in mice and non-human primates compared to vaccination with Fluzone alone. Mice vaccinated with JVRS-100-Fluzone and challenged with antigenically drifted strains of H1N1 (PR/8/34) and influenza B (B/Lee/40) viruses had higher grade protection, as measured by attenuation of weight loss and increased survival, compared to recipients of unadjuvanted vaccine. The results indicate that the JVRS-100 adjuvant substantially increases immunogenicity and protection from drifted-strain challenge using an existing influenza vaccine.

  6. Different immunity elicited by recombinant H5N1 hemagglutinin proteins containing pauci-mannose, high-mannose, or complex type N-glycans.

    Directory of Open Access Journals (Sweden)

    Shih-Chang Lin

    Full Text Available Highly pathogenic avian influenza H5N1 viruses can result in poultry and occasionally in human mortality. A safe and effective H5N1 vaccine is urgently needed to reduce the pandemic potential. Hemagglutinin (HA, a major envelope protein accounting for approximately 80% of spikes in influenza virus, is often used as a major antigen for subunit vaccine development. In this study, we conducted a systematic study of the immune response against influenza virus infection following immunization with recombinant HA proteins expressed in insect (Sf9 cells, insect cells that contain exogenous genes for elaborating N-linked glycans (Mimic and mammalian cells (CHO. While the antibody titers are higher with the insect cell derived HA proteins, the neutralization and HA inhibition titers are much higher with the mammalian cell produced HA proteins. Recombinant HA proteins containing tri- or tetra-antennary complex, terminally sialylated and asialyated-galactose type N-glycans induced better protective immunity in mice to lethal challenge. The results are highly relevant to issues that should be considered in the production of fragment vaccines.

  7. Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex

    Directory of Open Access Journals (Sweden)

    Craig ePrzysiecki


    Full Text Available Antibodies that neutralize infectivity of malaria sporozoites target the central repeat region of the circumsporozoite (CS protein, which in Plasmodium falciparum is comprised primarily of 30-40 tandem NANP tetramer repeats. We evaluated immunogenicity of an alum-adsorbed (NANP6 peptide conjugated to an outer membrane protein complex (OMPC derived from Neisseria meningitidis, a carrier protein used in a licensed H. influenzae pediatric vaccine. Mice immunized with alum-adsorbed (NANP6-OMPC, with or without Iscomatrix© as co-adjuvant, developed high levels of anti-repeat peptide antibody that inhibited in vitro invasion of human hepatoma cells by transgenic P. berghei sporozoites that express P. falciparum CS repeats (PfPb. Inhibition of sporozoite invasion in vitro correlated with in vivo resistance to challenge by the bites of PfPb infected mosquitoes. Challenged mice had > 90% reduction of hepatic stage parasites as measured by real-time PCR, and either sterile immunity, i.e. no detectable blood stage parasites, or delayed prepatent periods which indicate neutralization of a majority, but not all, sporozoites. Rhesus macaques immunized with two doses of (NANP6-OMPC/MAA formulated with Iscomatrix© developed anti-repeat antibodies that persisted for ~2 years. A third dose of (NANP6-OMPC/MAA+ Iscomatrix© at that time elicited strong anamnestic antibody responses. Rhesus macaque immune sera obtained post second and third dose of vaccine displayed high levels of sporozoite neutralizing activity in vitro that correlated with presence of high anti-repeat antibody titers. These preclinical studies in mice of different MHC haplotypes and a non-human primate support use of CS peptide-OMPC conjugates as a highly immunogenic platform to evaluate CS protective epitopes. Potential pre-erythrocytic vaccines can be combined with sexual blood stage vaccines as a multi-antigen malaria vaccine to block invasion and transmission of Plasmodium parasites

  8. Two Prp19-like U-box proteins in the MOS4-associated complex play redundant roles in plant innate immunity.

    Directory of Open Access Journals (Sweden)

    Jacqueline Monaghan


    Full Text Available Plant Resistance (R proteins play an integral role in defense against pathogen infection. A unique gain-of-function mutation in the R gene SNC1, snc1, results in constitutive activation of plant immune pathways and enhanced resistance against pathogen infection. We previously found that mutations in MOS4 suppress the autoimmune phenotypes of snc1, and that MOS4 is part of a nuclear complex called the MOS4-Associated Complex (MAC along with the transcription factor AtCDC5 and the WD-40 protein PRL1. Here we report the immuno-affinity purification of the MAC using HA-tagged MOS4 followed by protein sequence analysis by mass spectrometry. A total of 24 MAC proteins were identified, 19 of which have predicted roles in RNA processing based on their homology to proteins in the Prp19-Complex, an evolutionarily conserved spliceosome-associated complex containing homologs of MOS4, AtCDC5, and PRL1. Among these were two highly similar U-box proteins with homology to the yeast and human E3 ubiquitin ligase Prp19, which we named MAC3A and MAC3B. MAC3B was recently shown to exhibit E3 ligase activity in vitro. Through reverse genetics analysis we show that MAC3A and MAC3B are functionally redundant and are required for basal and R protein-mediated resistance in Arabidopsis. Like mos4-1 and Atcdc5-1, mac3a mac3b suppresses snc1-mediated autoimmunity. MAC3 localizes to the nucleus and interacts with AtCDC5 in planta. Our results suggest that MAC3A and MAC3B are members of the MAC that function redundantly in the regulation of plant innate immunity.

  9. Crystallization and preliminary crystallographic analysis of Arabidopsis thaliana EDS1, a key component of plant immunity, in complex with its signalling partner SAG101. (United States)

    Wagner, Stephan; Rietz, Steffen; Parker, Jane E; Niefind, Karsten


    In plants, the nucleocytoplasmic protein EDS1 (Enhanced disease susceptibility1) is an important regulator of innate immunity, coordinating host-cell defence and cell-death programs in response to pathogen attack. Arabidopsis thaliana EDS1 stabilizes and signals together with its partners PAD4 (Phytoalexin deficient4) and SAG101 (Senescence-associated gene101). Characterization of EDS1 molecular configurations in vitro and in vivo points to the formation of structurally and spatially distinct EDS1 homomeric dimers and EDS1 heteromeric complexes with either PAD4 or SAG101 as necessary components of the immune response. EDS1, PAD4 and SAG101 constitute a plant-specific protein family with a unique `EP' (EDS1-PAD4-specific) domain at their C-termini and an N-terminal domain resembling enzymes with an α/β-hydrolase fold. Here, the expression, purification and crystallization of a functional EDS1 complex formed by EDS1 and SAG101 from Arabidopsis thaliana are reported. The crystals belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 101.8, b = 115.9, c = 122.8 Å, and diffracted to 3.5 Å resolution.

  10. 3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.

    Directory of Open Access Journals (Sweden)

    Manuel A Patarroyo

    Full Text Available T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2 and is known to bind to HLA-DRbeta1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vbeta12 and Vbeta6 TCR gene families in 67% of HLA-DRbeta1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRbeta1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

  11. [Influence of combined rehabilitation treatment including novel non-pharmacological technologies on immune system of patients with seronegetive spondylarthritis]. (United States)

    Barnatskiĭ, V V; Grigor'eva, V D; Pershin, S B; Derevnina, N A; Gontar', E B


    The immune system was studied in 90 patients with seronegative spondylarthritis (SNSA). Of them, 60 patients had ankylosing spondylarthritis (30 patients with central and 30 patients with peripheral forms) and 30 patients with reactive arthritis. SNSA patients were found to have secondary immunodeficiency. Cellular immunity was characterized by a decreased count of T mu (helper cells), an increased count of T gamma (cytotoxic/suppressors) and suppressed functional activity of lymphocytes, humoral immunity--by a high concentration of circulating immune complexes in an increased concentration of serum immunoglobulins. Integral assessment of the changes in the immune system and clinical data in SNSA patients leads to the conclusion that water radon baths and decimetric wave therapy reach the highest efficacy in ankylosing spondylarthritis while water radon baths and low frequency ultrasound--in reactive arthritis, a complex of water radon baths and ultraphonophoresis of hydrocortisone--in ankylosing spondylarthritis and reactive arthritis.

  12. Effects of Local Circulations, Turbulent Internal Boundary Layers, and Elevated Industrial Plumes on Coastal Ozone Pollution in the Downwind Kaohsiung Urban-Industrial Complex

    Directory of Open Access Journals (Sweden)

    Yee-Lin Wu


    Full Text Available Linyuan (LY is a coastal station located down wind of the industrial city of Kaohsiung in southern Taiwan. This station is often affected by severe ozone pollution during sea breeze events. Intensive tethered ozone soundings were per formed at this station during a 4-day ozone episode in November, 2005. Back air trajectories were also calculated to track the origins of air masses arriving at the station during the experiment. The investigation revealed complicated ozone pro files in the lower at mo sphere (be low 1300 m both day and night. At night, industrial plumes forming no-ozone air layers were frequently distributed at 400 - 800 m. Mixing layers rapidly decreased from 800 - 1100 m down to 200 - 350 m in the late morning hours when sea breezes and thermal internal boundary layers (TIBLs developed. Recirculation of polluted in land air masses over the sea, the development of TIBLs, and the late development of sea-breeze events all are likely responsible for severe ozone pollution at the LY station. Elevated industrial plumes or ozone aloft above TIBLs revealed only aminor contribution to ozone pollution via a downward mixing process. Elevated ozone levels (140 - 170 ppb were of ten trapped within transitional layers of sea-breeze circulations at 600 - 800 m and were accompanied by ambient northerly flows parallel to the coast line, suggesting that an ozone pollution core likely formed over the west coast of Taiwan on ozone-episodic days when sea-breeze circulations developed.

  13. Characterizing complex polysera produced by antigen-specific immunization through the use of affinity-selected mimotopes.

    Directory of Open Access Journals (Sweden)

    Galina Denisova

    Full Text Available BACKGROUND: Antigen-based (as opposed to whole organism vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity. METHODOLOGY/PRINCIPAL FINDINGS: Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets. CONCLUSIONS/SIGNIFICANCE: By combining our novel strategy with existing methods of epitope prediction based on physical properties of an individual protein, we believe that this method offers a robust method for characterizing the breadth of epitope-specificity within a specific polyserum. This strategy is useful as a tool for monitoring immunity following vaccination and can also be used to define relevant epitopes for the creation of novel vaccines.

  14. In vivo expansion of regulatory T cells with IL-2/IL-2 mAb complexes prevents anti-factor VIII immune responses in hemophilia A mice treated with factor VIII plasmid-mediated gene therapy. (United States)

    Liu, Chao-Lien; Ye, Peiqing; Yen, Benjamin C; Miao, Carol H


    Generation of transgene-specific immune responses can constitute a major complication following gene therapy treatment. An in vivo approach to inducing selective expansion of Regulatory T (Treg) cells by injecting interleukin-2 (IL-2) mixed with a specific IL-2 monoclonal antibody (JES6-1) was adopted to modulate anti-factor VIII (anti-FVIII) immune responses. Three consecutive IL-2 complexes treatments combined with FVIII plasmid injection prevented anti-FVIII formation and achieved persistent, therapeutic-level of FVIII expression in hemophilia A (HemA) mice. The IL-2 complexes treatment expanded CD4(+)CD25(+)Foxp3(+) Treg cells five- to sevenfold on peak day, and they gradually returned to normal levels within 7-14 days without changing other lymphocyte populations. The transiently expanded Treg cells are highly activated and display suppressive function in vitro. Adoptive transfer of the expanded Treg cells protected recipient mice from generation of high-titer antibodies following FVIII plasmid challenge. Repeated plasmid transfer is applicable in tolerized mice without eliciting immune responses. Mice treated with IL-2 complexes mounted immune responses against both T-dependent and T-independent neoantigens, indicating that IL-2 complexes did not hamper the immune system for long. These results demonstrate the important role of Treg cells in suppressing anti-FVIII immune responses and the potential of developing Treg cell expansion therapies that induce long-term tolerance to FVIII.

  15. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Zhipeng Zeng


    Full Text Available CD4+CD25+Foxp3+ regulatory T cells (Treg cells have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI. We hypothesize that the interleukin- (IL- 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1 attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

  16. Noise-immune complex correlation for vasculature imaging based on standard and Jones-matrix optical coherence tomography (United States)

    Makita, Shuichi; Kurokawa, Kazuhiro; Hong, Young-Joo; Li, En; Miura, Masahiro; Yasuno, Yoshiaki


    A new optical coherence angiography (OCA) method, called correlation mapping OCA (cmOCA), is presented by using the SNR-corrected complex correlation. An SNR-correction theory for the complex correlation calculation is presented. The method also integrates a motion-artifact-removal method for the sample motion induced decorrelation artifact. The theory is further extended to compute more reliable correlation by using multi- channel OCT systems, such as Jones-matrix OCT. The high contrast vasculature imaging of in vivo human posterior eye has been obtained. Composite imaging of cmOCA and degree of polarization uniformity indicates abnormalities of vasculature and pigmented tissues simultaneously.

  17. Complexity

    CERN Document Server

    Gershenson, Carlos


    The term complexity derives etymologically from the Latin plexus, which means interwoven. Intuitively, this implies that something complex is composed by elements that are difficult to separate. This difficulty arises from the relevant interactions that take place between components. This lack of separability is at odds with the classical scientific method - which has been used since the times of Galileo, Newton, Descartes, and Laplace - and has also influenced philosophy and engineering. In recent decades, the scientific study of complexity and complex systems has proposed a paradigm shift in science and philosophy, proposing novel methods that take into account relevant interactions.

  18. A heterodimeric complex of the LRR proteins LRIM1 and APL1C regulates complement-like immunity in Anopheles gambiae

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, Richard H.G.; Steinert, Stefanie; Chelliah, Yogarany; Volohonsky, Gloria; Levashina, Elena A.; Deisenhofer, Johann (CNRS-UMR); (UTSMC)


    The leucine-rich repeat (LRR) proteins LRIM1 and APL1C control the function of the complement-like protein TEP1 in Anopheles mosquitoes. The molecular structure of LRIM1 and APL1C and the basis of their interaction with TEP1 represent a new type of innate immune complex. The LRIM1/APL1C complex specifically binds and solubilizes a cleaved form of TEP1 without an intact thioester bond. The LRIM1 and APL1C LRR domains have a large radius of curvature, glycosylated concave face, and a novel C-terminal capping motif. The LRIM1/APL1C complex is a heterodimer with a single intermolecular disulfide bond. The structure of the LRIM1/APL1C heterodimer reveals an interface between the two LRR domains and an extensive C-terminal coiled-coil domain. We propose that a cleaved form of TEP1 may act as a convertase for activation of other TEP1 molecules and that the LRIM1/APL1C heterodimer regulates formation of this TEP1 convertase.

  19. Circulation in blast driven instabilities (United States)

    Henry de Frahan, Marc; Johnsen, Eric


    Mixing in many natural phenomena (e.g. supernova collapse) and engineering applications (e.g. inertial confinement fusion) is often initiated through hydrodynamic instabilities. Explosions in these systems give rise to blast waves which can interact with perturbations at interfaces between different fluids. Blast waves are formed by a shock followed by a rarefaction. This wave profile leads to complex time histories of interface acceleration. In addition to the instabilities induced by the acceleration field, the rarefaction from the blast wave decompresses the material at the interface, further increasing the perturbation growth. After the passage of the wave, circulation circulation generated by the blast wave through baroclinic vorticity continues to act upon the interface. In this talk, we provide scaling laws for the circulation and amplitude growth induced by the blast wave. Numerical simulations of the multifluid Euler equations solved using a high-order accurate Discontinuous Galerkin method are used to validate the theoretical results.

  20. Diminished ability of erythrocytes from patients with systemic lupus erythematosus to limit opsonized immune complex deposition on leukocytes and activation of granulocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Rasmussen, J M; Voss, A;


    OBJECTIVE: To compare the ability of normal erythrocytes and erythrocytes from systemic lupus erythematosus (SLE) patients to bind immune complexes (IC), thereby inhibiting IC deposition on polymorphonuclear leukocytes (PMN) and the consequent induction of a PMN respiratory burst (RB). METHODS......, on stimulation with unlabeled IC. RESULTS: Erythrocyte-mediated inhibition of IC uptake by PMN reached a mean +/- SD maximum of 68 +/- 18% in controls and 29 +/- 51% in SLE patients (P erythrocytes from various donors......, IC binding to a standard preparation of PMN and their ROM production were inversely proportional to the number of type 1 complement receptors (CR1) per donor erythrocyte. Thus, the ROM production was higher in the presence of SLE patients' erythrocytes (125 +/- 67 CR1/erythrocyte) than...

  1. The Genome of the Obligately Intracellular Bacterium Ehrlichia canis Reveals Themes of Complex Membrane Structure and Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Doyle, C Kuyler [Center for Biodenfense and Emerging Infectious Diseases; Lykidis, A [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Francino, M P [U.S. Department of Energy, Joint Genome Institute; Chain, Patrick S [ORNL; Shin, M [U.S. Department of Energy, Joint Genome Institute; Malfatti, Stephanie [Lawrence Livermore National Laboratory (LLNL); Larimer, Frank W [ORNL; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Detter, J C [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Yu, X J [Center for Biodenfense and Emerging Infectious Diseases; Walker, D H [Center for Biodenfense and Emerging Infectious Diseases; McBride, J W [Center for Biodenfense and Emerging Infectious Diseases; Kyripides, N C [U.S. Department of Energy, Joint Genome Institute


    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, {alpha}-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n = 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n = 7).

  2. Structural basis for signaling by exclusive EDS1 heteromeric complexes with SAG101 or PAD4 in plant innate immunity. (United States)

    Wagner, Stephan; Stuttmann, Johannes; Rietz, Steffen; Guerois, Raphael; Brunstein, Elena; Bautor, Jaqueline; Niefind, Karsten; Parker, Jane E


    Biotrophic plant pathogens encounter a postinfection basal resistance layer controlled by the lipase-like protein enhanced disease susceptibility 1 (EDS1) and its sequence-related interaction partners, senescence-associated gene 101 (SAG101) and phytoalexin deficient 4 (PAD4). Maintainance of separate EDS1 family member clades through angiosperm evolution suggests distinct functional attributes. We report the Arabidopsis EDS1-SAG101 heterodimer crystal structure with juxtaposed N-terminal α/β hydrolase and C-terminal α-helical EP domains aligned via a large conserved interface. Mutational analysis of the EDS1-SAG101 heterodimer and a derived EDS1-PAD4 structural model shows that EDS1 signals within mutually exclusive heterocomplexes. Although there is evolutionary conservation of α/β hydrolase topology in all three proteins, a noncatalytic resistance mechanism is indicated. Instead, the respective N-terminal domains appear to facilitate binding of the essential EP domains to create novel interaction surfaces on the heterodimer. Transitions between distinct functional EDS1 heterodimers might explain the central importance and versatility of this regulatory node in plant immunity.

  3. Liposome, Immune Stimulating Complexes and Chitosan as the Re-search Status of Mucosal Immune Carrier%脂质体、免疫刺激复合物和壳聚糖作为黏膜免疫载体的研究现状

    Institute of Scientific and Technical Information of China (English)

    王立强(综述); 王洪军(审校)


    The biological characteristics and application in the field of aerosol vaccine of liposome, immune stim-ulating complexes and chitosan as the nasal mucosal immune carrier materials were summarized. The liposome, im-mune stimulating complexes and chitosan as vaccine carrier can enhance the immunogenicity of vaccine and the humoral and cellular immune level. Therefore, liposome, immune stimulating complexes and chitosan can be used as vaccine antigen to stimulate specific immune response of biological materials.%查阅国内外文献,采用整理归纳、引用和分析的方法,概述了鼻黏膜免疫载体材料脂质体、免疫刺激复合物和壳聚糖的生物学特性及其在气溶胶疫苗领域的应用。脂质体、免疫刺激复合物和壳聚糖作为气溶胶疫苗鼻黏膜免疫的载体,能够增强疫苗的免疫原性,提高机体的体液免疫和细胞免疫水平,因此,可作为疫苗抗原激发特异免疫应答的生物材料。

  4. 免疫检测器证据理论集成的机组复合故障诊断%Complex fault diagnosis of machine unit based on evidence theory and immune detector integrated

    Institute of Scientific and Technical Information of China (English)

    岑健; 胥布工; 张清华; 邵龙秋


    针对机组复合故障诊断准确率较低的状况,基于免疫机理的人工免疫智能方法,构建对故障比较敏感的无量纲指标免疫检测器.采用自适应调节匹配阈值和从非己空间产生的候选检测器,能有效减少黑洞和边界不清晰.通过免疫编程优化策略获得最佳识别能力的新特征指标.利用证据理论对多类免疫检测器进行集成诊断,提炼出能直接应用于复合故障诊断的优秀无量纲免疫检测器,机组实验结果表明,所得免疫检测器能快速、准确地进行复合故障诊断.%For the condition that lower accuracy exists in complex fault diagnosis of machine unit, an artificial immune intelligent method based on immune mechanism is proposed, dimensionless immune detectors are constructed and complex fault can be detect and diagnosed. Match thresholds are used and candidate detectors from nonself-space are generated, which can effectively reduce the black hole and unclear border. Immune programming is introduced into feature construct of complex fault diagnosis in order to obtain new feature parameter. A few type immune detectors are integrated and diagnosed by using evidential theory, which can directly be applied to complex fault diagnosis. These excellent immune detectors can improve the accuracy of complex fault diagnosis, and the experiment results show that complex fault can be accurately and rapidly diagnosed.

  5. Heteromeric Complexes of Native Collectin Kidney 1 and Collectin Liver 1 Are Found in the Circulation with MASPs and Activate the Complement System

    DEFF Research Database (Denmark)

    Henriksen, Maiken L; Brandt, Jette; Andrieu, Jean-Piere;


    of carbohydrates or acetylated molecules. During purification and characterization of native CL-K1 from plasma, we observed that collectin liver 1 (CL-L1) was copurified. Based on deglycosylation and nonreduced/reduced two-dimensional SDS-PAGE, we detected CL-K1 and CL-L1 in disulfide bridge-stabilized complexes...

  6. Algorithms for Finding the Inverses of Factor Block Circulant Matrices

    Institute of Scientific and Technical Information of China (English)


    In this paper, algorithms for finding the inverse of a factor block circulant matrix,a factor block retrocirculant matrix and partitioned matrix with factor block circulant blocks over the complex field are presented respectively. In addition, two algorithms for the inverse of a factor block circulant matrix over the quaternion division algebra are proposed.

  7. [Thymus endocrine function and the immune system indices of cancer patients after neutron and gamma therapy]. (United States)

    Grinevich, Iu A; Martynenko, S V; Baraboĭ, V A; Monich, A Iu; Tolstopiatov, B A; Konovalenko, V F; Protsyk, V S


    Patients with head and neck and locomotor system tumors received neutron therapy in the total doses of 4-8 and 12-14 Gy which was followed by a pronounced dose-dependent decrease in the serum thymus factor and total blood-lymphocyte levels. The latter changes were predominantly due to a decrease in the non-T-non-B cell concentration. Following the treatment, a rise in the level of circulating immune complexes and those of IgA and IgG was observed. Changes in the immune system proved less apparent in patients with locomotor system cancer who had been given 20 Gy of gamma-ray radiation.

  8. Immune Regulation by Self-Recognition

    DEFF Research Database (Denmark)

    Andersen, Mads Hald


    Circulating T cells that specifically target normal self-proteins expressed by regulatory immune cells were first described in patients with cancer, but can also be detected in healthy individuals. The adaptive immune system is distinguished for its ability to differentiate between self...... the direct targeting of cancer cells in addition to regulatory immune cells. Anti-Tregs provide the immune system with yet another level of immune regulation and contradict the notion that immune cells involved in the adjustment of immune responses only act as suppressor cells.......-antigens and foreign antigens. Thus, it was remarkable to discover T cells that apparently lacked tolerance to important self-proteins, eg, IDO, PD-L1, and FoxP3, expressed in regulatory immune cells. The ability of self-reactive T cells to react to and eliminate regulatory immune cells can influence general immune...

  9. Circulating levels of matrix metalloproteinase-9 (MMP-9, neutrophil gelatinase-associated lipocalin (NGAL and their complex MMP-9/NGAL in breast cancer disease

    Directory of Open Access Journals (Sweden)

    Nonni Afroditi


    Full Text Available Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9 is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.


    Ishchuk, T V; Kravchenko, N K; Raetska, Ya B; Ostapchenko, L I


    It is well known that the immune system has been actively involved in the regeneration and healing processes of post burn wounds. However, unanswered questions remain concerning the role of humoral immunity in the healing mechanisms and development of burn wound complications. We have developed an experimental model of chemical esophageal burn (CEB) which corresponds to esophageal burn in 1-8 years old children. We studied the features of humoral immunity upon CEB in rats. A decrease in IgG levels and an increase in levels of medium- and low- molecular circulating immune complexes (CIC) on the first day of esophageal burns were observed. On the 21st day of burn, we observed an increase in the IgG concentration and a tendency to accumulation of medium- and low-molecular CIC. The studied indicators can be used to differentiate CEB development and create a timeline of burn wounds.

  11. A novel method for high-throughput detection and quantification of neutrophil extracellular traps reveals ROS-independent NET release with immune complexes. (United States)

    Kraaij, Tineke; Tengström, Fredrik C; Kamerling, Sylvia W A; Pusey, Charles D; Scherer, H Ulrich; Toes, Rene E M; Rabelink, Ton J; van Kooten, Cees; Teng, Y K Onno


    A newly-described first-line immune defence mechanism of neutrophils is the release of neutrophil extracellular traps (NETs). Immune complexes (ICxs) induce low level NET release. As such, the in vitro quantification of NETs is challenging with current methodologies. In order to investigate the role of NET release in ICx-mediated autoimmune diseases, we developed a highly sensitive and automated method for quantification of NETs. After labelling human neutrophils with PKH26 and extracellular DNA with Sytox green, cells are fixed and automatically imaged with 3-dimensional confocal laser scanning microscopy (3D-CLSM). NET release is then quantified with digital image analysis whereby the NET amount (Sytox green area) is corrected for the number of imaged neutrophils (PKH26 area). A high sensitivity of the assay is achieved by a) significantly augmenting the area of the well imaged (11%) as compared to conventional assays (0.5%) and b) using a 3D imaging technique for optimal capture of NETs, which are topologically superimposed on neutrophils. In this assay, we confirmed low levels of NET release upon human ICx stimulation which were positive for citrullinated histones and neutrophil elastase. In contrast to PMA-induced NET release, ICx-induced NET release was unchanged when co-incubated with diphenyleneiodonium (DPI). We were able to quantify NET release upon stimulation with serum from RA and SLE patients, which was not observed with normal human serum. To our knowledge, this is the first semi-automated assay capable of sensitive detection and quantification of NET release at a low threshold by using 3D CLSM. The assay is applicable in a high-throughput manner and allows the in vitro analysis of NET release in ICx-mediated autoimmune diseases.

  12. The role of complement receptor type 1 (CR1, CD35) in determining the cellular distribution of opsonized immune complexes between whole blood cells: kinetic analysis of the buffering capacity of erythrocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Matthiesen, S H; Lyng, I;


    Erythrocytes (E) express complement receptor, type 1 (CR1, CD35), by which they bind opsonized immune complexes (IC) in competition with leucocytes expressing higher numbers of CR1 as well as other complement- and Fc-receptors. This may prevent inappropriate activation of phagocytic cells. We...

  13. Immunization with cationized BSA inhibits progression of disease in ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis. (United States)

    Kolbus, Daniel; Wigren, Maria; Ljungcrantz, Irena; Söderberg, Ingrid; Alm, Ragnar; Björkbacka, Harry; Nilsson, Jan; Fredrikson, Gunilla N


    Immune responses against modified self-antigens generated by hypercholesterolemia play an important role in atherosclerosis identifying the immune system as a possible novel target for prevention and treatment of cardiovascular disease. It has recently been shown that these immune responses can be modulated by subcutaneous injection of adjuvant. In the present study we immunized 25-week old ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis with adjuvant and two different concentrations of the carrier molecule cationized BSA (cBSA). Plasma levels of Th2-induced apolipoprotein B (apoB)/IgG1 immune complexes were increased in the cBSA immunized groups verifying induction of immunity against a self-antigen. Mice were sacrificed at 36 weeks of age and atherosclerosis was monitored by en face Oil red O staining of the aorta. Immunization with 100 μg cBSA inhibited plaque progression, whereas the lower dose (50 μg) did not. In addition, the higher dose induced a more stable plaque phenotype, indicated by a higher content of collagen and less macrophages and T cells in the plaques. Moreover, there was an increased ratio of Foxp3+/Foxp3⁻ T cells in the circulation suggesting activation of a regulatory T cell response. In conclusion, we show that immunization with cBSA induces an immune response against apoB as well as an activation of Treg cells. This was associated with development of a more stable plaque phenotype and reduced atherosclerosis progression.

  14. Treatment of Leishmania (Leishmania) Amazonensis-Infected Mice with a Combination of a Palladacycle Complex and Heat-Killed Propionibacterium acnes Triggers Protective Cellular Immune Responses (United States)

    Paladi, Carolina S.; da Silva, Danielle A. M.; Motta, Priscila D.; Garcia, Daniel M.; Teixeira, Daniela; Longo-Maugéri, Ieda M.; Katz, Simone; Barbiéri, Clara L.


    Palladacycle complex DPPE 1.2 was previously reported to inhibit the in vitro and in vivo infection by Leishmania (Leishmania) amazonensis. The aim of the present study was to compare the effect of DPPE 1.2, in association with heat-killed Propionibacterium acnes, on L. (L.) amazonensis infection in two mouse strains, BALB/c and C57BL/6, and to evaluate the immune responses of the treated animals. Foot lesions of L. (L.) amazonensis-infected mice were injected with DPPE 1.2 alone, or associated with P. acnes as an adjuvant. Analysis of T-cell populations in the treated mice and in untreated controls was performed by FACS. Detection of IFN-γ-secreting lymphocytes was carried out by an ELISPOT assay and active TGF-β was measured by means of a double-sandwich ELISA test. The treatment with DPPE 1.2 resulted in a significant reduction of foot lesion sizes and parasite burdens in both mouse strains, and the lowest parasite burden was found in mice treated with DPPE 1.2 plus P. acnes. Mice treated with DPPE 1.2 alone displayed a significant increase of TCD4+ and TCD8+ lymphocytes and IFN-γ secretion which were significantly higher in animals treated with DPPE 1.2 plus P. acnes. A significant reduction of active TGF-β was observed in mice treated with DPPE 1.2 alone or associated with P. acnes. Moreover, DPPE 1.2 associated to P. acnes was non-toxic to treated animals. The destruction of L. (L.) amazonensis by DPPE 1.2 was followed by host inflammatory responses which were exacerbated when the palladacycle complex was associated with P. acnes. PMID:28321209

  15. A monoclonal antibody against the human SUMO-1 protein obtained by immunization with recombinant protein and CpG-DNA-liposome complex. (United States)

    Kim, Dongbum; Lee, Joo Young; Song, Dae-Geun; Kwon, Sanghoon; Lee, Younghee; Pan, Cheol-Ho; Kwon, Hyung-Joo


    Post-translational modification regulated by conjugation of a small ubiquitin-like modifier (SUMO) is involved in various cellular processes. In this study, we expressed and purified recombinant human SUMO-1 (hSUMO-1). BALB/c mice were immunized with a complex of hSUMO-1 protein and Lipoplex(O) to produce hSUMO-1-specific antibodies. Using conventional hybridoma technology, we obtained four hybridoma clones derived from the mouse with the highest antibody titer against hSUMO-1. Based on Western blot analysis, our hSUMO-1 monoclonal antibody specifically recognizes hSUMO-1, but not other SUMO proteins. These results support that the anti-hSUMO-1 monoclonal antibody produced with the aid of Lipoplex(O) adjuvant is specific and that Lipoplex(O) is useful for development of monoclonal antibodies against recombinant protein. In addition, we analyzed human tissues to examine the distribution of hSUMO-1. Higher expression of hSUMO-1 was detected in normal adrenal gland, esophagus, pancreas, liver, stomach, kidney, and uterus than in corresponding cancer tissues, suggesting a tumor suppressive function of hSUMO-1.

  16. Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV Pentameric Complex Proteins GP129, 131 and 133

    Directory of Open Access Journals (Sweden)

    Josephine S. Gnanandarajah


    Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus (HCMV is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV, consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model.

  17. Microwave circulator design

    CERN Document Server

    Linkhart, Douglas K


    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  18. Molecular Typing of Mycobacterium Tuberculosis Complex by 24-Locus Based MIRU-VNTR Typing in Conjunction with Spoligotyping to Assess Genetic Diversity of Strains Circulating in Morocco.

    Directory of Open Access Journals (Sweden)

    Nada Bouklata

    Full Text Available Standard 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR typing allows to get an improved resolution power for tracing TB transmission and predicting different strain (sub lineages in a community.During 2010-2012, a total of 168 Mycobacterium tuberculosis Complex (MTBC isolates were collected by cluster sampling from 10 different Moroccan cities, and centralized by the National Reference Laboratory of Tuberculosis over the study period. All isolates were genotyped using spoligotyping, and a subset of 75 was genotyped using 24-locus based MIRU-VNTR typing, followed by first line drug susceptibility testing. Corresponding strain lineages were predicted using MIRU-VNTRplus database.Spoligotyping resulted in 137 isolates in 18 clusters (2-50 isolates per cluster: clustering rate of 81.54% corresponding to a SIT number in the SITVIT database, while 31(18.45% patterns were unique of which 10 were labelled as "unknown" according to the same database. The most prevalent spoligotype family was LAM; (n = 81 or 48.24% of isolates, dominated by SIT42, n = 49, followed by Haarlem (23.80%, T superfamily (15.47%, >Beijing (2.97%, > U clade (2.38% and S clade (1.19%. Subsequent 24-Locus MIRU-VNTR typing identified 64 unique types and 11 isolates in 5 clusters (2 to 3isolates per cluster, substantially reducing clusters defined by spoligotyping only. The single cluster of three isolates corresponded to two previously treated MDR-TB cases and one new MDR-TB case known to be contact a same index case and belonging to a same family, albeit residing in 3 different administrative regions. MIRU-VNTR loci 4052, 802, 2996, 2163b, 3690, 1955, 424, 2531, 2401 and 960 were highly discriminative in our setting (HGDI >0.6.24-locus MIRU-VNTR typing can substantially improve the resolution of large clusters initially defined by spoligotyping alone and predominating in Morocco, and could therefore be used to better study tuberculosis

  19. 10公斤以内婴幼儿复杂先天性心脏病的体外循环管理%Management of extra corporeal circulation in infants less than 10 kg with complex congenital heart diseases

    Institute of Scientific and Technical Information of China (English)

    向文星; 王晓莉; 张卫达; 叶俊龙


    Objectives To sum up the management experience of extracorporeal circulation (ECC) in 106 infants less than 10 kg with complex congenital heart diseases. Methods Clinical data and ECC information of the 106 subjects from January 2009 to December 2010 were reviewed. Composition of ECC priming solution of all 106 patients and requirements of priming flow rate in different temperatures were analyzed. All subjects' blood and organs were protected. Adoption of conventional ultrafiltration or modified ultrafiltration for maintaining the balance, of fluid intake and output were observed. Results Duration of ECC was 45-354 minutes and aortic clamping was 18-228 minutes. Urine output in bypass is 10-300 mL. Four patients died after surgery, which had no direct relationship with ECC Conclusions Reasonable priming solution, adequate drainage and effective priming flow, combined with conventional ultrafiltration or balanced ultrafiltration or modified ultrafiltration, protection of blood and organs,were the effective methods for ECC management in low weight infants with complex congenital heart diseases.%目的 总结106例10 kg以内婴幼儿复杂先天性心脏病的体外循环(extracorporeal circulation,ECC)管理体会.方法 回顾性分析2009年1月至2010年12月在广州军区医院住院的106例10 kg以内婴幼儿复杂先天性心脏病的临床资料和ECC资料.分析全组患儿ECC预充液的组成,不同温度时对灌注流量的要求;重视血液和各脏器的保护,行常规超滤和改良超滤以维持液体出入量的平衡.结果 体外循环时间45~354 min,主动脉阻断时间18~228 min,转流中尿量10~300 mL.术后死亡4例,与ECC无直接关系.结论 合理的预充,充分的引流与有效的灌注流量,联合应用常规超滤、平衡超滤和改良超滤,重视血液和各脏器的保护是管理低体质量婴幼儿复杂先天性心脏病ECC的有效方法.

  20. Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis

    DEFF Research Database (Denmark)

    Nielsen, C T; Østergaard, O; Rekvig, O P


    OBJECTIVE: A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls......, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. METHODS: Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow...... in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. RESULTS: Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P 

  1. Pauci-Immune Crescentic Glomerulonephritis: An ANCA-Associated Vasculitis (United States)

    Syed, Rafeel; Rehman, Amina; Valecha, Gautam; El-Sayegh, Suzanne


    Rapidly progressive glomerulonephritis (RPGN) is a syndrome signified by a precipitous loss of renal function, with features of glomerulonephritis including dysmorphic erythrocyturia and glomerular proteinuria. RPGN is associated with extensive crescent formation, and, thus, the clinical term RPGN is often used interchangeably with the pathologic term crescentic glomerulonephritis (CGN). From an immunopathologic standpoint, primary RPGN is divided into pauci-immune GN (PICG), anti-GBM GN, and immune complex GN. PICG, the most common etiology of primary RPGN, refers to a necrotizing glomerulonephritis with few or no immune deposits by immunofluorescence (IF) or electron microscopy (EM). In most patients, pauci-immune CGN is a component of a systemic small vessel vasculitis such as granulomatosis with polyangiitis (GPA). Approximately 90% of patients with PICG have circulating ANCA antibodies, leading to the nomenclature ANCA-associated vasculitis (AAV). Recent research has identified several other antibodies associated with PICG, which is now understood to be a complex spectrum of disease with considerable overlap in terms of clinical phenotype and outcomes. In addition, several genetic and environmental factors have recently been implicated in the pathogenesis of this disorder. With new prognostic classifications, enhanced understanding of immunopathologic mechanisms, and novel treatment paradigms, clinical and experimental interest in PICG remains high. PMID:26688808

  2. Artificial Immune Systems (2010)

    CERN Document Server

    Greensmith, Julie; Aickelin, Uwe


    The human immune system has numerous properties that make it ripe for exploitation in the computational domain, such as robustness and fault tolerance, and many different algorithms, collectively termed Artificial Immune Systems (AIS), have been inspired by it. Two generations of AIS are currently in use, with the first generation relying on simplified immune models and the second generation utilising interdisciplinary collaboration to develop a deeper understanding of the immune system and hence produce more complex models. Both generations of algorithms have been successfully applied to a variety of problems, including anomaly detection, pattern recognition, optimisation and robotics. In this chapter an overview of AIS is presented, its evolution is discussed, and it is shown that the diversification of the field is linked to the diversity of the immune system itself, leading to a number of algorithms as opposed to one archetypal system. Two case studies are also presented to help provide insight into the m...

  3. The murine cytomegalovirus immune evasion protein m4/gp34 forms biochemically distinct complexes with class I MHC at the cell surface and in a pre-Golgi compartment. (United States)

    Kavanagh, D G; Koszinowski, U H; Hill, A B


    We have recently demonstrated that the murine CMV (MCMV) gene m4 is an immune evasion gene that protects MCMV-infected targets from some virus-specific CTL clones. m4 encodes m4/gp34, a 34-kDa glycoprotein that binds to major histocompatibility complex class I in the endoplasmic reticulum and forms a detergent-stable complex that is exported to the surface of the cell. To investigate how m4/gp34 promotes CTL evasion, we analyzed the assembly and export of m4/gp34-K(b) complexes. We found that 50-70% of K(b) exported over the course of MCMV infection was m4/gp34 associated. Because these complexes are present at the cell surface, it is possible that m4 mediates CTL evasion by interfering with contact between class I and receptors on the T cell. In addition, we found that K(b) retained by the MCMV immune evasion gene m152 formed a novel type of complex with Endo H-sensitive m4/gp34; these complexes are distinguished from the exported complexes by being stable in 1% digitonin and unstable in 1% Nonidet P-40. Because this association occurs in a pre-Golgi compartment, m4/gp34 might also interfere with Ag presentation by affecting some aspect of class I assembly, such as peptide loading. Although m4/gp34 requires beta(2)-microglobulin to bind class I, there was no significant binding of m4/gp34 to beta(2)-microglobulin in the absence of class I H chain, demonstrating that m4/gp34 forms Nonidet P-40-stable complexes specifically with folded conformations of class I. We conclude that m4/gp34 promotes immune evasion by a novel mechanism involving altered assembly and/or T cell recognition of class I molecules.

  4. The immune system. (United States)

    Nicholson, Lindsay B


    All organisms are connected in a complex web of relationships. Although many of these are benign, not all are, and everything alive devotes significant resources to identifying and neutralizing threats from other species. From bacteria through to primates, the presence of some kind of effective immune system has gone hand in hand with evolutionary success. This article focuses on mammalian immunity, the challenges that it faces, the mechanisms by which these are addressed, and the consequences that arise when it malfunctions.

  5. Inflammatory response and extracorporeal circulation. (United States)

    Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander


    Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery.

  6. Bovine leukocyte antigen major histocompatibility complex class II DRB3*2703 and DRB3*1501 alleles are associated with variation in levels of protection against Theileria parva challenge following immunization with the sporozoite p67 antigen. (United States)

    Ballingall, Keith T; Luyai, Anthony; Rowlands, G John; Sales, Jill; Musoke, Anthony J; Morzaria, Subash P; McKeever, Declan J


    Initial laboratory trials of an experimental subunit vaccine against Theileria parva based on the 67-kDa major sporozoite surface antigen revealed a range of responses to challenge. We have analyzed convergence in seven sets of monozygotic twins which suggests that genetic factors may have an influence in determining the degree of protection provided by p67 immunization. In addition, we have examined whether allelic diversity at major histocompatibility complex class II loci influences protection. Analysis of bovine leukocyte antigen DRB3 diversity in 201 animals identified significant associations with vaccine success (DRB3*2703; P = 0.027) and vaccine failure (DRB3*1501; P = 0.013). Furthermore, DRB3*2703 was associated with the likelihood of immunized animals showing little to no clinical signs of disease following challenge. We discuss the acquired and innate immune mechanisms that may be behind the associations described here.

  7. Immune response (United States)

    ... and tetanus antitoxin are examples of passive immunization. BLOOD COMPONENTS The immune system includes certain types of white ... lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that ...

  8. Use of radioimmune assay in investigating reagents to be used in the immunocytochemical localization of hepatitis B surface antigen in immune complexes in the kidney of patients with membranous nephropathy and Australia antigenaemia

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe-Coote, S. (South African Medical Research Council, Tygerberg (South Africa). Inst. for Electron Microscopy)


    Radioimmune assay (RIA) was used to investigate the effect of fixatives on antigenicity of the hepatitis B surface antigen (HBsAg) and the effect of pronase on the elution of antibody (Ab) from the HBsAg-Ab complex. The effect of pronase on Ab elution was also tested on sections of kidney from a patient with the immune complex disease systemic lupus erythematosus (SLE). Immunoglobulin G (IgG) was located in pronase treated and untreated sections using the indirect immunoperoxidase technique. Glutareldehyde was shown to be the fixative of choice for studies involving HBsAg. All fixatives were shown to have less effect on antigenicity at 4/sup 0/C than at room temperature. Osmium tetroxide reduced antigenicity to one-third, even at 4/sup 0/C. RIA and SLE kidney section studies showed that Ab was eluted from immune complexes by pronase. Pre-fixation of the antigen (Ag) by glutaraldehyde appears to have no effect on the final elution, although fixation after pronase treatment seemed to enhance the elution effects. The availability of an RIA kit with HBsAg- and Ab-coated beads was of great assistance in evaluating reagents to be used in immunoperoxidase studies of HBsAg in immune complexes of patients with membranous nephropathy and Australia antigenaemia.

  9. Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil

    Institute of Scientific and Technical Information of China (English)

    Jian Cao; Zhongping Niu; Yongan Wang; Yiwen Jiang; Haoyu Liu; Binfeng Wang; Weitian Yin; Lisen Li


    BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.

  10. Differential regulation of spontaneous and immune complex-induced neutrophil apoptosis by proinflammatory cytokines. Role of oxidants, Bax and caspase-3. (United States)

    Ottonello, Luciano; Frumento, Guido; Arduino, Nicoletta; Bertolotto, Maria; Dapino, Patrizia; Mancini, Marina; Dallegri, Franco


    Neutrophil apoptosis represents a crucial step in the mechanisms governing the resolution of neutrophilic inflammation. Several soluble mediators of inflammation modulate neutrophil survival, retarding their apoptosis, whereas neutrophil activation by immune complexes (IC) results in the acceleration of apoptosis. To investigate neutrophil fate at the site of inflammation, we studied the effects of interleukin (IL)-2, IL-6, IL-8, IL-15, GM-CSF, and fMLP on spontaneous and IC-induced neutrophil apoptosis and the mechanisms regulating the survival of these cells. Spontaneous apoptosis was inhibited by GM-CSF, IL-6, and IL-15, but only GM-CSF overturned IC-induced apoptosis. No role of oxidants on the modulation of IC-dependent apoptosis was found. Indeed, fMLP or GM-CSF augmented the IC-dependent oxidative response, whereas the other compounds were ineffective. CGD neutrophils showed low levels of spontaneous apoptosis, but when exposed to IC, underwent a sharp increment of the apoptotic rate in a GM-CSF-inhibitable manner. Conversely, the expression of the proapoptotic protein Bax in 18-h aged neutrophils was down-regulated by GM-CSF, IL-6, and IL-15. Furthermore, IC induced a nearly threefold Bax up-regulation, which was completely reversed only by GM-CSF. Accordingly, the spontaneous activity of caspase-3 was inhibited by GM-CSF, IL-6, and IL-15. Furthermore, IC induced a sharp increment of enzymatic activity, and only GM-CSF inhibited the IC-dependent acceleration. Our results show that apoptosis of resting and IC-activated neutrophils is regulated differently, GM-CSF being the most potent neutrophil antiapoptotic factor. The results also unveil the existence of an oxidant-independent, Bax- and caspase-3-dependent, intracellular pathway regulating neutrophil apoptosis.

  11. Analysis of complex patterns of human exposure and immunity to Schistosomiasis mansoni: the influence of age, sex, ethnicity and IgE.

    Directory of Open Access Journals (Sweden)

    Angela Pinot de Moira

    Full Text Available BACKGROUND: Numerous factors may influence Schistosoma infection intensity and prevalence within endemic communities, including exposure-related factors such as local environment and behaviour, and factors relating to susceptibility to infection such as immunology and genetics. While animal studies performed in the laboratory can be tightly controlled, human populations are highly heterogeneous, varying according to demographic characteristics, genetic background and exposure to infection. The heterogeneous nature of human water contact behaviour in particular makes it difficult to distinguish between a lack of cercarial exposure and reduced susceptibility to infection as the cause for low levels of infection in the field. METHODS AND PRINCIPAL FINDINGS: In this study we investigate risk factors for Schistosoma mansoni infection in a rural Ugandan fishing community receiving treatment as part of a multi-disciplinary longitudinal reinfection study. More specifically, we examine the influence that age, sex and ethnic background have on susceptibility to reinfection after anti-helminth drug treatment, but use individual estimates of cercarial exposure and multivariable methods in an attempt to remove noise created by environmental and behavioural heterogeneities. We then investigate whether schistosome-specific IgE immune responses could account for any remaining variations in susceptibility to reinfection. Our findings suggest that observed ethnic- and sex-related variations in S. mansoni reinfection were due to variations in cercarial exposure, as opposed to biological differences in susceptibility to infection. Age-related differences in reinfection were not explained by exposure, however, and appeared linked to the balance of IgE and IgG(4 to the tegumental antigen SmTAL1 (formerly Sm22.6, which itself was significantly related to resistance to reinfection. CONCLUSIONS: This study highlights the benefit of taking a multidisciplinary approach in

  12. Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release. (United States)

    Truman, Jean-Philip; Al Gadban, Mohammed M; Smith, Kent J; Jenkins, Russell W; Mayroo, Nalini; Virella, Gabriel; Lopes-Virella, Maria F; Bielawska, Alicja; Hannun, Yusuf A; Hammad, Samar M


    Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fcγ receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B' (HSP70B') was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1β-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis.

  13. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes. (United States)

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro


    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

  14. Mountains and Tropical Circulation (United States)

    Naiman, Z.; Goodman, P. J.; Krasting, J. P.; Malyshev, S.; Russell, J. L.; Stouffer, R. J.


    Observed tropical convection exhibits zonal asymmetries that strongly influence spatial precipitation patterns. The drivers of changes to this zonally-asymmetric Walker circulation on decadal and longer timescales have been the focus of significant recent research. Here we use two state-of-the-art earth system models to explore the impact of earth's mountains on the Walker circulation. When all land-surface topography is removed, the Walker circulation weakens by 33-59%. There is a ~30% decrease in global, large-scale upward vertical wind velocities in the middle of the troposphere, but only minor changes in global average convective mass flux, precipitation, surface and sea-surface temperatures. The zonally symmetric Hadley circulation is also largely unchanged. Following the spatial pattern of changes to large-scale vertical wind velocities, precipitation becomes less focused over the tropics. The weakening of the Walker circulation, but not the Hadley circulation, is similar to the behavior of climate models during radiative forcing experiments: in our simulations, the weakening is associated with changes in vertical wind velocities, rather than the hydrologic cycle. These results indicate suggest that mountain heights may significantly influence the Walker circulation on geologic time scales, and observed changes in tropical precipitation over millions of years may have been forced by changes in tropical orography.


    Directory of Open Access Journals (Sweden)

    Savel’eva NN


    Full Text Available Introduction. Due to the high prevalence of chronic generalized periodontitis there is a need for a broader analysis of the causes and development of diseases, as well as the search for effective treatments for etiopathogenetical. The aim of this work was to study the effect of newly developed therapy on local immunity in patients CGP I and II severity with enterobiasis. Material & methods. The main group consisted of 32 people with СGP I degree and 60 people with СGP II severity who were treated according to our scheme. The control group consisted of 30 people with СGP I degree and 58 people with СGP II severity, treated with conventional treatment. The control group consisted of 30 people without periodontal disease and chronic diseases of other systems. All patients were studied the main group and the comparison group conducted a basic local therapeutic treatment of periodontal disease, including professional oral hygiene, temporary splinting of teeth, selective prishlifovyvanie teeth. For medical treatment of periodontal tissues using 0.05% - 0.2% solution of chlorhexidine bigluconate. Further treatment of patients of the main group carried out in 2 stages. At the first stage the main group received: irrigation and instillation of periodontal tissue in periodontal pockets antiseptic preparation "Dekasan" application keratoplastic drug "Katomas". Systemically administered drug tonic "Sage oil" probiotic "Kvertulin" immunomodulator "Erbisol". In the second phase, patients received: applications on the gums periodontal gel "Lizomukoid" systemically complex preparation "Оil extract from pumpkin seeds." All patients of the main group used toothpaste "Lacalut flora" and rinse "grapefruit". In the comparison group, patients received applications in periodontal pockets (drug Dalatsin C application to the gums (keratoplastic drug Aekol system - a probiotic Linex, immunomodulator "Echinacea compositum С". All patients with the comparison group

  16. A myriad of functions and complex regulation of the CCR7/CCL19/CCL21 chemokine axis in the adaptive immune system. (United States)

    Comerford, Iain; Harata-Lee, Yuka; Bunting, Mark D; Gregor, Carly; Kara, Ervin E; McColl, Shaun R


    The chemokine receptor CCR7 and its ligands CCL19 and CCL21 control a diverse array of migratory events in adaptive immune function. Most prominently, CCR7 promotes homing of T cells and DCs to T cell areas of lymphoid tissues where T cell priming occurs. However, CCR7 and its ligands also contribute to a multitude of adaptive immune functions including thymocyte development, secondary lymphoid organogenesis, high affinity antibody responses, regulatory and memory T cell function, and lymphocyte egress from tissues. In this survey, we summarise the role of CCR7 in adaptive immunity and describe recent progress in understanding how this axis is regulated. In particular we highlight CCX-CKR, which scavenges both CCR7 ligands, and discuss its emerging significance in the immune system.

  17. Circulating (CD3−CD19+CD20−IgD−CD27highCD38high) Plasmablasts: A Promising Cellular Biomarker for Immune Activity for Anti-PLA2R1 Related Membranous Nephropathy? (United States)

    Beukinga, Ingrid; Willard-Gallo, Karen; Nortier, Joëlle; Pradier, Olivier


    Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX), efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3−CD19+CD20−IgD−CD27highCD38high), a useful biomarker of RTX response in other autoimmune diseases, and memory (CD3−CD19+CD20+IgD−CD27+CD38−) and naive (CD3−CD19+CD20+IgD+CD27−CD38low) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow-up after RTX. RTX induced complete disappearance of CD19+ B cells, plasmablasts, and memory B cells as soon as day 15. Despite severe CD19+ lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells (days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more rapidly than memory B cells but still remained elevated as compared to day 0 of RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case report suggests that, besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN. PMID:27493452

  18. Immune Aspects of Female Infertility

    Directory of Open Access Journals (Sweden)

    Andrea Brazdova


    Full Text Available Immune infertility, in terms of reproductive failure, has become a serious health issue involving approximately 1 out of 5 couples at reproductive age. Semen that is defined as a complex fluid containing sperm, cellular vesicles and other cells and components, could sensitize the female genital tract. The immune rejection of male semen in the female reproductive tract is explained as the failure of natural tolerance leading to local and/or systemic immune response. Present active immune mechanism may induce high levels of anti-seminal/sperm antibodies. It has already been proven that iso-immunization is associated with infertility. Comprehensive studies with regards to the identification of antibody-targets and the determination of specific antibody class contribute to the development of effective immuno-therapy and, on the other hand, potential immuno-contraception, and then of course to complex patient diagnosis. This review summarizes the aspects of female immune infertility.

  19. Learning Circulant Sensing Kernels (United States)


    learned dictionaries. Examples of analytic dictionaries include the discrete cosine basis, various wavelets bases , as well as tight frames. Some of them...Compressive sensing based high resolution channel estimation for OFDM system. To appear in IEEE Journal of Selected Topics in Signal Processing, Special...theoretical and computational properties to a (partial) circulant matrix of the same size, our discussions below are based exclusively on the circulant

  20. Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection. (United States)

    Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R


    Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens.

  1. Isomorphic Operators and Functional Equations for the Skew-Circulant Algebra

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    Zhaolin Jiang


    Full Text Available The skew-circulant matrix has been used in solving ordinary differential equations. We prove that the set of skew-circulants with complex entries has an idempotent basis. On that basis, a skew-cyclic group of automorphisms and functional equations on the skew-circulant algebra is introduced. And different operators on linear vector space that are isomorphic to the algebra of n×n complex skew-circulant matrices are displayed in this paper.


    Institute of Scientific and Technical Information of China (English)

    张明霞; 林尔昕; 王淑民; 崔琢


    目的 了解特异性免疫复合物在脑囊虫病治疗过程中的意义。方法 用双单抗夹心ELISA法检测特异性免疫复合物:采用抗人IgG、IgM单抗包板,来捕获由血清提取的免疫复合物中的特异性IgG、IgM型免疫复合物,通过酶标抗囊虫单抗结合物显色,测其OD值。结果 IgG型免疫复合物在1疗程后含量较治疗前明显升高(P<0.05)以后各疗程则显著下降(P<0.01);IgM型免疫复合物的含量治疗前与1疗程后相比差别不显著,但随着疗程增加其含量逐渐下降(P<0.01);各疗程的临床反应加重发生率以第1疗程最高(P<0.005)。结论 IgG型免疫复合物可以作为治疗反应、疗效考核的依据。%Aim To observe the dynamic changes of specific immune complexover all courses of drug administration of patients with neurocysticercosis. Methods By using a double mono-cloned antibody sandwich ELISA assay the specific immune complex was detected.Employed anti-human IgG, IgM McAb as coated material, and HRP labeled anti-cysticerci McAb as recognizing system, specific immune complexes that extracted in sera were monitored. Results The immune complex level of IgG class rose significantly after the 1st course (P<0.05), and then gradually dropped off (P<0.01). On the other hand, that of IgM class did not change significantly after 1st course of treatment. It gradually declined with advancing course of drug administration (P<0.01). The incidence rate of clinical worsening after 1st course of treatment was the highest one among all courses (P<0.005).Conclusion This study indicates that immune complex level of IgG class is associated with the clinical worsening and the efficacy of therapy.

  3. Conceptual models of the wind-driven and thermohaline circulation

    NARCIS (Netherlands)

    Drijfhout, S.S.; Marshall, D.P.; Dijkstra, H.A.


    Conceptual models are a vital tool for understanding the processes that maintain the global ocean circulation, both in nature and in complex numerical ocean models. In this chapter we provide a broad overview of our conceptual understanding of the wind-driven circulation, the thermohaline circulatio

  4. Gaussian Fibonacci Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang


    Full Text Available Circulant matrices have become important tools in solving integrable system, Hamiltonian structure, and integral equations. In this paper, we prove that Gaussian Fibonacci circulant type matrices are invertible matrices for n>2 and give the explicit determinants and the inverse matrices. Furthermore, the upper bounds for the spread on Gaussian Fibonacci circulant and left circulant matrices are presented, respectively.

  5. Immune System

    NARCIS (Netherlands)

    Kuper, C.F.; Ruehl-Fehlert, C.; Elmore, S.A.; Parker, G.A.


    Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion t

  6. Immune System (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  7. Activation of the complement system and accumulation of hemoglobin-haptoglobin complexes in plasma during an adverse reaction to penicillin treatment. (United States)

    Brandslund, I; Svehag, S E; Teisner, B; Hyltoft Petersen, P


    A patient treated with penicillin intravenously developed a serum sickness-like reaction. Classical pathway complement (C) activation was indicated by quantitation of the split products C3c and C3d as well as demonstration of C4 conversion. Circulating immune complexes could, however, not be detected by the solid-phase Clq and PEG-precipitation methods. A concomitant accumulation of circulating hemoglobin-haptoglobin complexes and a marked fall in serum-fibronectin concentrations suggested saturation of the reticuloendothelial system. The plasma became a deep-red color, and a diffuse intravascular coagulation followed. The patient recovered completely upon discontinuation of penicillin administration.

  8. Artificial Immune Systems Tutorial

    CERN Document Server

    Aickelin, Uwe


    The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self-cells or non-self cells. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years. A novel computational intelligence technique, inspired by immunology, has emerged, called Artificial Immune Systems. Several concepts from the immune have been extracted an...

  9. Artificial Immune Systems

    CERN Document Server

    Aickelin, Uwe


    The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self-cells or non-self cells. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years. A novel computational intelligence technique, inspired by immunology, has emerged, called Artificial Immune Systems. Several concepts from the immune have been extracted an...

  10. Mammalian gut immunity

    Directory of Open Access Journals (Sweden)

    Benoit Chassaing


    Full Text Available The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells and hemopoietic (macrophages, dendritic cells, T-cells origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a "love-hate relationship." Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases.

  11. LA EVOLUCIÓN DE SISTEMAS COMPLEJOS: EL CASO DEL SISTEMA INMUNE EN ANIMALES The Evolution of Complex Systems: The Case of the Immune System in Animals

    Directory of Open Access Journals (Sweden)


    Full Text Available El sistema inmune en animales comprende una serie de mecanismos celulares y moleculares que de manera conjunta mantienen la integridad fisiológica y genética de los organismos. Convencionalmente se ha considerado la existencia de dos clases de inmunidad, la innata y la adaptativa. La primera es ancestral, con variabilidad limitada y baja discriminación, mientras que la segunda es altamente variable, específica y restringida a vertebrados mandibulados. La inmunidad adaptativa se basa en receptores de antígeno que se rearreglan somáticamente para generar una diversidad casi ilimitada de moléculas. Este mecanismo de recombinación somática muy probablemente emergió como consecuencia de un evento de transferencia horizontal de transposones y transposas bacterianas en el ancestro de los vertebrados mandibulados. El reciente descubrimiento en vertebrados no mandibulados e invertebrados de mecanismos de inmunidad adaptativa alternos, plantea la necesidad de considerar nuevos elementos en la construcción de un modelo evolutivo de la inmunidad en animales. Algunos de esos elementos se esbozan en este ensayo.The immune system in animals is composed by a series of cell and molecular mechanisms that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms

  12. Circulant Double Coverings of a Circulant Graph of Valency Five

    Institute of Scientific and Technical Information of China (English)

    Rong Quan FENG; Jin Ho KWAK


    Enumerating the isomorphism classes of several types of graph covering projections is one of the central research topics in enumerative topological graph theory. A covering of G is called circulant if its covering graph is circulant. Recently, the authors [Discrete Math., 277, 73-85 (2004)]enumerated the isomorphism classes of circulant double coverings of a certain type, called a typicalcovering, and showed that no double covering of a circulant graph of valency three is circulant. Also, in [Graphs and Combinatorics, 21, 386-400 (2005)], the isomorphism classes of circulant double coverings of a circulant graph of valency four are enumerated. In this paper, the isomorphism classes of circulant double coverings of a circulant graph of valency five are enumerated.

  13. Kernels in circulant digraphs

    Directory of Open Access Journals (Sweden)

    R. Lakshmi


    Full Text Available A kernel $J$ of a digraph $D$ is an independent set of vertices of $D$ such that for every vertex $w,in,V(D,setminus,J$ there exists an arc from $w$ to a vertex in $J.$ In this paper, among other results, a characterization of $2$-regular circulant digraph having a kernel is obtained. This characterization is a partial solution to the following problem: Characterize circulant digraphs which have kernels; it appeared in the book {it Digraphs - theory, algorithms and applications}, Second Edition, Springer-Verlag, 2009, by J. Bang-Jensen and G. Gutin.

  14. Decreased complement mediated binding of antibody//sup 3/-dsDNA immune complexes to the red blood cells of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, R.P.; Horgan, C.; Buschbacher, R.; Brunner, C.M.; Hess, C.E.; O' Brien, W.M.; Wanebo, H.J.


    The complement mediated binding of prepared antibody//sup 3/H-dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed.

  15. Structures of the ultra-high-affinity protein–protein complexes of pyocins S2 and AP41 and their cognate immunity proteins from pseudomonas aeruginosa


    Joshi, Amar; Grinter, Rhys; Josts, Inokentijs; Chen, Sabrina; Wojdyla, Justyna; Lowe, Edward; Kaminska, Renata; Sharp, Connor; McCaughey, Laura; Roszak, Aleksander; Cogdell, Richard; Byron, Olwyn; Walker, Daniel; Kleanthous, Colin


    How ultra-high-affinity protein–protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase–Im interaction is a model system for the study of high-affinity protein–protein interactions. However, despit...

  16. Immune complex stimulation of human neutrophils involves a novel Ca2+/H+ exchanger that participates in the regulation of cytoplasmic pH: flow cytometric analysis of Ca2+/pH responses by subpopulations. (United States)

    Bernardo, John; Hartlaub, Hilary; Yu, Xin; Long, Heidi; Simons, Elizabeth R


    The activation of human phagocytic leukocytes by immune complexes (IC) or opsonized microbes via their Fc and complement receptors has been well-described. The mechanisms involved in this process are complex and depend on the receptors involved. The biochemical events that lead to the destruction of invading organisms in turn display varying degrees of interdependence, but the controlling elements that lead to the ultimate killing of ingested organisms within phagosomes by lysosomal enzymes and reactive oxygen intermediates are still not completely understood. We have addressed these mechanisms by following and correlating the kinetics of responses by individual cells, using multiparameter flow cytometry. Using nonopsonized IC as stimuli, we document here the presence of a novel Ca(2)(+)/H(+) voltage-independent channel in human neutrophils, which helps to control their cytoplasmic pH.

  17. The fetal circulation. (United States)

    Kiserud, Torvid; Acharya, Ganesh


    Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology, but with important differences. The human fetus seems to circulate less blood through the placenta, shunt less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal sheep. However, there are substantial individual variations and the pattern changes with gestational age. The normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale are functionally closely related and represent an important distributional unit for the venous return. The left portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus, the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies: increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow.




    Introduction. Due to the high prevalence of chronic generalized periodontitis there is a need for a broader analysis of the causes and development of diseases, as well as the search for effective treatments for etiopathogenetical. The aim of this work was to study the effect of newly developed therapy on local immunity in patients CGP I and II severity with enterobiasis. Material & methods. The main group consisted of 32 people with СGP I degree and 60 people with СGP II severity who were...

  19. The Reticular Cell Network : A Robust Backbone for Immune Responses

    NARCIS (Netherlands)

    Textor, Johannes; Mandl, Judith N; de Boer, Rob J


    Lymph nodes are meeting points for circulating immune cells. A network of reticular cells that ensheathe a mesh of collagen fibers crisscrosses the tissue in each lymph node. This reticular cell network distributes key molecules and provides a structure for immune cells to move around on. During inf

  20. Levels of immune cells in transcendental meditation practitioners

    Directory of Open Access Journals (Sweden)

    Jose R Infante


    Conclusions: The technique of meditation studied seems to have a significant effect on immune cells, manifesting in the different circulating levels of lymphocyte subsets analyzed. The significant effect of TM on the neuroendocrine axis and its relationship with the immune system may partly explain our results.

  1. Humoral and Cellular Immune Response in Canine Hypothyroidism. (United States)

    Miller, J; Popiel, J; Chełmońska-Soyta, A


    Hypothyroidism is one of the most common endocrine diseases in dogs and is generally considered to be autoimmune in nature. In human hypothyroidism, the thyroid gland is destroyed by both cellular (i.e. autoreactive helper and cytotoxic T lymphocytes) and humoral (i.e. autoantibodies specific for thyroglobulin, thyroxine and triiodothyronine) effector mechanisms. Other suggested factors include impaired peripheral immune suppression (i.e. the malfunction of regulatory T cells) or an additional pro-inflammatory effect of T helper 17 lymphocytes. The aim of this study was to evaluate immunological changes in canine hypothyroidism. Twenty-eight clinically healthy dogs, 25 hypothyroid dogs without thyroglobulin antibodies and eight hypothyroid dogs with these autoantibodies were enrolled into the study. There were alterations in serum proteins in hypothyroid dogs compared with healthy controls (i.e. raised concentrations of α-globulins, β2- and γ-globulins) as well as higher concentration of acute phase proteins and circulating immune complexes. Hypothyroid animals had a lower CD4:CD8 ratio in peripheral blood compared with control dogs and diseased dogs also had higher expression of interferon γ (gene and protein expression) and CD28 (gene expression). Similar findings were found in both groups of hypothyroid dogs. Canine hypothyroidism is therefore characterized by systemic inflammation with dominance of a cellular immune response.

  2. Candida Immunity

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    Julian R. Naglik


    Full Text Available The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. C. albicans primarily infects immunocompromised individuals as a result of either immunodeficiency or intervention therapy, which highlights the importance of host immune defences in preventing fungal infections. The host defence system utilises a vast communication network of cells, proteins, and chemical signals distributed in blood and tissues, which constitute innate and adaptive immunity. Over the last decade the identity of many key molecules mediating host defence against C. albicans has been identified. This review will discuss how the host recognises this fungus, the events induced by fungal cells, and the host innate and adaptive immune defences that ultimately resolve C. albicans infections during health.

  3. Chromatin Remodeling and Plant Immunity. (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q


    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance?

  4. Detection of circulating immune complex in diagnosis of neurocysticercosis%囊尾蚴循环免疫复合物检测在脑囊尾蚴病诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    崔琢; 沈继龙



  5. Pre-existing adenovirus immunity modifies a complex mixed Th1 and Th2 cytokine response to an Ad5/HIV-1 vaccine candidate in humans.

    Directory of Open Access Journals (Sweden)

    Samuel O Pine

    Full Text Available The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, #NCT00849732. Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36 or Ad5-seropositive (titer >200; n = 34. Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes. At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008, and significantly more IP-10 (p = 0.0009, IL-2 (p = 0.006 and IL-10 (p = 0.05 in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these

  6. Modelled Circulation In Storfjorden (United States)

    Skogseth, R.; Asplin, L.

    The model area Storfjorden is situated between the islands Spitsbergen, Barentsöya and Edgeöya at the Svalbard Archipelago. The entrance of Storfjorden is defined by a shallow bank Storfjordbanken and some small islands Tusenöyane in southeast, and by an 115m deep sill at about 76 45' N in the south. Maximum depth in Storfjorden is 190m, which is surrounded by gradually shallower shelves in the north, the east and southeast. A steep bottom slope is present on the western side of Storfjorden. He- leysundet and Freemansundet, two sounds between respectively Spitsbergen and Bar- entsöya, and Barentsöya and Edgeöya, define two narrow and shallow entrances in the north and northeast connecting Storfjorden with the northwestern Barents Sea. Strong tidal currents exist in Heleysundet (4-5ms-1) and Freemansundet (2-3ms-1), but the general circulation in Storfjorden is not well known. The coastal current in Storfjor- den is cyclonic directed into Storfjorden south of Edgeöya from the East Spitsbergen Current and out of Storfjorden south of Spitsbergen where it is called Sørkappstrøm- men. A three-dimensional sigma layered numerical ocean model called Bergen Ocean Model (BOM) was used to simulate the circulation in Storfjorden with Freemansundet opened. Two simulations were carried out, one with heat flux (100 Wm-2) and one without heat flux from the ocean to the atmosphere. The heat flux was applied only in the proper fjord area north of the sill and not outside as a crude approximation of the effects of a polynya in the sea ice cover during winter. Both simulations had a 4km horizontal resolution and 21 sigma layers. The model is forced by winds (from the NCEP reanalyzed fields) and tides. Initial fields are from the DNMI/IMR climatol- ogy. The model simulation without heat flux gave a circulation heavily dependent on tidal forcing, showing strong tidal currents up to 2ms-1 in Freemansundet, between Tusenöyane and on Storfjordbanken southwest of Edgeöya. Earlier

  7. Cereral Circulation in Preeclampsia

    Directory of Open Access Journals (Sweden)

    A. A. Ivshin


    Full Text Available Objective: to evaluate the possibilities of using transcranial Doppler study in pregnant women and pueperas with preeclamp-sia. Subjects and methods. Two hundred and thirty-two pregnant women diagnosed as having varying preeclampsia were prospectively studied. A comparison group comprised 90 apparently healthy women in the third trimester of pregnancy. All the respondents underwent transcranial duplex scanning of the medial cerebral artery with the linear velocity values being determined. A number of the values reflecting the level of perfusion and intracranial pressures, hydrodynamic resistance in the system, cerebrovascular responsiveness and the state of the vascular wall were calculated. Correlation analysis was made between the parameters of cerebral circulation and the severity of preeclampsia, proteinuria, the severity of hydrops, and the parameters of central and peripheral hemodynamics. Results. The findings suggest that there is impaired cerebral perfusion in pregnant women and puerperas with varying preeclampsia, the severity of cerebral circulatory disorders being in proportion with that of preeclampsia. There is a close correlation between cerebral circulation and the individual criteria determining the severity of preeclampsia. The linear values of the Doppler spectrum, namely linear flow characteristics, are prognos-tically most significant. Conclusion. The introduction of transcranial Doppler study into obstetric care has permitted the authors not only to study cerebral circulatory disorders in healthy and pregnant women and puerperas with preeclampia in detail, but also to establish a number of highly significant prognostic criteria for the severity of this life-threatening complication of gestation. The results of transcranial Doppler study assist practitioners in timely and accurately solving the problems in the diagnosis of preeclampsia and in evaluating its severity. Cerebral circulatory values may be successfully used to

  8. Compressed Sensing for Thoracic MRI with Partial Random Circulant Matrices

    Directory of Open Access Journals (Sweden)

    Hideaki Haneishi


    Full Text Available The use of Circulant matrix as the sensing matrix in compressed sensing (CS scheme has recently been proposed to overcome the limitation of random or partial Fourier matrices. Aside from reducing computational complexity, the use of circulant matrix for MR image offers the feasibility in hardware implementations. This paper presents the simulation of compressed sensing for thoracic MR imaging with circulant matrix as the sensing matrix. The comparisons of reconstruction of three different type MR images using circulant matrix are investigated in term of number of samples, number of iteration and signal to noise ratio (SNR. The simulation results showed that Circulant Matrix works efficiently for encoding the MR image of respiratory organ, especially for smooth and sparse image in spatial domain.

  9. Resolvability in Circulant Graphs

    Institute of Scientific and Technical Information of China (English)

    Muhammad SALMAN; Imran JAVAID; Muhammad Anwar CHAUDHRY


    A set W of the vertices of a connected graph G is called a resolving set for G if for every two distinct vertices u,v ∈ V(G) there is a vertex w ∈ W such that d(u,w) ≠ d(v,w).A resolving set of minimum cardinality is called a metric basis for G and the number of vertices in a metric basis is called the metric dimension of G,denoted by dim(G).For a vertex u of G and a subset S of V(G),the distance between u and S is the number mins∈s d(u,s).A k-partition H ={S1,S2,...,Sk} of V(G) is called a resolving partition if for every two distinct vertices u,v ∈ V(G) there is a set Si in Π such that d(u,Si) ≠ d(v,Si).The minimum k for which there is a resolving k-partition of V(G) is called the partition dimension of G,denoted by pd(G).The circulant graph is a graph with vertex set Zn,an additive group ofintegers modulo n,and two vertices labeled i and j adjacent if and only if i - j (mod n) ∈ C,where C C Zn has the property that C =-C and 0(∈) C.The circulant graph is denoted by Xn,△ where A =|C|.In this paper,we study the metric dimension of a family of circulant graphs Xn,3 with connection set C ={1,-n/2,n - 1} and prove that dim(Xn,3) is independent of choice of n by showing that 3 for all n =0 (mod 4),dim(X,n,3) ={ 4 for all n =2 (mod 4).We also study the partition dimension of a family of circulant graphs Xn,4 with connection set C ={±1,±2} and prove that pd(Xn,4) is independent of choice of n and show that pd(X5,4) =5 and 3 forall odd n≥9,pd(Xn,4) ={ 4 for all even n ≥ 6 and n =7.

  10. Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.

    Directory of Open Access Journals (Sweden)

    Luisa Novellino

    Full Text Available Hepatitis B virus (HBV produces high quantities of subviral surface antigen particles (HBsAg which circulate in the blood outnumbering virions of about 1\\10(3-6 times. In individuals coinfected with the defective hepatitis Delta virus (HDV the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05 with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145 as well as immune regulatory (most frequent = miR-106b and miR-223. Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathogen. The finding that HBsAg particles carry selective pools of hepatocellular miRNAs opens new avenues of research to disentangle the complex interactions between host and HBV and provides a non invasive tool to study the physiopathology of liver epigenetics.

  11. Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs. (United States)

    Novellino, Luisa; Rossi, Riccardo L; Bonino, Ferruccio; Cavallone, Daniela; Abrignani, Sergio; Pagani, Massimiliano; Brunetto, Maurizia R


    Hepatitis B virus (HBV) produces high quantities of subviral surface antigen particles (HBsAg) which circulate in the blood outnumbering virions of about 1\\10(3-6) times. In individuals coinfected with the defective hepatitis Delta virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs) which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05) with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145) as well as immune regulatory (most frequent = miR-106b and miR-223). Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathogen. The finding that HBsAg particles carry selective pools of hepatocellular miRNAs opens new avenues of research to disentangle the complex interactions between host and HBV and provides a non invasive tool to study the physiopathology of liver epigenetics.

  12. Melatonin, immune function and aging

    Directory of Open Access Journals (Sweden)

    Perumal SR Pandi


    Full Text Available Abstract Aging is associated with a decline in immune function (immunosenescence, a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.

  13. Immunizations: Active vs. Passive (United States)

    ... Prevention > Immunizations > Immunizations: Active vs. Passive Safety & Prevention Listen Español Text Size Email Print Share Immunizations: Active vs. Passive Page Content Article Body Pediatricians can ...

  14. Curating the innate immunity interactome.

    LENUS (Irish Health Repository)

    Lynn, David J


    The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http:\\/\\/ is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.

  15. Anomalous Brain Dominance and the Immune System: Do Left-Handers Have Specific Immunological Patterns? (United States)

    Lengen, Charis; Regard, Marianne; Joller, Helen; Landis, Theodor; Lalive, Patrice


    Geschwind and Behan (1982) and Geschwind and Galaburda (1985a, 1985b, 1985c) suggested a correlation between brain laterality and immune disorders. To test whether this hypothesis holds true not only for the frequency of immune diseases and circulating autoantibodies, but extends also to cellular immunity, we examined the association between…

  16. North Atlantic Circulation (United States)

    Molinari, R.; Bryan, K.; Schott, F.

    The intensity of the North Atlantic winddriven and thermohaline circulation and the close proximity of many oceanographic installations make the North Atlantic a particularly favored region of the world ocean from the standpoint of research in ocean circulation. Recent increases in available data and advances in numerical modeling techniques served as the impetus to convene a joint workshop of modelers and observers working on the North Atlantic with the Scientific Committee on Oceanic Research (SCOR) Working Group (WG) 68 (“North Atlantic Circulation”). Goals of the workshop were to provide an update on data sets and models and to discuss the poleward heat flux problem and possible monitoring strategies. The joint Workshop/SCOR WG-68 meeting was convened by F. Schott (chairman of the working group; Rosenstiel School of Marine and Atmospheric Science, Miami, Fla.), K. Bryan (National Oceanic and Atmospheric Administration/ Geophysical Fluid Dynamics Laboratory (NOAA/GFDL)), and R. Molinari (NOAA/Atlantic Oceanographic and Meteorological Laboratory (NOAA/AOML)).

  17. Circulation of Stars (United States)

    Boitani, P.


    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  18. Estimation of immune complexes by a microplate-adapted C1q-Protein A enzyme-linked-immunosorbent-assay (C1q-PA-ELISA)

    DEFF Research Database (Denmark)

    Bjerrum, L; Glikmann, G; Jensenius, J C;


    . Bound IC was measured by use of alkaline phosphatase-labelled Protein A followed by the substrate para-nitro-phenyl-phosphate. A dose response was found for both delta IgG and BSA anti-BSA complexes, while variations in the concentration of monomer IgG did not affect the optical density. Elevated levels...

  19. The commensal microbiota drives immune homeostasis

    Directory of Open Access Journals (Sweden)

    Marie-Claire eArrieta


    Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

  20. Mechanisms regulating skin immunity and inflammation. (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O


    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  1. P-Selectin preserves immune tolerance in mice and is reduced in human cutaneous lupus. (United States)

    González-Tajuelo, Rafael; Silván, Javier; Pérez-Frías, Alicia; de la Fuente-Fernández, María; Tejedor, Reyes; Espartero-Santos, Marina; Vicente-Rabaneda, Esther; Juarranz, Ángeles; Muñoz-Calleja, Cecilia; Castañeda, Santos; Gamallo, Carlos; Urzainqui, Ana


    Mice deficient in P-Selectin presented altered immunity/tolerance balance. We have observed that the absence of P-Selectin promotes splenomegaly with reduced naïve T cell population, elevated activated/effector T cell subset, increased germinal center B and Tfh populations and high production of autoreactive antibodies. Moreover, 1.5-3-month-old P-selectin KO mice showed reduced IL-10-producing leukocytes in blood and a slightly reduced Treg population in the skin. With aging and, coinciding with disease severity, there is an increase in the IL17(+) circulating and dermal T cell subpopulations and reduction of dermal Treg. As a consequence, P-Selectin deficient mice developed a progressive autoimmune syndrome showing skin alterations characteristic of lupus prone mice and elevated circulating autoantibodies, including anti-dsDNA. Similar to human SLE, disease pathogenesis was characterized by deposition of immune complexes in the dermoepidermal junction and renal glomeruli, and a complex pattern of autoantibodies. More important, skin biopsies of cutaneous lupus erythematosus patients did not show increased expression of P-Selectin, as described for other inflammatory diseases, and the number of vessels expressing P-Selectin was reduced.

  2. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun


    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  3. The most common friend first immunization (United States)

    Nian, Fu-Zhong; Hu, Cha-Sheng


    In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts-Strogatz (WS) small-world network model and the Barabsi-Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. Project supported by the National Natural Science Foundation of China (Grant No. 61263019), the Program for International Science and Technology Cooperation Projects of Gansu Province, China (Grant No. 144WCGA166), and the Program for Longyuan Young Innovation Talents and the Doctoral Foundation of Lanzhou University of Technology, China.

  4. Health- and disease-associated species clusters in complex natural biofilms determine the innate immune response in oral epithelial cells during biofilm maturation. (United States)

    Langfeldt, Daniela; Neulinger, Sven C; Stiesch, Meike; Stumpp, Nico; Bang, Corinna; Schmitz, Ruth A; Eberhard, Jörg


    The aim of the present study was to verify our hypothesis concerning the differential induction of various antimicrobial and immunomodulatory responses in oral epithelial cells by diverse bacterial species clusters. For this purpose, oral biofilms between 1 and 14 days of maturation (36 volunteers) were co-incubated with gingival epithelial cells. Subsequently, human β-defensin (hBD)-2, hBD-3, LL-37, interleukin (IL)-1β, IL-6, IL-8 and IL-10 mRNA expression profiles were quantified by quantitative reverse transcription PCR. The correlation between bacterial species and the host innate immune response was determined by relating these results to existing 16S rRNA phylogenetic analysis by amplicon sequencing (Langfeldt et al. 2014. PLoS One 9: e87449). Data were analysed by multiple factor analysis. Transcription of hBD-2 and hBD-3 was significantly associated with the abundance of species of the Prevotella cluster and the absence of species of the Streptococcus cluster. IL-1β, -6, -8 and -10 mRNA syntheses were significant correlated with Leptotrichia species [Leptotrichia 302H02 (0.448, P oral epithelial cells during early stages of bacteria-host interactions.

  5. Lymph vessels: the forgotten second circulation in health and disease. (United States)

    Adamczyk, Lukasz A; Gordon, Kristiana; Kholová, Ivana; Meijer-Jorna, Lorine B; Telinius, Niklas; Gallagher, Patrick J; van der Wal, Allard C; Baandrup, Ulrik


    The lymphatic circulation is still a somewhat forgotten part of the circulatory system. Despite this, novel insights in lymph angiogenesis in health and disease, application of immune markers for lymphatic growth and differentiation and also the introduction of new imaging techniques to visualize the lymphatic circulation have improved our understanding of lymphatic function in both health and disease, especially in the last decade. These achievements yield better understanding of the various manifestations of lymph oedemas and malformations, and also the patterns of lymphovascular spread of cancers. Immune markers that recognize lymphatic endothelium antigens, such as podoplanin, LYVE-1 and Prox-1, can be successfully applied in diagnostic pathology and have revealed (at least partial) lymphatic differentiation in many types of vascular lesions.

  6. A new, rapid in vivo method to evaluate allergic responses through distinctive distribution of a fluorescent-labeled immune complex: Potential to investigate anti-allergic effects of compounds administered either systemically or topically to the skin. (United States)

    Yamaki, Kouya; Yoshino, Shin


    We herein established a new method to evaluate allergic responses in mice rapidly and easily with ethical improvement by reducing the number of animals used. A single intravenous injection of a mixture of anti-OVA monoclonal IgE and fluorescein-ovalbumin (FITC-OVA) induced the distinctive spotted distribution of FITC-OVA in skin, named "ASDIS (Anaphylaxis-dependent Spotted Distribution of a fluorescent-labeled Immune complex in Skin)", and this was easily detected by in vivo imaging. The parallel induction of hypothermia, scratching, serum histamine increases, and ASDIS as well as the inhibition of ASDIS by either the systemic administration of a histamine H1 receptor antagonist or mast cell-depleting antibody suggested that our method, which only required 15 min, induced these allergic responses including ASDIS. Relatively mild but significant ASDIS was induced also in mice with passive systemic anaphylaxis by the method, requiring 2 separate days. The painting of anti-histamines on the skin markedly reduced ASDIS in the painted area only, suggesting the potential of this model to simultaneously compare the anti-allergic effects of several candidate compounds with control drugs in the same mice. ASDIS was suggested to originate from extravasated FITC-OVA/OE-1 immune complexes from blood to skin tissues other than mast cells. Our new method has the advantages of rapidity, easy method, and lower animal numbers to evaluate anti-allergic compounds as well as the characteristics of the used antibody, antigen, labeling molecules, additives, and other formulations. Our model for inducing ASDIS may contribute to the development of anti-allergic drugs, especially those intended for application to the skin.

  7. Cellular immune responses to ESAT-6 discriminate between patients with pulmonary disease due to Mycobacterium avium complex and those with pulmonary disease due to Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Lein, A D; von Reyn, C F; Ravn, P;


    ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of the Mycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-gamma) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary...... disease due to either Mycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-gamma responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0...... (0%) of 8 controls. Significant IFN-gamma responses to M. tuberculosis purified protein derivative were detected in 23 (85%) of 27 M. tuberculosis disease patients, 2 (25%) of 8 MAC disease patients, and 5 (63%) of 8 healthy controls. M. avium sensitin was recognized in 24 (89%) of 27 M. tuberculosis...

  8. Lost circulation technology development status

    Energy Technology Data Exchange (ETDEWEB)

    Glowka, D.A.; Schafer, D.M.; Loeppke, G.E.; Scott, D.D.; Wernig, M.D.; Wright, E.K.


    Lost circulation is the loss of drilling fluid from the wellbore to fractures or pores in the rock formation. In geothermal drilling, lost circulation is often a serious problem that contributes greatly to the cost of the average geothermal well. The Lost Circulation Technology Development Program is sponsored at Sandia National Laboratories by the US Department of Energy. The goal of the program is to reduce lost circulation costs by 30--50% through the development of mitigation and characterization technology. This paper describes the technical progress made in this program during the period April 1991--March 1992. 8 refs.

  9. Percutaneous interventions in Fontan circulation

    Directory of Open Access Journals (Sweden)

    Eduardo Franco


    Conclusions: Interventional catheterization procedures are often necessary to reach and maintain the fragile Fontan circulation, mainly in patients with right morphology systemic ventricles and fenestrated Fontan conduits.

  10. Circulation control STOL aircraft design aspects (United States)

    Loth, John L.


    Since Davidson patented Circulation Control Airfoils in 1960, there have been only 2 aircraft designed and flown with circulation control (CC). Designing with CC is complex for the following reasons: the relation between lift increase and blowing momentum is nonlinear; for good cruise performance one must change the wing geometry in flight from a round to a sharp trailing edge. The bleed air from the propulsion engines or an auxiliary compressor, must be used efficiently. In designing with CC, the propulsion and control aspects are just as important as aerodynamics. These design aspects were examined and linearized equations are presented in order to facilitate a preliminary analysis of the performance potential of CC. The thrust and lift requirements for takeoff make the calculated runway length very sensitive to the bleed air ratio. Thrust vectoring improves performance and can offset nose down pitching moments. The choice of blowing jet to free stream velocity ratio determines the efficiency of applying bleed air power.

  11. Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury (United States)

    Zhang, Qin; Raoof, Mustafa; Chen, Yu; Sumi, Yuka; Sursal, Tolga; Junger, Wolfgang; Brohi, Karim; Itagaki, Kiyoshi; Hauser, Carl J.


    Injury causes a systemic inflammatory response syndrome (SIRS) clinically much like sepsis 1. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors 2. Similarly, cellular injury can release endogenous damage-associated molecular patterns (DAMPs) that activate innate immunity 3. Mitochondria are evolutionary endosymbionts that were derived from bacteria 4 and so might bear bacterial molecular motifs. We show here that injury releases mitochondrial DAMPs (MTD) into the circulation with functionally important immune consequences. MTD include formyl peptides and mitochondrial DNA. These activate human neutrophils (PMN) through formyl peptide receptor-1 and TLR9 respectively. MTD promote PMN Ca2+ flux and phosphorylation of MAP kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTD can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These can then signal through identical innate immune pathways to create a sepsis-like state. The release of such mitochondrial ‘enemies within’ by cellular injury is a key link between trauma, inflammation and SIRS. PMID:20203610

  12. Pauci-immune lupus nephritis: possibility or co-incidence? (United States)

    Cansu, Döndü Üsküdar; Temiz, Gökhan; Açıkalın, Mustafa F.; Korkmaz, Cengiz


    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with immune complex formation and renal involvement of lupus and may include several kinds of pathological conditions, but mostly, it is associated with immune complex-induced glomerular disease. Pauci-immune lupus nephritis is a very rare condition. We describe a 45-year-old female patient with pauci-immune crescentic necrotizing lupus nephritis and briefly discuss the possible mechanism and pathogenesis.

  13. Dynamics of immune system vulnerabilities (United States)

    Stromberg, Sean P.

    The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

  14. Immune disorders in hemodialysis patients. (United States)

    Sharif, Mohammad Reza; Chitsazian, Zahra; Moosavian, Mehdi; Raygan, Fariba; Nikoueinejad, Hassan; Sharif, Ali Reza; Einollahi, Behzad


    Immunologically, End Stage renal Disease (ESRD) is associated with some disorders in both innate and adaptive immune system in such a form that there is a coexistence of both immune activation and immune suppression. Although these disorders are complex yet thoroughly unknown, there is a close relation between the progressively defective immune system with side effects as well as mortality causes including cardiovascular problems, infections, and malignancies. From the other point, chronic inflammation as a major determinant of "dialysis syndrome" (including malnutrition, cachexia, and vasculopathy) is considered as the main factor of inability and mortality in dialysis patients. Such inflammation is generally arisen from immune system response to uremia and individual's repetitive contact with dialysis instruments and, in the long term, leads to premature aging via intensifying tissue degeneration. Therefore, the immune system is known as one of the most important therapeutic targets to reduce morbidity and mortality in uremic and dialysis patients.   This review addresses different aspects as well as mechanisms of immune system dysfunction and possible therapeutics in dialysis patients.


    Institute of Scientific and Technical Information of China (English)

    Xu Ying; Wei Guo


    A class of Quasi-Systematic Block-Circulant Low-Density Parity-Check (QSBC-LDPC) codes is proposed. Block-circulant LDPC codes have been studied a lot recently,because the simple structures of their parity-check matrices are very helpful to reduce the implementation complexities.QSBC-LDPC codes are special block-circulant LDPC codes with quasi-systematic parity-check ma-trices. The memories for encoders of QSBC-LDPC codes are limited,and the encoding process can be carried out in a simple recursive way with low complexities. Researches show that the QSBC-LDPC codes can provide remarkable performances with low encoding complexities.

  16. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults. (United States)

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng


    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

  17. TROPICAL METEOROLOGY & Climate: Hadley Circulation

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jian; Vecchi, Gabriel A.


    The Hadley circulation, a prominent circulation feature characterized by rising air near the Equator and sinking air in the subtropics, defines the position of dry subtropical areas and is a fundamental regulator of the earth’s energy and momentum budgets. The character of the Hadley circulation, and its related precipitation regimes, exhibits variation and change in response to both climate variability and radiative forcing changes. The strength and position of the Hadley circulation change from year to year paced by El Niño and La Niña events. Over the last few decades of the twentieth century, the Hadley cell has expanded poleward in both hemispheres, with changes in atmospheric composition (including stratospheric ozone depletion and greenhouse gas increases) thought to have contributed to its expansion. This article introduces the basic phenomenology and driving mechanism of the Hadley circulation and discusses its variations under both natural and anthropogenic climate forcings.

  18. Sino-Danish Brain Circulation

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe


    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...


    Directory of Open Access Journals (Sweden)

    O. O. Obukhova


    Full Text Available Abstract. In present work, we studied some interrelations between tobacco smoking and the processes of immune system stimulation in healthy blood donors. In our opinion, this issue is especially important for the big industrial center, with rather strong antigenic exposure of the organism. The levels of circulating immune complexes (CIC were used as a marker index which reflects specific antigen-antibody interactions during inflammation. According to the results obtained, the majority of persons who have high CIC levels were tobacco smokers (53.76%. Moreover, the percentage of persons with high CIC content, like as the mean values of this index is increased proportionally to the duration of smoking. A mixture of tobacco smoke components seems to exert direct toxic effect upon various compartments of the immune system and causes local irritation of bronchial tree, thus producing local and systemic inflammatory reaction. It is, possibly, an additional factor which determines activation of immune system, with a background of adverse antropogenic exposures typical to industrial centers. The data obtained allow us to affirm a toxic action of tobacco smoke upon the organism of smokers, with development of inflammatory reactions that are displayed as increased CIC levels at preclinical stage.


    Institute of Scientific and Technical Information of China (English)

    Dai Xiaoxia; Xiong Yongmin; Chu Yonglie; Wang Zhilun


    Objective To investigate the relationship between erythrocyte immune function and selenium (Se)level. Methods Forty-nine Kashin-Beck patients in endemic area aged 13- 16 years were divided into two groups and were orally given either selenized yeast or sodium selenite to provide 200 μg selenium per day for 12 weeks. Erythrocyte selenium level, glutathione peroxidase activity, the rosette formation rates of red blood cells complement receptor type Ⅰ(CR1), the immune function of red blood cells, and circulating immune complexes(CIC) were determined. Results After supplementing with selenium for 12 weeks, erythrocyte selenium level, glutathione peroxidase activity, the rosette formation rates of red blood cells CR1 were significantly increased. But the difference in rosette formation rates of IC and CIC content was not significant between before and after Se supplementation. Conclusion The increase of the immune function of the erythrocyte by selenium-supplement may be one of the effective mechanisms for the prevention of Kashin-Beck disease.

  1. Immune responses to improving welfare. (United States)

    Berghman, L R


    The relationship between animal welfare and the immune status of an animal has a complex nature. Indeed, the intuitive notion that "increased vigilance of the immune system is by definition better" because it is expected to better keep the animal healthy, does not hold up under scrutiny. This is mostly due to the fact that the immune system consists of 2 distinct branches, the innate and the adaptive immune system. While they are intimately intertwined and synergistic in the living organism, they are profoundly different in their costs, both in terms of performance and wellbeing. In contrast to the adaptive immune system, the action of the innate immune system has a high metabolic cost as well as undesirable behavioral consequences. When a pathogen breaches the first line of defense (often a mucosal barrier), that organism's molecular signature is recognized by resident macrophages. The macrophages respond by releasing a cocktail of pro-inflammatory cytokines (including interleukin-1 and -6) that signal the brain via multiple pathways (humoral as well as neural) of the ongoing peripheral innate immune response. The behavioral response to the release of proinflammatory cytokines, known as "sickness behavior," includes nearly all the behavioral aspects that are symptomatic for clinical depression in humans. Hence, undesired innate immune activity, such as chronic inflammation, needs to be avoided by the industry. From an immunological standpoint, one of the most pressing poultry industry needs is the refinement of our current veterinary vaccine arsenal. The response to a vaccine, especially to a live attenuated vaccine, is often a combination of innate and adaptive immune activities, and the desired immunogenicity comes at the price of high reactogenicity. The morbidity, albeit limited and transient, caused by live vaccines against respiratory diseases and coccidiosis are good examples. Thankfully, the advent of various post-genomics technologies, such as DNA

  2. Derivation of multipotent progenitors from human circulating CD14+ monocytes. (United States)

    Seta, Noriyuki; Kuwana, Masataka


    Circulating CD14(+) monocytes are originated from hematopoietic stem cells in the bone marrow and believed to be committed precursors for phagocytes, such as macrophages. Recently, we have reported a primitive cell population termed monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology in culture and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. MOMCs are derived from circulating CD14(+) monocytes, but circulating precursors for MOMCs still remain undetermined. Comparative analysis of gene expression profiles of MOMCs and other monocyte-derived cells has revealed that embryonic stem cell markers, Nanog and Oct-4, are specifically expressed by MOMCs. In vitro generation of MOMCs requires binding to fibronectin and exposure to soluble factors derived from activated platelets. MOMCs contain progenitors with capacity to differentiate into a variety of nonphagocytes, including bone, cartilage, fat, skeletal and cardiac muscle, neuron, and endothelium, indicating that circulating monocytes are more multipotent than previously thought. In addition, MOMCs are capable of promoting ex vivo expansion of human hematopoietic progenitor cells through direct cell-to-cell contact and secretion of a variety of hematopoietic growth factors. These findings obtained from the research on MOMCs indicate that CD14(+) monocytes in circulation are involved in a variety of physiologic functions other than innate and acquired immune responses, such as repair and regeneration of the damaged tissue.

  3. Recent progress in the understanding of host immunity to avian coccidiosis: IL-17 family cytokines as the sentinels on the intestinal mucosa (United States)

    The molecular and cellular mechanisms leading to immune protection against Eimeria avian coccidiosis are complex and include multiple aspects of innate and adaptive immunities. Innate immunity is mediated by various subpopulations of immune cells that recognize pathogen associated molecular patterns...

  4. Skin immune sentinels in health and disease. (United States)

    Nestle, Frank O; Di Meglio, Paola; Qin, Jian-Zhong; Nickoloff, Brian J


    Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.

  5. Immunity of multiplex networks via acquaintance vaccination (United States)

    Wang, Zhen; Zhao, Da-Wei; Wang, Lin; Sun, Gui-Quan; Jin, Zhen


    How to find the effective approach of immunizing a population is one open question in the research of complex systems. Up to now, there have been a great number of works focusing on the efficiency of various immunization strategies. However, the majority of these existing achievements are limited to isolated networks, how immunization affects disease spreading in multiplex networks seems to need further exploration. In this letter, we explore the impact of the acquaintance immunization in multiplex networks, where two kinds of immunization strategies, multiplex node-based acquaintance immunization and layer node-based acquaintance immunization, are proposed. With the generating function method, our theoretical framework is able to accurately calculate the critical immunization threshold which is one of the most important indexes to predict the epidemic regime. Moreover, we further uncover that, with the increment of degree correlation between network layers, the immunization threshold declines for multiplex node-based acquaintance immunization, but slowly increases for layer node-based acquaintance immunization.

  6. Immune cell interplay in colorectal cancer prognosis

    Institute of Scientific and Technical Information of China (English)

    Samuel; E; Norton; Kirsten; A; Ward-Hartstonge; Edward; S; Taylor; Roslyn; A; Kemp


    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, par-ticularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship betweencancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.

  7. Immunity and immunization in elderly. (United States)

    Bourée, Patrice


    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  8. The circulation physiology of agroecosystems

    Institute of Scientific and Technical Information of China (English)

    Cao Zhiping; Richard Dawson


    This paper represents an effort to enlarge the understanding of the biophysical foundation of agroecosystems by using an analogy with the circulation of the blood in the human body. The circulation function in the human body can be represented as arterial pressure. The factors affecting arterial pressure in the human body have direct counterparts in the cultivation-husbandry system. The relationship between circulation pressure and the factors affecting that pressure in the cultivation-husbandry system are similar to the relationship between the arterial pressure and factors affecting arterial pressure in the human body. Furthermore, circulation resistance in the cultivation-husbandry system can be shown to be analogous to the calculation of peripheral resistance in the human body by Poiseuille's formula.

  9. Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH) Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture. (United States)

    Martins, Cyro José de Moraes; Genelhu, Virginia; Pimentel, Marcia Mattos Gonçalves; Celoria, Bruno Miguel Jorge; Mangia, Rogerio Fabris; Aveta, Teresa; Silvestri, Cristoforo; Di Marzo, Vincenzo; Francischetti, Emilio Antonio


    The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity.

  10. Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture.

    Directory of Open Access Journals (Sweden)

    Cyro José de Moraes Martins

    Full Text Available The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH, endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR, adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity.

  11. A Clinical Study of Multitarget Remedy Pregnancy Complicating Acute Renal Failure by Extracorporeal Circulation Immune Purification%体外循环免疫净化技术多靶点救治妊娠并发急性肾衰竭的研究

    Institute of Scientific and Technical Information of China (English)

    孟建中; 吕苏一; 周春华; 何萍; 刘文渊; 王素霞; 葛彦明; 贾凤玉; 岳冀


    To investigate the influence of extracorporeal circulation immune purification (ECIP) which remedy pregnancy compli-cating acute renal failure ( ARF) under the guidance of acute kidney injury hierarchical diagnosis normality (AKIN) and pathologic di-agnosis on prognosis. (1) To observe the influence which interference occasion on the incidence of renal function delayed recovery and fatality rate. According to AKIN, thirty - seven patients were divided into following groups, 14 patients (37.84% ) executed ECIP dur-ing the stage of damage in AKI as group A, 23 patients (62.16% ) treated in the same way at the stage of exhaustion in AKI as group B. (2)To observe the dynamic state changes (ECIP pretherapy and post - treatment) of acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, the levels of serum creatinine (Scr) , uric acid (UA) ,cystatin C (CysC) .lactate dehydrogenase (LDH) were observed. 7 patients which renal function delayed recovery executed percataneous renal needle biopsy and got their pathologic changes analyzed. The result showed that (1) Oliguria happened in postpartum patients,their blood CysC.UA levels and APACHEII score also increased significantly,peaked at 48 h. Scr levels increased at postpartum 48 h and peaked at 72 h. Levels of blood CysC, UA, Scr, LDH and the APACHE Ⅱ score decreased obviously after ECIP. Correlation analysis showed that the content of blood UA were positively related to CysC (r = 0.61 ,P <0.05). (2)The renal functional rehabilitation rate (Scr back to the baseline) of group A were obviously higher than that of group B (P<0.05). (3)Renal function of 33 patients (89.19% ) got recovered. 2 patients (5.41% ) in group B were died of severe infection and multiorgan functional defection. 2 patients with dead kidney (5.41% ) depended on dialysis to main-tain life. (4)The major histologic types of the patients whose renal function recovery delayed were uremic syndrome hemolytic.crescen-tic glomerulonephritis

  12. Difference between immune-related pain induced by antigen-specific immune complex and inflammatory pain induced by formalin and the expression of macrophage migration inhibitory factor (mif) in two rat models%免疫复合物致疼痛与甲醛致炎性痛的大鼠模型比较及巨噬细胞游走抑制因子在两组模型中的表达

    Institute of Scientific and Technical Information of China (English)

    吴锐; 李荣亨


    目的 比较免疫复合物所致疼痛模型与甲醛致炎性疼痛模型的大鼠疼痛行为、局部炎症反应及巨噬细胞游走抑制因子在不同模型不同部位的表达,探讨免疫复合物所致疼痛的病理机制.方法 成年SD清洁级大鼠15只,随机分为正常对照组,甲醛组及免疫复合物组,每组5只.分别在大鼠右后足底注入20 μL PBS、甲醛及免疫复合物.于30 min、1h、2h、4h、8h、12 h测定疼痛行为.并于12 h后采血、取大鼠局部皮肤及脊髓测定巨噬细胞游走抑制因子(MIF)表达.结果 疼痛行为变化:在甲醛致炎后大鼠立刻出现明显的自发痛,疼痛阈值明显下降,注射足高度肿胀并于1h达高峰后逐渐缓解.免疫复合物组的疼痛阈值低峰在4h后,并持续至8h后逐渐缓解,注射足肿胀不明显.皮肤及脊髓的MIF表达在甲醛组明显增加(P<0.05),在免疫复合物组中无明显改变.结论 MIF参与炎症性疼痛病理过程,但无证据参与免疫复合物所致疼痛.抗原抗体复合物所致疼痛与甲醛炎性痛病理机制有一定区别.%Objective To investigate the differences between immune-related pain induced by antigen-specific immune complex and inflammatory pain induced by formalin. Methods Fifteen adult health SD rats were randomly divided into control group, formalin group and immune-complex group with 5 rats in each group. The right hindpaws of rats were respectively injected with PBS, formalin and rat IgG immune-complex. The changes of hindpaw thickness and pain behavior were observed at 0, 30 min, 1 h, 2 h, 4 h, 8h and 12 h after injection. Serum macrophage migration-inhibitory factor ( MIF) was detected by ELISA. Expression of MIF in the hindpaw skin and spinal cord was determined by RT- PCR. Results 1. Changes of nociceptive behavior; rats in the formalin group showed significant nociceptive behavior immediately, such as licking foot, limping and highly swollen foot which could not touch the ground

  13. Cancer, aging and immune reconstitution. (United States)

    Zanussi, Stefania; Serraino, Diego; Dolcetti, Riccardo; Berretta, Massimiliano; De Paoli, Paolo


    Aging is a complex phenomenon involving multiple physiological functions. Among these, very important are the modifications induced in the immune system; these modifications may be related to cancer development, a disease of older people. We herein describe the age-dependent alterations observed in the various arms of the immune system. Both innate and adaptive immunity are compromised during aging, a condition where an inflammatory status contributes to promote immune suppression and tumour growth. Collectively, aging of the immune system may produce detrimental consequences on the response against tumours in old patients. In fact, preclinical studies and clinical observations in humans have demonstrated age-associated alterations in antitumor immunity. Immunological recovery of old patients after conventional chemotherapy (CT) has not been fully investigated, while several studies conducted in patients undergoing blood stem cell transplantation have demonstrated that a delayed immune reconstitution associated with older age results in increased susceptibility to opportunistic infections and risk of tumour relapse. Cellular immunotherapy and vaccination are becoming viable options for improving survival and quality of life of cancer patients targeting both the host defences and the tumour. The clinical experience in elderly patients is still in its infancy, but available data indicate that these approaches are feasible and promising. A key problem in the studies on aging, immunity and cancer is that it is difficult to distinguish changes related to age from those related to cancer-dependent immunosuppression, but independent from the age of the subject. Longitudinal studies on aged healthy and cancer persons and the use of new immunological techniques may be required to clarify these issues.

  14. A novel recombinant Mycobacterium bovis bacillus Calmette-Guerin strain expressing human granulocyte macrophage colony-stimulating factor and Mycobacterium tuberculosis early secretory antigenic target 6 complex augments Th1 immunity

    Institute of Scientific and Technical Information of China (English)

    Xiaoling Yang; Lang Bao; Yihao Deng


    Since Mycobacterium bovis bacillus Calmette-Guerin strain (BCG) fails to protect adults from pulmonary tuberculosis (TB), there is an urgent need for developing a new vaccine. In this study, we constructed a novel recombinant BCG strain (rBCG) expressing human granulocyte macrophage colony-stimulating factor (GM-CSF) and the 6 kDa early secretory antigenic target (ESAT6) of Mycobacteriutn tuberculosis, named rBCG:GE (expressing GMCSFESAT6 complex), and evaluated the immunogenicity of the construct in BALB/c mice. Our results indicated that the rBCG:GE was able to induce higher titer of antibody than the conventional BCG, the rBCG:G (expressing GM-CSF)and the rBCG:E (expressing ESAT6). Moreover, the rBCG:GE also elicited a longer-lasting and stronger Thl cellular immune responses than the other groups, which was confirmed by the incremental proliferation of splenocytes, the increased percentages of CD4+ and CD8+ T cells of spleen, the elevated level of interferon-γ in splenocyte culture after tuberculin-purified protein derivative stimulation, and the increased concentration of GM-CSF in serum. The data presented here suggested the possibility that the recombinant BCG:GE might be a good vaccine candidate to TB.

  15. Local Immune Response to Upper Urinary Tract Infections in Children▿


    Kantele, Anu; Palkola, Nina; Arvilommi, Heikki; Honkinen, Olli; Jahnukainen, Timo; Mertsola, Jussi; Kantele, Jussi M.


    Vaccines are needed against urinary tract infections (UTIs) in children, as episodes of pyelonephritis (PN) may cause renal scarring. Local immune mechanisms are regarded to confer protection, yet they have been poorly characterized for children. This study explores the local immune response in children by looking for newly activated pathogen-specific antibody-secreting cells (ASC), expected to appear transiently in the circulation as a response to UTI. Urinary tract-originating ASC specific ...


    Institute of Scientific and Technical Information of China (English)

    Zhang Yuelin; Qiu Shudong; Shi Wei; Dang Xiaojun


    Objective To study the expression of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R),determine the alteration of erythrocytic immunity and T cell subgroup in the blood of outer circulation in patients with hypertensive cerebral hemorrhage so and to probe into the relationship between them, and to explore the clinical significance. Methods Enzyme linked immnunosorbent assay (ELISA) was used to determine the content of IL-2 and sIL-2R. The immunoadsorption was employed to examine the erythrocytic immune activity and its regulating function.Streptavidin-peroxidase(S-P) was used to determine the cell number of CD3 (cluster of differentiation3), CD4 and CD8. Results The content of IL-2 in the group with hypertensive cerebral hemorrhage was significantly lower than that in the control group (P<0.01), and the content of sIL-2R increased. Red blood cell C3b receptor (RBC. C3b R)and RBC immune adherence enhancing factor (RFEB) dropped greatly (P<0.01), while RBC immune complex rosette (RBC. ICR) and RBC immune adherence inhibiting factor (RFIR) increased greatly. The cell number of CD3 and CD4decreased (P<0.01) and there was no obvious change in CD8 (P<0.05). Conclusion The decrease of immune function was observed in patients with hypertensive cerebral hemorrhage. The determination of the content of IL-2, sIL-2R, erythrocytic immunity and the activity of T subgroup has an important clinical significance in the occurrence,development, treatment, and prognosis of hypertensive cerebral hemorrhage.

  17. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao


    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  18. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang


    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  19. Alternative adaptive immunity strategies: coelacanth, cod and shark immunity. (United States)

    Buonocore, Francesco; Gerdol, Marco


    The advent of high throughput sequencing has permitted to investigate the genome and the transcriptome of novel non-model species with unprecedented depth. This technological advance provided a better understanding of the evolution of adaptive immune genes in gnathostomes, revealing several unexpected features in different fish species which are of particular interest. In the present paper, we review the current understanding of the adaptive immune system of the coelacanth, the elephant shark and the Atlantic cod. The study of coelacanth, the only living extant of the long thought to be extinct Sarcopterygian lineage, is fundamental to bring new insights on the evolution of the immune system in higher vertebrates. Surprisingly, coelacanths are the only known jawed vertebrates to lack IgM, whereas two IgD/W loci are present. Cartilaginous fish are of great interest due to their basal position in the vertebrate tree of life; the genome of the elephant shark revealed the lack of several important immune genes related to T cell functions, which suggest the existence of a primordial set of TH1-like cells. Finally, the Atlantic cod lacks a functional major histocompatibility II complex, but balances this evolutionary loss with the expansion of specific gene families, including MHC I, Toll-like receptors and antimicrobial peptides. Overall, these data point out that several fish species present an unconventional adaptive immune system, but the loss of important immune genes is balanced by adaptive evolutionary strategies which still guarantee the establishment of an efficient immune response against the pathogens they have to fight during their life.

  20. Insect immune resistance to parasitoids

    Institute of Scientific and Technical Information of China (English)

    Yves Carton; Marylène Poirié; Anthony J. Nappi


    Insect host-parasitoid interactions involve complex physiological, biochemical and genetic interactions. Against endoparasitoids, immune-competent hosts initiate a blood cell-mediated response that quickly destroys the intruders and envelops them in a multilayered melanotic capsule. During the past decade, considerable progress has been made in identifying some of the critical components of the host response, mainly because of the use of efficient molecular tools. This review examines some of the components of the innate immune response of Drosophila, an insect that has served as an exceptionally good experimental model for studying non-self recognition processes and immune cell signaling mechanisms. Topics considered in this review include hematopoiesis, proliferation and adhesion of hemocytes, melanogenesis and associated cytotoxic molecules, and the genetic aspects of the host-parasitoid interaction.


    Institute of Scientific and Technical Information of China (English)

    阎锡德; S.Kuhn; P.Traub


    Autoantibodies in systemic lupus erythematosus which cross-react with double stranded DNA and in-termediate filament proteins are frequently reported.However,little is Known about the origin and the target of these antibodies.In this paper,a polyspecific monoclonal antibody,XY12,produced by the im-munization of genetically non-autoimmune mice with a DNA-protein complex is detsiled.Its antigen bind-ing patterms are very similar to the autoantibodies.The data suggest that these autoantibodies may be trig-gered by a circulating nucleoprotein.

  2. Circulating Fibronectin Controls Tumor Growth

    Directory of Open Access Journals (Sweden)

    Anja von Au


    Full Text Available Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.

  3. Immune correlates for dengue vaccine development. (United States)

    Srikiatkhachorn, Anon; Yoon, In-Kyu


    Dengue virus is the leading cause of vector-borne viral disease with four serotypes in circulation. Vaccine development has been complicated by the potential for both protection and disease enhancement during heterologous infection. Secondary infection triggers cross-reactive immune memory responses that have varying functional and epitope specificities that determine protection or risk. Strongly neutralizing antibodies to quaternary epitopes may be especially important for virus neutralization. Cell-mediated immunity dominated by Th1 functions may also play an important role. Determining an immune correlate of protection or risk would be highly beneficial for vaccine development but is hampered by mechanistic uncertainties and assay limitations. Clinical efficacy trials and human infection models along with a systems approach may provide future opportunities to elucidate such correlates.

  4. [Presence of immune complexes in ischemic stroke]. (United States)

    Gromadzka, G; Uchacz, I; Palasik, W; Ryglewicz, D; Korlak, J; Członkowska, A


    There is increasing evidence that inflammatory responses play an important role in the pathogenesis of atherosclerosis and cerebral infarct. The aim of this study was to determine the amount of immunocomplexes (i.c.) in patients with stroke in the early period of the disease. Studies were performed on 35 subjects. The concentration of immunocomplexes was determined with the precipitation method (3.5% polyethylenoglikol was used). Increased concentration of i.c. was found in patients with cerebral infarct (after 12 hours and 7 days). It suggests, that i.c. could be one of the markers for systemic inflammation and be important in the patogenesis of atherosclerosis and stroke.

  5. Nucleic acids in circulation: Are they harmful to the host?

    Indian Academy of Sciences (India)

    Indraneel Mittra; Naveen Kumar Nair; Pradyumna Kumar Mishra


    It has been estimated that 1011–1012 cells, primarily of haematogenous origin, die in the adult human body daily, and a similar number is regenerated to maintain homeostasis. Despite the presence of an efficient scavenging system for dead cells, considerable amounts of fragmented genetic material enter the circulation in healthy individuals. Elevated blood levels of extracellular nucleic acids have been reported in various disease conditions; such as ageing and age-related degenerative disorders, cancer; acute and chronic inflammatory conditions, severe trauma and autoimmune disorders. In addition to genomic DNA and nucleosomes, mitochondrial DNA is also found in circulation, as are RNA and microRNA. There is extensive literature that suggests that extraneously added nucleic acids have biological actions. They can enter into cells in vitro and in vivo and induce genetic transformation and cellular and chromosomal damage; and experimentally added nucleic acids are capable of activating both innate and adaptive immune systems and inducing a sterile inflammatory response. The possibility as to whether circulating nucleic acids may, likewise, have biological activities has not been explored. In this review we raise the question as to whether circulating nucleic acids may have damaging effects on the host and be implicated in ageing and diverse acute and chronic human pathologies.

  6. Understanding Herd Immunity. (United States)

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T


    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  7. Atmospheric Circulation of Terrestrial Exoplanets

    CERN Document Server

    Showman, Adam P; Merlis, Timothy M; Kaspi, Yohai


    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical and dynamical conditions, only a small fraction of which have yet been explored in detail. Our approach is to lay out the fundamental dynamical principles governing the atmospheric circulation on terrestrial planets--broadly defined--and show how they can provide a foundation for understanding the atmospheric behavior of these worlds. We first survey basic atmospheric dynamics, including the role of geostrophy, baroclinic instabilities, and jets in the strongly rotating regime (the "extratropics") and the role of the Hadle...

  8. Circulating Heat Shock Proteins in Women With a History of Recurrent Vulvovaginitis

    Directory of Open Access Journals (Sweden)

    P. C. Giraldo


    70-kDa heat shock proteins (hsp60 and hsp70, respectively in the circulation of women with or without a history of recurrent BV or candidal vaginitis and with or without a current lower genital tract infection. Heat shock protein expression is associated with a down-regulation of proinflammatory immune responses that would inhibit microbial infection.

  9. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald


    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulat......Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

  10. Systemic lupus erythematosus immune complexes increase the expression of SLAM family members CD319 (CRACC) and CD229 (LY-9) on plasmacytoid dendritic cells and CD319 on CD56(dim) NK cells. (United States)

    Hagberg, Niklas; Theorell, Jakob; Schlums, Heinrich; Eloranta, Maija-Leena; Bryceson, Yenan T; Rönnblom, Lars


    Patients with systemic lupus erythematosus (SLE) display an activated type I IFN system due to unceasing IFN-α release from plasmacytoid dendritic cells (pDCs) stimulated by nucleic acid-containing immune complexes (ICs). NK cells strongly promote the IFN-α production by pDCs; therefore, we investigated surface molecules that could be involved in the pDC-NK cell cross-talk. In human PBMCs stimulated with RNA-containing ICs (RNA-ICs), the expression of the signaling lymphocyte activation molecule (SLAM) family receptors CD319 and CD229 on pDCs and CD319 on CD56(dim) NK cells was selectively increased. Upregulation of CD319 and CD229 on RNA-IC-stimulated pDCs was induced by NK cells or cytokines (e.g., GM-CSF, IL-3). IFN-α-producing pDCs displayed a higher expression of SLAM molecules compared with IFN-α⁻ pDCs. With regard to signaling downstream of SLAM receptors, pDCs expressed SHIP-1, SHP-1, SHP-2, and CSK but lacked SLAM-associated protein (SAP) and Ewing's sarcoma-activated transcript 2 (EAT2), indicating that these receptors may act as inhibitory receptors on pDCs. Furthermore, pDCs from patients with SLE had decreased expression of CD319 on pDCs and CD229 on CD56(dim) NK cells, but RNA-IC stimulation increased CD319 and CD229 expression. In conclusion, this study reveals that the expression of the SLAM receptors CD319 and CD229 is regulated on pDCs and NK cells by lupus ICs and that the expression of these receptors is specifically altered in SLE. These results, together with the observed genetic association between the SLAM locus and SLE, suggest a role for CD319 and CD229 in the SLE disease process.

  11. β7 Integrin controls mast cell recruitment, whereas αE integrin modulates the number and function of CD8+ T cells in immune complex-mediated tissue injury. (United States)

    Yamada, Daisuke; Kadono, Takafumi; Masui, Yuri; Yanaba, Koichi; Sato, Shinichi


    Immune complex (IC) deposition causes significant tissue injury associated with various autoimmune diseases such as vasculitis. In the cascade of inflammation, cell-to-cell and cell-to-matrix adhesion via adhesion molecules are essential. To assess the role of αE and β7 integrin in IC-mediated tissue injury, peritoneal and cutaneous reverse-passive Arthus reaction was examined in mice lacking αE integrin (αE(-/-)) or β7 integrin (β7(-/-)). Both αE(-/-) and β7(-/-) mice exhibited significantly attenuated neutrophil infiltration in the peritoneal and cutaneous Arthus reaction. β7 integrin deficiency, not αE integrin deficiency, significantly reduced the number of mast cells in the peritoneal cavity, which was consistent with the result that mast cells expressed only α4β7 integrin, not αEβ7 integrin. αE(-/-) mice instead revealed the reduction of CD8(+) T cells in the peritoneal cavity, and nearly half of them in wild-type mice expressed αE integrin. These αE(+)CD8(+) T cells produced more proinflammatory cytokines than αE(-)CD8(+) T cells, and adoptive transfer of αE(+)CD8(+) T cell into αE(-/-) recipients restored cutaneous and peritoneal Arthus reaction. These results suggest that in the peritoneal and cutaneous reverse-passive Arthus reaction, α4β7 integrin is involved in the migration of mast cells for initial IC recognition. αEβ7 integrin, in contrast, contributes by recruiting αE(+)CD8(+) T cells, which produce more proinflammatory cytokines than αE(-)CD8(+) T cells and amplify IC-mediated inflammation.

  12. The Smc5/6 Complex Restricts HBV when Localized to ND10 without Inducing an Innate Immune Response and Is Counteracted by the HBV X Protein Shortly after Infection (United States)

    Daffis, Stephane; Ramakrishnan, Dhivya; Burdette, Dara; Peiser, Leanne; Salas, Eduardo; Ramos, Hilario; Yu, Mei; Cheng, Guofeng; Strubin, Michel; Delaney IV, William E.; Fletcher, Simon P.


    The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing HBV X protein (HBx), which targets Smc5/6 for degradation. However, the mechanism by which Smc5/6 suppresses HBV transcription and how HBx is initially expressed is not known. In this study we characterized viral kinetics and the host response during HBV infection of primary human hepatocytes (PHH) to address these unresolved questions. We determined that Smc5/6 localizes with Nuclear Domain 10 (ND10) in PHH. Co-localization has functional implications since depletion of ND10 structural components alters the nuclear distribution of Smc6 and induces HBV gene expression in the absence of HBx. We also found that HBV infection and replication does not induce a prominent global host transcriptional response in PHH, either shortly after infection when Smc5/6 is present, or at later times post-infection when Smc5/6 has been degraded. Notably, HBV and an HBx-negative virus establish high level infection in PHH without inducing expression of interferon-stimulated genes or production of interferons or other cytokines. Our study also revealed that Smc5/6 is degraded in the majority of infected PHH by the time cccDNA transcription could be detected and that HBx RNA is present in cell culture-derived virus preparations as well as HBV patient plasma. Collectively, these data indicate that Smc5/6 is an intrinsic antiviral restriction factor that suppresses HBV transcription when localized to ND10 without inducing a detectable innate immune response. Our data also suggest that HBx protein may be initially expressed by delivery of extracellular HBx RNA into HBV-infected cells. PMID:28095508

  13. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis. (United States)

    Slocum, C; Kramer, C; Genco, C A


    Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease.

  14. Randomness and pattern scale in the immune network

    NARCIS (Netherlands)

    Boer, R.J. de; Laan, J.D van der; Hogeweg, P.


    The immune system is a beautiful example of a complex information processing system. The complexity of the immune system is comparable to that of the nervous system. Both systems are comprised of a large number of different cell types communicating via the production of stimulatory or inhibitory mol

  15. Feeding Our Immune System: Impact on Metabolism

    Directory of Open Access Journals (Sweden)

    Isabelle Wolowczuk


    Full Text Available Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

  16. Fractal analysis of circulating platelets in type 2 diabetic patients. (United States)

    Bianciardi, G; Tanganelli, I


    This paper investigates the use of computerized fractal analysis for objective characterization by means of transmission electron microscopy of the complexity of circulating platelets collected from healthy individuals and from type 2 diabetic patients, a pathologic condition in which platelet hyperreactivity has been described. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension by box counting (measure of geometric complexity) was automatically calculated. The results showed that the platelet boundary observed by electron microscopy is fractal and that the shape of the circulating platelets is significantly more complex in the diabetic patients in comparison to healthy subjects (p fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation in diabetes mellitus.

  17. Circulation-preserving plane flows of incompressible viscous fluids (United States)

    Yin, W.-L.


    The present investigation is concerned with a systematic use of the method of complex variables in a study of (generally unsteady) plane solutions of the Navier-Stokes equation. Circulation-preserving flows are considered in the investigation. However, the employed method can also be applied to more general cases. A circulation-preserving plane solution of the Navier-Stokes equation possesses a biharmonic stream function. The stream function may, therefore, be expressed in terms of two complex analytic functions, taking into account Goursat's representation. Attention is given to differential equations in the complex form, the case of steady vorticity, the case of unsteady vorticity with a spatially constant vorticity gradient, solutions with logarithmic vorticity fields, and a proof of completeness.

  18. The biology of circulating tumor cells. (United States)

    Pantel, K; Speicher, M R


    Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice.

  19. Conservation of Circulation in Magnetohydrodynamics

    CERN Document Server

    Bekenstein, J D; Bekenstein, Jacob D.; Oron, Asaf


    We demonstrate, both at the Newtonian and (general) relativistic levels, theexistence of a generalization of Kelvin's circulation theorem (for pure fluids)which is applicable to perfect magnetohydrodynamics. The argument is based onthe least action principle for magnetohydrodynamic flow. Examples of the newconservation law are furnished. The new theorem should be helpful inidentifying new kinds of vortex phenomena distinct from magnetic ropes or fluidvortices.

  20. In vivo acoustic and photoacoustic focusing of circulating cells (United States)

    Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.


    In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models.

  1. Circulating Vitamin D and Risk of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Alan A. Arslan


    Full Text Available We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OHD and the risk of subsequent invasive epithelial ovarian cancer (EOC. The 25(OHD levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OHD levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59–2.01. In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OHD levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.

  2. Optimal Backward Perturbation Analysis for the Block Skew Circulant Linear Systems with Skew Circulant Blocks

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang


    Full Text Available We first give the block style spectral decomposition of arbitrary block skew circulant matrix with skew circulant blocks. Secondly, we obtain the singular value of block skew circulant matrix with skew circulant blocks as well. Finally, based on the block style spectral decomposition, we deal with the optimal backward perturbation analysis for the block skew circulant linear system with skew circulant blocks.

  3. Inflammation and immune system interactions in atherosclerosis. (United States)

    Legein, Bart; Temmerman, Lieve; Biessen, Erik A L; Lutgens, Esther


    Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. Today's picture is far more complex. Atherosclerosis is considered a chronic inflammatory disease that results in the formation of plaques in large and mid-sized arteries. Both cells of the innate and the adaptive immune system play a crucial role in its pathogenesis. By transforming immune cells into pro- and anti-inflammatory chemokine- and cytokine-producing units, and by guiding the interactions between the different immune cells, the immune system decisively influences the propensity of a given plaque to rupture and cause clinical symptoms like myocardial infarction and stroke. In this review, we give an overview on the newest insights in the role of different immune cells and subtypes in atherosclerosis.

  4. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy


    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  5. Relationships between maternal malaria and malarial immune responses in mothers and neonates

    DEFF Research Database (Denmark)

    Rasheed, F N; Bulmer, J N; De Francisco, A;


    Immune responses of 97 Gambian women and their neonates were studied. New methods distinguished between active and previous placental malaria, were used to examine relationships between maternal malaria and neonatal immune responses. Many placentas (61%) had active or previous malarial infection...... lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell-mediated malarial immune responses detected at birth remains to be established....

  6. Using network properties to evaluate targeted immunization algorithms

    Directory of Open Access Journals (Sweden)

    Bita Shams


    Full Text Available Immunization of complex network with minimal or limited budget is a challenging issue for research community. In spite of much literature in network immunization, no comprehensive research has been conducted for evaluation and comparison of immunization algorithms. In this paper, we propose an evaluation framework for immunization algorithms regarding available amount of vaccination resources, goal of immunization program, and time complexity. The evaluation framework is designed based on network topological metrics which is extensible to all epidemic spreading model. Exploiting evaluation framework on well-known targeted immunization algorithms shows that in general, immunization based on PageRank centrality outperforms other targeting strategies in various types of networks, whereas, closeness and eigenvector centrality exhibit the worst case performance.

  7. Ontogenetic changes in immunity and susceptibility to fungal infection in Mormon crickets Anabrus simplex. (United States)

    Srygley, Robert B


    Insects have innate immunity that may be weakened by resource allocation to growth. I measured enzymatic immunity, encapsulation response, and susceptibility to fungal infection in Mormon crickets of known age. Although the concentrations of circulating spontaneous and total phenoloxidase (PO) increased with age from the most recent molt in late instar nymphs (5th, 6th, and 7th) and 0-5 day old adults, mean values did not differ between stadia, indicating that circulating PO titers are knocked back with each molt. In contrast, encapsulation rate increased throughout nymphal development and adult maturation. No longer required to molt, adult PO titers increased steadily with age. Survivorship also increased with the age at which Metarhizium acridum fungus was applied to adults. I conclude that immunity relevant to defense against fungi continues to develop well into the adult stage. With each molt setting the insects back in circulating PO titers, very young adults are much like nymphs in enzymatic immunity.

  8. [Collective poliomyelitis immunity in the adult population and its impact on eradication of this infection]. (United States)

    Seĭbil', V B; Malyshkina, L P; Lavrova, I K; Efimova, V F


    Collective poliomyelitis immunity was studied in 6339 donors from 19 towns and cities of Russia. Its stress substantially varied in different towns and cities. Studies of strain-specific antibodies to vaccine and wild viruses of poliomyelitis in donors from 4 towns established that the immune persons were more in the town where wild polioviruses had previously circulated than in those where the circulation of wild polioviruses had been limited and immunity resulted from vaccination. Circulation of vaccine viruses and reversion of their neurovirulent properties should be expected in the town where there are low collective poliomyelitis immunity rates. It is concluded that it is impossible to eradicate poliomyelitis as infection today; it is possible only to eliminate the disease if further vaccination of children is performed with live poliomyelitis vaccine.

  9. [Prolactin as a modulator of antiparasitic immunity]. (United States)

    Płociński, Przemysław; Dzitko, Katarzyna; Długońska, Henryka


    Prolactin (PRL) is a polypeptide hormone of the pituitary origin, that expresses over 300 separate biological activities, including its involvement in the regulation of immune functions. The hormone's immune capacities are related, among others, to comitogenic activity, prevention of immune cell apoptosis, stimulation of interleukins and antibodies production. Prolactin acts as a potent positive modulator of immunity to some protozoan parasites. It is well established that the hormone stimulates IFN-gamma and many other TH1-type cytokines production during Toxoplasma gondii, Leishmania sp. and Acanthamoeba castellanii infections. Recent studies suggest that human prolactin may be a regulator of antiparasitic activity against Plasmodium falciparum. On the other hand pregnancy-associated hyperprolactinemia may have a relevant contribution to reactivation of latent infections caused by many helminthic parasites, like Ancylostoma sp. or Necator sp. It is possibly connected with the process of transmammary transmission of hookworm infection to breast-fed newborns. Moreover, an increase in endogenous circulating prolactin during late pregnancy and lactation in ewes infected with Haemonchus contortus, promotes the phenomenon of periparturient egg rise. High prolactin levels have also been seen in dairy cattle suffering from other trichostrongylids infections. In this article we have discussed the role of prolactin as an important regulator of immunity to parasites.

  10. The insect cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Michael R. Strand


    The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understanding of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources: progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources of a number of humoral effector molecules required for killing different foreign invaders.

  11. The Immune Epitope Database 2.0

    DEFF Research Database (Denmark)

    Hoof, Ilka; Vita, R; Zarebski, L;


    The Immune Epitope Database (IEDB, provides a catalog of experimentally characterized B and T cell epitopes, as well as data on Major Histocompatibility Complex (MHC) binding and MHC ligand elution experiments. The database represents the molecular structures recognized by adaptive...... immune receptors and the experimental contexts in which these molecules were determined to be immune epitopes. Epitopes recognized in humans, nonhuman primates, rodents, pigs, cats and all other tested species are included. Both positive and negative experimental results are captured. Over the course...

  12. Aging changes in immunity (United States)

    ... this page: // Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. Aging Changes and Their Effects on the Immune System ...

  13. Physiology of the fetal circulation. (United States)

    Kiserud, Torvid


    Our understanding of fetal circulatory physiology is based on experimental animal data, and this continues to be an important source of new insight into developmental mechanisms. A growing number of human studies have investigated the human physiology, with results that are similar but not identical to those from animal studies. It is time to appreciate these differences and base more of our clinical approach on human physiology. Accordingly, the present review focuses on distributional patterns and adaptational mechanisms that were mainly discovered by human studies. These include cardiac output, pulmonary and placental circulation, fetal brain and liver, venous return to the heart, and the fetal shunts (ductus venosus, foramen ovale and ductus arteriosus). Placental compromise induces a set of adaptational and compensational mechanisms reflecting the plasticity of the developing circulation, with both short- and long-term implications. Some of these aspects have become part of the clinical physiology of today with consequences for surveillance and treatment.

  14. Proper Sizing of Circulation Pumps

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Nørgaard, Jørgen


    , but the results can be applied to Europe in general. Despite the small sample of houses involved in the test, 15 houses, some rather safe conclusions can be drawn from the results, which showed that newly developed pumps with power consumption around 5-8 W, can perform the task of circulating the water......The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust...... sufficiently to keep the houses satisfactorily warm during the heating season of the test. The old replaced pumps used 5-10 times more power. In Europe alone, a gradual replacement of the present vastly oversized pumps with such small but sufficient pumps can save the construction of 17 large power plants...

  15. Journalism as Cultures of Circulation

    DEFF Research Database (Denmark)

    Bødker, Henrik


    The universe of journalism has always consisted of interspersed texts, meanings and practices. Yet, much journalism research has often isolated either texts and/or contexts and as such assumed relations between professional practices, informed (rational) readers and (conceived) core texts...... of journalism. It is, however, more important than ever to shift attention away from texts to the processes through which they are circulated. This is partly because the many cultural forms of journalism (textual, institutional, technological, material, behavioural and imagined) are undergoing significant......, likes, comments, searches, journalist roles, writing and reading positions and identities etc. Such forms will be traced within the mediation of a specific event with the overall aim of beginning a theorization of the landscape of journalism as highly interrelated cultures of circulation....

  16. Ocean circulation generated magnetic signals

    DEFF Research Database (Denmark)

    Manoj, C.; Kuvshinov, A.; Maus, S.


    Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification...... of ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume...... of the magnetic field, as compared to the ECCO simulation. Besides the expected signatures of the global circulation patterns, we find significant seasonal variability of ocean magnetic signals in the Indian and Western Pacific Oceans. Compared to seasonal variation, interannual variations produce weaker signals....

  17. Adaptive immunity in cancer immunology and therapeutics. (United States)

    Spurrell, Emma L; Lockley, Michelle


    The vast genetic alterations characteristic of tumours produce a number of tumour antigens that enable the immune system to differentiate tumour cells from normal cells. Counter to this, tumour cells have developed mechanisms by which to evade host immunity in their constant quest for growth and survival. Tumour-associated antigens (TAAs) are one of the fundamental triggers of the immune response. They are important because they activate, via major histocompatibility complex (MHC), the T cell response, an important line of defense against tumourigenesis. However, the persistence of tumours despite host immunity implies that tumour cells develop immune avoidance. An example of this is the up-regulation of inhibitory immune checkpoint proteins, by tumours, which induces a form of self-tolerance. The majority of monoclonal antibodies in clinical practice have been developed to target tumour-specific antigens. More recently there has been research in the down-regulation of immune checkpoint proteins as a way of increasing anti-tumour immunity.

  18. The Role of the Immune Response in Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Triozzi, Pierre L., E-mail: [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)


    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

  19. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses. (United States)

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas


    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.

  20. 2型糖尿病患者血清低密度脂蛋白免疫复合物的检测及临床意义%Low-density lipoprotein immune complexes in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    王雪琴; 崔世维; 金艳; 陶国华; 陈金锋; 吴刚


    采用ELISA法测定102例2型糖尿病(T2DM)患者(其中54例合并大血管病变)、45例大血管病变患者及30例正常对照者的血清低密度脂蛋白免疫复合物(LDL-ICs)浓度.T2DM及大血管病变患者血LDL-ICs浓度均高于正常对照者,糖尿病合并大血管病变者高于单纯糖尿病、单纯大血管病变患者;血清LDL-ICs浓度与体重指数、血糖化血红蛋白、血压、总胆固醇、甘油三酯水平呈正相关,与高密度脂蛋白胆固醇水平呈负相关,与低密度脂蛋白胆固醇水平无相关性.LDL-ICs、血压、糖化血红蛋白是糖尿病大血管病变的危险因素.%This study was designed to observe the clinical value of low-density lipoprotein immune complexes (LDL-ICs) in patients with type 2 diabetes mellitus (T2DM). Fifty-four patients with type 2 diabetes + macroangiopathy (DM-MA group), 48 patients with type 2 diabetes (DM group), 45 patients with macroangiopathy ( MA group), and 30 normal controls ( NC group) were enrolled. LDL-ICs levels in the DM-MA group were significantly higher than those in the other three groups. The levels of LDL-ICs in the MA group were higher than those in the NC and DM groups. There was a significant difference in LDL-ICs between the DM and NC groups. LDL-ICs levels were positively related with body mass index (BMI), glycesylated hemoglobin Alc(HbAlc), blood pressure, total cholesterol, and triglyceride. There was no significant relationship between low-density lipsprotcin cholesterol and LDL-ICs. A significantly negative correlation was recorded between high-density lipoprotein cholesterol and LDL-ICs. Our study suggests that LDL-ICs, blood pressure, and HbAlc may be risk factors of macroangiopathy in type 2 diabetic patients.

  1. Immune Disorder HSCT Protocol (United States)


    Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  2. The Immune System Game (United States)

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.


    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  3. Conservation of circulation in magnetohydrodynamics (United States)

    Bekenstein; Oron


    We demonstrate at both the Newtonian and (general) relativistic levels the existence of a generalization of Kelvin's circulation theorem (for pure fluids) that is applicable to perfect magnetohydrodynamics. The argument is based on the least action principle for magnetohydrodynamic flow. Examples of the new conservation law are furnished. The new theorem should be helpful in identifying new kinds of vortex phenomena distinct from magnetic ropes or fluid vortices.

  4. Conservation of Circulation in Magnetohydrodynamics


    Bekenstein, Jacob D.; Oron, Asaf


    We demonstrate, both at the Newtonian and (general) relativistic levels, the existence of a generalization of Kelvin's circulation theorem (for pure fluids) which is applicable to perfect magnetohydrodynamics. The argument is based on the least action principle for magnetohydrodynamic flow. Examples of the new conservation law are furnished. The new theorem should be helpful in identifying new kinds of vortex phenomena distinct from magnetic ropes or fluid vortices.

  5. Immune Dysfunction in Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Ishraga Elamin


    Full Text Available The association between immunity and neurodevelopmental disorders has been extensively investigated in autism, suggesting a potential involvement of both cellular and humoral immunity in the establishment of synaptic connectivity modulation during development. A similar link has been proposed also for Tourette syndrome (TS, a complex, multifactorial disorder, in which the interplay between genetic, environmental, hormonal and immunological factors might be relevant. Lymphocyte subpopulation analysis in TS suggests a possible systemic activation of several T- and B-cell subtypes, whereas the observed decreased numbers of T regulatory lymphocytes might predispose to autoimmunity. Genes related to both cell- and antibody-mediated immune responses may be over-expressed at specific ages in youngsters with TS. Data from cytokine measurements and transcriptomics profiles in TS patients are coherent with the systemic immune activation detected by studies on lymphocyte subpopulations. Moreover, TS patients have exhibited IgG3 and IgA dysgammaglobulinemia, which might predispose to recurrent infections and autoimmunity. To date, the association between TS and autoantibodies has not been demonstrated. Interestingly, however, there is a higher degree of maternal family history of autoimmune diseases among TS patients. Finally, TS patients could be prone to allergic illnesses (asthma, atopic dermatitis, rhinitis, conjunctivitis, but more work is needed in this area.

  6. Hall Effect Gyrators and Circulators (United States)

    Viola, Giovanni; DiVincenzo, David P.


    The electronic circulator and its close relative the gyrator are invaluable tools for noise management and signal routing in the current generation of low-temperature microwave systems for the implementation of new quantum technologies. The current implementation of these devices using the Faraday effect is satisfactory but requires a bulky structure whose physical dimension is close to the microwave wavelength employed. The Hall effect is an alternative nonreciprocal effect that can also be used to produce desired device functionality. We review earlier efforts to use an Ohmically contacted four-terminal Hall bar, explaining why this approach leads to unacceptably high device loss. We find that capacitive coupling to such a Hall conductor has much greater promise for achieving good circulator and gyrator functionality. We formulate a classical Ohm-Hall analysis for calculating the properties of such a device, and show how this classical theory simplifies remarkably in the limiting case of the Hall angle approaching 90°. In this limit, we find that either a four-terminal or a three-terminal capacitive device can give excellent circulator behavior, with device dimensions far smaller than the ac wavelength. An experiment is proposed to achieve GHz-band gyration in millimeter (and smaller) scale structures employing either semiconductor heterostructure or graphene Hall conductors. An inductively coupled scheme for realizing a Hall gyrator is also analyzed.

  7. Obesity, inflammation and the immune system. (United States)

    de Heredia, Fátima Pérez; Gómez-Martínez, Sonia; Marcos, Ascensión


    Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.

  8. Chronic fatigue syndrome and circulating cytokines: A systematic review. (United States)

    Blundell, S; Ray, K K; Buckland, M; White, P D


    There has been much interest in the role of the immune system in the pathophysiology of chronic fatigue syndrome (CFS), as CFS may develop following an infection and cytokines are known to induce acute sickness behaviour, with similar symptoms to CFS. Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a search was conducted on PubMed, Web of Science, Embase and PsycINFO, for CFS related-terms in combination with cytokine-related terms. Cases had to meet established criteria for CFS and be compared with healthy controls. Papers retrieved were assessed for both inclusionary criteria and quality. 38 papers met the inclusionary criteria. The quality of the studies varied. 77 serum or plasma cytokines were measured without immune stimulation. Cases of CFS had significantly elevated concentrations of transforming growth factor-beta (TGF-β) in five out of eight (63%) studies. No other cytokines were present in abnormal concentrations in the majority of studies, although insufficient data were available for some cytokines. Following physical exercise there were no differences in circulating cytokine levels between cases and controls and exercise made no difference to already elevated TGF-β concentrations. The finding of elevated TGF-β concentration, at biologically relevant levels, needs further exploration, but circulating cytokines do not seem to explain the core characteristic of post-exertional fatigue.

  9. Modelling Immune System: Principles, Models,Analysis and Perspectives

    Institute of Scientific and Technical Information of China (English)

    Xiang-hua Li; Zheng-xuan Wang; Tian-yang Lu; Xiang-jiu Che


    The biological immune system is a complex adaptive system. There are lots of benefits for building the model of the immune system. For biological researchers, they can test some hypotheses about the infection process or simulate the responses of some drugs. For computer researchers, they can build distributed, robust and fault tolerant networks inspired by the functions of the immune system. This paper provides a comprehensive survey of the literatures on modelling the immune system. From the methodology perspective, the paper compares and analyzes the existing approaches and models, and also demonstrates the focusing research effort on the future immune models in the next few years.

  10. Circulating endocannabinoids during hematopoietic stem cell transplantation: A pilot study

    Directory of Open Access Journals (Sweden)

    Jennifer M. Knight


    Conclusions: The eCB signaling system may have alternative sources and regulatory mechanisms in addition to the immune system. Given the significant associations with inflammatory molecules and depressive symptoms in the peri-transplant period, it is important to better understand this system and its potential implications in the setting of complex and stressful medical procedures such as HCT.

  11. Immune-priming in ant larvae: social immunity does not undermine individual immunity. (United States)

    Rosengaus, Rebeca B; Malak, Tanya; Mackintosh, Christopher


    Social insects deploy numerous strategies against pathogens including behavioural, biochemical and immunological responses. While past research has revealed that adult social insects can generate immunity, few studies have focused on the immune function during an insect's early life stages. We hypothesized that larvae of the black carpenter ant Camponotus pennsylvanicus vaccinated with heat-killed Serratia marcescens should be less susceptible to a challenge with an active and otherwise lethal dose of the bacterium. We compared the in vivo benefits of prior vaccination of young larvae relative to naive and ringer injected controls. Regardless of colony of origin, survival parameters of vaccinated individuals following a challenge were significantly higher than those of the other two treatments. Results support the hypothesis that ant larvae exhibit immune-priming. Based on these results, we can infer that brood care by workers does not eliminate the need for individual-level immunological responses. Focusing on these early stages of development within social insect colonies can start addressing the complex dynamics between physiological (individual level) and social (collective) immunity.

  12. Liquid biopsies for liquid tumors:emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    Jay Hocking; Sridurga Mithraprabhu; Anna Kalff; Andrew Spencer


    Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment.

  13. Circulating follistatin in relation to energy metabolism

    DEFF Research Database (Denmark)

    Hansen, Jakob Schiøler; Plomgaard, Peter


    Recently, substantial evidence has emerged that the liver contributes significantly to the circulating levels of follistatin and that circulating follistatin is tightly regulated by the glucagon-to-insulin ratio. Both observations are based on investigations of healthy subjects. These novel...... a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated...... with elevated levels of circulating follistatin have a metabolic denominator with decreased insulin sensitivity and/or hyperglucagoneimia....

  14. Environmental Isolation of Circulating Vaccine-Derived Poliovirus After Interruption of Wild Poliovirus Transmission - Nigeria, 2016. (United States)

    Etsano, Andrew; Damisa, Eunice; Shuaib, Faisal; Nganda, Gatei Wa; Enemaku, Ogu; Usman, Samuel; Adeniji, Adekunle; Jorba, Jaume; Iber, Jane; Ohuabunwo, Chima; Nnadi, Chimeremma; Wiesen, Eric


    In September 2015, more than 1 year after reporting its last wild poliovirus (WPV) case in July 2014 (1), Nigeria was removed from the list of countries with endemic poliovirus transmission,* leaving Afghanistan and Pakistan as the only remaining countries with endemic WPV. However, on April 29, 2016, a laboratory-confirmed, circulating vaccine-derived poliovirus type 2 (cVDPV2) isolate was reported from an environmental sample collected in March from a sewage effluent site in Maiduguri Municipal Council, Borno State, a security-compromised area in northeastern Nigeria. VDPVs are genetic variants of the vaccine viruses with the potential to cause paralysis and can circulate in areas with low population immunity. The Nigeria National Polio Emergency Operations Center initiated emergency response activities, including administration of at least 2 doses of oral poliovirus vaccine (OPV) to all children aged <5 years through mass campaigns; retroactive searches for missed cases of acute flaccid paralysis (AFP), and enhanced environmental surveillance. Approximately 1 million children were vaccinated in the first OPV round. Thirteen previously unreported AFP cases were identified. Enhanced environmental surveillance has not resulted in detection of additional VDPV isolates. The detection of persistent circulation of VDPV2 in Borno State highlights the low population immunity, surveillance limitations, and risk for international spread of cVDPVs associated with insurgency-related insecurity. Increasing vaccination coverage with additional targeted supplemental immunization activities and reestablishment of effective routine immunization activities in newly secured and difficult-to-reach areas in Borno is urgently needed.

  15. Microsurgical anatomy of the posterior circulation

    Directory of Open Access Journals (Sweden)

    Pai Balaji


    Full Text Available Context: The microsurgical anatomy of the posterior circulation is very complex and variable. Surgical approaches to this area are considered risky due to the presence of the various important blood vessels and neural structures. Aims: To document the microsurgical anatomy of the posterior circulation along with variations in the Indian population. Materials and Methods: The authors studied 25 cadaveric brain specimens. Microsurgical dissection was carried out from the vertebral arteries to the basilar artery and its branches, the basilar artery bifurcation, posterior cerebral artery and its various branches. Measurements of the outer diameters of the vertebral artery, basilar artery and posterior cerebral artery and their lengths were taken. Results: The mean diameter of the vertebral artery was 3.4 mm on the left and 2.9 mm on the right. The diameter of the basilar artery varied from 3-7 mm (mean of 4.3 mm. The length varied from 24-35 mm (mean of 24.9 mm. The basilar artery gave off paramedian and circumferential perforating arteries. The origin of the anterior inferior cerebellar artery (AICA varied from 0-21 mm (mean 10.0 mm from the vertebrobasilar junction. The diameter of the AICA varied from being hypoplastic i.e., < 0.5 mm to 2 mm (mean 1.0 mm. The superior cerebellar artery (SCA arises very close to the basilar bifurcation, in our series (1-3 mm from the basilar artery bifurcation. The diameter of the SCA varied from 0.5-2.5 mm on both sides. The posterior cerebral artery (PCA is divided into four segments. The PCA gave rise to perforators (thalamoperforators, thalamogeniculate arteries, circumflex arteries and peduncular arteries, medial posterior choroidal artery, lateral posterior choroidal artery and cortical branches. In 39 specimens the P1 segment was found to be larger than the posterior communicating artery, in six specimens it was found to be equal to the diameter of the posterior communicating artery and in five specimens it

  16. Autonomic nervous system and immune system interactions. (United States)

    Kenney, M J; Ganta, C K


    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological, and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines, and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease

  17. Matrix-free constructions of circulant and block circulant preconditioners

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chao; Ng, Esmond G.; Penczek, Pawel A.


    A framework for constructing circulant and block circulant preconditioners (C) for a symmetric linear system Ax=b arising from certain signal and image processing applications is presented in this paper. The proposed scheme does not make explicit use of matrix elements of A. It is ideal for applications in which A only exists in the form of a matrix vector multiplication routine, and in which the process of extracting matrix elements of A is costly. The proposed algorithm takes advantage of the fact that for many linear systems arising from signal or image processing applications, eigenvectors of A can be well represented by a small number of Fourier modes. Therefore, the construction of C can be carried out in the frequency domain by carefully choosing its eigenvalues so that the condition number of C{sup T} AC can be reduced significantly. We illustrate how to construct the spectrum of C in a way such that the smallest eigenvalues of C{sup T} AC overlaps with those of A extremely well while the largest eigenvalues of C{sup T} AC are smaller than those of A by several orders of magnitude. Numerical examples are provided to demonstrate the effectiveness of the preconditioner on accelerating the solution of linear systems arising from image reconstruction application.

  18. Artificial Immune Privileged Sites as an Enhancement to Immuno-Computing Paradigm


    Chingtham, Tejbanta Singh; Sahoo, G.; Ghose, M. K.


    The immune system is a highly parallel and distributed intelligent system which has learning, memory, and associative capabilities. Artificial Immune System is an evolutionary paradigm inspired by the biological aspects of the immune system of mammals. The immune system can inspire to form new algorithms learning from its course of action. The human immune system has motivated scientists and engineers for finding powerful information processing algorithms that has solved complex engineering p...

  19. Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial.

    Directory of Open Access Journals (Sweden)

    Lisa C Lindesmith


    Full Text Available Human noroviruses (NoVs are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP candidate vaccine in human volunteers.Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4 were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated.Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential

  20. Relationship between HMGB1 content and MHC-Ⅱ expression in circulating monocytes and spleen of mice challenged with zymosan

    Institute of Scientific and Technical Information of China (English)

    L(U) Yi; LU Jiang-yang; ZHAO Min; LI Zhi-hong; YANG Yi


    Objective: To observe the regularity of change in high mobility group protein box 1 (HMGB1) content in serum and spleen of mice with multiple organ dysfunction syndrome (MODS), to analyze the correlation between HMGB1 content and major histocompatibility complex (MHC)-Ⅱ-I-Ab expression on monocytes in blood and spleen, and to explore the effect of HMGB1 on immune function of circulating monocytes and splenocytes. Methods: One hundred 8-week-old male 57BL/6 mice were randomly divided into normal group and experimental group subdivided into 8 subgroups: 3, 8, 12 hours, 1, 2, 3, 5-7 days and 10-12 days post zymosan injection (PZI). MODS model was replicated by injecting zymosan into the peritoneal cavity. At each time point, blood and spleen were collected to detect HMGB1 content and the rate of I-Ab positive monocytes. Results: In normal and PZI 3-hour, 8-hour mice, serum HMGB1 was not detected, but it significantly increased at PZI 12 hours. In spleen of normal mice, there was low level of HMGB1 expression. In zymosan-treated mice, HMGB1 started to rise in spleen at PZI 3 hours. Subsequently, HMGB1 content in both serum and spleen significantly increased, and it reached the peak level in 1-2 days, decreased in 5 days, and then increased in 10-12 days. The number of I-Ab positive monocytes in circulating blood and spleen decreased at 1-2 days (t=9.589, 4.432, P<0.01) and 10-12 days following the challenge, forming a two trough like decrease, just corresponding with two-peak increase of HMGB1. However, at 3 hours after zyrnosan challenge, I-Ab expression on circulating monocytes was downregulated (t=5.977, P<0.01), while that in spleen upregulated (t=4.814, P<0.01). Conclusion: In mice with MODS, up-regulated HMGB1 expression can regulate I-Ab expression on monocytes to depress their ability of presenting antigen, which results in immune disturbance contributing development of MODS.

  1. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser


    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  2. Simultaneous immunization against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Elma Z Tchilian

    Full Text Available BACKGROUND: BCG, the only licensed vaccine against tuberculosis, provides some protection against disseminated disease in infants but has little effect on prevention of adult pulmonary disease. Newer parenteral immunization prime boost regimes may provide improved protection in experimental animal models but are unproven in man so that there remains a need for new and improved immunization strategies. METHODS AND FINDINGS: Mice were immunized parenterally, intranasally or simultaneously by both routes with BCG or recombinant mycobacterial antigens plus appropriate adjuvants. They were challenged with Mycobacterium tuberculosis (Mtb and the kinetics of Mtb growth in the lungs measured. We show that simultaneous immunization (SIM of mice by the intranasal and parenteral routes is highly effective in increasing protection over parenteral BCG administration alone. Intranasal immunization induces local pulmonary immunity capable of inhibiting the growth of Mtb in the early phase (the first week of infection, while parenteral immunization has a later effect on Mtb growth. Importantly, these two effects are additive and do not depend on priming and boosting the immune response. The best SIM regimes reduce lung Mtb load by up to 2 logs more than BCG given by either route alone. CONCLUSIONS: These data establish SIM as a novel and highly effective immunization strategy for Mtb that could be carried out at a single clinic visit. The efficacy of SIM does not depend on priming and boosting an immune response, but SIM is complementary to prime boost strategies and might be combined with them.

  3. Assessment of Radiation Risk by Circulating microRNAs (United States)

    Wang, Jufang


    Highly energized particles delivered by galactic cosmic rays as well as solar particle events are one of the most severe detrimental factors to the health of crews during long-term space missions. Researches related to the assessment of radiation risk have been carried out with ground-based accelerator facilities all around the world. Circulating microRNAs (miRNAs) in blood have the advantages of specificity and stability, which could be used as disease biomarkers and potential bio-dosimeters to monitor the radiation risk. Based on this backgroud, circulating miRNAs were isolated from blood after Kunming mice were whole-body exposed to 300MeV/u carbon ion beam which were generated by the Heavy Ion Research Facility in Lanzhou (HIRFL), and the levels of miRNA expression were detected by miRNA PCR array. It was found that more than one hundred of circulating miRNAs were responded to carbon ion irradiation. Among these radiosensitive miRNAs, most of them were closely associated with immune system and hematopoietic system. The miRNA levels changed more than 2-fold were further verified by qRT-PCR analysis following exposure to X rays and iron ion beam. Some miRNAs such as let-7a, miR-34a, miR-223 and miR-150 showed obvious radio-sensitivity and dose-dependent effect, demonstrating that they were potential biomarkers of radiation and could be used as ideal bio-dosimeters. Those findings indicate that with the properties of high radio-sensitivity and time-saving quantification method by standard PCR assay, circulating miRNAs may become potential biomarkers for radiation detection in space exploration.

  4. Circulating Mitochondrial DAMPs Are Not Effective Inducers of Proteinuria and Kidney Injury in Rodents. (United States)

    He, Jing; Lu, Yuqiu; Xia, Hong; Liang, Yaojun; Wang, Xiao; Bao, Wenduona; Yun, Shifeng; Ye, Yuting; Zheng, Chunxia; Liu, Zhihong; Shi, Shaolin


    Mitochondria in eukaryotic cells are derived from bacteria in evolution. Like bacteria, mitochondria contain DNA with unmethylated CpG motifs and formyl peptides, both of which have recently been shown to be damage associated molecular patterns (DAMPs) and induce immune response and cell injury. Based on the facts that circulating mitochondrial DAMPs (mtDAMPs) are increased in the patients of trauma or burn injury who also have proteinuria, that mtDAMPs can activate immune cells which in turn secrete glomerular permeability factors, that renal intrinsic cells express a variety of DAMP receptors, and that mtDAMPs can directly increase endothelial cell permeability in vitro, we hypothesized that mtDAMPs may be novel circulating factors inducing proteinuria and kidney injury. We tested this hypothesis by directly injecting mtDAMPs into rodents and examining urinary protein and kidney histology. We prepared mtDAMP samples, including mitochondrial DNA (mtDNA) and mitochondrial debris (MTD), from rodent liver. In mice, injection of mtDNA for 20 μg/ml initial concentration in circulation (much higher than the clinical range), did not cause any renal manifestations. However, an increased dose leading to 45 μg/ml initial concentration in circulation resulted in a transient, slight increase in urinary albumin. In rats, MTD injection resulting in 450 μg/ml initial concentration of MTD protein in circulation, which was much higher than the clinical range, caused mild, transient proteinuria and lung lesions. Multiple injections of such large amount of either mtDNA or MTD into rodents on 3 consecutive days also failed in inducing proteinuria and kidney injury. In summary, clinical levels of circulating mtDAMPs do not induce proteinuria and clinically irrelevant high levels of mtDAMPs cause only a transient and slight increase in urinary protein in rodents, suggesting that circulating mtDAMPs may not be responsible for the proteinuria and kidney injury in patients with trauma

  5. Immune-Mediated Muscle Diseases of the Horse. (United States)

    Durward-Akhurst, S A; Valberg, S J


    In horses, immune-mediated muscle disorders can arise from an overzealous immune response to concurrent infections or potentially from an inherent immune response to host muscle antigens. Streptococcus equi ss. equi infection or vaccination can result in infarctive purpura hemorrhagica (IPH) in which vascular deposition of IgA-streptococcal M protein complexes produces ischemia and complete focal infarction of skeletal muscle and internal organs. In Quarter Horse-related breeds with immune-mediated myositis, an apparent abnormal immune response to muscle antigens results in upregulation of major histocompatibility complex class (MHC) I and II on muscle cell membranes, lymphocytic infiltration of lumbar and gluteal myofibers, and subsequent gross muscle atrophy. Rarely, an inflammatory event results in myositis with subsequent systemic calcinosis characterized by a pathognomonic hyperphosphatemia and high fatality rate. This review presents an overview of these immune-mediated myopathies and highlights clinical and pathological features as well as the suspected pathophysiology.

  6. Metabolism of nanomaterials in vivo: blood circulation and organ clearance. (United States)

    Wang, Bing; He, Xiao; Zhang, Zhiyong; Zhao, Yuliang; Feng, Weiyue


    occurring between NMs and between NMs and the biological milieu after the introduction of NMs into living systems may further influence the blood circulation and clearance profiles of NMs. These interactions can alter properties such as agglomeration, phase transformations, dissolution, degradation, protein adsorption, and surface reactivity. The physicochemical properties of NMs change dynamically in vivo thereby making the metabolism of NMs complex and difficult to predict. The development of in situ, real-time, and quantitative techniques, in vitro assays, and the adaptation of physiologically-based pharmacokinetic (PBPK) and quantitative structure-activity relationship (QNSAR) modeling for NMs will streamline future in vivo studies.

  7. Fritz Schott's Contributions to the Understanding of the Ocean Circulation (United States)

    Visbeck, M.


    The ocean circulation and its central significance for global climate lay at the heart of Fritz's research. In the context of hard-won data from his more than 30 research cruises to key regions of the Atlantic and Indian oceans, he made fundamental contributions to our understanding of the wind-driven and thermohaline ocean circulation. His insights and explorations of circulation and dynamics of the tropical Indian and Atlantic Oceans have led the field and provided a large part of the basis for planning large, international experiments. Fritz's work is also distinguished by his making exceptional use of modeling results, increasingly as the models have improved. His research has provided a much clearer correspondence between the observed ocean-structure and dynamical theory-noting both theoretical successes and limitations. Besides his general interest in the physical oceanography of the World Oceans, most of his research was devoted to the dynamics of tropical oceans with its intense and highly variable current systems. Concerning the Indian Ocean, Fritz's investigated the response of the Somali Current system to the variable monsoon winds in the early 1980's, obtaining high-quality, hydrographic surveys and the first long term direct measurement of ocean currents from moored arrays. His analyses and interpretations provided a synthesis of the complex circulations there. In the tropical Atlantic Ocean Fritz research focused on the western boundary circulation with important contributions to the understanding of the North Brazil Current retroflection, and the variability of the shallow and deep western boundary currents. Trying to solve the fundamental question ‘what is the role of the tropical ocean for climate variability', Fritz initiated large multinational research programs under the umbrella of the World Climate Research Projects WOCE (World Ocean Circulation Experiment) and CLIVAR (Climate Variability and Predictability). Fritz was the initiator and

  8. Vitamin-mediated regulation of intestinal immunity

    Directory of Open Access Journals (Sweden)

    Jun eKunisawa


    Full Text Available The intestine is exposed continuously to complex environments created by numerous injurious and beneficial non-self antigens. The unique mucosal immune system in the intestine maintains the immunologic homeostasis between the host and the external environment. Crosstalk between immunocompetent cells and endogenous (e.g., cytokines and chemokines as well as exogenous factors (e.g., commensal bacteria and dietary materials achieves the vast diversity of intestinal immune functions. In addition to their vital roles as nutrients, vitamins now also are known to have immunologically crucial functions, specifically in regulating host immune responses. In this review, we focus on the immunologic functions of vitamins in regulating intestinal immune responses and their roles in moderating the fine balance between physiologic and pathologic conditions of the intestine.

  9. The impact of oceanic heat transport on the atmospheric circulation

    CERN Document Server

    Knietzsch, Marc-Andre; Lunkeit, Frank


    A general circulation model of intermediate complexity with an idealized earthlike aquaplanet setup is used to study the impact of changes in the oceanic heat transport on the global atmospheric circulation. Focus is put on the Lorenz energy cycle and the atmospheric mean meridional circulation. The latter is analysed by means of the Kuo-Eliassen equation. The atmospheric heat transport compensates the imposed oceanic heat transport changes to a large extent in conjunction with significant modification of the general circulation. Up to a maximum about 3PW, an increase of the oceanic heat transport leads to an increase of the global mean near surface temperature and a decrease of its equator-to-pole gradient. For larger transports, the gradient is reduced further but the global mean remains approximately constant. This is linked to a cooling and a reversal of the temperature gradient in the tropics. A larger oceanic heat transport leads to a reduction of all reservoirs and conversions of the Lorenz energy cycl...

  10. Circulation Produced by a Flapping Wing During Stroke Reversal (United States)

    Burge, Matthew; Ringuette, Matthew


    We investigate the circulation behavior of the 3D flow structures formed during the stroke-reversal of a 2-degree-of-freedom flapping wing in hover. Previous work has related circulation peaks to the unsteady wing kinematics and forces. However, information from experiments detailing contributions from the multiple, 3D flow structures is lacking. The objective of this work is to quantitatively study the spanwise circulation as well as the spanwise flow which advects vorticity in the complex loop topology of a flapping wing during stroke reversal. We analyze the flow features of a scaled wing model using multi-plane stereo digital particle image velocimetry in a glycerin-water mixture. Data plane locations along the wing span are inspired by the time-resolved behavior of the 3D vortex structures observed in our earlier flow visualization studies. As with our prior work, we vary dimensionless parameters such as the pitching reduced frequency to understand their effect on the circulation. This research provides insight into the vortex dynamics produced by the coupled rotational and pitching wing motions during stroke reversal, when lift generation is challenging. This work is supported by the National Science Foundation, Award Number 1336548, supervised by Dr. Dimitrios Papavassiliou.

  11. 类风湿关节炎患者血纤维蛋白原免疫复合物的检测和意义%Significance of Detecting the Immune Complexes Contain Fibrinogen in Patients with Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    王艾丽; 吉滢; 郑田; 严孝岭; 刘国瑞; 贾煊


    Objective To explore the diagnostic value and significance of immune complexes contain fibrinogen(Fb-IC) in patients with rheumatoid arthritis (RA). Methods Fb-ICs were determined by ELISA using anti-human Fb antibody,the serum sample of 126 patients with RA,75 patients with non-RA diseases (lung cancer,systemic lupus erythematosus,undiffer-entiated connective tissue disease and kidney disease) and 34 healthy controls were involved in this study. The consistency of results was compared with that of Clq binding ELISA assay. The correlation of Fb-ICs to anti-cyclic citrullinated pepdide (CCP) and rheumatoid factor (RF) were analysed. Results The Fb-ICs positive rates of RA group,non-RA disease group and healthy control group were 53. 17% (67/126) ,10. 67% (8/75) and 5. 88% (2/34) respectively. The positive rate of RA group was significantly higher than other two groups (X2 = 36. 31 and 22. 16, P<0. 001). The sensitivity of Fb-ICs was 53. 17% with high specificity ( 90. 00%) in RA. The coincidence for both ELISA methods of anti- Fb and Clq was 75%,the results were related (Kappa values>0. 4). There was 55. 3% and 62. 2% Fb-ICs-positive patients with anti-CCP and RF-positive respectively. Conclusion Fb-ICs presents a reasonable sensitivity with high specificity to RA and it is valuable to RA diagnosis. More than 50% of anti-CCP antibodies and RF-positive RA patients existed Fb-ICs and it may be the pathogenic mechanism of RA and conduce to diagnostic value for RA.%目的 检测类风湿关节炎(RA)患者血清中含纤维蛋白原免疫复合物(Fb-IC),探讨Fb-IC在RA中的意义.方法 用抗Fb抗体建立ELISA法检测126例RA,75例其他疾病包括肺癌、系统性红斑狼疮(SLE)、未分化结缔组织病(UCTD)、肾脏疾病患者血清中Fb-ICs,另设健康对照34例.将该法结果与C1q结合法检测ICs的结果进行比较.分析RA患者Fb-IC与抗环瓜氨酸肽(CCP)抗体、类风湿因子( RF)的关系.结果 RA组、非RA疾病组和对

  12. Intestinal circulation during inhalation anesthesia

    Energy Technology Data Exchange (ETDEWEB)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.


    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  13. Origins of adaptive immunity. (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister


    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  14. Human immune system variation. (United States)

    Brodin, Petter; Davis, Mark M


    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

  15. Proteomics and insect immunity

    Directory of Open Access Journals (Sweden)

    L Shi


    Full Text Available Insect innate immunity is both a model for vertebrate immunity as well as a key system that impactsmedically important pathogens that are transmitted by insects. Recent developments in proteomics andprotein identification techniques combined with the completion of genome sequences for Anophelesgambiae and Drosophila melanogaster provided the tools for examining insect immunity at a new level ofmolecular detail. Application of proteomics to insect immunity resulted in predictions of new roles inimmunity for proteins already known in other contexts (e.g. ferritin, transferrin, Chi-lectins and helped totarget specific members of multi-gene families that respond to different pathogens (e.g. serine proteases,thioester proteins. In addition, proteomics studies verify that post-translational modifications play a keyrole in insect immunity since many of the identified proteins are modified in some way. These studiescomplement recent work on insect transcriptomes and provide new directions for further investigation ofinnate immunity.

  16. [Herd immunity against poliomyelitis in children in the Moscow Region]. (United States)

    Seĭbil', V B; Malyshkina, L P; Tamazian, G V; Konopleva, T N; Uspenskaia, E S


    Herd immunity against poliomyelitis was studied in 1391 children and adolescents from 10 towns of the Moscow Region. It was ascertained that the values of herd immunity against poliomyelitis virus type 1 were high everywhere and those of herd immunity against poliomyelitis virus type 2 were high and very high in 9 towns and below the WHO minimum levels (80%). The values of herd immunity against poliomyelitis virus type 3; they were lower than the required minimum in 2 towns and very low in 2 other towns arouse alarm. The study of strain-specific antibodies to vaccine-derived and wild polioviruses has demonstrated that wild poliomyelitis viruses have not circulated in the areas of the examinees in the past decade.

  17. Secondary recurrent miscarriage and H-Y immunity

    DEFF Research Database (Denmark)

    Nielsen, Henriette Svarre


    BACKGROUND Approximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized...... against male-specific minor histocompatibility (H-Y) antigens, and H-Y immunity can cause graft-versus-host disease after stem-cell transplantation. We proposed the H-Y hypothesis that aberrant H-Y immunity is a causal factor for SRM. METHODS This is a critical review of the H-Y hypothesis based on own....... Maternal carriage of HLA-class II alleles presenting H-Y antigens to immune cells is associated with a reduced live birth rate and increased risk of obstetric complications in surviving pregnancies in SRM patients with a firstborn boy. In early pregnancy, both antibodies against HLA and H-Y antigens...

  18. Antibody-Mediated Immunity against Tuberculosis: Implications for Vaccine Development


    Achkar, Jacqueline M; Casadevall, Arturo


    There is an urgent need for new and better vaccines against tuberculosis (TB). Current vaccine design strategies are generally focused on the enhancement of cell-mediated immunity. Antibody-based approaches are not being considered, mostly due to the paradigm that humoral immunity plays little role in the protection against intracellular pathogens. Here, we reappraise and update the increasing evidence for antibody-mediated immunity against Mycobacterium tuberculosis, discuss the complexity o...

  19. Immune responses and immune-related gene expression profile in orange-spotted grouper after immunization with Cryptocaryon irritans vaccine. (United States)

    Dan, Xue-Ming; Zhang, Tuan-Wei; Li, Yan-Wei; Li, An-Xing


    In order to elucidate the immune-protective mechanisms of inactivated Cryptocaryon irritans vaccine, different doses of C. irritans theronts were used to immunize orange-spotted grouper (Epinephelus coioides). We measured serum immobilization titer, blood leukocyte respiratory burst activity, serum alternative complement activity, and serum lysozyme activity weekly. In addition, the expression levels of immune-related genes such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), major histocompatibility complexes I and II (MHC I and II), and transforming growth factor-β1 (TGF-β1) were determined in spleen and gills. The results showed that the immobilization titer, respiratory burst activity, and alternative complement activity of immunized fish were significantly increased, and the levels of the last two immune parameters in the high-dose vaccine group were significantly higher than in the low-dose vaccine group. Serum lysozyme activity in the high-dose vaccine group was significantly higher than in the PBS control group. Vaccination also regulated host immune-related gene expression. For example, at 2- and 3- weeks post immunization, IL-1β expression in the high-dose vaccine group spleen was significantly increased. At 4-weeks post immunization, the fish were challenged with a lethal dose of parasite, and the survival rates of high-dose vaccine group, low-dose vaccine group, PBS control group, and adjuvant control group were 80%, 40%, 0%, and 10% respectively. These results demonstrate that inactivated C. irritans vaccination improves specific and nonspecific immune responses in fish, enhancing their anti-parasite ability. These effects are vaccine antigen dose-dependent.

  20. Immunity and immune modulation in Trypanosoma cruzi infection. (United States)

    Cardillo, Fabíola; de Pinho, Rosa Teixeira; Antas, Paulo Renato Zuquim; Mengel, José


    Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies.

  1. Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis. (United States)

    Araújo, Márcio Sobreira Silva; de Andrade, Renata Aline; Sathler-Avelar, Renato; Magalhães, Camila Paula; Carvalho, Andréa Teixeira; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Mello, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins-Filho, Olindo Assis


    In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL).

  2. An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity. (United States)

    Gazzaniga, Francesca S; Blackburn, Elizabeth H


    Telomerase is a ribonucleoprotein complex that adds telomeric DNA to the ends of linear chromosomes. It contains two core canonical components: the essential RNA component, hTR, which provides the template for DNA synthesis, and the reverse transcriptase protein component, hTERT. Low telomerase activity in circulating peripheral blood mononuclear cells has been associated with a variety of diseases. It is unknown, however, whether telomerase, in addition to its long-term requirement for telomere maintenance, is also necessary for short-term immune cell proliferation and survival. We report that overexpression of enzymatically inactive hTR mutants protected against dexamethasone-induced apoptosis in stimulated CD4 T cells. Furthermore, hTR knockdown reproducibly induced apoptosis in the absence of any detectable telomere shortening or DNA damage response. In contrast, hTERT knockdown did not induce apoptosis. Strikingly, overexpression of hTERT protein caused apoptosis that was rescued by overexpression of enzymatically inactive hTR mutants. Hence, we propose that hTR can function as a noncoding RNA that protects from apoptosis independent of its function in telomerase enzymatic activity and long-term telomere maintenance in normal human immune cells. These results imply that genetic or environmental factors that alter hTR levels can directly affect immune cell function to influence health and disease.

  3. The immune system as a self-centered network of lymphocytes. (United States)

    Santori, Fabio R


    This essay makes a brief historical and comparative review of selective and network theories of the immune system which is presented as a chemical sensory system with immune and non-immune functions. The ontogeny of immune networks is the result of both positive and negative selection of lymphocytes to self-epitopes that serve as a "template" for the recognition of foreign antigens. The development of immune networks progresses from single individual clones in early ontogeny into complex "information processing networks" in which lymphocytes are linked to inhibitory and stimulatory immune cells. The results of these regulatory interactions modulate immune responses and tolerance.


    Institute of Scientific and Technical Information of China (English)


    Objective In order to investigate the relationship between erythrocyte immune function and seleni- um(Se) level. Method Red blood cell immune adherence(RCIA) function,serum RCIA regulatory factor, blood Se content and activities of glutathione peroxidase(GPX) of residents in Keshan disease(KD) endemic and non-endemic areas were comparatively studied. Forty-eight residents in KD endemic area aged 13~ 16 years were divided into 2 groups. The residents in the experimental group were orally given 200μg Se daily as Se yeast for 12 weeks, and their erythrocyte Se content and activity of glutathione peroxidase (GPX),RCIA function,serum RCIA regulatory function and circulating immune complexes(CIC) content were determined. Results The results showed that the rosette for- mation rates of erythrocyte and blood Se levels of the residents in KD area were significantly lower and the rosette formation inhibitory rate of serum RCIA of the residents in KD area was significantly higher than those in the non-endemic area. Erythrocyte Se contents, GPX activities and rosette formation rates of erythrocyte were sig- nificantly increased and the rosette formation inhibitory rates of serum RICA were significantly decreased after sup- plementing Se,but the difference in the contents of serum CIC was not significant. Conclusion The increase of ery- throcyte immune function by Se-supplement might be one of the effective mechanisms in the prevention of KD by Se- supplement.

  5. Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice

    Energy Technology Data Exchange (ETDEWEB)

    Vignali, D.A.A.; Bickle, Q.D.; Taylor, M.G.


    Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes and platelets, and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) reponse to schistosomular antigens. However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions ('foci') around parasites were similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity nor serum anti-schistosomulum extract antibody levels were affected. The pattern of /sup 125/I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential.

  6. Immune hemolytic anemia (United States)

    Anemia - immune hemolytic; Autoimmune hemolytic anemia (AIHA) ... for no reason, the condition is called idiopathic autoimmune hemolytic anemia . The antibodies may also be caused by: Complication ...

  7. Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer. (United States)

    Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong


    Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

  8. Eicosanoids: Exploiting Insect Immunity to Improve Biological Control Programs

    Directory of Open Access Journals (Sweden)

    David Stanley


    Full Text Available Insects, like all invertebrates, express robust innate, but not adaptive, immune reactions to infection and invasion. Insect immunity is usually resolved into three major components. The integument serves as a physical barrier to infections. Within the hemocoel, the circulating hemocytes are the temporal first line of defense, responsible for clearing the majority of infecting bacterial cells from circulation. Specific cellular defenses include phagocytosis, microaggregation of hemocytes with adhering bacteria, nodulation and encapsulation. Infections also stimulate the humoral component of immunity, which involves the induced expression of genes encoding antimicrobial peptides and activation of prophenoloxidase. These peptides appear in the hemolymph of challenged insects 6–12 hours after the challenge. Prostaglandins and other eicosanoids are crucial mediators of innate immune responses. Eicosanoid biosynthesis is stimulated by infection in insects. Inhibition of eicosanoid biosynthesis lethally renders experimental insects unable to clear bacterial infection from hemolymph. Eicosanoids mediate specific cell actions, including phagocytosis, microaggregation, nodulation, hemocyte migration, hemocyte spreading and the release of prophenoloxidase from oenocytoids. Some invaders have evolved mechanisms to suppress insect immunity; a few of them suppress immunity by targeting the first step in the eicosanoid biosynthesis pathways, the enzyme phospholipase A2. We proposed research designed to cripple insect immunity as a technology to improve biological control of insects. We used dsRNA to silence insect genes encoding phospholipase A2, and thereby inhibited the nodulation reaction to infection. The purpose of this article is to place our view of applying dsRNA technologies into the context of eicosanoid actions in insect immunity. The long-term significance of research in this area lies in developing new pest management

  9. A blood circulation model for reference man

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, R.W.; Eckerman, K.F. [Oak Ridge National Lab., TN (United States). Health Sciences Research Div.; Williams, L.R. [Indiana Univ., South Bend, IN (United States). Div. of Liberal Arts and Sciences


    This paper describes a dynamic blood circulation model that predicts the movement and gradual dispersal of a bolus of material in the circulation after its intravascular injection into an adult human. The main purpose of the model is to improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The total blood volume is partitioned into the blood contents of 24 separate organs or tissues, right heart chambers, left heart chambers, pulmonary circulation, arterial outflow to the systemic tissues (aorta and large arteries), and venous return from the systemic tissues (large veins). As a compromise between physical reality and computational simplicity, the circulation of blood is viewed as a system of first-order transfers between blood pools, with the delay time depending on the mean transit time across the pool. The model allows consideration of incomplete, tissue-dependent extraction of material during passage through the circulation and return of material from tissues to plasma.

  10. Mucosal Regulatory T Cells and T Helper 17 Cells in HIV-Associated Immune Activation. (United States)

    Pandiyan, Pushpa; Younes, Souheil-Antoine; Ribeiro, Susan Pereira; Talla, Aarthi; McDonald, David; Bhaskaran, Natarajan; Levine, Alan D; Weinberg, Aaron; Sekaly, Rafick P


    Residual mucosal inflammation along with chronic systemic immune activation is an important feature in individuals infected with human immunodeficiency virus (HIV), and has been linked to a wide range of co-morbidities, including malignancy, opportunistic infections, immunopathology, and cardiovascular complications. Although combined antiretroviral therapy (cART) can reduce plasma viral loads to undetectable levels, reservoirs of virus persist, and increased mortality is associated with immune dysbiosis in mucosal lymphoid tissues. Immune-based therapies are pursued with the goal of improving CD4(+) T-cell restoration, as well as reducing chronic immune activation in cART-treated patients. However, the majority of research on immune activation has been derived from analysis of circulating T cells. How immune cell alterations in mucosal tissues contribute to HIV immune dysregulation and the associated risk of non-infectious chronic complications is less studied. Given the significant differences between mucosal T cells and circulating T cells, and the immediate interactions of mucosal T cells with the microbiome, more attention should be devoted to mucosal immune cells and their contribution to systemic immune activation in HIV-infected individuals. Here, we will focus on mucosal immune cells with a specific emphasis on CD4(+) T lymphocytes, such as T helper 17 cells and CD4(+)Foxp3(+) regulatory T cells (Tregs), which play crucial roles in maintaining mucosal barrier integrity and preventing inflammation, respectively. We hypothesize that pro-inflammatory milieu in cART-treated patients with immune activation significantly contributes to enhanced loss of Th17 cells and increased frequency of dysregulated Tregs in the mucosa, which in turn may exacerbate immune dysfunction in HIV-infected patients. We also present initial evidence to support this hypothesis. A better comprehension of how pro-inflammatory milieu impacts these two types of cells in the mucosa will

  11. Evaluation of the establishment of herd immunity in the population by means of serological surveys and vaccination coverage. (United States)

    Plans-Rubió, Pedro


    The necessary herd immunity blocking the transmission of an infectious agent in the population is established when the prevalence of protected individuals is higher than a critical value, called the herd immunity threshold. The establishment of herd immunity in the population can be determined using the vaccination coverage and seroepidemiological surveys. The vaccination coverage associated with herd immunity (V(c)) can be determined from the herd immunity threshold and vaccine effectiveness. This method requires a vaccine-specific effectiveness evaluation, and it can be used only for the herd immunity assessment of vaccinated communities in which the infectious agent is not circulating. The prevalence of positive serological results associated with herd immunity can be determined from the herd immunity threshold, in terms of prevalence of antibodies (p(c)) and serological test performance. The herd immunity is established when the prevalence of antibodies is higher than pc. This method can be used to assess the establishment of herd immunity in different population groups, both when the infectious agent is circulating and when it is not possible to assess vaccine effectiveness. The herd immunity assessment in Catalonia, Spain, showed that the additional vaccination coverage required to establish herd immunity was 3-6% for measles, mump and varicella and 11% poliovirus type III in school children, 17-59% for diphtheria in youth and adults and 25-46% for persussis in school children, youth and adults.

  12. Pattern Recognition Receptors in Innate Immunity, Host Defense, and Immunopathology (United States)

    Suresh, Rahul; Mosser, David M.


    Infection by pathogenic microbes initiates a set of complex interactions between the pathogen and the host mediated by pattern recognition receptors. Innate immune responses play direct roles in host defense during the early stages of infection, and they also exert a profound influence on the generation of the adaptive immune responses that ensue.…

  13. [State of collective immunity to poliomyelitis in Moscow donors]. (United States)

    Seĭbil', V B; Malyshkina, L P; Lavrova, I K; Efimova, V F; Sadovnikova, V N


    Immunity induced by immunization with oral poliomyelitis vaccine has long been considered to last for life, similarly to immunity developing after infection with wild poliomyelitis virus. Vaccine virus cannot circulate among the immune population for a long time. The vaccination of children against poliomyelitis, carried out in the course of many years, has made it possible to suggest that a considerable number of immune persons were present among the adult population. The examination of 1,030 Moscow donors has revealed that antibodies to poliomyelitis virus of types 1, 2 and 3 were detected in 47.3%, 45.5% and 76.4% of the examinees respectively, the values of the average geometric titers being low. It is known that passages of poliomyelitis vaccine virus through nonimmune persons may result in emergence of revertant viruses with increased neurovirulence. The nonimmune adult population, especially the mothers of vaccinated and revaccinated children, may serve as favorable environment for the circulation of vaccine viruses and the appearance of revertant viruses.

  14. [Ecology of indigenious arbovirus in Alsace. Tick Central European Encephalitis. I.--Complex Ixodes ricinus--bank voles. II.--Study of bank voles population immunity. III.--Virologic results in bank voles population (author's transl)]. (United States)

    Chatelain, J; Hannoun, C; Rodhain, F; Chatelain, J; Hannoun, C; Salmon, A M; Ardoin, P; Chatelain, J; Hannoun, C; Sureau, P


    I.--After showing that bank voles are parasited only by Ixodes ricinus larvae, the authors attempt to found different factors (demographic, biometric, and sexual) who favor individual parasitism. The authors conclude to absent of anti tick immunity for this rodent specie. II.--The search for anti-central european encephalitis antibodies (I.H.A.) are shown that 2 p. cent animals were immuns. Yearly and monthly chronologies of antibodies apparition are shown, factors favoring the growth of specific Central european encephalitis antibodies are discussed. III.--The Central european encephalitis tick viral infection of bank vole is studied according to the number of viral strains isolated from different viscera. The monthly chronology of this infection is shown.

  15. Immune responses to bioengineered organs (United States)

    Ochando, Jordi; Charron, Dominique; Baptista, Pedro M.; Uygun, Basak E.


    Purpose of review Organ donation in the United States registered 9079 deceased organ donors in 2015. This high percentage of donations allowed organ transplantation in 29 851 recipients. Despite increasing numbers of transplants performed in comparison with previous years, the numbers of patients that are in need for a transplant increase every year at a higher rate. This reveals that the discrepancy between the demand and availability of organs remains fundamental problem in organ transplantation. Recent findings Development of bioengineered organs represents a promising approach to increase the pool of organs for transplantation. The technology involves obtaining complex three-dimensional scaffolds that support cellular activity and functional remodeling though tissue recellularization protocols using progenitor cells. This innovative approach integrates cross-thematic approaches from specific areas of transplant immunology, tissue engineering and stem cell biology, to potentially manufacture an unlimited source of donor organs for transplantation. Summary Although bioengineered organs are thought to escape immune recognition, the potential immune reactivity toward each of its components has not been studied in detail. Here, we summarize the host immune response toward different progenitor cells and discuss the potential implications of using nonself biological scaffolds to develop bioengineered organs. PMID:27926545

  16. Linear thermal circulator based on Coriolis forces. (United States)

    Li, Huanan; Kottos, Tsampikos


    We show that the presence of a Coriolis force in a rotating linear lattice imposes a nonreciprocal propagation of the phononic heat carriers. Using this effect we propose the concept of Coriolis linear thermal circulator which can control the circulation of a heat current. A simple model of three coupled harmonic masses on a rotating platform permits us to demonstrate giant circulating rectification effects for moderate values of the angular velocities of the platform.

  17. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets. (United States)

    van Unen, Vincent; Li, Na; Molendijk, Ilse; Temurhan, Mine; Höllt, Thomas; van der Meulen-de Jong, Andrea E; Verspaget, Hein W; Mearin, M Luisa; Mulder, Chris J; van Bergen, Jeroen; Lelieveldt, Boudewijn P F; Koning, Frits


    Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.

  18. Impact of pre-existing MSP142-allele specific immunity on potency of an erythrocytic Plasmodium falciparum vaccine

    Directory of Open Access Journals (Sweden)

    Bergmann-Leitner Elke S


    Full Text Available Abstract Background MSP1 is the major surface protein on merozoites and a prime candidate for a blood stage malaria vaccine. Preclinical and seroepidemiological studies have implicated antibodies to MSP1 in protection against blood stage parasitaemia and/or reduced parasite densities, respectively. Malaria endemic areas have multiple strains of Plasmodium falciparum circulating at any given time, giving rise to complex immune responses, an issue which is generally not addressed in clinical trials conducted in non-endemic areas. A lack of understanding of the effect of pre-existing immunity to heterologous parasite strains may significantly contribute to vaccine failure in the field. The purpose of this study was to model the effect of pre-existing immunity to MSP142 on the immunogenicity of blood-stage malaria vaccines based on alternative MSP1 alleles. Methods Inbred and outbred mice were immunized with various recombinant P. falciparum MSP142 proteins that represent the two major alleles of MSP142, MAD20 (3D7 and Wellcome (K1, FVO. Humoral immune responses were analysed by ELISA and LuminexTM, and functional activity of induced MSP142-specific antibodies was assessed by growth inhibition assays. T-cell responses were characterized using ex vivo ELISpot assays. Results Analysis of the immune responses induced by various immunization regimens demonstrated a strong allele-specific response at the T cell level in both inbred and outbred mice. The success of heterologous regimens depended on the degree of homology of the N-terminal p33 portion of the MSP142, likely due to the fact that most T cell epitopes reside in this part of the molecule. Analysis of humoral immune responses revealed a marked cross-reactivity between the alleles. Functional analyses showed that some of the heterologous regimens induced antibodies with improved growth inhibitory activities. Conclusion The development of a more broadly efficacious MSP1 based vaccine may be

  19. A brief etymology of the collateral circulation. (United States)

    Faber, James E; Chilian, William M; Deindl, Elisabeth; van Royen, Niels; Simons, Michael


    It is well known that the protective capacity of the collateral circulation falls short in many individuals with ischemic disease of the heart, brain, and lower extremities. In the past 15 years, opportunities created by molecular and genetic tools, together with disappointing outcomes in many angiogenic trials, have led to a significant increase in the number of studies that focus on: understanding the basic biology of the collateral circulation; identifying the mechanisms that limit the collateral circulation's capacity in many individuals; devising methods to measure collateral extent, which has been found to vary widely among individuals; and developing treatments to increase collateral blood flow in obstructive disease. Unfortunately, accompanying this increase in reports has been a proliferation of vague terms used to describe the disposition and behavior of this unique circulation, as well as the increasing misuse of well-ensconced ones by new (and old) students of collateral circulation. With this in mind, we provide a brief glossary of readily understandable terms to denote the formation, adaptive growth, and maladaptive rarefaction of collateral circulation. We also propose terminology for several newly discovered processes that occur in the collateral circulation. Finally, we include terms used to describe vessels that are sometimes confused with collaterals, as well as terms describing processes active in the general arterial-venous circulation when ischemic conditions engage the collateral circulation. We hope this brief review will help unify the terminology used in collateral research.

  20. Role of Circulating Fibrocytes in Cardiac Fibrosis

    Institute of Scientific and Technical Information of China (English)

    Rong-Jie Lin; Zi-Zhuo Su; Shu-Min Liang; Yu-Yang Chen; Xiao-Rong Shu; Ru-Qiong Nie; Jing-Feng Wang


    Objective: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis.Data Sources: This review is based on the data from 1994 to present obtained from PubMed.The search terms were "circulating fibrocytes" and "cardiac fibrosis".Study Selection: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected.Results: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics ofhematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+).They can produce extracellular matrix and many cytokines.It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis.Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts.Conclusions: Circulating fibrocytes are effector cells in cardiac fibrosis.