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Sample records for acquired immune deficiency

  1. Cryptosporidiosis in the acquired immune deficiency syndrome.

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    Cooper, D A; Wodak, A; Marriot, D J; Harkness, J L; Ralston, M; Hill, A; Penny, R

    1984-10-01

    Cryptosporidiosis was found in a patient with the acquired immune deficiency syndrome. The microbiological and morphological features of this newly recognized opportunistic infection are distinctive and diagnostic.

  2. Acquired immune deficiency syndrome: review.

    Science.gov (United States)

    Scully, C; Cawson, R A; Porter, S R

    1986-07-19

    Acquired immunodeficiency syndrome (AIDS) is reviewed for dental practitioners, with an emphasis on oral findings; the clinical course, diagnosis, reporting, treatment, prognosis, transmission, and epidemiology are also covered. HIV infection has an incubation period that may be associated with glandular fever, a prodrome called AIDS-Related Complex (ARC) characterized by lymphadenopathy, low fever, weight loss, night sweats, diarrhea, oral candidosis, nonproductive cough and recurrent infections. AIDS is characterized by opportunistic infections. Over 50% present with pneumocystis carinii pneumonia, 21% with Kaposi's sarcoma, and 6% have both. The AIDS virus causes direct neurological symptoms in some cases. Oral candidosis (thrush) in a young male without a local cause such as xerostomia or immune suppression is strongly suggestive of AIDS. Other oral manifestations are severe herpes simplex, varicella-zoster, Epstein-Barr virus, cytomegalovirus, venereal warts, aphthous ulceration, mycobacterial oral ulcers, oral histoplasmosis, sinusitis and osteomyelitis of the jaw. Hairy leukoplakia, usually seen on the lateral border of the tongue, is probably caused by Epstein-Barr virus. Kaposi's sarcoma, an endothelial cell tumor, is characteristic of AIDS, and in 50% of patients is oral or perioral. Cervical lymph node enlargement will be seen in those with ARC as well as AIDS. No guidelines have been issued by the Department of Health and Social Security for dental surgeons in the UK for reporting AIDS cases. Although HIV virions have been isolated from saliva, there are no known incidents of transmission via saliva. HIV is less likely to be transmitted by needle stick injuries than, for example hepatitis B (25% risk), especially if the blood is from a carrier rather than a full blown AIDS case.

  3. Hyperthyroidism caused by acquired immune deficiency syndrome.

    Science.gov (United States)

    Wang, J-J; Zhou, J-J; Yuan, X-L; Li, C-Y; Sheng, H; Su, B; Sheng, C-J; Qu, S; Li, H

    2014-01-01

    Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. This is the first reported case of hyperthyroidism caused by AIDS. AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

  4. An unusual ocular presentation of acquired immune deficiency syndrome

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    Arunachalam Cynthia

    2008-01-01

    Full Text Available A 50-year-old male who presented with bilateral keratomalacia and on subsequent evaluation was found to be human immunodeficiency virus (HIV positive is being reported. A MEDLINE search of the literature did not reveal any report of keratomalacia as the initial presenting feature of HIV/ acquired immune deficiency syndrome.

  5. Acquired Immune Deficiency Syndrome: A Preliminary Examination of the Effects on Gay Couples and Coupling.

    Science.gov (United States)

    Carl, Douglas

    1986-01-01

    The Acquired Immune Deficiency Syndrome (AIDS) epidemic significantly influences attitudes about life and lifestyles. Homosexuals have to give increased consideration to coupling, the nature of coupled relationships, sex and intimacy, and death long before the normal time. Discusses impact of AIDS on the early stages of gay coupling and on the…

  6. Acquired Immune Deficiency Syndrome: A Preliminary Examination of the Effects on Gay Couples and Coupling.

    Science.gov (United States)

    Carl, Douglas

    1986-01-01

    The Acquired Immune Deficiency Syndrome (AIDS) epidemic significantly influences attitudes about life and lifestyles. Homosexuals have to give increased consideration to coupling, the nature of coupled relationships, sex and intimacy, and death long before the normal time. Discusses impact of AIDS on the early stages of gay coupling and on the…

  7. Meningitis and stridor in advanced Human immunodeficiency virus/acquired immune deficiency syndrome

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    Naidoo P

    2013-09-01

    Full Text Available P Naidoo, D Pillay, S SamanDepartment of Internal Medicine, Port Shepstone Regional Hospital, University of KwaZulu-Natal, South AfricaAbstract: A 37-year-old female presented confused with a preceding history of severe headache. After clinical examination and investigations, she was diagnosed with disseminated tuberculosis (including central nervous system involvement, and Human immunodeficiency virus/acquired immune deficiency syndrome. Her hospital stay was complicated. She developed stridor and a cerebrovascular accident with left hemiplegia. She died approximately 2 weeks after admission. The potential causes of her stridor included a mediastinal mass or a central mechanism secondary to tuberculosis meningitis. Limited resources precluded definitive imaging of the chest to rule out a mediastinal mass. Further, an autopsy was not done. Despite these limitations, this case is unique because it reports the presence of both stridor and tuberculosis meningitis in an adult patient.Keywords: Human immunodeficiency virus, acquired immune deficiency syndrome, meningitis, stridor, tuberculosis

  8. Audiological and Ontological Findings in Acquired Immune-Deficiency Syndrome (AIDS

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    Farzaneh Vadoudfam

    2001-05-01

    Full Text Available The human immunodeficiency virus (HIV is the virus that causes AIDS (acquired immune-deficiency syndrome. Head and neck are the most common sites in contamination with this virus. HIV can affect outer, middle and inner parts of the ear. Changing in the color of the skin, effusion, infection and sudden hearing loss are some types of the audiological and ontological findings in such patients.

  9. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy

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    Drane, W.E.; Tipler, B.M.

    1987-06-01

    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  10. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy.

    Science.gov (United States)

    Drane, W E; Tipler, B M

    1987-06-01

    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  11. Meningitis and stridor in advanced Human immunodeficiency virus/acquired immune deficiency syndrome

    OpenAIRE

    Naidoo P; Pillay D; Saman S

    2013-01-01

    P Naidoo, D Pillay, S SamanDepartment of Internal Medicine, Port Shepstone Regional Hospital, University of KwaZulu-Natal, South AfricaAbstract: A 37-year-old female presented confused with a preceding history of severe headache. After clinical examination and investigations, she was diagnosed with disseminated tuberculosis (including central nervous system involvement), and Human immunodeficiency virus/acquired immune deficiency syndrome. Her hospital stay was complicated. She developed stri...

  12. Human immunodeficiency virus/acquired immune deficiency syndrome: Using drug from mathematical perceptive.

    Science.gov (United States)

    Chatterjee, Amar Nath; Saha, Shubhankar; Roy, Priti Kumar

    2015-11-12

    Entry of acquired immune deficiency syndrome virus into the host immune cell involves the participation of various components of host and viral cell unit. These components may be categorized as attachment of the viral surface envelope protein subunit, gp120, to the CD4(+) receptor and chemokine coreceptors, CCR5 and CXCR4, present on T cell surface. The viral fusion protein, gp41, the second cleaved subunit of Env undergoes reconfiguration and the membrane fusion reaction itself. Since the CD4(+) T cell population is actively involved; the ultimate outcome of human immunodeficiency virus infection is total collapse of the host immune system. Mathematical modeling of the stages in viral membrane protein-host cell receptor-coreceptor interaction and the effect of antibody vaccine on the viral entry into the susceptible host cell has been carried out using as impulsive differential equations. We have studied the effect of antibody vaccination and determined analytically the threshold value of drug dosage and dosing interval for optimum levels of infection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that systematic drug dosage of the immune cells leads to longer and improved lives.

  13. Social capital of Iranian patients living with acquired immune deficiency syndrome and associated factors.

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    Ansari, S K; Nedjat, S; Jabbari, H; Saiepour, N; Heris, M J

    2015-12-13

    This study investigated the social capital of Iranian patients living with acquired immune deficiency syndrome (AIDS) and the associated factors. In a cross-sectional study the Integrated Social Capital Questionnaire was filled by a sequential sample of 300 patients visiting a referral counselling centre in Tehran. The patients' social capital scores were around 50% in the trust, social cohesion, collective action and cooperation and political empowerment domains. The groups and networks membership domain scored the lowest (27.1%). In regression analysis, employment status was significantly associated with groups and networks membership; age, marital status and financial status were associated with collective action and cooperation; period of disease awareness and marital status affected social cohesion and inclusion; and having risky behaviour affected empowerment and political action. Efforts are needed to enhance the social capital of those patients living with AIDS who are younger, unemployed, divorced/widowed, with risky behaviours and shorter disease awareness.

  14. Coping Strategies of Patients with Haemophilia as a Risk Group for AIDS (Acquired Immune Deficiency Syndrome). Brief Research Report.

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    Naji, Simon; And Others

    1986-01-01

    Plans are described for a 2-year project whose major focus is the identification of ways in which patients with hemophilia and their families assimilate, interpret, and act on information about Acquired Immune Deficiency Syndrome (AIDS). Findings will be related to perceived risk, anxiety levels, and the development of coping strategies.…

  15. AIDS: Acquired Immune Deficiency Syndrome, Information and Procedural Guidelines for Providing Services to Persons with AIDS/HTLV-III.

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    Montana State Dept. of Health and Environmental Sciences, Helena.

    This manual presents information about the disease, Acquired Immune Deficiency Syndrome (AIDS), and guidelines for service delivery to Montana residents who have been diagnosed with AIDS or related disorders. The first section describes the disease's causes, symptoms, and transmission; risk factors; high-risk populations; prevention suggestions;…

  16. Can we find a solution to the human immunodeficiency virus/acquired immune deficiency syndrome controversy? Is acquired immune deficiency syndrome the consequence of continuous excessive stressing of the body?

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    Hässig, A; Wen-Xi, L; Stampfli, K

    1996-04-01

    The time of re-evaluation of the role of human immunodeficiency viruses in the pathogenesis of acquired immune deficiency syndrome has now come, now that methods are available for the direct detection of human immunodeficiency viruses and for the detection of cellular anti-human immunodeficiency virus immune reactions. It has been shown that human immunodeficiency virus infections are common among anti-human immunodeficiency virus antibody negative high-risk individuals. The disease is brought under control by cellular immune reactions and the anti-human immunodeficiency virus antibody test remains negative. Apart from proof that infection with human immunodeficiency viruses has occurred, a positive result in an anti-human immunodeficiency virus-antibody test is also an indication of an independent immunosuppression state. According to the definition of the Centers of Disease Control classical acquired immune deficiency syndrome is the consequence of infection with human immunodeficiency virus in association with continuous excessive stress, such as observed in the known risk groups. At the center of the pathogenetic process is hypercortisolism-determined damage of T lymphocytes, in which insufficiency of thymus is prominent. For this reason, in our view, there are indications for shifting efforts from the prophylaxis of infection with human immunodeficiency viruses to the prophylaxis of acquired immune deficiency syndrome by reducing stress factors.

  17. Acquired color vision deficiency.

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    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations.

  18. Penicillium marneffei chylous ascites in acquired immune deficiency syndrome: A case report

    Institute of Scientific and Technical Information of China (English)

    Yin-Zhong Shen; Zhen-Yan Wang; Hong-Zhou Lu

    2012-01-01

    Penicillium marneffei (P.marneffei) infection usually occurs with skin,bone marrow,lung or hepatic involvement.However,no cases of P.marneffei infection with chylous ascites have been reported thus far.In this report,we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P.marneffei infection causing chylous ascites.We describe the details of the case,with an emphasis on treatment regimen.This patient was treated with amphotericin B for 3 mo,while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen,but cultures in ascitic fluid were persistently positive for P.marneffei.The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo.P.marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients.High-dose voriconazole is an effective,well-tolerated and convenient option for the treatment of systemic infections with P.marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

  19. Blood donors at high risk of transmitting the acquired immune deficiency syndrome.

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    Contreras, M; Hewitt, P E; Barbara, J A; Mochnaty, P Z

    1985-03-09

    The acquired immune deficiency syndrome (AIDS) occurs most commonly in homosexual men. This group carries the greatest risk of transmitting AIDS by blood transfusion. Both promiscuous and nonpromiscuous male homosexuals should refrain from giving blood. A leaflet stating this advice was prepared by the Department of Health and Social Security, United Kingdom. In July 1984 a questionnaire was given to all donors attending a blood donor clinic in the west end of London, England. 53% were male. Donors were given a leaflet on AIDS and a questionnaire to complete in private. Those who considered themselves to be in a high risk group were asked to designate their blood for research purposes only. Serum samples from donors who confirmed that they were in the high risk category were tested for antihepatitis B core antigen and anti-human T lymphotropic virus type III (anti-HTLV-III) in addition to the routine screening of donors for hepatitis B surface antigen and syphilis. All high risk donors were men. Homosexuality was the only high risk factor. Of 5000 questionnaires administered between July and October, 614 were not completed or had ambiguous answers. 38 donors who completed the questionnaire beonged to a high risk group. Of these, 7 were positive for antihepatitis B core antigen; none were positive for anti-HTLV-III, T pallidum hemagglatination, or hepatits B surface antigen. Although the homosexual donors had a much lower incidence of sexually transmitted disease than those attending special clinics, this should not encourage complacency. All possible measures must be taken to prevent homosexuals from donating blood.

  20. Bilateral Central Retinal Vein Occlusions Combined with Artery Occlusions in A Patient with Acquired Immune Deficiency Syndrome

    Institute of Scientific and Technical Information of China (English)

    Feng Wen; Xuemei Chen; Haitai Li; Ruiduan Liao; Dezheng Wu

    2002-01-01

    Purpose: This is the first report of a bilateral nonischemic central retinal vein occlusionscombined with artery occlusions in a patient with acquired immune deficiency syndrome(AIDS). Methods: Case report. Results: A 22-year-old Chinese(male) with a positive human immunodeficiency virus(HIV) infection developed bilateral nonischemic central retinal vein occlusions combinedwith artery occlusions and severe vision loss. The manifestations of the fundus andfluorescein angiography were similar in both eyes.Conclusion: This case report provides the evidences that central retinal vein and arteryocclusions are probably part of the spectrum of AIDS vascular diseases.

  1. Acquired immune deficiency syndrome (AIDS) in the United States in 1986: etiology, epidemiology, clinical manifestations, and dental implications.

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    Anneroth, G; Anneroth, I; Lynch, D P

    1986-12-01

    The acquired immune deficiency syndrome (AIDS) results from a lymphotropic retrovirus (HTLV-III) infection and is characterized by specific opportunistic infections and malignancies. The virus is transmitted primarily by semen and blood. Infection is limited principally to defined risk groups, i.e., homosexual men and intravenous drug users. Head and neck manifestations include cervical lymphadenopathy and Kaposi's sarcoma. Oral manifestations include Kaposi's sarcoma, candidiasis, hairy leukoplakia, precocious periodontal disease, xerostomia, herpes simplex, recurrent aphthae, erythema multiforme, and venereal warts. Although HTLV-III is present in saliva, there are no reported cases of transmission secondary to dental procedures. Appropriate precautions and techniques are recommended in treating patients at risk for AIDS.

  2. Roundtable for the Development of Drugs and Vaccines Against Acquired Immune Deficiency Syndrome (AIDS)

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    1994-05-06

    AIDS) SUBTITLE: Workshop Summary: Government and Industry .. Collaboration in AIDS Drug Development Aoneealon Foy PTIS ’IA& ----- DTI ’ TAB PRINCIPAL ...8217 stating that the government should generally acquire the principal or exclusine rights to inventions derived from federally supported research. IPAs w, ould...obligation to adminiter its patent rights in a responsible manner that benefits societN This mean,,, for one thing. not privatizing patents covering

  3. Acquired immune deficiency syndrome in Thailand. A report of two cases.

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    Limsuwan, A; Kanapa, S; Siristonapun, Y

    1986-03-01

    As a major tourist attraction for heterosexuals and homosexuals, Thailand stands to experience major increases in the rate of acquired immunodeficiency syndrome (AIDS). This article describes 2 AIDS cases in Thailand, including the 1st documented case. The 1st case involved a 28-year-old unmarried Thai male who travelled to the US in 1981 for postgraduate work and had contact with both female prostitutes and homosexual men. In 1982-83, the patient demonstrated fever, fatigue, meningitis, and finally Pneumocystis carinii. He was hospitalized in 1984 for fever, bilateral deafness, and diarrhea. Serologic analysis revealed antibodies to human T-cell lymphotropic virus type III (HTLV- III). Death occurred in January 1985. The 2nd patient was a 52-year- old single man who had moved from West Germany to Thailand 10 years previously to admission in 1985 for upper gastrointestinal bleeding. The patient, a homosexual, make frequent visits to Germany and was an alcoholic. The initial clinical diagnosis was ruptured esophageal varices with cirrhosis. The patient further had a history of herpes simplex genitalis. The subsequent course of the disease process included massive blood loss and interstitial pneumonitis. Serology revealed antibodies to HTLV-III. Death occurred in August 1985. Both of these patients belonged to groups at high risk of AIDS and had clinical, serologic, and immunologic indicators that enabled confirmation of the AIDS diagnosis.

  4. Quality of life among people living with acquired immune deficiency syndrome receiving anti-retroviral therapy: a study from Nepal

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    Giri S

    2013-09-01

    Full Text Available Smith Giri, Maniraj Neupane, Sushil Pant, Utsav Timalsina, Sagar Koirala, Santosh Timalsina, Sashi Sharma Department of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal Purpose: The present study was undertaken to determine the impact of acquired immune deficiency syndrome (AIDS on the quality of life of affected individuals in Nepal. Patients and methods: A cross sectional study was done among 70 individuals attending the Anti-Retroviral Therapy clinic of the University Hospital in Nepal. Quality of life (QOL was evaluated using World Health Organization Quality of life questionnaire (WHO QOL-BREF instrument. Statistical analysis was done using SPSS Version 17.0. Results: The median scores with interquartile range (IQR in four domains of QOL in descending order were physical (61; IQR 22, social (58; IQR 33, environmental (56; IQR 13, and psychological (54; IQR 8. Older age was associated with lower perceived overall QOL. Females were more likely to have lower QOL scores in the social and psychological domains. Higher CD4 counts and a married status were significant predictors of higher QOL scores in the environmental domain. Conclusion: Being older, female, single, and having advanced clinical stage is associated with lower QOL scores in people living with AIDS. Lowest QOL scores were seen in the psychological domain suggesting the need of psychological interventions. Keywords: quality of life, AIDS, Nepal, WHO QOL-BREF

  5. Epstein-Barr virus myelitis and Castleman's disease in a patient with acquired immune deficiency syndrome: a case report

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    Balderacchi Jasminka

    2011-05-01

    Full Text Available Abstract Introduction Few cases of Epstein-Barr virus myelitis have been described in the literature. Multi-centric Castleman's disease is a lymphoproliferative disorder that is well known for its associations with the human immunodeficiency virus, human herpes virus 8, and Kaposi's sarcoma. The concurrent presentation of these two diseases in a patient at the same time is extremely unusual. Case Presentation We describe the case of a 43-year-old Caucasian man with acquired immune deficiency syndrome who presented with fever, weight loss and diffuse lymphadenopathy, and was diagnosed with multi-centric Castleman's disease. He presented three weeks later with lower extremity weakness and urinary retention, at which time cerebrospinal fluid contained lymphocytic pleocytosis and elevated protein. Magnetic resonance imaging demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of myelitis. Our patient was ultimately diagnosed with Epstein-Barr virus myelitis, as Epstein-Barr virus DNA was detected by polymerase chain reaction in the cerebrospinal fluid. Conclusion To the best of our knowledge, this is the first case of multi-centric Castleman's disease followed by acute Epstein-Barr virus myelitis in a human immunodeficiency virus-infected patient. Clinicians caring for human immunodeficiency virus-infected patients should be vigilant about monitoring patients with increasing lymphadenopathy, prompting thorough diagnostic investigations when necessary.

  6. [Changes of acquired immune deficiency syndrome related knowledge, attitudes, behaviors and their influencing factors among college students in Beijing].

    Science.gov (United States)

    2017-06-18

    To compare acquired immune deficiency syndrome (AIDS) related knowledge, attitudes, behaviors and their influencing factors among college students in different years in Beijing, and to provide evidence for targeted health education among college students in future. College students were selected by the stratified cluster sampling method, and a questionnaire survey was conducted among college students in year 2006 and 2016 in Beijing. The sample sizes were 1 800 and 3 001 college students, respectively. The contents of the questionnaire included: socio-demographic characteristics, AIDS related knowledge, AIDS related attitude, sex intercourse and its related risk behaviors, condom use intension, and AIDS related health education. Compared with the year 2006, the average AIDS knowledge scores of college students in year 2016 dropped from 12.78±1.95 to 11.90±2.56 (t=12.91, Pinfluencing factors of intention on condom use were male (OR=0.713), self-efficacy of condom purchase (OR=0.876), never received sex education before college (OR=0.752), self-efficacy of condom use (OR=1.135), belief of condom use (OR=1.775), and attitude towards AIDS patients (OR=1.136). AIDS related knowledge, attitudes and behaviors among college students have been changed, AIDS related health education should be designed and improved based on new characteristics of college students. AIDS health education in colleges should pay more attention to sex attitude and sex responsibility and self-protection awareness among college students as well.

  7. Project youth inform--a school-based sexually transmitted disease/acquired immune deficiency syndrome education programme.

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    Soon, T; Chan, R K; Goh, C L

    1995-07-01

    A pilot project, ¿Youth Inform¿ endorsed by the Ministry of Health and Ministry of Education, Singapore, was undertaken in 1992 for 2 years. It aims to enhance sexually transmitted disease (STDs)/human immunodeficiency virus (HIV) control in Singapore by providing structured information for young people between the ages of 16 to 20 years in Polytechnics, Junior Colleges, Centralised Institutes and Pre-University Centres. Project Youth Inform comprises 8 components. They include a focus group discussion, a training seminar for teachers, a lecture/slide presentation cum question-and-answer session, an educational booklet/bookmark, exhibitions, a video, provisions for anonymous questions, and an evaluation. The programme is conducted during school hours at the premises of the institutions and the attendance per session is between 150 to 350 students. A total of 152 sessions have been completed for all the schools. It is ongoing and is currently administered by the School Health Service and Training and Health Education Department. Feedback from principals, teachers and students was gathered formally through surveys and informally through interviews and observations. One thousand students were randomly selected for the survey to assess their responses towards the programme. Eighty-six percent reported that they found it educational and informative. Indicators found to have an influence on the effectiveness of the programme were timing, vocabulary used (medical terms) and integration of the programme into the school's curriculum. In conclusion, Project Youth Inform was on the whole positively received. However, it is essential to constantly accommodate and adapt to new facts and methods of teaching and maintain close coordination with the Ministries and the schools. An effective STD/acquired immune deficiency syndrome programme is an important step towards the prevention, management and control of the epidemic.

  8. Effect of traditional Chinese medicine for treating human immunodeficiency virus infections and acquired immune deficiency syndrome: Boosting immune and alleviating symptoms.

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    Zou, Wen; Wang, Jian; Liu, Ying

    2016-01-01

    To respond to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic in China, the integration of antiretroviral therapy (ART) and traditional Chinese medicine (TCM) has important implications in health outcomes, especially in China where the use of TCM is widespread. The National Free TCM Pilot Program for HIV Infected People began in 5 provinces (Henan, Hebei, Anhui, Hubei, and Guangdong) in 2004, and quickly scaled up to 19 provinces, autonomous regions, and municipalities in China including some places with high prevalence, 26,276 adults have been treated thus far. Usually, people with HIV infection seek TCM for four main reasons: to enhance immune function, to treat symptoms, to improve quality of life, and to reduce side effects related to medications. Evidences from randomized controlled clinical trials suggested some beneficial effects of use of traditional Chinese herbal medicine for HIV infections and AIDS. More proofs from large, well-designed, rigorous trials is needed to give firm support. Challenges include interaction between herbs and antiretroviral drugs, stigma and discrimination. The Free TCM Program has made considerable progress in providing the necessary alternative care and treatment for HIV-infected people in China, and has strong government support for continued improvement and expansion, establishing and improving a work mechanism integrating Chinese and Western medicines.

  9. The earliest cases of human immunodeficiency virus type 1 group M in Congo-Kinshasa, Rwanda and Burundi and the origin of acquired immune deficiency syndrome.

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    Vangroenweghe, D

    2001-06-29

    The early cases of acquired immune deficiency syndrome and human immunodeficiency virus type 1 (HIV-1) infection in the 1960s and 1970s in Congo-Kinshasa (Zaire), Rwanda and Burundi are reviewed. These countries appear to be the source of the HIV-1 group M epidemic, which then spread outwards to neighbouring Tanzania and Uganda in the east, and Congo-Brazzaville in the west. Further spread to Haiti and onwards to the USA can be explained by the hundreds of single men from Haiti who participated in the UNESCO educational programme in the Congo between 1960 and 1975.

  10. Clinical features and treatment of hepatitis B virus and hepatitis C virus co-infection among patients with acquired immune deficiency syndrome

    Institute of Scientific and Technical Information of China (English)

    杨蓉蓉

    2014-01-01

    Objective To estimate the clinical features of hepatitis B virus(HBV)and hepatitis C virus(HCV)co-infection among acquired immune deficiency syndrome(AIDS)patients and the interaction of lamivudine(3 TC)contained antiretroviral therapy(ART)with hepatitis virus replication.Methods From 2004 to 2010,199human immunodeficiency virus(HIV)/HBV coinfected patients admitted to Zhongnan Hospital of Wuhan University were enrolled,including 76 cases of HIV/HBV/HCV triple infection and 123 cases of

  11. Unified-planning, graded-administration, and centralized-controlling: a management modality for treating acquired immune deficiency syndrome with Chinese medicine in Henan Province of China.

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    Xu, Li-Ran; Guo, Hui-jun; Liu, Zhi-bin; Li, Qiang; Yang, Ji-ping; He, Ying

    2015-04-01

    Henan Province in China has a major epidemic of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Chinese medicine (CM) has been used throughout the last decade, and a management modality was developed, which can be described by unified-planning, graded-administration, and centralized-controlling (UGC). The UGC modality has one primary concept (patient-centered medicine from CM theory), four basic foundations (classifying administrative region, characteristics of CM on disease treatment, health resource conditions, and distribution of patients living with HIV), six important relationships (the "three uniformities and three combinations," and the six relationships therein guide the treatment of AIDS with CM), and four key sections (management, operation, records, and evaluation). In this article, the authors introduce the UGC modality, which could be beneficial to developing countries or resource-limited areas for the management of chronic infectious disease.

  12. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  13. Epidemiology of children with acquired immune deficiency syndrome (stage 3): A referral hospital-based study in Iran.

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    Movahedi, Zahra; Mahmoudi, Shima; Pourakbari, Babak; Keshavarz Valian, Nasrin; Sabouni, Farah; Ramezani, Amitis; Bahador, Abbas; Mamishi, Setareh

    2016-01-01

    Lack of recognition of human immunodeficiency virus (HIV) infection especially in children and delayed implementation of effective control programs makes HIV infection as a major cause for concern. Information on HIV epidemiology in Iran as well as other Islamic countries is limited. The aim of our study was to describe the clinical manifestation and laboratory finding of HIV infected children who were admitted to a referral Children Medical Center (CMC) in Tehran, Iran, during 11 years from January 2002 to January 2013. This was a retrospective study carried out over a period of 11 years. The records of all patients attending to the CMC with confirmed acquired immunodeficiency syndrome (AIDS) were screened. The patients were evaluated for social circumstance, family history, age, gender, clinical, and laboratory features. Clinical data including fever, respiratory distress, diarrhea, rash, etc. as well as laboratory tests including complete blood count, serum glucose level, electrolytes, liver function test, cultures, CD4 lymphocyte count were evaluated. During the study period, 32 HIV positive children were enrolled. The majority of patients were presented with weight loss, prolonged fever, respiratory infection and chronic diarrhea. In this study, salmonella infections as well as streptococcal pneumonia and candida infections followed by, tuberculosis and Pseudomonas aeruginosa infections were the predominant opportunistic infections. Since the number of HIV-positive children has been alarmingly increasing in recent years and perinatal transmission is the most common route of HIV infection in children, essential recommendations for prenatal HIV testing as well as appropriate antiretroviral therapy by HIV infected mothers are needed.

  14. Findings from the Horizontes Acquired Immune Deficiency Syndrome Education project: the impact of indigenous outreach workers as change agents for injection drug users.

    Science.gov (United States)

    Birkel, R C; Golaszewski, T; Koman, J J; Singh, B K; Catan, V; Souply, K

    1993-01-01

    A human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) intervention using indigenous outreach workers was implemented with Hispanic injection drug users (IDUs) and their sexual partners in three locations: Laredo, Texas; San Diego, California; and San Juan, Puerto Rico. A total of 2,169 subjects were contacted, given health education, HIV antibody testing, and follow-up counseling. This article reports on the 1,616 IDUs (75%) who completed the initial and follow-up interviews. The results indicated significant increases in health knowledge on AIDS, decreases in needle risk drug taking behaviors, some decreases in sex risk behaviors, and more realistic perceptions of personal AIDS risk. Using multivariate analyses, gender (male) and increasing age (older than age 25 years) were the strongest predictors of behavior change. Surprisingly, the identification of a positive HIV serostatus was not a significant predictor of behavior change. Although intended as a comparison study between contrasting levels of intervention, logistical and administrative problems undermined the use of a true quasi-experimental design. Nonetheless, the results from this research suggest that the use of indigenous outreach workers is an effective means of combatting the spread of HIV in this difficult to reach population. Some programmatic recommendations are provided for future efforts of this kind, particularly in relation to role conflicts experienced by outreach workers.

  15. The correlation between perceived social support and illness uncertainty in people with human immunodeficiency virus/acquired immune deficiency syndrome in Iran

    Directory of Open Access Journals (Sweden)

    Moosa Sajjadi

    2015-01-01

    Full Text Available Background: Illness uncertainty is a source of a chronic and pervasive psychological stress for people living with human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS (PLWH, and largely affects their quality of life and the ability to cope with the disease. Based on the uncertainty in illness theory, the social support is one of the illness uncertainty antecedents, and influences the level of uncertainty perceived by patients. Aim: To examine uncertainty in PLWH and its correlation with social support in Iran. Materials and Methods: This cross-sectional correlational study was conducted with 80 PLWH presenting to AIDS Research Center, Tehran, Iran in 2013. The data collected using illness uncertainty and social support inventories were analyzed through Pearson′s correlation coefficient, Spearman′s correlation coefficient, and regression analysis. Results: The results showed a high level of illness uncertainty in PLWH and a negative significant correlation between perceived social support and illness uncertainty ( P = 0.01, r = -0.29. Conclusion: Uncertainty is a serious aspect of illness experience in Iranian PLWH. Providing adequate, structured information to patients as well as opportunities to discuss their concerns with other PLWH and receive emotional support from their health care providers may be worthwhile.

  16. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...... in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  17. Influence of the home environment on the prevention of mother to child transmission of human immunodeficiency virus/acquired immune-deficiency syndrome in South Africa.

    Science.gov (United States)

    Sewnunan, A; Modiba, L M

    2015-01-01

    The human immunodeficiency virus and acquired immune-deficiency syndrome (HIV/AIDS) is still a 'family crises' which marks the beginning of the deterioration of the family unit and the trauma in the emotional, psychological and material lives of both the mother and child. In South African context where the majority of HIV-positive mothers are young single women who live in extended families, disclosure to the sexual partner alone is not an adequate condition for the success of prevention of mother to child transmission (PMTCT). In South Africa, close to one in three women who attend antenatal clinics are HIV positive. KwaZulu-Natal is one of the worst affected provinces, where as many as 40-60% of pregnant women attending antenatal services are living with HIV infection. The study sought to investigate the link between the home environment and its contribution to the success of the programme on PMTCT of HIV/AIDS. A qualitative, explorative, descriptive and contextual study was used in this study to explore whether the home environment for the support system is available for the HIV-positive women on the PMTCT programme. The population of this study included all women who have undergone counselling and tested HIV positive and who have joined the programme on PMTCT of HIV/AIDS in a specific hospital in KwaZulu-Natal Province. Although 14 women agreed to participate in the study, only 10 women were interviewed as saturation was attained. Data were collected using semi-structured interview schedule. Interviews were audio-taped and field notes were taken. Content analysis was used and it was done manually. This study revealed that one of the major issues still surrounding HIV/AIDS and PMTCT is that of non-disclosure, selective disclosure and the stigma and discrimination that surrounds this disease.

  18. Knowledge and attitude of Indian clinical dental students towards the dental treatment of patients with human immunodeficiency virus (HIV)/acquired immune-deficiency syndrome (AIDS).

    Science.gov (United States)

    Oberoi, Sukhvinder Singh; Marya, Charu Mohan; Sharma, Nilima; Mohanty, Vikrant; Marwah, Mohita; Oberoi, Avneet

    2014-12-01

    Oral health care of patients with human immunodeficiency virus (HIV)/acquired immune-deficiency syndrome (AIDS) is a growing area of concern. Information on HIV- and AIDS-related knowledge among dental students provides a crucial foundation for efforts aimed at developing an appropriate dental curriculum on HIV and AIDS. The purpose of this study was to assess the knowledge and attitude of Indian clinical dental students towards the treatment of patients with HIV/AIDS and perceived sources of information regarding HIV-related issues. Data were collected from clinical dental students (third year, fourth year and internship) from three dental institutions in Delhi National Capital Region (NCR). The questions assessed the knowledge and attitude towards treatment of patients with HIV and the perceived source of information related to HIV. The willingness to treat HIV-positive patients among dental students was 67.0%, and 74.20% were confident of treating a patient with HIV/AIDS. The potential problems in rendering treatment to these patients were effect on the attitude of other patients (49.90%) and staff fears (52.50%). The correct knowledge regarding the infection-control practice (barrier technique) was found among only 15.50% of respondents. The respondents had sufficient knowledge regarding the oral manifestations of HIV/AIDS. There was no correlation between the knowledge and attitude score, demonstrating a gap between knowledge and attitude among dental students regarding treatment of HIV-infected patients. Appropriate knowledge has to be delivered through the dental education curriculum, which can instil confidence in students about their ability to manage HIV-positive patients. © 2014 FDI World Dental Federation.

  19. 获得性免疫缺陷综合征合并肠结核1例%A case report of acquired immune deficiency syndrome complicated with intestinal tuberculosis

    Institute of Scientific and Technical Information of China (English)

    黄绍萍; 程计林; 赵玉洁; 史佩炯; 马学东; 冯艳玲

    2009-01-01

    Acquired immune deficiency syndrome (AIDS) complicated with intestinal tuberculosis is rarely reported. Due to lack of typical clinical and endoscopic characteristics,it is easy to be misdiagnosed. In this article,we report and analyze a case of AIDS patient with intestinal tuberculosis,which might be helpful to raise awareness and reduce misdiagnosis or mistreatment.%文献报道获得性免疫缺陷综合征(acquired immune deficiency syndrome,AIDS)合并肠结核很少,临床表现和内镜特点不典型,易误诊.本文对1例手术证实为合并肠结核的AIDS病例进行分析,旨在提高对AIDS继发肠病的诊断认识,减少误诊误治.

  20. Sexually Transmitted Infections Among Hospitalized Patients With Human Immunodeficiency Virus Infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) in Zahedan, Southeastern Iran.

    Science.gov (United States)

    Hashemi-Shahri, Seyed Mohammad; Sharifi-Mood, Batool; Kouhpayeh, Hamid-Reza; Moazen, Javad; Farrokhian, Mohsen; Salehi, Masoud

    2016-09-01

    Studies show that nearly 40 million people are living with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) around the world and since the beginning of the epidemic, about 35 million have died from AIDS. Heterosexual intercourse is the most common route for transmission of HIV infection (85%). People with a sexually transmitted infection (STI), such as syphilis, genital herpes, chancroid, or bacterial vaginosis, are more likely to obtain HIV infection during sex. On the other hand, a patient with HIV can acquire other infections such as hepatitis C virus (HCV) and hepatitis B virus (HBV) and also STIs. Co-infections and co-morbidities can affect the treatment route of patients with HIV/AIDs. Sometimes, physicians should treat these infections before treating the HIV infection. Therefore, it is important to identify co-infection or comorbidity in patients with HIV/AIDS. This study was conducted in order to understand the prevalence of HIV/AIDS/STI co-infection. In this cross-sectional study, we evaluated all HIV/AIDS patients who were admitted to the infectious wards of Boo-Ali hospital (Southeastern Iran) between March 2000 and January 2015. All HIV/AIDS patients were studied for sexually transmitted infections (STI) such as syphilis, gonorrhea, hepatitis B virus (HBV) and genital herpes. A questionnaire including data on age, sex, job, history of vaccination against HBV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (anti-HBs), HCV-Ab, venereal disease research laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-Abs) test, and urine culture was designed. Data was analyzed by the Chi square test and P values of VDRL. The FTA-Abs was positive for all patients who were positive for VDRL. Gonorrhea was found in seven patients (17%) and three cases had genital herpes in clinical examinations. All patients who had positive test results for these STIs

  1. The evolution of costly acquired immune memory

    National Research Council Canada - National Science Library

    Best, Alex; Hoyle, Andy

    2013-01-01

    A key feature of the vertebrate adaptive immune system is acquired immune memory, whereby hosts launch a faster and heightened response when challenged by previously encountered pathogens, preventing full infection...

  2. Clinical characteristics of 275 pediatric cases of acquired immune deficiency syndrome%儿童艾滋病275例临床特点分析

    Institute of Scientific and Technical Information of China (English)

    赵燕; 庞琳; 云鹰; 刘中夫; 张福杰; 豆智慧; 程跃武; 唐志荣; 刘爱文; 彭国平; 乔晓春; 赵红心

    2008-01-01

    Objective To study the clinical characteristic of acquired immune deficiency syndrome (AIDS) patients younger than 15 years old and to explore the influence of human immunodeficiency virus (HIV) infection on them. Methods The clinical information, including demographic profile, clinical stages of the disease, laboratory test results and developmental status were gathered from 275 antiretroviral therapy naive patients. Results Seventy eight point nine percent patients were infected by vertical transmission. Sixteen percent were infected by receiving blood products. The average age was (7.6±3. 7) years, with 5 cases younger than 1 year old, 104 cases ranging from 1 - 5 years and 166 cases elder than 6 years. Seventy point one percent patients were classified as stage 3 or 4 according to World Health Organization definitions. The average CD4 count was ( 137 ± 159 )/μL, ( 304 ± 317 ) /μL and ( 1 246 ± 776 )/μL respectively in children elder than 6 years, ranging from 1 to 5 years and younger than 1 year. One hundred and eighty one cases suffered from anemia on different severity grading. The most common HIV related symdromes included persistent fever, skin damage, persistent diarrhea, oral candidiasis and recurrent upper respiratory tract infection. Among these infected children, 49. 6% showed height lower than x - 2s and 19. 9% showed weight lower than x - 2s. Conclusions Most survival pediatric AIDS patients are elder than 6 years. HIV infection can significantly affect the children's immune system function,growth and development.%目的 研究15岁以下AIDS患者的临床特点,了解HIV对患儿的影响.方法 分析275例即将入选接受高效抗反转录病毒治疗患者的临床资料,对人口学、流行病学、临床分期、实验室特点及生长发育状况进行分析.结果 275例AIDS患者主要以母婴途径传播为主,占78.9%,输血及血制品传播的为16.0%.平均年龄(7.6±3.7)岁,其中1岁以内5例,1~5岁104例,6

  3. The evolution of costly acquired immune memory

    OpenAIRE

    Best, A.; Hoyle, A

    2013-01-01

    A key feature of the vertebrate adaptive immune system is acquired immune memory, whereby hosts launch a faster and heightened response when challenged by previously encountered pathogens, preventing full infection. Here, we use a mathematical model to explore the role of ecological and epidemiological processes in shaping selection for costly acquired immune memory. Applying the framework of adaptive dynamics to the classic SIR (Susceptible-Infected-Recovered) epidemiological model, we focus...

  4. The evolution of costly acquired immune memory.

    Science.gov (United States)

    Best, Alex; Hoyle, Andy

    2013-07-01

    A key feature of the vertebrate adaptive immune system is acquired immune memory, whereby hosts launch a faster and heightened response when challenged by previously encountered pathogens, preventing full infection. Here, we use a mathematical model to explore the role of ecological and epidemiological processes in shaping selection for costly acquired immune memory. Applying the framework of adaptive dynamics to the classic SIR (Susceptible-Infected-Recovered) epidemiological model, we focus on the conditions that may lead hosts to evolve high levels of immunity. Linking our work to previous theory, we show how investment in immune memory may be greatest at long or intermediate host lifespans depending on whether immunity is long lasting. High initial costs to gain immunity are also found to be essential for a highly effective immune memory. We also find that high disease infectivity and sterility, but intermediate virulence and immune period, increase selection for immunity. Diversity in host populations through evolutionary branching is found to be possible but only for a limited range of parameter space. Our model suggests that specific ecological and epidemiological conditions have to be met for acquired immune memory to evolve.

  5. 德昌县艾滋病流行特征分析%Analysis on Epidemic Characteristics of Acquired Immune Deficiency Syndrome in Dechang County

    Institute of Scientific and Technical Information of China (English)

    施朝瑜

    2011-01-01

    Objective To understand the epidemiological trend of acquired immune deficiency syndrome (AIDS) in Dechang County so as to provide a scientific base for prevention and control of AIDS. Methods Descriptive epidemiological analysis was conducted on the AIDS epidemic data in Dechang county. Results From 1995 when the first case of HIV infection was confirmed to August 2011, a total of 262 cases of HIV/AIDS were reported with a total infection rate of 18. 95/100 000. From 2008 to 2010, the reported infections showed rapid growth. The annual infection rate of male was 26. 57/100 000 and female 11. 05/100 000 with a significant difference (Χ2 =43. 94, P = 0. 002). The ratio of male to female infections was 2. 49 : 1. Most of the AIDS cases were young adults aged between 20 and 45 years and old people aged between 55 and 75 years old who occupied 93. 49% of the total infectious cases. The number of reported AIDS cases of farmer and unknown occupations accounted for 82. 4% and there was an obvious occupations peak. Most patients in the county were infected by heterosexual sexual contact and injecting drugs, which accounted for 64. 89% and 32. 82% of the total respectively. The AIDS cases of 29 infected couples and 3 mother-to-child transmission. Conclusions AIDS epidemic growth is rapid in Dechang county with the situation being quite grim. We should enhance the AIDS prevention propaganda in the publicity, to raise national awareness of AIDS prevention. The related departments should cooperate to regulate the illegal entertainment and strengthen the management of migrant workers. The counseling and testing network should be improved so as to raise the detection rate and control the spread of AIDS.%目的 掌握德昌县艾滋病流行趋势,为制订防控措施提供准确依据.方法 利用描述流行病学方法分析德昌县1995年以来艾滋病疫情资料.结果 自1995年德昌县报告首例艾滋病感染者至2011年8月共报告艾滋病感染者/患者262

  6. [Niacin deficiency and cutaneous immunity].

    Science.gov (United States)

    Ikenouchi-Sugita, Atsuko; Sugita, Kazunari

    2015-01-01

    Niacin, also known as vitamin B3, is required for the synthesis of coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Niacin binds with G protein-coupled receptor (GPR) 109A on cutaneous Langerhans cells and causes vasodilation with flushing in head and neck area. Niacin deficiency due to excessive alcohol consumption, certain drugs or inadequate uptake in diet causes pellagra, a photosensitivity dermatitis. Recently several studies have revealed the mechanism of photosensitivity in niacin deficiency, which may pave a way for new therapeutic approaches. The expression level of prostaglandin E synthase (PTGES) is up-regulated in the skin of both pellagra patients and niacin deficient pellagra mouse models. In addition, pellagra is mediated through prostaglandin E₂-EP4 (PGE₂-EP4) signaling via reactive oxygen species (ROS) production in keratinocytes. In this article, we have reviewed the role of niacin in immunity and the mechanism of niacin deficiency-induced photosensitivity.

  7. Immune Gamma Globulin Therapeutic Indications in Immune Deficiency and Autoimmunity.

    Science.gov (United States)

    Yang, Luanna; Wu, Eveline Y; Tarrant, Teresa K

    2016-07-01

    Immune gamma globulin (IgG) has a long history in the treatment of both primary immune deficiency and autoimmune disorders. Disease indications continue to expand and new-generation products increase the versatility of delivery. This review encompasses a historical perspective as well as current and future implications of human immune globulin for the treatment of immune-mediated illness.

  8. Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

    Science.gov (United States)

    Berenguer, Juan; Rodríguez-Castellano, Elena; Carrero, Ana; Von Wichmann, Miguel A; Montero, Marta; Galindo, María J; Mallolas, Josep; Crespo, Manuel; Téllez, María J; Quereda, Carmen; Sanz, José; Barros, Carlos; Tural, Cristina; Santos, Ignacio; Pulido, Federico; Guardiola, Josep M; Rubio, Rafael; Ortega, Enrique; Montes, María L; Jusdado, Juan J; Gaspar, Gabriel; Esteban, Herminia; Bellón, José M; González-García, Juan

    2017-08-01

    We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4(+) T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

  9. Behcet's disease in acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Beenish Siddiqui

    2016-01-01

    Full Text Available HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top.

  10. [Clinical features and characteristics of community-acquired pneumonia associated with iron deficiency anemia in children of pre-school age].

    Science.gov (United States)

    Smiian, O I; Romanova, T O; Vasylyshyn, Kh I; Bynda, T P; Popov, S V; Vasyl'ieva, O H; Lypovs'ka, V V

    2014-01-01

    The most common clinical signs of community-acquired pneumonia associated with iron deficiency anemia in children of pre-preschool age are defined. Indicators of immunity cellular link in children with community-acquired pneumonia are studied. It is established that acute illness is characterized by disturbances in cellular immunity that are more expressed in patients with concomitant iron deficiency anemia.

  11. Eosinophilia associated with disorders of immune deficiency or immune dysregulation

    Science.gov (United States)

    Williams, Kelli W.; Milner, Joshua D.; Freeman, Alexandra F.

    2015-01-01

    Synopsis Elevated serum eosinophil levels have been associated with multiple disorders of immune deficiency or immune dysregulation. Although primary immunodeficiency diseases (PIDD) are rare, it is important to consider these in the differential diagnosis of patients with eosinophilia. This review discusses the clinical features, laboratory findings, diagnosis, and genetic basis of disease of several disorders of immune deficiency or dysregulation – all which have documented eosinophilia as part of the syndrome. The article includes autosomal dominant hyper IgE syndrome, DOCK8 deficiency, PGM3 deficiency, ADA-SCID, Omenn syndrome, Wiskott-Aldrich syndrome, Loeys-Dietz syndrome, autoimmune lymphoproliferative syndrome, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, Comel-Netherton syndrome, and severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM). PMID:26209898

  12. Antibiotic prophylaxis in primary immune deficiency disorders.

    Science.gov (United States)

    Kuruvilla, Merin; de la Morena, Maria Teresa

    2013-01-01

    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

  13. 遵义市红花岗区艾滋病疫情分析%An Analysis on Epidemic Situation of Acquired Immune Deficiency Syndrome in Honghuagang District in Zunyi City and Adjustment of Its Prevention and Cure Strategies

    Institute of Scientific and Technical Information of China (English)

    明杰; 卢太书

    2011-01-01

    Objective: To investigate the epidemic status of acquired immune deficiency syndrome ( AIDS) in Honghuagang district, analyze the affecting factors, and so as to adjust prevention and cure strategies effectively. Methods: AIDS monitoring was carried out in high risk crowds such as drug users, sex workers, gay men, pregnant women and prisoners. Ethology data were analyzed. Prevention and cure effects were evaluated. Results: Since 2003 that the demonstration area of integrated AIDS prevention and control began to work, effectiveness of AIDS prevention and control has become remarkable in this region, showing as establishment of an effective working system, and gradual strengthening of intervention to behavior of high-risk groups. Conclusions: AIDS integrated prevention and control measures in Honghuagang district are suitable. The effects are significant. Reinforcing AIDS prevention and cure work among sex workers and gay men should be emphasized in adjusting of prevention and control strategies.%目的:了解艾滋病疫情现状,分析艾滋病流行因素,为有效调整艾滋病防治策略提供依据.方法:对吸毒人群、性服务者、男-男性行为人群、孕妇及在押人员等高危人群或重点人群作HIV监测,依据1998-2009年的调查资料和监测数据分析其行为学资料,评价防治效果.结果:1998-2003年报告5例艾滋病感染者,1998-2009年共感染123例,2009年艾滋病感染者52例;各类调查人群对艾滋病知晓率提高,性服务人群安全套使用率87.1%(2008年),2009年美沙酮治疗人数1 411人.结论:红花岗区艾滋病综合防治措施效果显著.

  14. Immune recognition of ADAMTS13 in acquired TTP

    NARCIS (Netherlands)

    Verbij, F.C.

    2017-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a severe thrombotic micro-angiopathy presenting with hemolytic anemia and thrombocytopenia that results from an acquired or congenital functional deficiency of the von Willebrand factor cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with

  15. Primary Immune Deficiency Treatment Consortium (PIDTC) report

    NARCIS (Netherlands)

    L.M. Griffith (Linda); M. Cowan (Morton); L.D. Notarangelo (Luigi Daniele); R. Kohn (Robert); J. Puck (Jennifer); S.-Y. Pai (Sung-Yun); B. Ballard (Barbara); S.C. Bauer (Sarah); J. Bleesing (Jack); M. Boyle (Marcia); R.W. Brower (Ronald); R.H. Buckley (Rebecca); M. van der Burg (Mirjam); L.M. Burroughs (Lauri); F. Candotti (Fabio); A. Cant (Andrew); T. Chatila (Talal); C. Cunningham-Rundles (Charlotte); M.C. Dinauer (Mary); J. Dvorak (Jennie); A. Filipovich (Alexandra); L.A. Fleisher (Lee); H.B. Gaspar (Bobby); T. Gungor (Tayfun); E. Haddad (Elie); E. Hovermale (Emily); F. Huang (Faith); A. Hurley (Alan); M. Hurley (Mary); S.K. Iyengar (Sudha); E.M. Kang (Elizabeth); B.R. Logan (Brent); J.R. Long-Boyle (Janel); H. Malech (Harry); S.A. McGhee (Sean); S. Modell (Sieglinde); S. Modell (Sieglinde); H.D. Ochs (Hans); R.J. O'Reilly (Richard); R. Parkman (Robertson); D. Rawlings (D.); J.M. Routes (John); P. Shearer (P.); T.N. Small (Trudy); H. Smith (H.); K.E. Sullivan (Kathleen); P. Szabolcs (Paul); A.J. Thrasher (Adrian); D. Torgerson; P. Veys (Paul); K. Weinberg (Kenneth); J.C. Zuniga-Pflucker (Juan Carlos)

    2014-01-01

    textabstractThe Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SC

  16. FLASH形式在中学生预防艾滋病教育活动中的作用%Effects of FLASH on health education of acquired immune deficiency syndrome in middle school students

    Institute of Scientific and Technical Information of China (English)

    韩娟; 赵丽娜; 时俊新; 杨森焙; 宋阎超; 陈宏平

    2009-01-01

    目的:探讨FLASH形式在预防艾滋病教育活动中的作用,了解中学生对预防艾滋病的相关知识和态度.方法:在湖北省大冶市和宜昌市秭归县的4所中学采用分层整群抽样的方法抽取在校学生共1 211人,用自制的中学生预防艾滋病生活技能教育的FLASH片进行专题教育,并对其教育前后的预防艾滋病相关知识、态度进行问卷调查.结果:调查对象对艾滋病流行趋势、艾滋病与青少年的关系以及对艾滋病主要传播途径认识,教育后正确回答率提高至80%以上,而对艾滋病的概念以及蚊虫叮咬、同性恋、纹身等认识提高不足80%.结论:中学生仍需加强预防艾滋病知识的教育,教育形式应多样化.FLASH形式生动活泼,教育效果显著,但因其稍纵即逝,会影响教育效果,可作为辅助教材.%Objective: To explore the effects of FLASH on health education of acquired immune deficiency syndrome (AIDS), un-derstand the related knowledge and attitude to AIDS prevention in middle school students. Methods: 1 211 students were selected from 4 middle school by stratified cluster sampling, then health education of AIDS prevention was carried out in the form of self-designed FLASH,the related knowledge and attitude to AIDS prevention of middle school students before and after health education were observed. Results:The accuracy rates of prevailing trend of AIDS, the relationship between AIDS and adolescents, major spread approaches of AIDS after heslth education were increased to over 80%, but the others improved less than 80% such as the meaning of AIDS, mosquito and insect bite, ho-mesexuallty and tattoo and so on. Conclusion: The middle school students still need to strengthen AIDS preventive education which shouldbe multiple modes and be enjoyed by them. FLASH is a lifelike and brisk mode enjoyed by the students which education effect is marked,but it may be an assistant teaching material because it is easy to go in

  17. Epidemiological characteristics of acquired immune deficiency syndrome in Shandong Province from 1992 to 2011%山东省1992年至2011年艾滋病流行特征分析

    Institute of Scientific and Technical Information of China (English)

    张娜; 王国永; 杨兴光; 苏生利; 康殿民; 陶小润

    2013-01-01

    目的 分析山东省AIDS的流行特征,为其预防控制提供依据.方法 对1992年至2011年山东省报告的HIV感染者和AIDS患者(HIV/AIDS)的流行病学资料进行统计分析.结果 1992年至2011年累计报告HIV/AIDS患者4313例;年均报告发病率为2.39/100万,历年报告发病率呈上升趋势;报告发病率居前5位的城市是济南市、青岛市、淄博市、潍坊市和威海市,分别为5.72/100万、4.39/100万、3.29/100万、3.10/100万和3.02/100万;报告男性年均发病率为3.74/100万,高于女性的1.39/100万,差异有统计学意义(x2=743.96,P<0.05);20岁年龄组发病率最高,为5.56/100万;57.18%为性传播感染,同性传播感染数占当年报告病例数的构成比由2004年的1.82%上升到2011年的37.49%.结论 山东省AIDS疫情形势严峻,地区分布不平衡,性传播为主要传播途径,同性传播增加明显.%Objective To investigate the epidemiological characteristics of acquired immune deficiency syndrome (AIDS) in Shandong Province,and to provide scientific evidence for formulating prevention and control strategy and carrying out effective measures.Methods Epidemiological data of reported human immunodeficiency virus (HIV) infection and AIDS cases (HIV/AIDS) in Shandong Province from 1992 to 2011 were analyzed.Results A total of 4313 cases of HIV/AIDS were confirmed and reported by the end of 2011,with an average incidence of 2.39 parts per million (ppm) annually.An upward trend was showed for annual reported incidence.The top 5 cities of incidence were Ji'nan,Qingdao,Zibo,Weifang and Weihai,which were 5.72 ppm,4.39 ppm,3.29 ppm,3.10 ppm and 3.02 ppm,respectively.The average annual reported incidence was 3.74 ppm for male,which was significantly higher than that for female (1.39 ppm; x2 =743.96,P<0.05).The reported incidence was highest among 20-29 age group (5.56 ppm),with 57.18% of homosexual transmission.The proportion of homosexual transmission in annual reported cases

  18. Ophthalmic manifestations in acquired immune deficiency syndrome patients with cryptococcal meningitis%获得性免疫缺陷综合征合并隐球菌性脑膜炎的眼部病变特征分析

    Institute of Scientific and Technical Information of China (English)

    毛菲菲; 孙挥宇; 李丹

    2015-01-01

    Objective Analysis ophthalmic manifestations in acquired immune deficiency syndrome(AIDS) patients with cryptococcal meningitis.Methods Retrospective study.Forty AIDS patients (including 32 men and 8 women) with cryptococcal meningitis were studied.The age of the patients varied from 11 to 67 years,average on (38 ± 12) years (mean ± standard deviation).All the patients underwent detailed ocular examinations including corrected visual acuity,eye movement,intraocular pressure,slit lamp microscope,indirect ophthalmoscope and color fundus photography.The CD4+ T cell count was evaluated and Lumbar puncture was done to examine the cerebral spinal fluid(CSF).Eighteen patients were followed up for a period between 2weeks to 4years.Four patients died during hospitalization.The remaining 18 patients failed to be followed up due to moving away.Results Binocular diplopia were present in 3 patients.It showed Binocular or monocular abducens nerve palsy.Papilledema were found in 37 eyes of 19 cases.One person had unilateral papilledema.Among 19 cases,24 eyes of 12 cases were accompanied with peripapillary hemorrhages and 7 cases of 13 eyes without peripapillary hemorrhages.Optic atrophy occurs in 6 cases of 12 eyes and multifocal choroiditis in 2 cases of 4 eyes.Twenty-seven eyes of 14 patients had normal fundus or cytomegalovirus retinitis(CMVR) only.Conclusions AIDS patients with cryptococcal meningitis merger may be accompanied by a variety of eye complications.Papilledema are the most common manifestations.%目的 探讨获得性免疫缺陷综合征(AIDS)合并隐球菌性脑膜炎患者眼部表现.方法 回顾性研究.观察40例AIDS合并隐球菌性脑膜炎患者眼部病变特点,其中男性32例,女性8例,男女比例4∶1,年龄11~67岁,平均年龄(38±12)岁,对所有患者均行视力、眼球运动、眼压、裂隙灯显微镜、散瞳间接检眼镜眼底检查及眼底彩色照相.所有患者进行CD4+T淋巴细胞的检测,

  19. Passively acquired challenge immunity to enterotropic coronavirus in mice.

    Science.gov (United States)

    Homberger, F R; Barthold, S W

    1992-01-01

    Maternally-derived passive immunity of infant mice to challenge infection with enterotropic coronavirus mouse hepatitis virus strain Y (MHV-Y) was studied. Pups born to both naive and immune dams, but nursed by naive foster dams, were susceptible to infection, while naive or immune pups nursed by immune foster dams were protected. The MHV infectious dose was identical among naive pups inoculated at 1, 2, 3, or 4 weeks of age. Pups nursing immune dams resisted infection when inoculated at 1, 2, or 3 weeks of age. Three week old pups were protected only if they were allowed access to their immune dams. Pups born to MHV immune dams 4 in consecutive litters acquired equal MHV IgG titers in serum and whey and were all protected against challenge infection. Only pups actively ingesting immune whey at the time of or within two hours after virus inoculation were effectively protected. Pups born to dams immunized by oral inoculation with live MHV acquired both MHV-specific IgA and IgG in their whey, while pups born to dams immunized with killed virus acquired only IgG. Both IgA and IgG, but not IgG alone, were required for complete protection.

  20. 艾滋病合并肠系膜淋巴结结核11例临床分析%Diagnosis and treatment of 11 patients with acquired immune deficiency syndrome complicated with tuberculosis of mesenteric lymph nodes

    Institute of Scientific and Technical Information of China (English)

    刘艳; 余卫业; 陆普选; 刘映霞; 姚思敏; 蔡雄茂; 薛海珍

    2009-01-01

    Objective To study the clinical features of acquired immune deficiency syndrome (AIDS)complicated with tuberculosis of mesenteric lymph nodes.Methods Cases(n=153)with AIDS complicated with tuberculosis hospitalized in this hospital from September 1999 to December 2008 were retrospectively analyzed.Mesenteric lymph node tuberculosis was found in 11 cases,including 7 males and 4 females.One patient was 8 years old,and the other 10 were over 22 years(ranging from 8 to 55 years).Results In patients with AIDS complicated with tuberculosis,7%(11/158)had tuberculosis of the mesenteric lymph nodes.The CD_4~+ cell count was less than 50 ×10~6 cells/L in 8 cases,and(50-100)×10~6 cells/L in 3 cases.The symptoms included fever(11/11),abdominal pain(11/11),abdominal distension(11/11),night sweat(7/11),weisgt loss(10/11),diarrhea(7/11),anemia(5/11),abdominal mass(3/11),and ascites(1/11).Abdominal ultrasound showed multiple enlarged mesenteric lymph nodes in all of the 11 cases,and abdominal CT scanning presented typical enhanced ring shadows.Biopsy of mesenteric lymph nodes was obtained from 2 cases,and both revealed tuberculoma,caseoua necrosis.Longerhan cell infiltration,and positive stain for fast anti-acid bacilli.Enlarged mesenteric lymph nodes became smaller and disappeared after treatment with antituberculous drugs for 6 months and highly active antiretroviral therapy(HAART)for 5 months in all the 11 patients.Conclusions There were no specific clinical manifestations in AIDS patients with tuberculosis of mesenteric lymph nodes.However,AIDS patients with CD_4~+ cell count less than 50×10~6 cells/L miight be more prone to developing tuberculosis of the mesenteric lymph nodes.Abdominal CT scanning with typical strengthened ring shadow is suggestive of the diagnosis.Anti-tuberculous therapy combined with HAART is recommended for the treatment of patients with suspected tuberculosis.%目的 探讨艾滋病合并肠系膜淋巴结结核的临床特点.方法 回顾性

  1. 艾滋病合并机会性感染的临床特征和诊疗分析%Analysis on Clinical Features of Acquired Immune Deficiency Syndrome Combined with Opportunistic Infections and Its Diagnosis and Treatment

    Institute of Scientific and Technical Information of China (English)

    赵贺红; 冯萍; 肖贵宝; 徐开菊; 杨志勇

    2011-01-01

    目的 探讨艾滋病患者合并机会性感染的临床特征并评价其治疗效果.方法 回顾分析2003年-2009年53例确诊为艾滋病患者的临床资料,对患者合并机会性感染的临床特征,包括发生机会性感染的时间、发生机会性感染时CD+T细胞计数、起病急缓、严重程度等,进行观察和分析,并给予国家推荐的标准治疗方案进行治疗,通过临床症状、病毒载量、CD+T细胞计数、影像学监测进行疗效分析,随访时间为初治至出院后6年.结果 53例艾滋病患者均为重症感染,41例为混合感染,其中2个以上部位感染者为36例(67.9%),2种以上病原体感染者为28例(52.8%),3种以上病原体感染者13例(24.5%).最常见的机会性感染为结核35.8%(19/53);其次为卡氏肺孢子菌肺炎30.2%(16/53);败血症20.8%(11/53),此外,尚有隐球菌感染15.1%(8/53)、弓形虫感染3.8%(2/53)、带状疱疹病毒感染7.5%(4/53)、念珠菌感染17.0%(9/53)、巨细胞病毒感染7.5%(4/53)、合并乙肝11.3%(6/53)、丙肝3.8%(2/53).机会性感染治疗有效率为77.4%(41/53),病死率为22.6%(12/53),其中隐球菌脑膜炎或混合感染者病死率最高.结论艾滋病患者在CD+T细胞计数<350/mm3时各种机会感染明显升高,且随着CD+4T细胞计数的下降呈增高趋势,艾滋病合并机会性感染最常见的是结核,其次卡氏肺孢子菌肺炎;合并结核的治疗效果较好,合并隐球菌脑病的病死率最高.早期启动高效抗逆转录病毒治疗效果好.%Objective To investigate the clinical characteristics of acquired immune deficiency syndrome (AIDS) combined with opportunistic infections and its treatment. Methods We retrospectively analyzed the clinical data of 53 patients diagnosed to have AIDS in our hospital between 2003 and 2009. The clinical features (such as time of the onset of opportunistic infections, CD4+ T cells value at the onset, severity of the infection, etc

  2. Prophylactic immunoglobulin therapy in secondary immune deficiency

    DEFF Research Database (Denmark)

    Agostini, Carlo; Blau, Igor-Wolfgang; Kimby, Eva

    2016-01-01

    INTRODUCTION: In primary immunodeficiency (PID), immunoglobulin replacement therapy (IgRT) for infection prevention is well-established and supported by a wealth of clinical data. On the contrary, very little evidence-based data is available on the challenges surrounding the use of Ig......RT in secondary immune deficiencies (SID), and most published guidelines are mere extrapolations from the experience in PID. AREAS COVERED: In this article, four European experts provide their consolidated opinion on open questions surrounding the prophylactic use of IgRT in SID, based on their clinical...

  3. Acquired immune heterogeneity and its sources in human helminth infection.

    Science.gov (United States)

    Bourke, C D; Maizels, R M; Mutapi, F

    2011-02-01

    Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The 'trade-off' between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

  4. Heat Shock Proteins: Stimulators of Innate and Acquired Immunity

    Directory of Open Access Journals (Sweden)

    Camilo A. Colaco

    2013-01-01

    Full Text Available Adjuvants were reintroduced into modern immunology as the dirty little secret of immunologists by Janeway and thus began the molecular definition of innate immunity. It is now clear that the binding of pathogen-associated molecular patterns (PAMPs by pattern recognition receptors (PRRs on antigen presenting cells (APCs activates the innate immune response and provides the host with a rapid mechanism for detecting infection by pathogens and initiates adaptive immunity. Ironically, in addition to advancing the basic science of immunology, Janeway’s revelation on induction of the adaptive system has also spurred an era of rational vaccine design that exploits PRRs. Thus, defined PAMPs that bind to known PRRs are being specifically coupled to antigens to improve their immunogenicity. However, while PAMPs efficiently activate the innate immune response, they do not mediate the capture of antigen that is required to elicit the specific responses of the acquired immune system. Heat shock proteins (HSPs are molecular chaperones that are found complexed to client polypeptides and have been studied as potential cancer vaccines. In addition to binding PRRs and activating the innate immune response, HSPs have been shown to both induce the maturation of APCs and provide chaperoned polypeptides for specific triggering of the acquired immune response.

  5. 1995-2014年河南省周口市 AIDS 流行特征分析%Epidemiological Characteristics of Acquired Immune Deficiency Syndrome in Zhoukou, He′nan Province From 1995 to 2014

    Institute of Scientific and Technical Information of China (English)

    张林

    2015-01-01

    Objective To investigate the epidemiological characteristics of acquired immune deficiency syndrome (AIDS) in Zhoukou and to provide scientific evidence for the formulation of prevention and control strategies .Methods We collected the data of HIV-infected patients and AIDS patients in Zhoukou from the Information System for AIDS Prevention and Control of China′s Information System for Disease Prevention and Control , with a time range of 1995 to 2014.Results From 1995 to 2014, the total reported number of HIV -infected people and AIDS patients in Zhoukou was 9 187, among which 8 215 (89.42%) were AIDS patents and 3 254 (35.42%) died.After the exclusion of deceased patients , there were 5 933 HIV-infected patients and AIDS patients surviving , accounted for 67.37/105 in all permanent residents of Zhoukou and of which 5 164 were AIDS patients.From 1995 to 2003, with the HIV/AIDS monitoring strengthened , the detected HIV -infected and AIDS patients had been increasing year by year; 2004 witnessed more reported cases than other years , for HIV census was carried out on FPDs this year; from 2005 to 2012, the number of reported cases was in a decreasing trend; from 2013 to 2014, the disease showed a slight rebound .From 2006, death cases began to decrease year by year .HIV-infected patients and AIDS patients of Zhoukou distributed in 204 villages or towns in 10 districts or counties, and significant differences (χ2 =1 181.0, P<0.01) existed among the 10 counties or districts in the proportion of surviving cases in permanent residents .There were five first-class AIDS counties and five second -class AIDS counties.Among HIV-infected patients and AIDS patients , the number of male patients was more than female patients , with a ratio of 1.23∶1; the patients were aged from 2 to 82, with a majority ranging from 30 to 60, accounting for 83.37% (7 659/9 187).Ratio of survival cases in permanent residents varied significantly among the groups of different genders, ages

  6. Naturally acquired immunity to Plasmodium falciparum malaria in Africa

    DEFF Research Database (Denmark)

    Hviid, Lars

    2005-01-01

    protective immunity to P. falciparum malaria is acquired following natural exposure to the parasites is beginning to emerge, not least thanks to studies that have combined clinical and epidemiological data with basic immunological research. This framework involves IgG with specificity for clonally variant......Infection by Plasmodium falciparum parasites can lead to substantial protective immunity to malaria, and available evidence suggest that acquisition of protection against some severe malaria syndromes can be fairly rapid. Although these facts have raised hopes that the development of effective...

  7. Primary Immune Deficiencies – Principles of Care

    Science.gov (United States)

    Chapel, Helen; Prevot, Johan; Gaspar, Hubert Bobby; Español, Teresa; Bonilla, Francisco A.; Solis, Leire; Drabwell, Josina

    2014-01-01

    Primary immune deficiencies (PIDs) are a growing group of over 230 different disorders caused by ineffective, absent or an increasing number of gain of function mutations in immune components, mainly cells and proteins. Once recognized, these rare disorders are treatable and in some cases curable. Otherwise untreated PIDs are often chronic, serious, or even fatal. The diagnosis of PIDs can be difficult due to lack of awareness or facilities for diagnosis, and management of PIDs is complex. This document was prepared by a worldwide multi-disciplinary team of specialists; it aims to set out comprehensive principles of care for PIDs. These include the role of specialized centers, the importance of registries, the need for multinational research, the role of patient organizations, management and treatment options, the requirement for sustained access to all treatments including immunoglobulin therapies and hematopoietic stem cell transplantation, important considerations for developing countries and suggestions for implementation. A range of healthcare policies and services have to be put into place by government agencies and healthcare providers, to ensure that PID patients worldwide have access to appropriate and sustainable medical and support services. PMID:25566243

  8. PRIMARY IMMUNE DEFICIENCIES – PRINCIPLES OF CARE

    Directory of Open Access Journals (Sweden)

    Helen eChapel

    2014-12-01

    Full Text Available Primary Immune Deficiencies (PIDs are a growing group of over 230 different disorders caused by ineffective, absent or an increasing number of gain of function mutations in immune components (mainly cells and proteins. Once recognised, these rare disorders are treatable and in some cases curable. Otherwise untreated PIDs are often chronic, serious or even fatal. The diagnosis of PIDs can be difficult due to lack of awareness and facilities for diagnosis, and management of PIDs is complex. This document was prepared by a worldwide multi-disciplinary team of specialists; it aims to set out comprehensive principles of care for PIDs. These include the role of specialised centres, the importance of registries, the need for multinational research, the role of patient organisations, management and treatment options, the requirement for sustained access to all treatments including immunoglobulin (Ig therapies and HSCT, important considerations for developing countries and suggestions for implementation. A range of healthcare policies and services have to be put into place by government agencies and healthcare providers, to ensure that PID patients world-wide have access to appropriate and sustainable medical and support services.

  9. Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance

    Science.gov (United States)

    Hugo, Willy; Shi, Hubing; Sun, Lu; Piva, Marco; Song, ChunYing; Kong, Xiangju; Moriceau, Gatien; Hong, Aayoung; Dahlman, Kimberly B.; Johnson, Douglas B.; Sosman, Jeffrey A.; Ribas, Antoni; Lo, Roger S.

    2015-01-01

    SUMMARY Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression, and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T-cell inflammation prior to MAPKi therapy preceded CD8 T-cell deficiency/exhaustion and loss of antigen-presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi-resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity. PMID:26359985

  10. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...... on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...... participate in intercellular bridging. Finally, current studies suggest that CR2 may also play a role in the determination of B-cell tolerance towards self-antigens and thereby hold the key to the previously observed correlation between deficiencies of the early complement components and autoimmune disease....

  11. Acquired and natural immunity to gonococcal infection in chimpanzees.

    Science.gov (United States)

    Kraus, S J; Brown, W J; Arko, R J

    1975-01-01

    Despite the fact that gonorrhea is our most common reportable infectious disease, little is known about natural and acquired resistance to Neisseria gonorrhoeae. With the chimpanzee model, which mimics human gonococcal infection in signs, symptoms, and host response, a natural resistance to gonococcal challenge was found. One aspect of this natural resistance became evident when the cervix and oral pharynx resisted more gonococci than the urethra. Natural resistance was also shown when environmental factors were found to influence resistance to gonococcal pharyngitis. In addition to natural resistance a postinfection-acquired immunity to the gonococcus was demonstrated. Following gonococcal pharyngitis, this anatomical location successfully resisted more gonococci than were initially resisted. Similarly, more gonococci were successfully resisted in rechallenging the urethra. These findings are related to the clinic situation and suggest possible new approaches to gonorrhea control. PMID:805797

  12. Primary Immune Deficiency Treatment Consortium (PIDTC) report.

    Science.gov (United States)

    Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D; Kohn, Donald B; Puck, Jennifer M; Pai, Sung-Yun; Ballard, Barbara; Bauer, Sarah C; Bleesing, Jack J H; Boyle, Marcia; Brower, Amy; Buckley, Rebecca H; van der Burg, Mirjam; Burroughs, Lauri M; Candotti, Fabio; Cant, Andrew J; Chatila, Talal; Cunningham-Rundles, Charlotte; Dinauer, Mary C; Dvorak, Christopher C; Filipovich, Alexandra H; Fleisher, Thomas A; Bobby Gaspar, Hubert; Gungor, Tayfun; Haddad, Elie; Hovermale, Emily; Huang, Faith; Hurley, Alan; Hurley, Mary; Iyengar, Sumathi; Kang, Elizabeth M; Logan, Brent R; Long-Boyle, Janel R; Malech, Harry L; McGhee, Sean A; Modell, Fred; Modell, Vicki; Ochs, Hans D; O'Reilly, Richard J; Parkman, Robertson; Rawlings, David J; Routes, John M; Shearer, William T; Small, Trudy N; Smith, Heather; Sullivan, Kathleen E; Szabolcs, Paul; Thrasher, Adrian; Torgerson, Troy R; Veys, Paul; Weinberg, Kenneth; Zuniga-Pflucker, Juan Carlos

    2014-02-01

    The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

  13. Modulation of host immunity and reproduction by horizontally acquired Wolbachia.

    Science.gov (United States)

    Pigeault, Romain; Braquart-Varnier, Christine; Marcadé, Isabelle; Mappa, Gaëtan; Mottin, Elmina; Sicard, Mathieu

    2014-11-01

    The Wolbachia are symbiotic bacteria vertically transmitted from one host generation to another. However, a growing amount of data shows that horizontal transfers of Wolbachia also frequently occur within and between host species. The consequences of the arrival of new symbionts on host physiology can be studied by their experimental introduction in asymbiotic hosts. After experimental transfers of the eight major isopod Wolbachia strains in the isopod Porcellio dilatatus only two of them (wCon and wDil) were found to (1) have no pathogenic effect on the host and (2) be able to pass vertically to the host offspring. In the present work, we studied the influence of these two strains, able to complete an horizontal transfer, on immunity and reproduction of P. dilatatus at two stages of the transfer: (1) in recipient hosts that encounter the symbionts: to test the influence of symbiont when acquired during host life and (2) in vertically infected offspring: to test the influence of a symbiotic interaction occurring all lifelong. The impact of Wolbachia varied depending on the stage: there were clearer effects in vertically infected individuals than in those that acquired the symbionts during their lives. Moreover, the two Wolbachia strains showed contrasted effects: the strain wCon tended to reduce the reproductive investment but to maintain or increase immune parameters whilst wDil had positive effects on reproductive investment but decreased the investment in some immune parameters. These results suggest that horizontally acquisition of Wolbachia can influence the balance between host immune and reproductive traits.

  14. Aire deficiency promotes TRP-1 specific immune rejection of melanoma

    Science.gov (United States)

    Zhu, Meng-Lei; Nagavalli, Anil; Su, Maureen A.

    2013-01-01

    The thymic transcription factor AIRE prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1 specific T cells without affecting thymic numbers of regulatory T cells. Aire deficient mice displayed elevated T cell immune responses that were associated with suppression of melanoma outgrowth. Further, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wildtype host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma, and how manipulating TRP-1 specific T cell negative selection may offer a logical strategy to enhance immune rejection of melanoma. PMID:23370329

  15. Aire deficiency promotes TRP-1-specific immune rejection of melanoma.

    Science.gov (United States)

    Zhu, Meng-Lei; Nagavalli, Anil; Su, Maureen A

    2013-04-01

    The thymic transcription factor autoimmune regulator (Aire) prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1-specific T cells without affecting thymic numbers of regulatory T cells. Aire-deficient mice displayed elevated T-cell immune responses that were associated with suppression of melanoma outgrowth. Furthermore, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wild-type host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma and how manipulating TRP-1-specific T-cell negative selection may offer a logical strategy to enhance immune rejection of melanoma. ©2013 AACR.

  16. Characteristics of Colon Microbiocenosis in Toddlers with Community-Acquired Pneumonia Associated with Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    O.I. Smiyan

    2014-03-01

    Thus, impaired bowel microbiota in children with community-acquired pneumonia associated with iron deficiency anemia may be a reason to include probiotic preparation into the complex of pathogenetic therapy.

  17. Relationship between Acquired Deficiency of Vitamin K-dependent Clotting Factors And Hemorrhage

    Institute of Scientific and Technical Information of China (English)

    杨锐; 张小平; 魏文宁; 洪梅; 杨焰; 胡豫

    2010-01-01

    This study examined the changes of activities of vitamin K-dependent clotting factors(VKDCF) under various pathological conditions and explored the relationship between acquired deficiency of VKDCFs and hemorrhage.Clinical data of 35 patients who were diagnosed as having acquired deficiency of VKDCF were retrospectively analyzed.Coagulation factors involved in the intrinsic and extrinsic pathways were detected in these patients and 41 control subjects.The results showed that the average activities of VKDCFs...

  18. Investigation on HIV/AIDS coinfected with HBV/HCV in acquired immune deficiency syndrome area%某艾滋病治疗示范区HIV/AIDS患者合并HBV/HCV感染调查

    Institute of Scientific and Technical Information of China (English)

    梁红霞; 张倩; 余祖江; 钮正春; 李志勤; 潘延凤; 赵清霞; 李建生; 何云

    2011-01-01

    Objective To investigate the incidence of HIV/AIDS coinfected with HBV and/or HCV in some country of Henan province and the clinical features. Methods Serum samples were obtained from 187 HIV - infected patients who transmitted by paid blood donation. ELISA was used to detect HBV erologic markers( HbsAg, Anti - HBs, HbeAg, anti - Hbe and anti - HBc) and HCV antibody. Flow Cytometry were used to detect CD4 + T cell count. Nested PCR was used to amplify surface protein region of HBV DNA. Results Among 187 HIV - infected patients, 9 patients (4. 81% )were HBsAg positive, 178 patients (95. 19% ) HBsAg negative; 143 patients (76. 47% ) anti - HCV positive, 44 patients( 23. 53% ) anti - HCV negative; 6 patients HIV -1, HBV and HCV triple infection. Of the 143 anti - HCV positive patients, 42 patients (29. 37% ) were coinfected with occult HBV infection, in the 44 anti - HCV negative patients, 11 patients (25. 00% ) were coinfected with occult HBV infection, the disparity had no statistical significance (P > 0. 05 ). The positive patients of HbsAg, anti - HBs, isolated anti - HBc andthe CD4 + cell counts were undifferentiated between anti - HCV positive patients and anti - HCV negative patients ( P > 0. 05 ) . Conclusions In the HIV - infected patients who transmitted by paid blood donation, the HBsAg positive rate is lower than common population, and the HCV infection rate is higher than common population; It is found that occult HBV infection did occurs in HIV - infected patients. HBV DNA testing is necessary in the HIV - infected patients who are HBsAg negative; The occult HBV infection rate of HIV - infected patients who are coinfected with HCV isrit increase.%目的 探讨人免疫缺陷病毒-1 (HIV -1) /AIDS患者合并乙型肝炎病毒(HBV)/丙型肝炎病毒(HCV)感染情况及发病特点.方法 分析国家"十一五重大专项"课题中河南某获得性免疫缺陷综合征(Acquired immunodeficiency syndrome,AIDS)示范区中187

  19. Children with congenital deficiencies or acquired amputations of the lower limbs : functional aspects

    NARCIS (Netherlands)

    Boonstra, AM; Rijnders, LJM; Groothoff, J W; Eisma, W H

    2000-01-01

    The aim of the study was to evaluate the use of prostheses, some secondary complications and functional aspects among children who had a congenital leg deficiency or an acquired leg amputation. Rehabilitation physicians were asked to refer children, aged 1-18 years, with a leg deficiency or amputati

  20. Acquired Immune Deficiency Syndrome, Risky Sexual Behavior and Abortion

    Directory of Open Access Journals (Sweden)

    Marshall H. Medoff

    2012-01-01

    Full Text Available Problem statement: incidence of abortion in the United States has steadily declined since 1990. The question is why? Approach: This study, using multiple linear regression, examines whether women’s unprotected sexual activity is deterred by the risk of contracting AIDS as reflected in decreased abortion rates. Results: The empirical evidence consistently finds that the prevalence of AIDS reduces the risky (unprotected sexual activity of women of childbearing ages 15-44 as reflected in their abortion rates. The empirical results remain robust for the abortion rates of teens ages 15-17 and for teens ages 15-19. Conclusion: The empirical results suggest that the behavioral modification induced by the prevalence of AIDS accounted for 21% of the decrease in abortion rates over the time period 1992-2005.

  1. Eye Complications of Acquired Immune Deficiency Syndrome (AIDS ...

    African Journals Online (AJOL)

    Skoludek_R

    HIV associated eye disease now occurs in 50-90% of patients at one point in the course ... Although no population studies have been conducted to .... It affects skin, mucus membrane, internal organs and lymph nodes. Ocular Kaposi Sarcoma (figure 2) presents on the lid or ... many hours in the sun working on farms or other.

  2. Analysis of 7 Misdiagnosed Cases of Acquired Immune Deficiency Syndrome with Neurological Symptoms at Onset%以神经系统症状首发的获得性免疫缺陷综合征七例误诊原因分析

    Institute of Scientific and Technical Information of China (English)

    叶茂斌; 陈研林; 叶飞; 张临洪

    2015-01-01

    目的:探讨以神经系统症状首发的获得性免疫缺陷综合征( acquired immune deficiency syndrome, AIDS)的发病机制、误诊原因及防范措施。方法回顾性分析我院2007年1月—2013年12月误诊的以神经系统症状首发的AIDS 7例的临床资料。结果本组6例以头痛、头晕就诊,伴记忆力减退2例,伴腹胀、厌食1例;1例以左上肢麻木就诊。均否认毒品接触史、冶游史及输血史。7例首诊考虑后循环缺血5例,躯体化障碍和脑梗死各1例,给予相应治疗,症状均无缓解,进一步行人类免疫缺陷病毒( human immunodeficiency virus, HIV)抗体定量检查及蛋白印迹确认试验阳性,确诊AIDS,转疾病预防控制中心治疗。结论以神经系统症状首发的AIDS易误诊。耐心细致病史询问、发散诊断思维和及时进行特异性医技检查可减少或避免其误诊误治。%Objective To investigate the first symptom of AIDS in nervous system, and analyze the misdiagnosis cause, and enhance awareness of AIDS. Methods Retrospective analysis of 7 misdiagnosed acquired immune deficiency syndrome ( AIDs) cases with neurological symptoms at onset admitted to our hospital during January 2007 and December 2013 was made. Results There were cases of headaches and dizziness in 6 patients, with memory disorder in 2 patients, with abdominal disten-sion anorexia in 1 patient;Body lack of power in 1 patient. All the patients denied drug exposure history, amusement history and blood transfusion history. In the 7 cases, 5 cases were misdiagnosed as posterior circulation ischemia, 1 case was misdiagnosed as somatization disorder, and 1 case of left upper limb weakness patient was misdiagnosed as cerebral infarction. After corre-sponding treatment there was no sings of relief in symptoms. HIV antibody test result was positive, and validation test later con-firmed AIDS, and then the patients were transferred to the center for disease control and prevention for

  3. 抗病毒联合抗结核药物在艾滋病合并肺结核患者治疗中应用分析%Analysis of the application of anti-virus combined with anti-tuberculosis drugs in the treatment of acquired immune deficiency syndrome complicated with pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    贾中毅

    2015-01-01

    Objective:To explore the application effect of anti-virus combined with anti-tuberculosis drugs in the treatment of acquired immune deficiency syndrome complicated with pulmonary tuberculosis.Methods:32 patients with AIDS combined with tuberculosis were selected.They were given AZT+NVP+DDI antiviral regimen and 2H3R3Z3E3/7H3R3 regimen for tuberculosis treatment.We compared the treatment effect.Results:In 23 cases of HIV/AIDS/TB double infections,15 cases were clinically cured;5 cases completed one course;chest X-ray of 3 cases showed focus was absorbed and they continued to take medicine.Compared with before treatment,the CD4+T lymphocyte count at 6 months and 9 months after treatment was significantly improved(P<0.05). Conclusion:The dual anti infection treatment program of anti tuberculosis and anti-virus can effectively control tuberculosis and improve the immunity of HIV patients.%目的:探讨抗病毒联合抗结核药物在艾滋病合并肺结核患者治疗中应用效果。方法:收治艾滋病合并肺结核患者32例,采用AZT+NVP+DDI抗病毒方案治疗及2H3R3Z3E3/7H3R3抗结核方案治疗,比较治疗效果。结果:23例HIV/AIDS/TB双重感染患中,15例临床治愈,5例完成1个疗程,3例胸片提示病灶吸收好转继续服药。治疗6个月、9个月的CD4+T淋巴细胞计数较治疗前均有明显提高(P<0.05)。结论:该抗结核抗病毒双重抗感染治疗方案,可达到有效控制结核病,提高HIV患者免疫力。

  4. Gene therapy for primary adaptive immune deficiencies.

    Science.gov (United States)

    Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana-Calvo, Marina

    2011-06-01

    Gene therapy has become an option for the treatment of 2 forms of severe combined immunodeficiency (SCID): X-linked SCID and adenosine deaminase deficiency. The results of clinical trials initiated more than 10 years ago testify to sustained and reproducible correction of the underlying T-cell immunodeficiency. Successful treatment is based on the selective advantage conferred on T-cell precursors through their expression of the therapeutic transgene. However, "first-generation" retroviral vectors also caused leukemia in some patients with X-linked SCID because of the constructs' tendency to insert into active genes (eg, proto-oncogenes) in progenitor cells and transactivate an oncogene through a viral element in the long terminal repeat. These elements have been deleted from the vectors now in use. Together with the use of lentiviral vectors (which are more potent for transducing stem cells), these advances should provide a basis for the safe and effective extension of gene therapy's indications in the field of primary immunodeficiencies. Nevertheless, this extension will have to be proved by examining the results of the ongoing clinical trials.

  5. New genetic discoveries and primary immune deficiencies.

    Science.gov (United States)

    Hernandez-Trujillo, Vivian

    2014-04-01

    The field of immunology has undergone recent discoveries of genetic causes for many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has led to increased understanding behind the pathophysiology of these diseases. Since these diseases are rare, the patients are frequently misdiagnosed early in the presentation of their illnesses. The identification of new genes has increased our opportunities for recognizing and making the diagnosis in patients with PIDD before they succumb to infections that may result secondary to their PIDD. Some mutations lead to a variety of presentations of severe combined immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead to SCID phenotypes have been identified in recent years. Other mutations associated with some genetic syndromes have associated immunodeficiency and are important for making the diagnosis of primary immunodeficiency in patients with some syndromes, who may otherwise be missed within the larger context of their syndromes. A variety of mutations also lead to increased susceptibility to infections due to particular organisms. These patterns of infections due to specific organisms are important keys in properly identifying the part of the immune system which is affected in these patients. This review will discuss recent genetic discoveries that enhance our understanding of these complex diseases.

  6. Successful treatment of an acquired haemorrhagic diathesis due to factor X deficiency with chemotherapy

    NARCIS (Netherlands)

    de Jager, E; Bieger, R; Castel, A; Kluin, PM

    2001-01-01

    A 70-yr-old woman presented with a severe haemorrhagic diathesis due to an acquired factor X deficiency. A plasma infusion study showed that exogenous factor X was eliminated very effectively from the patient's circulation. A bone marrow biopsy was consistent with plasma cell dyscrasia. Neither an a

  7. Intravenous zinc therapy for acquired zinc deficiency secondary to gastric bypass surgery: a case report.

    Science.gov (United States)

    Vick, Garrett; Mahmoudizad, Rod; Fiala, Katherine

    2015-01-01

    Zinc deficiency may result from either a congenitally inherited defect of zinc absorption or is acquired secondarily from a variety of factors affecting dietary zinc intake, absorption, or loss. We report a case of acquired zinc deficiency secondary to gastric bypass surgery that resulted in vulvar cutaneous manifestations of delayed onset, with failure to clear after oral supplementation with zinc. The patient experienced improvement of symptoms only after administration of intravenous zinc supplementation. Upon review of the current literature, it is thought that the patient's original suboptimal response to oral supplementation and improvement after receiving intravenous zinc were related to the intentional surgical alteration and bypass of the absorptive capacity of the duodenum and jejunum. With the current prevalence of obesity and availability of surgical weight loss therapies, it is important to be mindful of the resulting nutritional deficiencies, their clinical manifestations, and factors affecting the efficacy of therapeutic approaches as seen in this case.

  8. Psychological change of patients with human immunodeficiency virus infection or acquired immune deficiency syndrome%艾滋病患者及人类免疫缺陷病毒感染者心理健康状况及其影响因素

    Institute of Scientific and Technical Information of China (English)

    王建宁; 屈文妍

    2010-01-01

    目的 了解艾滋病患者及人类免疫缺陷病毒(HIV)感染者心理健康状况,并探讨其影响因素.方法 确诊艾滋病患者及HIV检测阳性者共94例为研究组,38名健康人作为对照组,对二者进行症状自评量表(SCL-90)、社会支持量表、应付方式问卷(CSQ)及艾森克人格问卷(EPQ)测评.结果 研究组SCL-90的强迫、抑郁、焦虑及精神病因子分显著高于对照组(P<0.05或0.01),研究组内部男性抑郁因子分和偏执因子分均高于女性,其SCL-90多个因子与CSQ和EPQ多个因子之间存在显著相关关系,相关系数在0.21~0.70之间.结论 艾滋病患者及HIV感染者心理健康状况不良,以情绪障碍为主,应进行心理社会支持和治疗.%Objective To investigate the mental health status of adults with human immunodeficiency virus (HIV)infection or acquired immune deficiency syndrome(AIDS).Methods Ninety-four patients with HIV infection or AIDS and 38 healthy subjects were enrolled and filled in the Symptom Checklist 90(SCL-90),Coping Styles Questionnaire(CSQ)and Eysenck Personality Questionnaire(EPQ).Results in SCL-90,the scores of compulsion ,depression,anxiety and psychoticism factor were significantly increased in the patient group(all P<0.05).In the study group,the scores of depression and paranoid ideation factors of male patients were higher than those of female patients.For the participants with HIV infection or AIDS,several factors of SCL-90 were correlative with CSQ and EPQ(r=0.21 to 0.70).Conclusion Emotional disorders may be the most common mental problem of patients with HIV infection or AIDS,and social and psychological supports should be needed.

  9. Exploratory efficacy endpoints in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)

    NARCIS (Netherlands)

    Webber, Chris; Patton, Michael; Patterson, Scott; Schmoele-Thoma, Beate; Huijts, Susanne M; Bonten, Marc J M

    2017-01-01

    BACKGROUND: The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) assessed vaccine-type community-acquired pneumonia (VT-CAP) and vaccine-type invasive pneumococcal disease (VT-IPD) prevention with 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ⩾65years. We report

  10. Defects of colour vision: A review of congenital and acquired colour vision deficiencies

    Directory of Open Access Journals (Sweden)

    Nabeela Hasrod

    2016-03-01

    Full Text Available Colour vision deficiencies (CVDs can be categorised as being congenital or acquired. Some CVDs are already present at birth, as inherited conditions that are the result of changes at the photo-pigment level and are non-pathological, incurable and do not change over time. Examples are red-green defects which are inherited as an X-linked recessive trait. Acquired CVD develops secondary to ocular and systemic conditions or as a side effect of certain medications or sometimes toxic effects of chemicals, and trauma and ageing can also be important in some CVDs.

  11. Importance of pharmacokinetic studies in the management of acquired factor X deficiency.

    Science.gov (United States)

    Lim, Ming Y; McCarthy, Timothy; Chen, Sheh-Li; Rollins-Raval, Marian A; Ma, Alice D

    2016-01-01

    Up to 14% of individuals with systemic AL amyloidosis develop acquired factor X deficiency, which occurs due to adsorption of factor X onto amyloid fibrils. Although baseline factor X levels are not predictive of bleeding risk in these patients, serious hemorrhagic complications can occur, particularly during invasive procedures. Optimal management strategies to attenuate bleeding risk in these patients are unknown. We describe our experience in the management of acquired factor X deficiency, secondary to systemic AL amyloidosis, in a case series of three patients who received prothrombin complex concentrates (PCCs) for treatment and prevention of bleeding events. We performed a retrospective review extracting information on baseline demographics, laboratory data, pharmacokinetic (PK) studies, and clinically documented bleeding events. Our case series demonstrates that individuals with acquired factor X deficiency secondary to amyloidosis have variable laboratory and clinical responses to PCCs. This is likely due to distinct amyloid loads and fibril sequences, leading to different binding avidities for factor X. Our data emphasize the importance of performing PK testing prior to any invasive procedures to determine the dose and frequency interval to achieve adequate factor X levels for hemostasis, given the variable response between individuals.

  12. Microflora analysis of a child with severe combined immune deficiency

    Science.gov (United States)

    Taylor, G. R.; Kropp, K. D.; Molina, T. C.

    1978-01-01

    The paper presents a microflora analysis of a 5-year-old male child with severe combined immune deficiency who was delivered by Caesarean section and continuously maintained in an isolator. Despite precautions, it was found that the child had come in contact with at least 54 different microbial contaminants. While his skin autoflora was similar to that of a reference group of healthy male adults in numbers of different species and the number of viable cells present per square centimeter of surface area, the subject's autoflora differed from the reference group in that significantly fewer anaerobic species were recovered from the patient's mouth and feces. It is suggested that the child's remaining disease free shows that the reported bacteria are noninvasive or that the unaffected components of the child's immune defense mechanisms are important.

  13. Qualitative study on the protective factors of resilience among children in rural areas in acquired immune deficiency syndrome(HIV/AIDS)-Affected families%我国部分农村地区受艾滋病影响儿童心理弹性的保护性因素研究

    Institute of Scientific and Technical Information of China (English)

    史从戎; 张曼华; 王宇; 来源; 高保兴; 乔晓春

    2011-01-01

    [目的]调查山西省某艾滋病比较集中的地区,探讨该区受艾滋病影响儿童心理弹性的保护性因素.[方法]采用儿童焦虑性情绪障碍筛查表和儿童抑郁障碍自评量表,将受艾滋病影响儿童筛分为心理弹性组与非弹性组,再采用半结构访谈的方法,对弹性组的儿童进行调查. [结果]受艾滋病影响儿童心理弹性的保护性因素可划分为四个因素.家庭因素包括父母的关心和支持、民主的教育方式、父母的榜样力量;学校包括老师的关心、同伴的支持;认知包括对父母的评价、相信自己、对未来的期望;行为包括倾诉、寻求帮助、感恩与回报. [结论]在对受艾滋病影响儿童进行心理干预时,应综合考虑家庭、学校、认知、行为等因素.促进其心理弹性的发展,增进其心理健康.%[Objective] To explore the protective factors of resilience among children in acquired immune deficiency syndrome(HIV/AIDS)-Affected families in Shanxi. [Methods] Children in HIV/AIDS families were allocated into resilience group and non-resilience group by The Screen for Child Anxiety Related Emotional Disorders and Depression Self-rating Scale for Children. Then semi-structured interviews were conducted among the resilience group. [Results] The protective factors of resilience among children include four factors. The factor of family consists of care of parents, democratic family education and a good example of parents. Care of teachers and support of peers were included in the factor of school.Estimate of parents, belief in themselves and expectation for the future were organized into the factors of cognition. Pouring out, searching for help and thanksgiving were packed in the factors of behaviors. [Conclusion] Family, school, cognition and behavior should be considered comprehensively in the psychological intervention for the children in HIV/AIDS family to make them more resilient and more healthy.

  14. BACE1-Deficient Mice Exhibit Alterations in Immune System Pathways.

    Science.gov (United States)

    Stertz, L; Contreras-Shannon, V; Monroy-Jaramillo, N; Sun, J; Walss-Bass, C

    2016-12-21

    BACE1 encodes for the beta-site amyloid precursor protein cleaving enzyme 1 or β-secretase. Genetic deletion of Bace1 leads to behavioral alterations and affects midbrain dopaminergic signaling and memory processes. In order to further understand the role of BACE1 in brain function and behavior, we performed microarray transcriptome profiling and gene pathway analysis in the hippocampus of BACE1-deficient mice compared to wild type. We identified a total of 91 differentially expressed genes (DEGs), mostly enriched in pathways related to the immune and inflammation systems, particularly IL-9 and NF-κB activation pathways. Serum levels of IL-9 were elevated in BACE1-deficient mice. Our network analysis supports an intimate connection between immune response via NF-κB and BACE1 signaling through the NRG1/Akt1 pathway. Our findings warrant future mechanistic studies to determine if BACE1 signaling and the IL-9 pathway interact to alter behavior and brain function. This study opens new avenues in the investigation of hippocampus-related neuroimmunological and neuroinflammation-associated disorders.

  15. Toward immunogenetic studies of amphibian chytridiomycosis: Linking innate and acquired immunity

    Science.gov (United States)

    Richmond, J.Q.; Savage, Anna E.; Zamudio, Kelly R.; Rosenblum, E.B.

    2009-01-01

    Recent declines in amphibian diversity and abundance have contributed significantly to the global loss of biodiversity. The fungal disease chytridiomycosis is widely considered to be a primary cause of these declines, yet the critical question of why amphibian species differ in susceptibility remains unanswered. Considerable evidence links environmental conditions and interspecific variability of the innate immune system to differential infection responses, but other sources of individual, population, or species-typical variation may also be important. In this article we review the preliminary evidence supporting a role for acquired immune defenses against chytridiomycosis, and advocate for targeted investigation of genes controlling acquired responses, as well as those that functionally bridge the innate and acquired immune systems. Immunogenetic data promise to answer key questions about chytridiomycosis susceptibility and host-pathogen coevolution, and will draw much needed attention to the importance of considering evolutionary processes in amphibian conservation management and practice. ?? 2009 by American Institute of Biological Sciences.

  16. Clinical characteristics and innate immunity in patients with community-acquired pneumonia

    NARCIS (Netherlands)

    Endeman, H.

    2009-01-01

    Community-acquired pneumonia (CAP) is the most common infectious disease requiring hospitalisation in the Western world. In spite of improving antibiotic regiments, CAP still has significant mortality. In non-immune compromised patients, Streptococcus pneumoniae is the most frequently isolated micro

  17. Immune response against Sporothrix schenckii in TLR-4-deficient mice.

    Science.gov (United States)

    Sassá, Micheli Fernanda; Ferreira, Lucas Souza; Ribeiro, Livia Carolina de Abreu; Carlos, Iracilda Zeppone

    2012-07-01

    For many fungal diseases, macrophages are the major cell population implicated in host protection, primarily by their ability to eliminate the invading fungal pathogen through phagocytosis. In sporotrichosis, this remains true, because of macrophages’ ability to recognize Sporothrix schenckii through specific receptors for some of the fungus’ cellular surface constituents. Further confirmation for macrophages’ pivotal role in fungal diseases came with the identification of toll-like receptors, and the subsequent numerous associations found between TLR-4 deficiency and host susceptibility to diverse fungal pathogens. Involvement of TLR-4 in immune response against sporotrichosis has been conducted to investigate how TLR-4 signaling could affect inflammatory response development through evaluation of H2O2 production and IL-1β, IL-6 and TGF-β release during the course of S. schenckii infection on TLR-4-deficient mice. The results showed that macrophages are largely dependent on TLR-4 for inflammatory activation and that in the absence of TLR-4 signaling, increased TGF-β release may be one of the contributing factors for the abrogated inflammatory activation of peritoneal exudate cells during mice sporotrichosis.

  18. Iron Deficiency Impairs Intra-Hepatic Lymphocyte Mediated Immune Response.

    Directory of Open Access Journals (Sweden)

    Eliano Bonaccorsi-Riani

    Full Text Available Hepatic expression of iron homeostasis genes and serum iron parameters predict the success of immunosuppression withdrawal following clinical liver transplantation, a phenomenon known as spontaneous operational tolerance. In experimental animal models, spontaneous liver allograft tolerance is established through a process that requires intra-hepatic lymphocyte activation and deletion. Our aim was to determine if changes in systemic iron status regulate intra-hepatic lymphocyte responses. We used a murine model of lymphocyte-mediated acute liver inflammation induced by Concanavalin A (ConA injection employing mice fed with an iron-deficient (IrDef or an iron-balanced diet (IrRepl. While the mild iron deficiency induced by the IrDef diet did not significantly modify the steady state immune cell repertoire and systemic cytokine levels, it significantly dampened inflammatory liver damage after ConA challenge. These findings were associated with a marked decrease in T cell and NKT cell activation following ConA injection in IrDef mice. The decreased liver injury observed in IrDef mice was independent from changes in the gut microflora, and was replicated employing an iron specific chelator that did not modify intra-hepatic hepcidin secretion. Furthermore, low-dose iron chelation markedly impaired the activation of isolated T cells in vitro. All together, these results suggest that small changes in iron homeostasis can have a major effect in the regulation of intra-hepatic lymphocyte mediated responses.

  19. The Study on the Ferrokinetics and Acquired Immunity in Repeated Hookworm Infections

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mun Ho; Lee, Pyl Ung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1967-09-15

    In order to confirm whether acquired immunity or resistance can be developed by the repeated hookworm infections, the 150 mature actively moving filariform ancylostoma duodenale larvae obtained from the severe hookworm anemia patients were orally given to 8 healthy volunteers in three divided doses, 50 in each, at 5 day interval. Also the hematological changes as well as several ferrokinetics using {sup 59}Fe were done and were compared with 10 controls. The clinical symptoms and signs were checked every day for the first 3 weeks and then twice weekly until the end of the experiment. The appearance of the ova in the stool was examined by the formalin ether method and the ova was counted by the Stoll's method. The following laboratory tests were done:1) Red blood cell count, venous blood hematocrit (micromethod), hemoglobin count (cyanomethemoglobin method) were checked every 5 to 7 day interval. 2) Plasma iron concentration (Barkan's modified method) was determined every 2 to 3 week interval. 3) Radioisotope studies:a) Ferrokinetics: Huff et al and Bothwell's method were applied. Erythropoietic Index (% of normal)= ['Subject's turnover/100 ml whole bloodX100'] over ['Average normal turnover/100 ml whole blood'] b) Quantitative measurement of the gastrointestinal absorption of iron:Radioiron ({sup 59}Fe) balance method was applied. c) Determination of the plasma erythropoietin activity: Fried's method was applied. Following were the results: 1) The serum iron level was lower. The red cell volume was decreased, but with relative increase of plasma volume. 2) The plasma iron disappearance time was accelerated and the plasma iron turnover rate was decreased. The red cell iron turnover rate was markedly increased, while all of the red cell iron concentration, circulating red cell iron, plasma iron pool were decreased. The daily iron pool turnover and red cell renewal rate were increased. 3) The erythropoietic index

  20. Relationship of levels of serum carcinoembryonic antigen and pathological imaging changes of lungs in patients with acquired immune deficiency syndrome (AIDS)%AIDS患者血清CEA水平与胸部影像学关系的临床观察

    Institute of Scientific and Technical Information of China (English)

    王家驷; 王廷杰; 王平飞; 张雪漫; 冉梅

    2013-01-01

    目的:探讨AIDS患者血清癌胚抗原(CEA)增高与胸部病变的关系。方法观察2008年1月至2011年12月间因胸部疾病入住四川省达州市中心医院呼吸内科且确诊为AIDS感染者,选取同时有胸部CT检查及血清CEA检测资料的病例68例,包括男性54例,女性14例,年龄26~78岁,平均年龄51.10岁,分析临床病史、症状、胸部CT影像学变化与血清CEA水平之间的关系。结果68例AIDS患者中,CEA增高者占44.12%,平均年龄较CEA正常组偏大3.22岁;发热、咳嗽症状患者两组间比例接近,主诉气促及合并真菌感染者是CEA正常者的1倍,而乏力盗汗、胸部不适等其他主诉则约是CEA正常者的1/2(47.83%)。CEA正常组的均值是(2.04±1.34)ng/ml,CEA增高组为(8.28±4.54)ng/ml;组间差异有显著统计学意义(P <0.001),CEA增高组发生胸部磨玻璃影(GGO)的几率是CEA正常者的4倍,而CEA正常组斑片影则约为CEA增高组的1倍;AIDS患者胸部GGO影像的密度和范围不同,其CEA的平均水平出现相应的水平差异;而未合并GGO的胸部团块影、纵膈增大及纤维索条影者CEA水平在0.00~10.93 ng/ml,与GGO者比较差异有显著统计学意义(P <0.001)。结论 AIDS患者血CEA增高可能与胸部磨玻璃影的形成相关,是CEA的一种非肿瘤性特性,可能与PCP感染相关。%Objective To approach relative of increased levels of serum carcinoembryonic antigen (CEA) to pathological changes of lunges in patients with acquired immune deficiency syndrome (AIDS). Methods The patients with diagnosed AIDS admitted on the basis of illness in department of respiratory medicine of our hospital (general hospital) from Jan 2008 to Dec 2011 were prospectively observed, in which 68 cases of patients (male 54, female 14, age range 26-78 years old, means 51.10 years old) with serum CEA data and CT detections of thorax were selected, and the relevance

  1. Fundus white spots and acquired night blindness due to vitamin A deficiency.

    Science.gov (United States)

    Genead, Mohamed A; Fishman, Gerald A; Lindeman, Martin

    2009-12-01

    To report a successfully treated case of acquired night blindness associated with fundus white spots secondary to vitamin A deficiency. An ocular examination, electrophysiologic testing, as well as visual field and OCT examinations were obtained on a 61-year-old man with vitamin A deficiency who had previously undergone gastric bypass surgery. The patient had a re-evaluation after treatment with high doses of oral vitamin A. The patient was observed to have numerous white spots in the retina of each eye. Best-corrected visual acuity was initially 20/80 in each eye, which improved to 20/40-1 OU after oral vitamin A therapy for 2 months. Full field electroretinogram (ERG) testing, showed non-detectable rod function and a 34 and 41% reduction for 32-Hz flicker and single flash cone responses, respectively, below the lower limits of normal. Both rod and cone functions markedly improved after initiation of vitamin A therapy. Vitamin A deficiency needs to be considered in a patient with white spots of the retina in the presence of poor night vision.

  2. Acquired idiopathic ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in a population from Japan.

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    Masanori Matsumoto

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a type of thrombotic microangiopathy (TMA. Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai ADAMTS13-deficient TTP (ADAMTS13 activity <5% were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01, while older patients were more likely to die during the TTP hospitalization (p<0.05. Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort and gender composition (60% to 100% female in the other cohort. We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed.

  3. 用伴时Cox回归模型进行艾滋病抗病毒治疗病例的生存分析%The survival analysis on antiretroviral therapy cas es of acquired immune deficiency syndrome based on time-dependent Cox regression model

    Institute of Scientific and Technical Information of China (English)

    白芳; 樊华山; 卫军; 杜培军; 薛子东; 仇超; 徐建青

    2014-01-01

    Objective To evaluate the effectiveness of free antiretroviral therapy(ART) in adults and the factors influence ART outcome. Methods A retrospective cohort study was conducted Shanxi province. All qualified ART recipients were enrolled in the national free ART program from June 2004 to December 2012. Statistical analysis was conducted by SPSS software (version 19.0), use the t test and chi-square test, with Cox regression model for survival analysis. Results One thousand eight hundred and eighty-seven cases were included in the study. The rates for participants, who survived, who were deceased for acquired immune deficiency syndrome (AIDS) related diseases, who withdrawal from the treatment, who transferred to other hospital and who lost for follow-up were 83.1%, 13.5%, 1.4%, 1.2% and 0.8%, respectively. The cumulative survival rates were 0.91, 0.89, 0.88, 0.86, 0.85, 0.82, 0.80, 0.79 and 0.79 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 and 8.0 years after treatment initiation, respectively. The medians of CD4+T cell count were 143.5 cells/μL prior to treatment and 205.3 cells/μL post treatment. 18.2% of ART recipients had their viral loads below detection limit before therapy and this percentage increased to 89.1% after therapy. In the multivariate Cox proportional hazard model, CD4+T cell count and BMI before treatment initiation, and the age start therapy were significantly associated with survival time. The Hazard ratio was 4.05, 3.44 and 3.68, respectively. Record the count of CD4+T lymphocyte after antiretroviral treatment, the difference of CD4+T lymphocyte count between before antiretroviral treatment and after, 3 covariates had been produced by the viral load program generates after antiretroviral treatment , 15 variables had been proved to be statistically and professional significance before antiretroviral treatment. Analysis above all variables based on multi factor time-dependent Cox regression model. There were statistical differences between the

  4. Polyprenols as possible factors that determine an instructive role of the innate immunity in the acquired immune response.

    Science.gov (United States)

    Pronin, Alexander V; Grigorieva, Ekaterina A; Sanin, Alexander V; Narovlyansky, Alexander N; Ozherelkov, Sergei V; Deyeva, Anna V; Danilov, Leonid L; Maltsev, Sergei D; Najid, Abderrahim

    2002-07-01

    Polyprenols are an integral part of all living cells including prokaryotic and eukaryotic ones. These compounds take part in biosynthesis of glycoproteins. We have found that phosphates of polyprenols may act as effective antiviral agents with a wide spectrum of activity. One of such antiviral agents received from Pinus sativum polyprenols was named phosprenyl. Earlier we showed that phosprenyl expressed direct antiviral effect, while having mild immunomodulatory activity. In the present study we further evaluated influence of phosprenyl on the immune system. The drug was found to inhibit an early phase of IL-1 and Con A interaction in spleen cells as well as lypoxigenase activity and expression of IL-2 receptors. At the same time, phosprenyl induced NK cell activity and early TNF-alpha production. Basing on all these data we proposed that polyprenols could be considered as a "label" which grants a possibility to the innate immune system to recognize infection at the early stages and govern the acquired immunity.

  5. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience.

    Science.gov (United States)

    Coppo, Paul; Schwarzinger, Michael; Buffet, Marc; Wynckel, Alain; Clabault, Karine; Presne, Claire; Poullin, Pascale; Malot, Sandrine; Vanhille, Philippe; Azoulay, Elie; Galicier, Lionel; Lemiale, Virginie; Mira, Jean-Paul; Ridel, Christophe; Rondeau, Eric; Pourrat, Jacques; Girault, Stéphane; Bordessoule, Dominique; Saheb, Samir; Ramakers, Michel; Hamidou, Mohamed; Vernant, Jean-Paul; Guidet, Bertrand; Wolf, Martine; Veyradier, Agnès

    2010-04-23

    Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count < 30 x 10(9)/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.2, P<.001), serum creatinine level < or =200 micromol/L (OR 23.4, 95% CI 8.8-62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0-8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.

  6. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience.

    Directory of Open Access Journals (Sweden)

    Paul Coppo

    Full Text Available Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA. In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count < 30 x 10(9/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.2, P<.001, serum creatinine level < or =200 micromol/L (OR 23.4, 95% CI 8.8-62.5, P<.001, and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0-8.0, P<.05. When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.

  7. Immune Deficiency Influences Juvenile Social Behavior and Maternal Behavior

    Science.gov (United States)

    Quinnies, Kayla M.; Cox, Kimberly H.; Rissman, Emilie F.

    2017-01-01

    Mice with severe combined immunodeficiency (SCID) lack functional T and B-lymphocytes, and have impaired cognitive abilities. Here, we assessed social behaviors in male SCID and C57BL/6 (B6) juvenile mice. In a social preference task, SCID mice spent more time than B6 mice investigating a novel adult male mouse. In a social recognition task, SCID mice habituated to a novel ovariectomized mouse, but failed to show dishabituation when presented with an unfamiliar individual. We hypothesized that partial immune restoration could normalize behaviors. SCID pups (postnatal day 7) received either saline or splenocytes from normal donors. Splenocyte-replaced SCID mice spent less time interacting with a novel mouse than saline-injected SCID or B6 control mice. Again, control SCID mice failed to dishabituate to a novel mouse, but splenocyte-replaced SCID mice showed dishabituation. In both of these studies B6 and SCID pairs were used to produce offspring that remained with their dams until weaning. There are no studies of maternal behavior in SCID dams; therefore to investigate the potential role for this factor we quantified maternal behavior in SCID and B6 dams; several significant differences were found. To control for differences in maternal care we mated heterozygous SCIDs to produce offspring. These homozygous SCID and WT offspring reared by dams of the same genotypes displayed similar responses to a novel mouse; however, in the social recognition task SCID males did not display dishabituation to a novel mouse. Taken together, our data indicate that gene by environment interactions influence social interactions in immune deficient mice. PMID:26030431

  8. Prolonged survival and immune reconstitution after chagasic meningoencephalitis in a patient with acquired immunodeficiency syndrome

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    Corti Marcelo

    2006-01-01

    Full Text Available We report a case of cerebral meningoencephalitis due to Trypanosoma cruzi in a patient with acquired immunodeficiency syndrome. The patient presented with seizures and focal neurological signs. Definitive diagnosis of chagasic meningoencephalitis was made by demonstration of free trypomastigote forms in the cerebrospinal fluid. Benznidazol was prescribed with clinical and neurological improvement. Antiretroviral drugs improved cellular immunity and three years later the patient presents a good clinical condition with immune reconstitution and undetectable viral load. Chagasic meningoencephalitis has a poor prognosis when specific treatment is not initiated or is delayed. A high index of diagnosis is necessary for early diagnosis and treatment, especially in endemic areas for Trypanosoma cruzi infection.

  9. How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID).

    Science.gov (United States)

    Kohn, Donald B; Gaspar, H Bobby

    2017-02-14

    Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

  10. Importance of both innate immunity and acquired immunity for rapid expulsion of S. venezuelensis.

    Directory of Open Access Journals (Sweden)

    Koubun eYasuda

    2014-03-01

    Full Text Available In the first part of this review, we described the relevant roles of endogenous IL-33 for accumulation of ILC2 and eosinophils even in the lungs of Rag2-/- mice. ATII cells express IL-33 in their nucleus and infection with S.venezuelensis induces IL-33 production by increasing the number of ATII cells possibly by the action of chitin. IL-33 from ATII cells induces ILC2 proliferation and at the same time activates them to produce IL-5 and IL-13, which in combination induce lung eosinophilic inflammation, aiding to expel infected worms in the lungs. In the second part, we showed that, although AID-/- mice normally develop Th2 cells and intestinal mastocytosis after infection with S.venezuelensis, they need adoptive transfers of immune sera from S.venezuelensis-infected mice to obtain the capacity to promptly expel S.venezuelensis. Thus, intestinal nematode infection induces various Th2 immune responses (eg., Th2 cell, ILC2, goblet cell hyperplasia, intestinal mastocytosis, smooth muscle cell contraction, local and systemic eosinophilia and high serum level of IgE and IgG1. However, all of them are not necessary for rapid expulsion of intestinal nematodes. Instead, some combinations of Th2 immune responses are essentially required.

  11. Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired Immunity

    Science.gov (United States)

    Hirai, Toshiro; Yoshioka, Yasuo; Udaka, Asako; Uemura, Eiichiro; Ohe, Tomoyuki; Aoshima, Hisae; Gao, Jian-Qing; Kokubo, Ken; Oshima, Takumi; Nagano, Kazuya; Higashisaka, Kazuma; Mashino, Tadahiko; Tsutsumi, Yasuo

    2016-10-01

    The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific antibody production and ovalbumin-specific T cell responses in vivo, although T cell-independent antibodies responses were not affected by C60-P. Together, our data suggest that fullerene derivatives can suppress acquired immune responses that require T cells.

  12. Haemoglobin C and S role in acquired immunity against Plasmodium falciparum malaria.

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    Federica Verra

    Full Text Available A recently proposed mechanism of protection for haemoglobin C (HbC; beta6Glu-->Lys links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS; ii total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria.

  13. The role of acquired immunity in the spread of human papillomavirus (HPV: explorations with a microsimulation model.

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    Suzette M Matthijsse

    Full Text Available BACKGROUND: Knowledge of the natural history of human papillomavirus (HPV, in particular the role of immunity, is crucial in estimating the (cost- effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. METHODS: We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. RESULTS: A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. CONCLUSIONS: Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer.

  14. Antigen-specific acquired immunity in human brucellosis: implications for diagnosis, prognosis, and vaccine development

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    Anthony P Cannella

    2012-02-01

    Full Text Available Brucella spp. are facultative intracellular Gram negative bacteria with specific tropism for monocytes/macrophages. Clinical manifestations of brucellosis are primarily immune-mediated and not thought to be due to bacterial virulence factors. Acquired immunity to brucellosis has been studied through observations of naturally infected hosts (cattle, goats, laboratory mouse models, and human infection. Cell-mediated immunity drives the clinical manifestations of human disease after exposure to Brucella species but high antibody responses are not associated with protective immunity. The precise mechanisms by which cell-mediated immune responses confer protection or lead to disease manifestations remain poorly understood. Descriptive studies of immune responses in human brucellosis show that TH1 (interferon-gamma are associated with dominant immune responses, findings consistent with animal studies. Whether these T cell responses are protective, or determine the different clinical responses associated with brucellosis is unknown, especially with regard to undulant fever manifestations, relapsing disease, or are associated with responses to distinct sets of Brucella spp. antigens are unknown. Few data regarding T cell responses in terms of specific recognition of Brucella spp. protein antigens and peptidic epitopes, either by CD4+ or CD8+ T cells, have been identified in human brucellosis patients. Additionally because current attenuated Brucella vaccines used in animals cause human disease, there is a true need for a recombinant protein subunit vaccine for human brucellosis, as well as for improved diagnostics in terms of prognosis and identification of unusual forms of brucellosis. This review will focus on current understandings of antigen-specific immune responses induced by Brucella protein antigens that has promise for yielding new insights into vaccine and diagnostics development, and for understanding pathogenetic mechanisms of human

  15. Materno-Fetal Transmission of Human Immune Deficiency Virus

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    Axel Schäfer

    1997-01-01

    Full Text Available Mother-to-child transmission of human immune deficiency virus (HIV is a multifactorial event highly associated with advanced maternal HIV disease and obstetric incidents taking place during parturition. Thus, various approaches to prevention may be beneficial. Although the time and the route of materno-fetal HIV transmission are still not sufficiently clear, much speaks in favor of a late HIV transmission, most probably taking place during parturition or the phase before the delivery. The fetus is remarkably protected by the placenta and the intact fetal membranes against many viral infections during gestation. These conditions change at parturition and the chance for a transition of HIV-infected carrier cells or virus into the fetal compartment increases. Proinflammatory cytokines secreted at the materno-fetal interface accumulate in amniotic fluid and may chemoattract and stimulate potentially HIV-infected immunocytes. After rupture of membranes, maternal cells of the decidua are directly exposed to the amniotic fluid. Aside from the contamination of the fetal skin at vaginal delivery as a debatable route of infection, blood-to-blood contacts and the fetal swallowing of contaminated amniotic fluid may be the major path of fetal HIV infection. For the fetal prophylaxis of an intrauterine infection, the application of zidovudine is recommended. However, cesarian section before the onset of labor leads also to a diminution of the transmission rate. As the transmission seems to have both systemic and local causes, it makes sense to combine different intervention strategies. Whether a combination of zidovudine and elective cesarean section can lower the transmission risk further has to be evaluated.

  16. Acquired protein C deficiency in a child with acute myelogenous leukemia, splenic, renal, and intestinal infarction.

    Science.gov (United States)

    Farah, Roula A; Jalkh, Khalil S; Farhat, Hussein Z; Sayad, Paul E; Kadri, Adel M

    2011-03-01

    We report the case of a 6-year-old boy diagnosed with acute promyelocytic leukemia (AML-M3V) when he presented with pallor, abdominal pain, anorexia, and fatigue. Induction chemotherapy was started according to the AML-BFM 98 protocol along with Vesanoid (ATRA, All-trans retinoic acid). On the sixth day of induction, he developed splenic and gallbladder infarcts. Splenectomy and cholecystectomy were performed while chemotherapy induction continued as scheduled. Four days later, he developed ischemic areas in the kidneys and ischemic colitis in the sigmoid colon. Hypercoagulation studies showed severe deficiency of protein C. Tests showed protein C 16% (reference range 70-140%), protein S 87% (reference range 70-140%), antithrombin III 122% (reference range 80-120%), prothrombin time 13.6 s (reference = 11.3), INR (international normalized ratio) 1.21, partial thromboplastin time 33 s (reference = 33), fibrinogen 214 mg/dl, D-dimer 970 μg/ml, factor II 98%, and that antinuclear antibody, antiphospholipid antibodies, mutation for factor II gene (G20210A), and mutation for Arg506 Gln of factor V were all negative (factor V Leiden). There was no evidence of clinical disseminated intravascular coagulation (DIC). He was treated with low molecular weight heparin and did well. He continues to be in complete remission 7 years later with normal protein C levels. Acquired protein C deficiency can occur in a variety of settings and has been reported in acute myelocytic leukemia. However, clinically significant thrombosis in the absence of clinical DIC, such as our case, remains extremely rare.

  17. Economic impact of routine opt-out antenatal human immune deficiency virus screening: A systematic review.

    Science.gov (United States)

    Ibekwe, Everistus; Haigh, Carol; Duncan, Fiona; Fatoye, Francis

    2017-03-02

    To evaluate the economic impact of routine testing of human immune deficiency virus in antenatal settings. Many children are being infected with human immune deficiency virus through mother-to-child transmission of the virus. Most of these infections are preventable if the mothers' human immune deficiency virus status is identified in a timely manner and appropriate interventions put in place. Routine human immune deficiency virus testing is widely acclaimed as a strategy for universal access to human immune deficiency virus testing and is being adopted by developed and developing poor income countries without recourse to the economic impact. A systematic review of published articles. Extensive electronic searches for relevant journal articles published from 1998-2015 when countries began to implement routine antenatal HIV testing on their own were conducted in the following databases: Science Direct, MEDLINE, SCOPUS, JSTOR, CINAHL and PubMed with search terms as listed in Box 2. Manual searches were also performed to complement the electronic identification of high-quality materials. There were no geographical restrictions, but language was limited to English. Fifty-five articles were retrieved; however, ten were eligible and included in the review. The findings showed that many programmes involving routine human immune deficiency virus testing for pregnant women compared to the alternatives were cost-effective and cost saving. Data from the reviewed studies showed cost savings between $5,761.20-$3.69 million per case of previously undiagnosed maternal human immune deficiency virus-positive infection prevented. Overall, cost-effectiveness was strongly associated with the prevalence rate of human immune deficiency virus in the various settings. Routine human immune deficiency virus testing is both cost-effective and cost saving compared to the alternatives. However, there are wide variations in the methodological approaches to the studies. Adopting standard

  18. Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases

    Science.gov (United States)

    2017-03-16

    Severe Combined Immunodeficiency (SCID); Immunodeficiency With Predominant T-cell Defect, Unspecified; Severe Chronic Neutropenia; Chronic Granulomatous Disease (CGD); Hyper IgE Syndromes; Hyper IgM Deficiencies; Wiskott-Aldrich Syndrome; Mendelian Susceptibility to Mycobacterial Disease; Common Variable Immune Deficiency (CVID)

  19. Pyelonephritis during pregnancy: A cause for an acquired deficiency of protein Z

    Science.gov (United States)

    Nien, Jyh Kae; Romero, Roberto; Hoppensteadt, Debra; Erez, Offer; Espinoza, Jimmy; Soto, Eleazar; Kusanovic, Juan Pedro; Gotsch, Francesca; Kim, Chong Jai; Mittal, Pooja; Fareed, Jawed; Santolaya, Joaquin; Chaiworapongsa, Tinnakorn; Edwin, Samuel; Pineles, Beth; Hassan, Sonia

    2010-01-01

    Objective Pyelonephritis has a more severe course during pregnancy than in the non-pregnant state. This has been attributed to the increased susceptibility of pregnant women to microbial products. An acquired protein Z deficiency has been reported when there is excessive thrombin activity. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma protein Z concentrations. Study Design A cross-sectional study was conducted to compare plasma protein Z concentrations between normal pregnant women (n=71) and pregnant women with pyelonephritis (n=42). Protein Z concentrations were measured by ELISA. Parametric and non-parametric statistics were used for analysis. Results Patients with pyelonephritis had a significantly lower median plasma concentration of protein Z than did patients with normal pregnancies [median 2.14 μg/mL (0.4-3.4) vs. median 2.36 μg/mL (1.09-3.36); p=0.03]. There was no difference in the median plasma concentration of anti-protein Z antibodies between patients with pyelonephritis and those with normal pregnancies. Conclusion The median maternal plasma protein Z concentration was significantly lower in patients with pyelonephritis during pregnancy than in patients with normal pregnancies. PMID:18828054

  20. Regulation of naturally acquired mucosal immunity to Streptococcus pneumoniae in healthy Malawian adults and children.

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    Sarah J Glennie

    Full Text Available Worldwide, invasive pneumococcal disease caused by Streptococcus pneumoniae is most common in young children. In adults, disease rates decline following intermittent colonization and the acquisition of naturally acquired immunity. We characterized mucosal and systemic pneumococcal-specific T-cell responses in African children and adults who contend with intense rates of colonization, up to 100% and 60% respectively. We find most Malawian children have high pneumococcal-specific T-cell responses in tonsil tissue and peripheral blood. In addition, frequent commensalism generates CD25(hi (Tregs which modulate mucosal pneumococcal-specific T-cell responses in some children and ≥50% of adults. We propose that immune regulation may prolong pneumococcal colonization and predispose vulnerable individuals to disease.

  1. Does age acquired immunity confer selective protection to common serotypes of Campylobacter jejuni?

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    Ogden Iain D

    2005-08-01

    Full Text Available Abstract Background Campylobacter infection is a major cause of bacterial gastrointestinal disease. Exposure to Campylobacter is known to produce an immune response in humans that can prevent future symptomatic infections. Further, studies of the general population have shown that seroprevalence to Campylobacter increases with age. Methods A large collection of serotyped Campylobacter isolates, obtained from human clinical faecal samples, were analysed by comparing the ratio of uncommon to common serotypes by different age groups, using χ2 tests. Results We have identified that older age groups, as well as having generally lower incidence, are significantly less likely to be infected by the more common serotypes. Conclusion These results are indicative of acquired immunity, however, further studies are needed to rule out the confounding effects of the variations in exposure pathways experienced by different age groups.

  2. The role of acquired immunity in the spread of human papillomavirus (HPV): explorations with a microsimulation model

    NARCIS (Netherlands)

    Matthijsse, S.M.; Rosmalen, J. van; Hontelez, J.A.; Bakker, R; Kok, I.M. de; Ballegooijen, M. van; Vlas, S.J. de

    2015-01-01

    BACKGROUND: Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already

  3. The role of acquired immunity in the spread of human papillomavirus (HPV): explorations with a microsimulation model

    NARCIS (Netherlands)

    Matthijsse, S.M.; Rosmalen, J. van; Hontelez, J.A.; Bakker, R; Kok, I.M. de; Ballegooijen, M. van; Vlas, S.J. de

    2015-01-01

    BACKGROUND: Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already

  4. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Castelli, Roberto

    2016-02-01

    Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.

  5. Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.

    Science.gov (United States)

    Meehan, Cristina Adelia; Cochran, Elaine; Kassai, Andrea; Brown, Rebecca J; Gorden, Phillip

    2016-01-01

    The lipodystrophies represent a class of diseases characterized by leptin deficiency. Leptin deficiency is associated with a severe form of the metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes, and ovarian dysfunction. Metreleptin is the pharmaceutical derived product that has been approved by the Food and Drug Administration (FDA) to treat the severe metabolic abnormalities of the generalized forms of lipodystrophy. Herein we describe the properties of metreleptin, its use in patients, which includes the administration of the drug and how it may be acquired by medical professionals as well as its safety, tolerability, and properties. Finally, we speculate on future uses and development of metreleptin.

  6. Salivary Defense Proteins: Their Network and Role in Innate and Acquired Oral Immunity

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    Gábor Fábián

    2012-04-01

    Full Text Available There are numerous defense proteins present in the saliva. Although some of these molecules are present in rather low concentrations, their effects are additive and/or synergistic, resulting in an efficient molecular defense network of the oral cavity. Moreover, local concentrations of these proteins near the mucosal surfaces (mucosal transudate, periodontal sulcus (gingival crevicular fluid and oral wounds and ulcers (transudate may be much greater, and in many cases reinforced by immune and/or inflammatory reactions of the oral mucosa. Some defense proteins, like salivary immunoglobulins and salivary chaperokine HSP70/HSPAs (70 kDa heat shock proteins, are involved in both innate and acquired immunity. Cationic peptides and other defense proteins like lysozyme, bactericidal/permeability increasing protein (BPI, BPI-like proteins, PLUNC (palate lung and nasal epithelial clone proteins, salivary amylase, cystatins, prolin-rich proteins, mucins, peroxidases, statherin and others are primarily responsible for innate immunity. In this paper, this complex system and function of the salivary defense proteins will be reviewed.

  7. Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.

    Science.gov (United States)

    Baker, Gregory J; Chockley, Peter; Yadav, Viveka Nand; Doherty, Robert; Ritt, Michael; Sivaramakrishnan, Sivaraj; Castro, Maria G; Lowenstein, Pedro R

    2014-09-15

    Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1-deficient glioma cells could be eradicated by host NK cells before the initiation of an antitumor T-cell response. In vitro experiments demonstrated that galectin-1-deficient GL26-Cit glioma cells are ∼3-fold more sensitive to NK-mediated tumor lysis than galectin-1-expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells. Cancer Res; 74(18); 5079-90. ©2014 AACR. ©2014 American Association for Cancer Research.

  8. 某艾滋病治疗示范区人免疫缺陷病毒感染者合并隐匿性乙型肝炎病毒感染的调查分析%A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients in acquired immune deficiency syndrome area

    Institute of Scientific and Technical Information of China (English)

    梁红霞; 陈媛媛; 周荣; 张倩; 潘延凤; 谷军生; 李娟; 江河清; 余祖江

    2010-01-01

    Objective To assess the prevalence of occult HBV infection in HIV-infected patients inacquired immune deficiency syndrome area. Methods Serum samples were obtained from 97 HIV-infected patients who transmitted by paid blood donation. ELISA was used to detect HBV erologic markers (HBsAg, Anti-HBs, HBeAg, anti-HBe and anti-HBc) and HCV antibody. Flow Cytometry were used to detect CD4 +T cell count. Nested PCR was used to amplify surface protein region of HBV DNA. Results Ninety two patients were HBsAg negative in the 97 HIV-infected patients(94. 85% ). Twenty seven patients were co-infected with occult hepatitis B virus infection in the 92 HBsAg negative patients (29. 35% ).Seventy three patients were co-infected with HCV in the 92 HBsAg negative patients(79.35% ). CD4 cell count of subjects with occult HBV infection were significantly lower (212. 11 ± 133. 1 cells/mm3 versus 318.9 ± 172.2 cells/mm3, respectively, P <0. 01 ). A significantly higher prevalence of isolated anti-HBc was observed in HIV-infected subjects co-infectionded with occult HBV infection [62. 96% ( 13 of 27 )versus 18.46% (15 of 65 ) , P < 0. 01]. No statistical significant association could be established between the age, sex and whether co-infected with HCV. Conclusion It is found that occult HBV infection did occurs in HIV-infected patients. Individuals co-infected with HIV and occult HBV infection are more likely to have isolated anti-HBc than subjects with HIV alone. Co-infection with HIV and occult HBV is more%目的 调查分析某艾滋病治疗示范区人免疫缺陷病毒(HIV)-1感染者中隐匿性乙型肝炎病毒(HBV)感染的情况及其影响因素.方法 采集某艾滋病治疗示范区97例经血感染HIV-1的感染者的血浆,采用酶联免疫吸附试验(ELISA)检测乙型肝炎表面抗原与抗体(HBsAg与抗HBs)、乙型肝炎e抗原与抗体(HBeAg与抗Hbe)、乙型肝炎核心抗体(抗HBc)及丙型肝炎抗体(抗HCV);采用吸附柱法抽提HBV DNA;采用巢

  9. Ecoimmunity in Darwin's finches: invasive parasites trigger acquired immunity in the medium ground finch (Geospiza fortis.

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    Sarah K Huber

    Full Text Available BACKGROUND: Invasive parasites are a major threat to island populations of animals. Darwin's finches of the Galápagos Islands are under attack by introduced pox virus (Poxvirus avium and nest flies (Philornis downsi. We developed assays for parasite-specific antibody responses in Darwin's finches (Geospiza fortis, to test for relationships between adaptive immune responses to novel parasites and spatial-temporal variation in the occurrence of parasite pressure among G. fortis populations. METHODOLOGY/PRINCIPAL FINDINGS: We developed enzyme-linked immunosorbent assays (ELISAs for the presence of antibodies in the serum of Darwin's finches specific to pox virus or Philornis proteins. We compared antibody levels between bird populations with and without evidence of pox infection (visible lesions, and among birds sampled before nesting (prior to nest-fly exposure versus during nesting (with fly exposure. Birds from the Pox-positive population had higher levels of pox-binding antibodies. Philornis-binding antibody levels were higher in birds sampled during nesting. Female birds, which occupy the nest, had higher Philornis-binding antibody levels than males. The study was limited by an inability to confirm pox exposure independent of obvious lesions. However, the lasting effects of pox infection (e.g., scarring and lost digits were expected to be reliable indicators of prior pox infection. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration, to our knowledge, of parasite-specific antibody responses to multiple classes of parasites in a wild population of birds. Darwin's finches initiated acquired immune responses to novel parasites. Our study has vital implications for invasion biology and ecological immunology. The adaptive immune response of Darwin's finches may help combat the negative effects of parasitism. Alternatively, the physiological cost of mounting such a response could outweigh any benefits, accelerating population decline. Tests

  10. Ecoimmunity in Darwin's finches: invasive parasites trigger acquired immunity in the medium ground finch (Geospiza fortis).

    Science.gov (United States)

    Huber, Sarah K; Owen, Jeb P; Koop, Jennifer A H; King, Marisa O; Grant, Peter R; Grant, B Rosemary; Clayton, Dale H

    2010-01-06

    Invasive parasites are a major threat to island populations of animals. Darwin's finches of the Galápagos Islands are under attack by introduced pox virus (Poxvirus avium) and nest flies (Philornis downsi). We developed assays for parasite-specific antibody responses in Darwin's finches (Geospiza fortis), to test for relationships between adaptive immune responses to novel parasites and spatial-temporal variation in the occurrence of parasite pressure among G. fortis populations. We developed enzyme-linked immunosorbent assays (ELISAs) for the presence of antibodies in the serum of Darwin's finches specific to pox virus or Philornis proteins. We compared antibody levels between bird populations with and without evidence of pox infection (visible lesions), and among birds sampled before nesting (prior to nest-fly exposure) versus during nesting (with fly exposure). Birds from the Pox-positive population had higher levels of pox-binding antibodies. Philornis-binding antibody levels were higher in birds sampled during nesting. Female birds, which occupy the nest, had higher Philornis-binding antibody levels than males. The study was limited by an inability to confirm pox exposure independent of obvious lesions. However, the lasting effects of pox infection (e.g., scarring and lost digits) were expected to be reliable indicators of prior pox infection. This is the first demonstration, to our knowledge, of parasite-specific antibody responses to multiple classes of parasites in a wild population of birds. Darwin's finches initiated acquired immune responses to novel parasites. Our study has vital implications for invasion biology and ecological immunology. The adaptive immune response of Darwin's finches may help combat the negative effects of parasitism. Alternatively, the physiological cost of mounting such a response could outweigh any benefits, accelerating population decline. Tests of the fitness implications of parasite-specific immune responses in Darwin

  11. Sepsis as a cause of acquired Protein C and Protein S deficiency- A case report and literature review

    Directory of Open Access Journals (Sweden)

    Arun Kannan

    2014-03-01

    Full Text Available Warfarin Induced Skin Necrosis is a well-known complication in patients being started on warfarin without adequate bridging . The mechanism is thought to be due to protein C deficiency . We present a rather unusual cause of protein C deficiency due to sepsis resulting in warfarin induced skin necrosis. 43 year old lady who has been on chronic warfarin therapy secondary to anti phospholipid syndrome was admitted to the hospital for acute ischemic cerebellar stroke. Warfarin was held due to acute thrombocytopenia. She was discharged after restarting the warfarin. She presented back with septic shock due to pneumonia. She was found to have multiple necrotic areas consistent with skin necrosis. Unfortunately, patient died due to multi organ failure despite goal directed therapy. This case demonstrates the importance of recognizing the sepsis as an acquired cause of protein C deficiency.

  12. DOCK8 Immune Deficiency as a Model for Primary Cytoskeletal Dysfunction

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    Sean A. McGhee

    2010-01-01

    Full Text Available DOCK8 deficiency is a newly described primary immune deficiency resulting in profound susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia, but lacking in the skeletal manifestations commonly seen in hyper IgE syndrome, which it otherwise resembles. Although little is known about the DOCK8 protein, it resembles other atypical guanine exchange factors in the DOCK family, and is known to bind to CDC42. This suggests that a likely role for DOCK8 is in modulating signals that trigger cytoskeletal reorganization. As a result, DOCK8 may also be related to other immune deficiencies that involve the cytoskeleton and Rho GTPase signaling pathways, such as Wiskott-Aldrich syndrome and Rac2 deficiency.

  13. Herd immunity acquired indirectly from interactions between the ecology of infectious diseases, demography and economics.

    Science.gov (United States)

    Bonds, Matthew H; Rohani, Pejman

    2010-03-01

    Patterns of morbidity and mortality around the globe are determined by interactions between infectious diseases and systematic human socioeconomic processes. The most obvious of these patterns is that the greatest burdens of infectious diseases are found among the poor, who lack the basic resources for disease prevention and treatment. Yet, it is becoming increasingly clear that many infectious diseases are themselves causes of poverty owing to their effects on labour productivity. A particularly subtle phenomenon that receives little attention in the epidemiology literature and is especially important for poor communities is the role of the birth rate as an important direct cause of high disease burdens. Because of their high rates of transmission and life-long immunity, the persistence of many child diseases such as measles relies on high rates of reproduction as their source of susceptible individuals. Thus, there are significant direct health benefits of lower fertility rates, which are further enhanced by interactions with economic processes. Indeed, fertility, poverty and disease all interact with each other in important and predictable ways that can be built into traditional disease ecology models. We present such a model here that provides insights into the long-term effect of policy interventions. For example, because of indirect income effects, herd immunity may be acquired with lower vaccine coverage than previously thought. Reductions in the disease burden can also occur through lower fertility. Our model thus provides a disease ecology framework that is useful for the analysis of demographic transitions.

  14. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

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    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

    1987-11-01

    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

  15. Induction of protective CTL immunity against peptide transporter TAP-deficient tumors through dendritic cell vaccination.

    Science.gov (United States)

    Chambers, Benedict; Grufman, Per; Fredriksson, Vanoohi; Andersson, Kenth; Roseboom, Marjet; Laban, Sandra; Camps, Marcel; Wolpert, Elisabeth Z; Wiertz, Emmanuel J H J; Offringa, Rienk; Ljunggren, Hans-Gustaf; van Hall, Thorbald

    2007-09-15

    A large proportion of human cancers show deficiencies in the MHC class I antigen-processing machinery. Such defects render tumors resistant to immune eradication by tumoricidal CTLs. We recently identified a unique population of CTL that selectively targets tumor immune-escape variants through recognition of MHC-presented peptides, termed TEIPP (T cell epitopes associated with impaired peptide processing), expressed on cells lacking functional TAP-peptide transporters. Previously, we showed that vaccination with TEIPP peptides mediates protection against TAP-deficient tumors. Here, we further explored the concept of TEIPP-targeted therapy using a dendritic cell (DC)-based cellular vaccine. Impairment of TAP function in DC induced the presentation of endogenous TEIPP antigens by MHC class I molecules, and immunization with these DCs protected mice against the outgrowth of TAP-deficient lymphomas and fibrosarcomas. Immune analysis of vaccinated mice revealed strong TEIPP-specific CTL responses, and a crucial role for CD8(+) cells in tumor resistance. Finally, we show that TEIPP antigens could be successfully induced in wild-type DC by introducing the viral TAP inhibitor UL49.5. Our results imply that immune intervention strategies with TAP-inhibited DC could be developed for the treatment of antigen processing-deficient cancers in humans.

  16. Combined immune deficiency in a patient with a novel NFKB2 mutation.

    Science.gov (United States)

    Lindsley, Andrew W; Qian, Yaping; Valencia, C Alexander; Shah, Kara; Zhang, Kejian; Assa'ad, Amal

    2014-11-01

    NFKB2 encodes the p100/p52 protein, a critical mediator of the canonical and noncanonical NFkB signaling pathways. Here we report the comprehensive immune evaluation of a child with a novel NFKB2 mutation and provide evidence that aberrant NFKB2 signaling not only causes humoral immune deficiency, but also interferes with the TCR-mediated proliferation of T cells. These observations expand the known phenotype associated with NFKB2 mutations.

  17. Parental vitamin deficiency affects the embryonic gene expression of immune-, lipid transport- and apolipoprotein genes

    Science.gov (United States)

    Skjærven, Kaja H.; Jakt, Lars Martin; Dahl, John Arne; Espe, Marit; Aanes, Håvard; Hamre, Kristin; Fernandes, Jorge M. O.

    2016-10-01

    World Health Organization is concerned for parental vitamin deficiency and its effect on offspring health. This study examines the effect of a marginally dietary-induced parental one carbon (1-C) micronutrient deficiency on embryonic gene expression using zebrafish. Metabolic profiling revealed a reduced 1-C cycle efficiency in F0 generation. Parental deficiency reduced the fecundity and a total of 364 genes were differentially expressed in the F1 embryos. The upregulated genes (53%) in the deficient group were enriched in biological processes such as immune response and blood coagulation. Several genes encoding enzymes essential for the 1-C cycle and for lipid transport (especially apolipoproteins) were aberrantly expressed. We show that a parental diet deficient in micronutrients disturbs the expression in descendant embryos of genes associated with overall health, and result in inherited aberrations in the 1-C cycle and lipid metabolism. This emphasises the importance of parental micronutrient status for the health of the offspring.

  18. Impact of iron deficiency anemia on the function of the immune system in children

    Science.gov (United States)

    Hassan, Tamer Hasan; Badr, Mohamed Ahmed; Karam, Nehad Ahmed; Zkaria, Marwa; El Saadany, Hosam Fathy; Abdel Rahman, Doaa Mohamed; Shahbah, Doaa Abdallah; Al Morshedy, Salah Mohamed; Fathy, Manar; Esh, Asmaa Mohamed Hosni; Selim, Amal Mohamed

    2016-01-01

    Abstract The importance of iron deficiency as a public health problem is based ultimately on the seriousness of its consequences on health. The most extensively investigated consequences of iron deficiency involve work performance and immune function. The significance of the effects on work performance is generally accepted. In contrast, data on the influence of iron deficiency on immune function are often perceived as being confusing and contradictory. We aimed to evaluate the effect of iron deficiency anemia on humoral, cellular, nonspecific immunity, and also the effect on the cytokines that are the key factors of many immunologic steps. Forty children with iron deficiency anemia and 20 age and sex-matched healthy children were included. All children were subjected to full medical history, thorough clinical examination, complete blood count, iron indices (serum iron, serum total iron-binding capacity, serum ferritin, and transferrin saturation), immunoglobulin assay (IgA, IgG, and IgM), interleukin (IL)-6 serum level, study of T-lymphocyte subsets, and evaluation of phagocytic function of macrophages and oxidative burst activity of neutrophils. Patients had significantly lower IgG levels, IL-6, phagocytic activity, and oxidative burst of neutrophils than controls, although there was no significant difference between patients and controls with regard to other immunoglobulins and CD4/CD8 ratio. There was significantly positive correlation between serum iron and IL-6 serum level. We concluded that humoral, nonspecific immunity (phagocytic activity and oxidative burst), and the IL-6 are influenced in patients with iron deficiency anemia. Study of these abnormalities after correction of iron deficiency is strongly needed. PMID:27893677

  19. Impact of iron deficiency anemia on the function of the immune system in children.

    Science.gov (United States)

    Hassan, Tamer Hasan; Badr, Mohamed Ahmed; Karam, Nehad Ahmed; Zkaria, Marwa; El Saadany, Hosam Fathy; Abdel Rahman, Doaa Mohamed; Shahbah, Doaa Abdallah; Al Morshedy, Salah Mohamed; Fathy, Manar; Esh, Asmaa Mohamed Hosni; Selim, Amal Mohamed

    2016-11-01

    The importance of iron deficiency as a public health problem is based ultimately on the seriousness of its consequences on health. The most extensively investigated consequences of iron deficiency involve work performance and immune function. The significance of the effects on work performance is generally accepted. In contrast, data on the influence of iron deficiency on immune function are often perceived as being confusing and contradictory.We aimed to evaluate the effect of iron deficiency anemia on humoral, cellular, nonspecific immunity, and also the effect on the cytokines that are the key factors of many immunologic steps.Forty children with iron deficiency anemia and 20 age and sex-matched healthy children were included. All children were subjected to full medical history, thorough clinical examination, complete blood count, iron indices (serum iron, serum total iron-binding capacity, serum ferritin, and transferrin saturation), immunoglobulin assay (IgA, IgG, and IgM), interleukin (IL)-6 serum level, study of T-lymphocyte subsets, and evaluation of phagocytic function of macrophages and oxidative burst activity of neutrophils.Patients had significantly lower IgG levels, IL-6, phagocytic activity, and oxidative burst of neutrophils than controls, although there was no significant difference between patients and controls with regard to other immunoglobulins and CD4/CD8 ratio. There was significantly positive correlation between serum iron and IL-6 serum level.We concluded that humoral, nonspecific immunity (phagocytic activity and oxidative burst), and the IL-6 are influenced in patients with iron deficiency anemia. Study of these abnormalities after correction of iron deficiency is strongly needed.

  20. Related progress of CT-guided percutaneous biopsy in the thoracic complications of acquired immune deficiency syndrome and occupational exposure prevention%CT引导下经皮穿刺活检术在获得性免疫缺陷综合征胸部并发症中的应用及职业暴露防护相关进展

    Institute of Scientific and Technical Information of China (English)

    王青

    2011-01-01

    CT-guided percutaneous biopsy in the thoracic complications of acquired immunodeficiency syndrome (AIDS)is the main clear diagnosis method.The application of technical solutions, complications and prevention, occupational exposure protection principles and methods of CT-guided percutaneous biopsy in thoracic complications of AIDS were reviewed in this article.%CT引导下经皮穿刺活检术是确诊获得性免疫缺陷综合征(AIDS)胸部并发症的主要方法.本文对CT引导下经皮穿刺活检术在AIDS胸部并发症中应用的技术方案、并发症及预防,职业暴露防护原则及方法进行综述.

  1. 38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

    Science.gov (United States)

    2010-07-01

    ... appropriate system. 6302Leprosy (Hansen's Disease): As active disease 100 Note: A 100 percent evaluation shall...-infectious diseases, immune disorders and nutritional deficiencies. 4.88b Section 4.88b Pensions, Bonuses... Ratings Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.88b Schedule of ratings...

  2. Infection-derived lipids elicit a novel immune deficiency circuitry in arthropods

    Science.gov (United States)

    The insect Immune Deficiency (IMD) pathway resembles the tumor necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties elicit the IMD signaling cascade remains unknown. Here, we disclose thoug...

  3. Studies on the prevention and control of human immune deficiency virus associated tuberculosis

    NARCIS (Netherlands)

    Chakezha, T.

    2014-01-01

    The overall question the thesis intended to answer was how to optimise interventions for the prevention and control of human immune deficiency virus (HIV) -associated tuberculosis (TB) in high TB and HIV burden settings such as South Africa. In these settings the incidence of and mortality from TB

  4. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

    Directory of Open Access Journals (Sweden)

    Adriana Secatto

    Full Text Available 5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/- mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO(-/- mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

  5. HepG2 cells acquire stem cell-like characteristics after immune cell stimulation.

    Science.gov (United States)

    Wang, Hang; Yang, Miqing; Lin, Ling; Ren, Hongzhen; Lin, Chaotong; Lin, Suling; Shen, Guoying; Ji, Binfeng; Meng, Chun

    2016-02-01

    The presence of cancer stem cells (CSCs) is currently regarded as one of the main culprits of tumor formation and therapy failure. It is known that chronic inflammation is associated with CSCs, but it is not clear yet how inflammation affects the development of CSCs. In the present study we aimed to examine the relationship between cancer cell stimulation mediated by immune cells and the acquisition of a CSC-like phenotype. Cancer cells derived from single hepatocarcinoma HepG2 cells were treated with mouse splenic B cells (MSBCs) and mouse peritoneal macrophage cells (MPMCs), respectively. The stem cell-like characteristics of the resulting HepG2 cells (MSBC-HepG2 and MPMC-HepG2) were evaluated using different assays, including biomarker assays, in vitro tumoroid and colony forming assays, in vivo tumor forming assays and signal transduction pathway activation assays. Various stemness characteristics of HepG2 cells, including self-renewal, proliferation, chemoresistance and tumorigenicity were evaluated. The expression levels of stemness-related genes and its encoded proteins in the MSBC-HepG2 and MPMC-HepG2 cells were assessed using RT-PCR and FACS analyses. We found that MSBC-HepG2 and MPMC-HepG2 cells possess hepatic CSC properties, including persistent self-renewal, extensive proliferation, drug resistance, high tumorigenic capacity and over-expression of CSC-related genes and proteins (i.e., EpCAM, ALDH, CD133 and CD44), compared to the parental cells. We also found that 1x10(3) MSBC-HepG2 and MPMC-HepG2 cells were able to form tumors in NOD/SCID mice and that the Notch and SHH signaling pathways were highly activated in MSBC-HepG2 cells. We conclude that the immune system may have a double-edge effect on cancer development. On one hand, immune cells such as B lymphocytes and macrophages may recognize, attack and eliminate cancer cells, whereas on the other hand, they may promote a subset of cancer cells to acquire stem cell-like characteristics.

  6. To Analyze the Training Effect on Clinical Nursing Practice of Acquired Immune Deifciency Syndrome for Nursing Staff%分析护理人员艾滋病临床护理实践的培训效果

    Institute of Scientific and Technical Information of China (English)

    黄翠英

    2015-01-01

    目的:分析护理人员艾滋病临床护理实践的培训效果。方法选择我院执业护士80名,对所有护理人员均给予艾滋病临床护理实践培训,比较培训前后的艾滋病相关知识掌握情况。结果培训后护理人员的艾滋病综合知识得分优于培训前,两者比较,P<0.05,差异具有统计学意义。结论通过艾滋病临床护理实践培训,可以让护理人员更好掌握艾滋病的相关知识。%Objective Analysis analyze the training effect on clinical nursing practice of acquired immune deifciency syndrome for nursing staff. Methods Selected 80 cases nurse practitioner in our hospital, all of them were given acquired immune deficiency syndrome training for clinical nursing practice, compared the grasp knowledge situation before and after nursing practice. Results After training nursing staff's comprehensive acquired immune deficiency syndrome knowledge score was better than before the training, P<0.05, had difference statistical significance. Conclusion Nursing staff can grasp acquired immune deifciency syndrome relevant knowledge better with clinical nursing practice of acquired immune deifciency syndrome.

  7. Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity.

    Science.gov (United States)

    Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B; King, Janet; Fung, Ellen B

    2016-10-01

    Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency.

  8. Care for eyes of patients with acquired immune deficiency syndrome complicated with cryptococcal meningitis%获得性免疫缺陷综合征合并隐球菌性脑膜炎患者的眼部护理

    Institute of Scientific and Technical Information of China (English)

    许雪静; 柳月红; 刘彬彬; 董愉

    2016-01-01

    Objective To summarize the complications and nursing methods for eyes of the patients with acquired immunodeficiency syndrome (AIDS)and Cryptococcal meningitis. Methods Total of 42 AIDS patients complicated with Cryptococcal meningitis infection in eyes were analyzed, while the nursing plans were summarized. Results There were 19 cases (37 eyes) with papilledemas; 6 cases (12 eyes) with optic atrophy; 2 cases (4 eyes) with multifocal choroiditis; 3 cases (6 eyes) with diplopias; one eye of a patient with cytomegalovirus retinitis (CMVR). Eleven cases were with normal fundus. Among the 84 eyes, the visual acuity of 17 eyes were light perception to 0.1; 12 eyes were 0.12-0.3. The cases with the visual acuities less than 0.3 were 34.52%. The visual acuities of 55 eyes with the 0.4 to 1.0. Conclusions In clinical nursing, it is beneficial for the patients to manage the condition and improve the quality of life, by observing the change of intracranial pressure, visual acuity and fundus closely, and the exercises of life skills and vision trainings for patients with low visions were improved.%目的:总结获得性免疫缺陷综合征(AIDS)合并隐球菌性脑膜炎患者的眼部并发症及眼部护理方法。方法回顾性分析42例AIDS合并隐球菌性脑膜炎患者的眼部并发症,总结其护理方案。结果19例患者(37只眼)出现视乳头水肿,6例患者(12只眼)出现视神经萎缩,2例患者(4只眼)出现脉络膜病灶,3例患者(6只眼)出现复视,1例患者单眼合并巨细胞病毒性视网膜炎(CMVR)。11例患者眼底正常。42例患者(84只眼)中17只眼视力为光感~0.1,12只眼视力为0.12~0.3,视力≤0.3的患眼占总数的34.5%,55只眼视力为0.4~1.0。结论临床护理工作中应密切观察患者的颅内压、视力及眼底变化,对低视力患者加强生活技能及视力的训练,有利于控制病情,提高患者的生活质量。

  9. The Role of Nuclear Medicine in the Staging and Management of Human Immune Deficiency Virus Infection and Associated Diseases

    NARCIS (Netherlands)

    Ankrah, Alfred O; Glaudemans, Andor W J M; Klein, Hans C; Dierckx, Rudi A J O; Sathekge, Mike

    2017-01-01

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, r

  10. Passive transfer of naturally acquired specific immunity against West Nile Virus to foals in a semi-feral pony herd.

    Science.gov (United States)

    Wilkins, Pamela A; Glaser, Amy L; McDonnell, Sue M

    2006-01-01

    Horses naturally exposed to West Nile Virus (WNV) or vaccinated against WNV develop humoral immunity thought to be protective against development of clinical disease in exposed or infected animals. No reports evaluate the efficacy of passive transfer of naturally acquired specific WNV humoral immunity from dam to foal. The purpose of this study was to investigate passive transfer of naturally acquired immunity to WNV to foals born in a herd of semi-feral ponies, not vaccinated against WNV, in an endemic area, with many dams having seroconverted because of natural exposure. Microwell serum neutralization titers against WNV were determined in all mares and foals. Serum IgG concentration was determined in foals by serial radial immunodiffusion. Differences in IgG concentration between seropositive and seronegative foals were examined by means of the Mann-Whitney U-test. Linear regression was used to evaluate the association between mare and foal titers. Seventeen mare-foal pairs were studied; 1 foal had inadequate IgG concentration. IgG concentration was not different between seronegative and seropositive foals (P = .24). Mare and foal titers were significantly correlated in foals with adequate passive transfer of immunity (Spearman's rho = .84; P 90% of the foal's titer was explained by the mare's titer (R2 = 0.91; P immunity to WNV is present in pony foals with adequate passive transfer of immunity born to seroconverted mares.

  11. Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients

    Directory of Open Access Journals (Sweden)

    Raquel Ruiz-García

    2017-07-01

    Full Text Available GATA binding protein 2 (GATA2 deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 gene. Clinical manifestations range from neutropenia, lymphedema, deafness, to severe viral and mycobacterial infections, bone marrow failure, and acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell, B- and natural killer (NK-cell deficiency. We studied the T-cell and NK-cell compartments of four GATA2-deficient patients to assess if changes in these lymphocyte populations could be correlated with clinical phenotype. Patients with more severe clinical complications demonstrated a senescent T-cell phenotype whereas patients with lower clinical score had undetectable changes relative to controls. In contrast, patients’ NK-cells demonstrated an immature/activated phenotype that did not correlate with clinical score, suggesting an intrinsic NK-cell defect. These studies will help us to determine the contribution of T- and NK-cell dysregulation to the clinical phenotype of GATA2 patients, and may help to establish the most accurate therapeutic options for these patients. Asymptomatic patients may be taken into consideration for hematopoietic stem cell transplantation when dysregulation of T-cell and NK-cell compartment is present.

  12. [Clinical characteristics of highly active antiretroviral therapy-associated immune reconstruction inflammation in acquired immunodeficiency syndrome].

    Science.gov (United States)

    Liu, Meng; Zheng, Yu-Huang; Zhou, Guo-Qiang; Zhou, Hua-Ying; Chen, Zi; He, Yan; Chen, Xia; Zheng, Li-Wen; Jia, Lu; He, Mei

    2011-02-01

    To summarize the morbidity, mortality, clinical manifestations and risk factors for IRIS (immune reconstruction inflammatory syndrome) during HAART (highly active antiretroviral therapy) in China. From October 2007 to September 2009, a prospective cohort of 238 AIDS (acquired immunodeficiency syndrome) patients on HAART from Hunan and Jianxi provinces was recruited for a follow-up of 24 weeks. And 47 and 191 patients were assigned into the IRIS and non-IRIS groups respectively. The data of general information, clinical manifestations and treatment of two groups were collected and compared. Blood samples were collected in both groups at pre-and post-HAART 12 weeks, 24 weeks for HIV viral load and CD4(+) cell count examinations. A statistical analysis was performed. A total of 47 (19.7%) IRIS cases was analyzed. The median onset of IRIS was 28 (9 - 36) days. And 29 (61.7%) cases of tuberculosis IRIS were found. There was no significant difference in age, gender, route of transmission and antiretroviral regimens between the IRIS and non-IRIS groups. At baseline, Weeks 12 and 24, both groups showed a significant decline of viral load. And there was no significant difference between them. Both groups showed a significant increase of CD4(+) cell count. But there was no significant difference between two groups. However, the baseline CD4(+) cell count was markedly lower in the IRIS group than that in the non-IRIS group. In 85.1% (40/47) of cases, the CD4(+) cell count was HIV RNA viral load decreases in both IRIS and non-IRIS groups without any significant difference. The patients with a CD4(+) cell count < 100/µl are more vulnerable to develop IRIS.

  13. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet.

    Science.gov (United States)

    Mabuchi, Yuko; Frankel, Theresa L

    2016-03-01

    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons.

  14. Acquired hookworm immunity in the golden hamster (Mesocricetus auratus) elicited by living Necator americanus third-stage infective larvae.

    Science.gov (United States)

    Xue, Jian; Zhan, Bin; Guo, Jian; He, Na; Qiang, Hui-qing; Hotez, Peter; Xiao, Shu-hua

    2012-01-01

    The aim of the study is to demonstrate and understand the acquired immunity in golden hamsters (Mesocricetus auratus) elicited by primary Necator americanus infective third-stage larvae (L3) infection. Hamsters infected with 150 L3 for 1, 2, 3, 6 and 10 weeks, were challenged with the same number of L3 and sacrificed 25 days post challenge. The primarily infected hamsters exhibited 99-100% protection against subsequent L3 challenge compared to un-infected naive hamsters. The acquired immunity was developed as early as 1 week post L3 infection and lasted up to 10 weeks. Similar protective immunity was obtained in hamsters infected with N. americanus L3 and then treated orally with a single of 100mg/kg albendazole, followed by challenge with N. americanus L3 4 and 8 weeks post-treatment. The infected hamsters exhibited a rise in IgG antibodies against L3 and juvenile adult worm antigens. Histological examination showed that challenging L3 were trapped in the skin of primarily infected hamsters and surrounded or infiltrated by different inflammatory cells. The trapped L3 were damaged and dead followed by the formation of granulomas encasing dead worms. The results demonstrate that hamsters primarily infected with N. americanus L3 develop acquired immunity against re-infection.

  15. Constitutive and Acquired Serotonin Deficiency Alters Memory and Hippocampal Synaptic Plasticity.

    Science.gov (United States)

    Fernandez, Sebastian P; Muzerelle, Aude; Scotto-Lomassese, Sophie; Barik, Jacques; Gruart, Agnès; Delgado-García, José M; Gaspar, Patricia

    2017-01-01

    Serotonin (5-HT) deficiency occurs in a number of brain disorders that affect cognitive function. However, a direct causal relationship between 5-HT hypo-transmission and memory and underlying mechanisms has not been established. We used mice with a constitutive depletion of 5-HT brain levels (Pet1KO mice) to analyze the contribution of 5-HT to different forms of learning and memory. Pet1KO mice exhibited a striking deficit in novel object recognition memory, a hippocampal-dependent task. No alterations were found in tasks for social recognition, procedural learning, or fear memory. Viral delivery of designer receptors exclusively activated by designer drugs was used to selectively silence the activity of 5-HT neurons in the raphe. Inhibition of 5-HT neurons in the median raphe, but not the dorsal raphe, was sufficient to impair object recognition in adult mice. In vivo electrophysiology in behaving mice showed that long-term potentiation in the hippocampus of 5-HT-deficient mice was altered, and administration of the 5-HT1A agonist 8-OHDPAT rescued the memory deficits. Our data suggest that hyposerotonergia selectively affects declarative hippocampal-dependent memory. Serotonergic projections from the median raphe are necessary to regulate object memory and hippocampal synaptic plasticity processes, through an inhibitory control mediated by 5-HT1A receptors.

  16. Immune deficiency in Ataxia-Telangiectasia: a longitudinal study of 44 patients.

    Science.gov (United States)

    Chopra, C; Davies, G; Taylor, M; Anderson, M; Bainbridge, S; Tighe, P; McDermott, E M

    2014-05-01

    Ataxia-Telangiectasia (A-T) is a genetic condition leading to neurological defects and immune deficiency. The nature of the immune deficiency is highly variable, and in some cases causes significant morbidity and mortality due to recurrent sinopulmonary infections. Although the neurological defects in A-T are progressive, the natural history of the immune deficiency in A-T has not been evaluated formally. In this study we analyse the clinical history and immunological data in 44 patients with A-T who attended the National Ataxia-Telangiectasia clinic in Nottingham between 2001 and 2011. Using patient medical records and Nottingham University Hospitals (NUH) National Health Service Trust medical IT systems, data regarding clinical history, use of immunoglobulin replacement therapy, total immunoglobulin levels, specific antibody levels and lymphocyte subset counts were obtained. T cell receptor spectratyping results in some patients were already available and, where possible, repeat blood samples were collected for analysis. This study shows that subtle quantitative changes in certain immunological parameters such as lymphocyte subset counts may occur in patients with A-T over time. However, in general, for the majority of patients the severity of immune deficiency (both clinically and in terms of immunological blood markers) does not seem to deteriorate significantly with time. This finding serves to inform the long-term management of this cohort of patients because, if recurrent respiratory tract infections present later in life, then other contributory factors (e.g. cough/swallowing difficulties, underlying lung disease) should be investigated aggressively. Our findings also offer some form of reassurance for parents of children with A-T, which is otherwise a progressively severely debilitating condition. © 2014 British Society for Immunology.

  17. Suspected primary immune deficiency in a Donge de Bordeaux dog : short communication

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2002-07-01

    Full Text Available A young Donge de Bordeaux dog was presented with chronic intermittent antibiotic responsive gastrointestinal and respiratory disease. Further evaluation showed bacterial lymphadenitis, bacterial tracheitis, normal white cell and differential cell counts, hypogammaglobulinaemia, and the absence of B-lymphocytes but the presence of T-lymphocytes in the lymphoid tissue stained with lymphocyte markers. As the dog came from a narrow genetic base, with related dogs showing similar clinical signs, possible B-cell congenital immune deficiency was suspected.

  18. Nutritional zinc deficiency, immune capacity and malaria : a study on mediators of immunity to malaria caused by Plasmodium falciparum in African children

    NARCIS (Netherlands)

    Mbugi, E.V.

    2009-01-01

    This thesis aimed at investigating the role of genetic and nutritional factors that affect the immune response to malaria in Tanzanian children. The introductory chapter (Chapter 1) reviews the importance of nutritional deficiencies, particularly of zinc, and presents the hypothesis that such defici

  19. Acquired absolute vitamin K deficiency in a patient undergoing warfarin therapy.

    Science.gov (United States)

    Takada, Hiroaki; Toru, Hifumi; Bunya, Naofumi; Kiriu, Nobuaki; Kato, Hiroshi; Koido, Yuichi; Yasuhiro, Kuroda

    2014-06-01

    We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old woman was admitted to our hospital because of dyspnea and sore throat diagnosed as pharyngitis 1 week before admission. On admission, the sore throat had exacerbated and dyspnea developed. She had history of atrial fibrillation, for which warfarin 1.5 mg/d was started approximately 10 years prior and her international normalized ratio (INR) had been maintained at an acceptable therapeutic level. Blood results revealed unmeasurable INR and abnormally prolonged activated partial thromboplastin time (APTT). She was diagnosed with adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20 mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the coagulopathy responded to intravenous VK administration, the patient was clinically diagnosed with warfarin-related relative VKD. Approximately 1 month later, she returned with complaints of sore throat. Blood results indicated abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent adenoiditis and VK deficient coagulopathy. The patient’s serum VK levels were low (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg) and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated. Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in patients undergoing warfarin therapy is primarily caused by, relative VKD. However, the possibility of warfarin-related absolute VKD should be suspected when INRis not sufficiently improved by intravenous VK administration.

  20. Vitamin D Deficiency Reduces the Immune Response, Phagocytosis Rate, and Intracellular Killing Rate of Microglial Cells

    Science.gov (United States)

    Onken, Marie Luise; Schütze, Sandra; Redlich, Sandra; Götz, Alexander; Hanisch, Uwe-Karsten; Bertsch, Thomas; Ribes, Sandra; Hanenberg, Andrea; Schneider, Simon; Bollheimer, Cornelius; Sieber, Cornel; Nau, Roland

    2014-01-01

    Meningitis and meningoencephalitis caused by Escherichia coli are associated with high rates of mortality and neurological sequelae. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. Vitamin D has potent effects on human immunity, including induction of antimicrobial peptides (AMPs) and suppression of T-cell proliferation, but its influence on microglial cells is unknown. The purpose of the present study was to determine the effects of vitamin D deficiency on the phagocytosis rate, intracellular killing, and immune response of murine microglial cultures after stimulation with the Toll-like receptor (TLR) agonists tripalmitoyl-S-glyceryl-cysteine (TLR1/2), poly(I·C) (TLR3), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9). Upon stimulation with high concentrations of TLR agonists, the release of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was decreased in vitamin D-deficient compared to that in vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1 after stimulation of microglial cells with high concentrations of TLR3, -4, and -9 agonists and intracellular killing of E. coli K1 after stimulation with high concentrations of all TLR agonists were lower in vitamin D-deficient microglial cells than in the respective control cells. Our observations suggest that vitamin D deficiency may impair the resistance of the brain against bacterial infections. PMID:24686054

  1. Pancytopenia and cutaneous cryptococcosis as an indicator disease of acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    R Khuraijam

    2015-01-01

    Full Text Available We present a case of pancytopenia and cutaneous cryptococcosis in a young girl with no complaints of fever, headache and vomiting. Fine-needle aspiration cytology and further investigation for pancytopenia revealed presence of Cryptococcus in skin and bone marrow aspirates. Fungal cultures of the skin aspirates, blood and bone marrow confirmed cryptococcal infection. Counselling and human immunodeficiency virus (HIV test revealed the status of the patient to be retropositive. Although meningitis is the commonest manifestation of cryptococcosis among HIV-infected patients, rare cutaneous manifestation with pancytopenia but with no meningeal signs indicate the HIV status in an endemic area of penicilliosis, Manipur.

  2. Gallium scans of the thorax in patients with acquired immune deficiency syndrome (AIDS): Description and utilization

    Energy Technology Data Exchange (ETDEWEB)

    Le, G.; Chen, D.C.P.; Siegel, M.E.

    1984-01-01

    The pattern of distribution of gallium uptake in the thorax was investigated in patients (pts) with AIDS. Eleven pts (ages 18-53), all active homosexual males suspected of having acute pulmonary infection were studied. Ga lung scans were performed at 24-48 and/or 72 hrs. post injection. The diagnosis of AIDS was based on appropriate clinical and laboratory findings. The Ga activity in the lung was graded from zero = background to 4+ which is > liver activity. Eight of eleven pts have positive Ga scan while seven of eleven pts had positive CXR. Six pts had both positive CXR and Ga scan. One pt had a positive Ga scan with negative CXR, and one with positive CXR and negative Ga scan. The positive Ga scans included 3 pts with 4+ diffuse uptake, two pts with 2+ diffuse uptake, two pts with 1+ diffuse uptake, and two with hilar node uptake. Three pts have focal increased uptake superimposed on diffuse uptake. Two pts with 4+ diffuse uptake had mild abnormality on their CXR. One pt with 4+ uptake in the initial scan shows decreased activity on follow-up with clinical improvement after therapy. Thus, all but two pts with positive Ga scans had diffuse lung uptake. These two patients alone had B cell immunoblastic sarcoma and oral candidiasis. The pattern of Ga lung uptake in pts with AIDS reveal that a majority of positive scans are diffuse (6/8) and the intensity may suggest more active disease than CXR (2 normal) and, thus, the study may be useful in detecting changes from atypical pulmonary infection in this population.

  3. Communication and education as vaccine against the spread of acquired immune deficiency syndrome (AIDS) in Africa.

    Science.gov (United States)

    Soola, E O

    1991-01-01

    Attention is focused on the segmentation of the audience (urban, rural, urban slum) and messages, and on how appropriate communication and educational strategies can be adopted to create awareness of AIDS among the African population. It is important to determine the scope, nature, and content of the message in addition to the delivery of these messages through proper channels. Channels of communication vary in reach and influence, and different segments of the population vary in the capacity to absorb information. Rural people are considered susceptible because of their penchant for continually using injections for treatment of any ailment; the source of concern is unsterilized needles and syringes. The semantics of AIDs is discussed to emphasize the problem of how to identify AIDs among the multiplicity of languages in individual countries. For instance, in Nigeria there may be 150-400 languages, and these languages lack systematically developed metalanguage and specialized vocabularies. The view that local language use must be one way, linear is accepted, and the difficulties surmounted. Local languages may be used to transmit information of a nontechnical nature. The literate minority should have access to detailed information on causes, modes of transmission, symptoms, treatment or management, but not everyone needs this extent of detail. The rural and urban residents should know about the incurability of the disease, the mode of transmission, its symptoms, and what should be done if someone is suspected of having an HIV infection. Already the Hausa of Nigeria have a term for AIDs, Karya-Garkuwa, which suggests a disease that breaks down the mechanism of the biological functioning of the body. Communicators must be knowledgeable and able to effectively transmit facts not myths. Of the 3 modes of transmission (sex, blood, mother to child), sexual transmission is the most important. Blood routes are through transfusions, contaminated blood products for hemophilia patients, contaminated needles and syringes of intravenous drug users, unsterilized needles and syringes used for medical treatment, knives for circumcision or body marking, razor blades in barber shops, and toothbrushes. All media should be used as well as community based informal and political channels. Traditional communication modes in rural areas are required. A multidisciplinary team of experts in modern and traditional media and instructional communication design and operation is needed.

  4. A rare radiological manifestation of disseminated tuberculous spondylitisin acquired immune deficiency syndrome patient: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Won; Koo, Joon Bum; Kim, Tae Eun [Dept. of of Radiology, Dongguk University Ilsan Hospital, Dongguk University School of Medicine, Goyang (Korea, Republic of)

    2016-04-15

    The spine is the most common site of skeletal involvement in tuberculosis. The radiologic features are reportedly characterized by destruction of the vertebral body, subligamentous extension or subchondral penetration, frequent paravertebral abscess formation and late involvement of the disk space. We experienced a case of a 25-year-old male who was a human immunodeficiency virus carrier without antiretroviral therapy. Incidental findings on abdominal computed tomography included multiple well-demarcated and ovoid osteolytic lesions with hyperdense rims disseminated in the thoracic, lumbar, and sacrum vertebrae, as well as in both ilii. On the lumbar spine magnetic resonance imaging, multiple small round lesions of isointense signal intensity with peripheral hyperintense rims were found on both T1- and T2-weighted imaging. The lesions had peripheral rim enhancement on gadolinium-enhanced T1-weighted imaging. Based on our experience, this rare image finding is one of the manifestations of disseminated tuberculosis.

  5. Immune deficiency vs. immune excess in inflammatory bowel diseases-STAT3 as a rheo-STAT of intestinal homeostasis.

    Science.gov (United States)

    Leppkes, Moritz; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory "rheo-STAT".

  6. Transgenic petunia with the iron(III-phytosiderophore transporter gene acquires tolerance to iron deficiency in alkaline environments.

    Directory of Open Access Journals (Sweden)

    Yoshiko Murata

    Full Text Available Iron is an essential nutrient for all plants. However, terrestrial plants often suffer from iron deficiency in alkaline soil due to its extremely low solubility. Alkaline soil accounts for about 30% of all cultivated ground in the world. Plants have evolved two distinct strategies, I and II, for iron uptake from the soil. Dicots and non-graminaceous monocots use Strategy I, which is primarily based on the reduction of iron(III to iron(II and the uptake of iron(II by the iron-regulated transporter, IRT1. In contrast, graminaceous plants use Strategy II to efficiently acquire insoluble iron(III. Strategy II comprises the synthesis and secretion of iron-chelating phytosiderophores, such as mugineic acids and the Yellow Stripe 1 transporter proteins of the iron(III-phytosiderophore complex. Barley, which exhibits the highest tolerance to iron deficiency in alkaline soil among graminaceous plants, utilizes mugineic acids and the specific iron(III-mugineic acids transporter, HvYS1. In this study, we established the transgenic plant Petunia hybrida, which originally had only Strategy I, by introducing the HvYS1 transporter gene derived from barley. When the transgenic plants were grown hydroponically in media containing the iron(III-2'-deoxymugineic acid complex, free 2'-deoxymugineic acid and its iron(III complex were detected in the root extract of the transgenic plant by electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry. The growth of the transgenic petunia was significantly better than that of the control host in alkaline conditions. Consequently, the transgenic plant acquired a significantly enhanced tolerance to alkaline hydroponic media in the presence of the iron(III-2'-deoxymugineic acid complex. Furthermore, the flower color of the transgenic plant deepened. The results showed that iron-phytosiderophore complexes and their transporters can potentially be utilized to overcome the worldwide iron uptake problems

  7. Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection.

    Science.gov (United States)

    García-Quintanilla, Meritxell; Pulido, Marina R; Pachón, Jerónimo; McConnell, Michael J

    2014-01-01

    The increasing clinical importance of infections caused by multidrug resistant Acinetobacter baumannii warrants the development of novel approaches for prevention and treatment. In this context, vaccination of certain patient populations may contribute to reducing the morbidity and mortality caused by this pathogen. Vaccines against Gram-negative bacteria based on inactivated bacterial cells are highly immunogenic and have been shown to produce protective immunity against a number of bacterial species. However, the high endotoxin levels present in these vaccines due to the presence of lipopolysaccharide complicates their use in human vaccination. In the present study, we used a laboratory-derived strain of A. baumannii that completely lacks lipopolysaccharide due to a mutation in the lpxD gene (IB010), one of the genes involved in the first steps of lipopolysaccharide biosynthesis, for vaccination. We demonstrate that IB010 has greatly reduced endotoxin content (infection tissue bacterial loads and significantly lower serum levels of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6 compared to control mice in a mouse model of disseminated A. baumannii infection. Importantly, immunized mice were protected from infection with the ATCC 19606 strain and an A. baumannii clinical isolate. These data suggest that immunization with inactivated A. baumannii whole cells deficient in lipopolysaccharide could serve as the basis for a vaccine for the prevention of infection caused by A. baumannii.

  8. The multiplicity of Plasmodium falciparum infections is associated with acquired immunity to asexual blood stage antigens.

    NARCIS (Netherlands)

    Mayengue, P.I.; Luty, A.J.F.; Rogier, C.; Baragatti, M.; Kremsner, P.G.; Ntoumi, F.

    2009-01-01

    We evaluated the relationship between immune response markers and the multiplicity of Plasmodium falciparum infections in order to assess the validity of the latter as an indicator of the acquisition of anti-malarial immunity. Parasite populations present during malaria episodes of 64 Gabonese child

  9. Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in EGFR-Mutant and ALK-Positive Lung Cancers

    Science.gov (United States)

    2015-08-01

    AWARD NUMBER: W81XWH-13-1-0227 TITLE: Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in...TYPE Annual 3. DATES COVERED 1 Aug 2014 - 31 Jul 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Deficient BIM Expression as a Mechanism of Intrinsic...time of resistance. We are now using these patient-derived cell lines to assess BIM levels and apoptotic response to next-generation inhibitors. The

  10. Acquired Form of Angioedema of the Head and Neck Related to a Deficiency in C1-Inhibitor: A Case Report with a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Bassel Hallak

    2012-01-01

    Full Text Available Angioedema related to a deficiency in the C1-inhibitor protein is characterized by its lack of response to therapies including antihistamine, steroids, and epinephrine. In the case of laryngeal edema, mortality rate is approximately 30 percent. The first case of the acquired form of angioedema related to a deficiency in C1-inhibitor was published in 1972. In our paper, we present a case of an acquired form of angioedema of the oropharyngeal region secondary to the simultaneous occurrence of two causative factors: neutralization of C1-inhibitor by an autoantibody and the use of an angiotensin convertin enzyme inhibitor.

  11. Selenium Deficiency Attenuates Chicken Duodenal Mucosal Immunity via Activation of the NF-κb Signaling Pathway.

    Science.gov (United States)

    Liu, Zhe; Qu, Yanpeng; Wang, Jianfa; Wu, Rui

    2016-08-01

    Selenium (Se) deficiency can cause intestinal mucosal inflammation, which is related to activation of nuclear transcription factor kappa-B (NF-κB) signaling pathway. However, the mechanism of inflammatory response in chicken duodenal mucosa caused by Se deficiency and its relationship with the NF-κB signaling pathway remain elusive. In this study, we firstly obtained Se-deficient chickens bred with 0.01 mg/kg Se and the normal chickens bred with 0.4 mg/kg Se for 35 days. Then, NF-κB signaling pathway, secretory immunoglobulin A (SIgA), inflammatory cytokines, oxidized glutathione, glutathione peroxidase, and glutathione activities were determined. The results showed that Se deficiency obviously enhanced p50, p65, and p65 DNA-binding activities. The phosphorylation of IκB-α and phosphorylation of kappa-B kinase subunit alpha (IKKα) and IKKα were elevated, but IκB-α was decreased (P mucosal immunity via activation of NF-κB signaling pathway regulated by redox activity, which suggested that Se is a crucial host factor involved in regulating inflammation.

  12. The immune response in SAPHO syndrome: deficiency, hyper- responsiveness, or both?

    Science.gov (United States)

    Hayem, Gilles; Hurtado-Nedelec, Margarita; Chollet-Martin, Sylvie

    2013-01-01

    The pathophysiology of SAPHO syndrome still remains to be determined. However, like in other forms of spondylarthritides, this rare condition seems to result from the combination of genetic, environmental and immunological factors. Surely, SAPHO syndrome cannot be simply regarded as the adult form of the 'caricatural' DIRA (deficiency in interleukin-1 receptor antagonist) syndrome, although this purely genetic disease also causes multiple osteomyelitis and pustular rashes. An initial bacterial trigger, mainly represented by the cutaneous saprophyte Propionibacterium acnes, could take advantage of a selective deficiency of the innate immunity, implicating neutrophils. This could elicit thereafter a 'hyperimmune' reaction, as in other chronic inflammatory conditions like reactive arthritis, Crohn's disease or hidradenitis suppurativa. The reported efficacy of either longterm antibiotic regimens (especially with azithromycin) or immunomodulatory biologic agents targetting TNF-α or IL-1 supports the concept of a post- or para-infectious hyperresponsiveness disorder, with a convincing rationale for 'hybrid' therapies.

  13. Recent advances in transplantation for primary immune deficiency diseases: a comprehensive review.

    Science.gov (United States)

    de la Morena, M Teresa; Nelson, Robert P

    2014-04-01

    Hematopoietic cell transplantation (HCT) is a curative therapeutic option for severe combined immunodeficiency (SCID), a group of diseases which otherwise carry life expectancies that are of limited duration and quality. Survival following HCT for SCID has improved from approximately 23 to 91 % over the last 40 years. Success with SCID prompted efforts to apply HCT to the therapeutic challenge of well over 20 molecularly defined primary immune deficiency diseases (PID). Such success is due to both early recognition of PIDs and advances in the field of transplantation. Such advances include high-resolution HLA DNA donor-recipient matching, expansion of donor sources, better tolerated conditioning, new antibiotics, and wider availability. International collaborative efforts have provided patients and caregivers information that permit better treatment decisions now, and direct clinicians and investigators to ensure progress in the future. Pioneers in screening for SCID have taken steps to correct the fundamental challenge to successful treatment, which is the rapid discovery and characterization of cases and offering the transplant option to an affected child early in life; blood spot testing for T and B cell receptor quantification is now available to a growing fraction of newborns. Organizations including the Primary Immune Deficiency Treatment Consortium in the USA, The European Society for Primary Immunodeficiency, the European Group for Blood and Marrow Transplantation, the Pediatric Blood and Marrow Transplant Consortium, the United States Immunodeficiency Network, the Immune Deficiency Foundation, and the Jeffrey Modell Foundation are contributing mightily to increase awareness and standardize optimal utilization to the benefit of patients. This review will update the allergist-immunologist concerning disease presentations, indications for transplantation, methodologies, conditioning regimens, and clinical outcomes for patients with PID for which timely HCT is

  14. Vitamin d deficiency in a multiethnic healthy control cohort and altered immune response in vitamin D deficient European-American healthy controls.

    Directory of Open Access Journals (Sweden)

    Lauren L Ritterhouse

    Full Text Available In recent years, vitamin D has been shown to possess a wide range of immunomodulatory effects. Although there is extensive amount of research on vitamin D, we lack a comprehensive understanding of the prevalence of vitamin D deficiency or the mechanism by which vitamin D regulates the human immune system. This study examined the prevalence and correlates of vitamin D deficiency and the relationship between vitamin D and the immune system in healthy individuals.Healthy individuals (n = 774 comprised of European-Americans (EA, n = 470, African-Americans (AA, n = 125, and Native Americans (NA, n = 179 were screened for 25-hydroxyvitamin D [25(OHD] levels by ELISA. To identify the most noticeable effects of vitamin D on the immune system, 20 EA individuals with severely deficient (24.8 ng/mL vitamin D levels were matched and selected for further analysis. Serum cytokine level measurement, immune cell phenotyping, and phosphoflow cytometry were performed.Vitamin D sufficiency was observed in 37.5% of the study cohort. By multivariate analysis, AA, NA, and females with a high body mass index (BMI, >30 demonstrate higher rates of vitamin D deficiency (p<0.05. Individuals with vitamin D deficiency had significantly higher levels of serum GM-CSF (p = 0.04, decreased circulating activated CD4+ (p = 0.04 and CD8+ T (p = 0.04 cell frequencies than individuals with sufficient vitamin D levels.A large portion of healthy individuals have vitamin D deficiency. These individuals have altered T and B cell responses, indicating that the absence of sufficient vitamin D levels could result in undesirable cellular and molecular alterations ultimately contributing to immune dysregulation.

  15. Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions.

    Science.gov (United States)

    Górski, A; Castronovo, V; Stepień-Sopniewska, B; Grieb, P; Ryba, M; Mrowiec, T; Korczak-Kowalska, G; Wierzbicki, P; Matysiak, W; Dybowska, B

    1994-07-01

    Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.

  16. Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.

    Science.gov (United States)

    Sayour, Elias J; Mousallem, Talal; Van Mater, David; Wang, Endi; Martin, Paul; Buckley, Rebecca H; Barfield, Raymond C

    2016-10-01

    Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids. © 2016 Wiley Periodicals, Inc.

  17. Pertactin deficient Bordetella pertussis present a better fitness in mice immunized with an acellular pertussis vaccine.

    Science.gov (United States)

    Hegerle, N; Dore, G; Guiso, N

    2014-11-20

    Bordetella pertussis is the etiologic agent of whooping cough and has been the target of vaccination for over fifty years. The latest strategies include the use of acellular pertussis vaccines that induce specific immunity against few virulence factors amongst which pertactin is included in three and five component acellular pertussis vaccines. Recently, it has been reported that B. pertussis clinical isolates loose the production of this adhesin in regions reaching high vaccine coverage with vaccines targeting this virulence factor. We here demonstrate that isolates not producing pertactin are capable of sustaining longer infection as compared to pertactin producing isolates in an in vivo model of acellular pertussis immunization. Loosing pertactin production might thus provide a selective advantage to these isolates in this background, which could account for the upraise in prevalence of these pertactin deficient isolates in the population.

  18. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner.

    Science.gov (United States)

    Ablasser, Andrea; Hemmerling, Inga; Schmid-Burgk, Jonathan L; Behrendt, Rayk; Roers, Axel; Hornung, Veit

    2014-06-15

    Cytosolic detection of DNA is crucial for the initiation of antiviral immunity but can also cause autoimmunity in the context of endogenous nucleic acids being sensed. Mutations in the human 3' repair exonuclease 1 (TREX1) have been linked to the type I IFN-associated autoimmune disease Aicardi-Goutières syndrome. The exact mechanisms driving unabated type I IFN responses in the absence of TREX1 are only partly understood, but it appears likely that accumulation of endogenous DNA species triggers a cell-autonomous immune response by activating a cytosolic DNA receptor. In this article, we demonstrate that knocking out the DNA sensor cyclic GMP-AMP synthase completely abrogates spontaneous induction of IFN-stimulated genes in TREX1-deficient cells. These findings indicate a key role of cyclic GMP-AMP synthase for the initiation of self-DNA-induced autoimmune disorders, thus providing important implications for novel therapeutic approaches.

  19. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact

    OpenAIRE

    Scholz, Jean L.; Crowley, Jenni E.; Tomayko, Mary M.; Steinel, Natalie; O'Neill, Patrick J.; Quinn, William J; Goenka, Radhika; Miller, Juli P; Cho, Yun Hee; Long, Vatana; Ward, Chris; Migone, Thi-Sau; Shlomchik, Mark J.; Cancro, Michael P.

    2008-01-01

    We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells ...

  20. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.

    Science.gov (United States)

    Agostoni, Angelo; Aygören-Pürsün, Emel; Binkley, Karen E; Blanch, Alvaro; Bork, Konrad; Bouillet, Laurence; Bucher, Christoph; Castaldo, Anthony J; Cicardi, Marco; Davis, Alvin E; De Carolis, Caterina; Drouet, Christian; Duponchel, Christiane; Farkas, Henriette; Fáy, Kálmán; Fekete, Béla; Fischer, Bettina; Fontana, Luigi; Füst, George; Giacomelli, Roberto; Gröner, Albrecht; Hack, C Erik; Harmat, George; Jakenfelds, John; Juers, Mathias; Kalmár, Lajos; Kaposi, Pál N; Karádi, István; Kitzinger, Arianna; Kollár, Tímea; Kreuz, Wolfhart; Lakatos, Peter; Longhurst, Hilary J; Lopez-Trascasa, Margarita; Martinez-Saguer, Inmaculada; Monnier, Nicole; Nagy, István; Németh, Eva; Nielsen, Erik Waage; Nuijens, Jan H; O'grady, Caroline; Pappalardo, Emanuela; Penna, Vincenzo; Perricone, Carlo; Perricone, Roberto; Rauch, Ursula; Roche, Olga; Rusicke, Eva; Späth, Peter J; Szendei, George; Takács, Edit; Tordai, Attila; Truedsson, Lennart; Varga, Lilian; Visy, Beáta; Williams, Kayla; Zanichelli, Andrea; Zingale, Lorenza

    2004-09-01

    Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

  1. Development of vaccines against Plasmodium falciparum malaria: taking lessons from naturally acquired protective immunity

    DEFF Research Database (Denmark)

    Hviid, Lars

    2007-01-01

    The acquisition of substantial anti-malarial protection in people naturally exposed to P. falciparum is often cited as evidence that malaria vaccines can be developed, but is rarely used to guide the development. We are pursuing the development of vaccines based on antigens and immune responses...

  2. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management.

    Science.gov (United States)

    Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D; Puck, Jennifer M; Buckley, Rebecca H; Candotti, Fabio; Conley, Mary Ellen; Fleisher, Thomas A; Gaspar, H Bobby; Kohn, Donald B; Ochs, Hans D; O'Reilly, Richard J; Rizzo, J Douglas; Roifman, Chaim M; Small, Trudy N; Shearer, William T

    2009-12-01

    More than 20 North American academic centers account for the majority of hematopoietic stem cell transplantation (HCT) procedures for primary immunodeficiency diseases (PIDs), with smaller numbers performed at additional sites. Given the importance of a timely diagnosis of these rare diseases and the diversity of practice sites, there is a need for guidance as to best practices in management of patients with PIDs before, during, and in follow-up for definitive treatment. In this conference report of immune deficiency experts and HCT physicians who care for patients with PIDs, we present expert guidance for (1) PID diagnoses that are indications for HCT, including severe combined immunodeficiency disease (SCID), combined immunodeficiency disease, and other non-SCID diseases; (2) the critical importance of a high degree of suspicion of the primary care physician and timeliness of diagnosis for PIDs; (3) the need for rapid referral to an immune deficiency expert, center with experience in HCT, or both for patients with PIDs; (4) medical management of a child with suspicion of SCID/combined immunodeficiency disease while confirming the diagnosis, including infectious disease management and workup; (5) the posttransplantation follow-up visit schedule; (6) antimicrobial prophylaxis after transplantation, including gamma globulin administration; and (7) important indications for return to the transplantation center after discharge. Finally, we discuss the role of high-quality databases in treatment of PIDs and HCT as an element of the infrastructure that will be needed for productive multicenter clinical trials in these rare diseases.

  3. Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?

    Directory of Open Access Journals (Sweden)

    Moreno-Reyes Rodrigo

    2009-04-01

    Full Text Available Abstract Background About 20–30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation. Presentation of the hypothesis We hypothesize that low availability of 1,25-dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in the vitamin D receptor or in its activating/inactivating enzymes, contributes to the appearance of IRIS. Furthermore, drug interactions with the enzymatic pathways of vitamin D could favour the development of IRIS. Testing the hypothesis Our hypothesis could be explored by a case-control study to assess the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral treatment who develop and do not develop IRIS. Implications of the hypothesis If the role of vitamin D in IRIS is confirmed, we would be able to screen patients at risk for IRIS by screening for vitamin D deficiency. After confirmation by means of a clinical trial, vitamin D supplementation could be a cheap and safe way to reduce the incidence of IRIS.

  4. Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  5. Role of B Cells and Antibodies in Acquired Immunity against Mycobacterium tuberculosis

    Science.gov (United States)

    Achkar, Jacqueline M.; Chan, John; Casadevall, Arturo

    2015-01-01

    Accumulating evidence has documented a role for B cells and antibodies (Abs) in the immunity against Mycobacterium tuberculosis (Mtb). Passive transfer studies with monoclonal antibodies (mAbs) against mycobacterial antigens have shown protection against the tubercle bacillus. B cells and Abs are believed to contribute to an enhanced immune response against Mtb by modulating various immunological components in the infected host including the T-cell compartment. Nevertheless, the extent and contribution of B cells and Abs to protection against Mtb remains uncertain. In this article we summarize the most relevant findings supporting the role of B cells and Abs in the defense against Mtb and discuss the potential mechanisms of protection. PMID:25301934

  6. Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report

    Directory of Open Access Journals (Sweden)

    Van Den Oord Joost

    2010-12-01

    Full Text Available Abstract Rothmund-Thomson syndrome (RTS(OMIM 268400 is a rare autosomal recessive genodermatosis characterized by poikiloderma, small stature, skeletal and dental abnormalities, cataract and an increased risk of cancer. It is caused by mutations in RECQL4 at 8q24. Immune deficiency is not described as a classical feature of the disease. Here we report the appearance of granulomatous skin lesions complicating primary Varicella Zoster Virus infection in a toddler with Rothmund Thomson syndrome and immune deficiency. Although granulomatous disorders are sometimes seen after Herpes zoster, they are even more rare after Varicella primary infection. Granulomas have hitherto not been described in Rothmund-Thomson syndrome. With this report we aim to stress the importance of screening for immune deficiency in patients with Rothmund-Thomson syndrome.

  7. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2.

    Science.gov (United States)

    Molina, H; Holers, V M; Li, B; Fung, Y; Mariathasan, S; Goellner, J; Strauss-Schoenberger, J; Karr, R W; Chaplin, D D

    1996-04-16

    Complement receptor 1 (CR1, CD35) and complement receptor 2 (CR2, CD21) have been implicated as regulators of B-cell activation. We explored the role of these receptors in the development of humoral immunity by generating CR1- and CR2-deficient mice using gene-targeting techniques. These mice have normal basal levels of IgM and of IgG isotypes. B- and T-cell development are overtly normal. Nevertheless, B-cell responses to low and high doses of a T-cell-dependent antigen are impaired with decreased titers of antigen-specific IgM and IgG isotypes. This defect is not complete because there is still partial activation of B lymphocytes during the primary immune response, with generation of splenic germinal centers and a detectable, although reduced, secondary antibody response. These data suggest that certain T-dependent antigens manifest an absolute dependence on complement receptors for the initiation of a normally robust immune response.

  8. Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces.

    Science.gov (United States)

    Mulder, Imke E; Schmidt, Bettina; Stokes, Christopher R; Lewis, Marie; Bailey, Mick; Aminov, Rustam I; Prosser, James I; Gill, Bhupinder P; Pluske, John R; Mayer, Claus-Dieter; Musk, Corran C; Kelly, Denise

    2009-11-20

    Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development. Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in early-life environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoor-housed pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results. Early-life environment significantly affects both microbial composition of the adult gut and mucosal innate immune function. We observed that a

  9. Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces

    Directory of Open Access Journals (Sweden)

    Pluske John R

    2009-11-01

    Full Text Available Abstract Background Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development. Results Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in early-life environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoor-housed pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results. Conclusion Early-life environment significantly affects both microbial composition of the adult

  10. Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths.

    Science.gov (United States)

    Oeser, K; Schwartz, C; Voehringer, D

    2015-05-01

    Approximately one-third of the world population is infected with gastrointestinal helminths. Studies in mouse models have demonstrated that the cytokines interleukin (IL)-4 and IL-13 are essential for worm expulsion, but the critical cellular source of these cytokines is poorly defined. Here, we compared the immune response to Nippostrongylus brasiliensis in wild-type, T cell-specific IL-4/IL-13-deficient and general IL-4/IL-13-deficient mice. We show that T cell-derived IL-4/IL-13 promoted T helper 2 (Th2) polarization in a paracrine manner, differentiation of alternatively activated macrophages, and tissue recruitment of innate effector cells. However, innate IL-4/IL-13 played the critical role for induction of goblet cell hyperplasia and secretion of effector molecules like Mucin5ac and RELMβ in the small intestine. Surprisingly, T cell-specific IL-4/IL-13-deficient and wild-type mice cleared the parasite with comparable efficiency, whereas IL-4/IL-13-deficient mice showed impaired expulsion. These findings demonstrate that IL-4/IL-13 produced by cells of the innate immune system is required and sufficient to initiate effective type 2 immune responses resulting in protective immunity against N. brasiliensis.

  11. Nutritional zinc deficiency, immune capacity and malaria : a study on mediators of immunity to malaria caused by Plasmodium falciparum in African children

    NARCIS (Netherlands)

    Mbugi, E.V.

    2009-01-01

    This thesis aimed at investigating the role of genetic and nutritional factors that affect the immune response to malaria in Tanzanian children. The introductory chapter (Chapter 1) reviews the importance of nutritional deficiencies, particularly of zinc, and presents the hypothesis that such

  12. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact.

    Science.gov (United States)

    Scholz, Jean L; Crowley, Jenni E; Tomayko, Mary M; Steinel, Natalie; O'Neill, Patrick J; Quinn, William J; Goenka, Radhika; Miller, Juli P; Cho, Yun Hee; Long, Vatana; Ward, Chris; Migone, Thi-Sau; Shlomchik, Mark J; Cancro, Michael P

    2008-10-07

    We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.

  13. Bruton's Tyrosine Kinase Deficiency Inhibits Autoimmune Arthritis in Mice but Fails to Block Immune Complex-Mediated Inflammatory Arthritis.

    Science.gov (United States)

    Nyhoff, Lindsay E; Barron, Bridgette L; Johnson, Elizabeth M; Bonami, Rachel H; Maseda, Damian; Fensterheim, Benjamin A; Han, Wei; Blackwell, Timothy S; Crofford, Leslie J; Kendall, Peggy L

    2016-08-01

    Bruton's tyrosine kinase (BTK) is a B cell signaling protein that also contributes to innate immunity. BTK inhibitors prevent autoimmune arthritis but have off-target effects, and the mechanisms of protection remain unknown. We undertook these studies using genetic deletion to investigate the role of BTK in adaptive and innate immune responses that drive inflammatory arthritis. BTK-deficient K/BxN mice were generated to study the role of BTK in a spontaneous model that requires both adaptive and innate immunity. The K/BxN serum-transfer model was used to bypass the adaptive system and elucidate the role of BTK in innate immune contributions to arthritis. BTK deficiency conferred disease protection to K/BxN mice, confirming outcomes of BTK inhibitors. B lymphocytes were profoundly reduced, more than in other models of BTK deficiency. Subset analysis revealed loss of B cells at all developmental stages. Germinal center B cells were also decreased, with downstream effects on numbers of follicular helper T cells and greatly reduced autoantibodies. In contrast, total IgG was only mildly decreased. Strikingly, and in contrast to small molecule inhibitors, BTK deficiency had no effect in the serum-transfer model of arthritis. BTK contributes to autoimmune arthritis primarily through its role in B cell signaling and not through innate immune components. © 2016, American College of Rheumatology.

  14. Innate versus acquired immune response in the pathogenesis of recurrent idiopathic pericarditis.

    Science.gov (United States)

    Cantarini, Luca; Luca, Cantarini; Imazio, Massimo; Massimo, Imazio; Brucato, Antonio; Antonio, Brucato; Lucherini, Orso Maria; Maria, Lucherini Orso; Galeazzi, Mauro; Mauro, Galeazzi

    2010-04-01

    The pathogenesis of recurrent pericarditis is still poorly understood and may be related either to viral infections or autoimmune and autoinflammatory disorders. The immune system plays a major role in the pathogenesis of the disease, modulating individual responses to different noxa and explaining the variable reported recurrence rate (ranging from 20% to 50% of patients) following an attack of acute or recurrent pericarditis. Increasing interest is currently being devoted to autoinflammatory disorders, a group of conditions characterized by spontaneously relapsing and remitting bouts of systemic inflammation without apparent involvement of antigen-specific T cells or significant production of auto-antibodies. Ongoing basic and clinical research is needed to provide further evidence for the understanding of this common and troublesome disease, and to develop targeted and more efficacious therapies. Copyright 2009 Elsevier B.V. All rights reserved.

  15. Autosomal recessive PGM3 mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment

    Science.gov (United States)

    Zhang, Yu; Yu, Xiaomin; Ichikawa, Mie; Lyons, Jonathan J.; Datta, Shrimati; Lamborn, Ian T.; Jing, Huie; Kim, Emily S.; Biancalana, Matthew; Wolfe, Lynne A.; DiMaggio, Thomas; Matthews, Helen F.; Kranick, Sarah M.; Stone, Kelly D.; Holland, Steven M.; Reich, Daniel S.; Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua; Freeman, Alexandra F.; Freeze, Hudson H.; Su, Helen C.; Milner, Joshua D.

    2014-01-01

    Background Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy. Objective To define a genetic syndrome of severe atopy, elevated serum IgE, immune deficiency, autoimmunity, and motor and neurocognitive impairment. Methods Eight patients from two families who had similar syndromic features were studied. Thorough clinical evaluations, including brain MRI and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T cell cytokine production were measured. Whole exome sequencing was performed to identify disease-causing mutations. Immunoblotting, qRT-PCR, enzymatic assays, nucleotide sugar and sugar phosphate analyses along with MALDI-TOF mass spectrometry of glycans were used to determine the molecular consequences of the mutations. Results Marked atopy and autoimmunity were associated with increased TH2 and TH17 cytokine production by CD4+ T cells. Bacterial and viral infection susceptibility were noted along with T cell lymphopenia, particularly of CD8+ T cells, and reduced memory B cells. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurological abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced UDP-GlcNAc, along with decreased O- and N-linked protein glycosylation in patients’ cells. These results define a new Congenital Disorder of Glycosylation. Conclusions Autosomal recessive, hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability and hypomyelination. PMID:24589341

  16. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

    Science.gov (United States)

    Shelton, Jennifer M G; Corran, Patrick; Risley, Paul; Silva, Nilupa; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Craik, Rachel; Cornelius, Victoria; Hensmann, Meike; Molloy, Sile; Sepulveda, Nuno; Clark, Taane G; Band, Gavin; Clarke, Geraldine M; Spencer, Christopher C A; Kerasidou, Angeliki; Campino, Susana; Auburn, Sarah; Tall, Adama; Ly, Alioune Badara; Mercereau-Puijalon, Odile; Sakuntabhai, Anavaj; Djimdé, Abdoulaye; Maiga, Boubacar; Touré, Ousmane; Doumbo, Ogobara K; Dolo, Amagana; Troye-Blomberg, Marita; Mangano, Valentina D; Verra, Frederica; Modiano, David; Bougouma, Edith; Sirima, Sodiomon B; Ibrahim, Muntaser; Hussain, Ayman; Eid, Nahid; Elzein, Abier; Mohammed, Hiba; Elhassan, Ahmed; Elhassan, Ibrahim; Williams, Thomas N; Ndila, Carolyne; Macharia, Alexander; Marsh, Kevin; Manjurano, Alphaxard; Reyburn, Hugh; Lemnge, Martha; Ishengoma, Deus; Carter, Richard; Karunaweera, Nadira; Fernando, Deepika; Dewasurendra, Rajika; Drakeley, Christopher J; Riley, Eleanor M; Kwiatkowski, Dominic P; Rockett, Kirk A

    2015-08-28

    Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of

  17. The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation

    Directory of Open Access Journals (Sweden)

    Roy Moncayo

    2015-06-01

    Conclusions: We interpret the elevated thyroid vascularization and low magnesium levels as signs of an inflammatory process related to the musculoskeletal changes. Improvement of thyroid function and morphology can be achieved after correcting the influence of stressors together with the supplementation regime. We hypothesize that the central biochemical event in thyroid disease is that of an acquired, altered mitochondrial function due to deficiency of magnesium, selenium, and coenzyme Q10.

  18. Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection

    Science.gov (United States)

    Ahn, Danielle; Peñaloza, Hernán; Wang, Zheng; Wickersham, Matthew; Parker, Dane; Patel, Purvi; Koller, Antonius; Chen, Emily I.; Bueno, Susan M.; Uhlemann, Anne-Catrin; Prince, Alice

    2016-01-01

    Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant Klebsiella pneumoniae ST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6Chi monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with other K. pneumoniae strains, KP35 induced global changes in the phagocytic response identified with proteomics, including evasion of Ca2+ and calpain activation necessary for phagocytic killing, confirmed in functional studies with neutrophils. This comprehensive analysis of an ST258 K. pneumoniae isolate reveals ongoing genetic adaptation to host microenvironments and innate immune clearance mechanisms that complements its repertoire of antimicrobial resistance genes and facilitates persistence in the lung. PMID:27777978

  19. TLR7 Deficiency Leads to TLR8 Compensative Regulation of Immune Response against JEV in Mice

    Science.gov (United States)

    Awais, Muhammad; Wang, Ke; Lin, Xianwu; Qian, Wenjie; Zhang, Nan; Wang, Chong; Wang, Kunlun; Zhao, Ling; Fu, Zhen F.; Cui, Min

    2017-01-01

    Japanese encephalitis virus (JEV) is a highly fatal pathogen to human beings. Toll-like receptor 7 (TLR7) plays a role as the first host defense against most single-stranded RNA flaviviruses. This study aims to investigate the role of TLR7 in inducing adaptive immune response in mice against JEV. In vitro and in vivo studies were conducted to examine the expression of toll-like receptors (TLRs) in mice. After JEV infection, physical parameters of mice (survival rate and body weight) were evaluated, and organs or cells were collected for further analysis. The expression of TLR7 was increased significantly as compare to other TLR molecules post-JEV infection. The expression of CD80, CD86, and CD273 on bone marrow-derived dendritic cells was increased significantly in TLR7−/− mice. Furthermore, viral load was also increased significantly in TLR7−/− mice as compare to C57BL/6 mice. But there was no significant difference among survival rate and body weight in TLR7−/− mice as compare to C57BL/6. Interestingly, we also found that TLR8 was upregulated in TLR7−/− mice. The study concluded that TLR8 was upregulated in TLR7-deficient mice, and it might play a compensatory role in the immune response in TLR7−/− mice.

  20. Immunization with cationized BSA inhibits progression of disease in ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis.

    Science.gov (United States)

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

    2011-06-01

    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.

  1. Immune endocrinological evaluation in patients with severe vascular acquired brain injuries: therapeutical approaches.

    Science.gov (United States)

    Amico, Angelo Paolo; Terlizzi, Annamaria; Annamaria, Terlizzi; Megna, Marisa; Marisa, Megna; Megna, Gianfranco; Gianfranco, Megna; Damiani, Sabino; Sabino, Damiani

    2013-06-01

    It is known that in severe acquired brain injuries there is process of neuroinflammation, with the activation of a local and general stress response. In our study we considered six patients with disorders of consciousness (five in vegetative state and one in minimal consciousness state) in subacute phase, which had both a clinical assessment and a functional imaging (fMRI): in all these patients we analised blood levels of osteopontin (OPN), a cytokin involved in neuroinflammation but also in neurorepair with a still discussed role. Besides we studied the lymphocyte subsets and blood levels of some hormones (ADH, ACTH, PRL, GH, TSH, fT3, fT4). We found a positive correlation between the levels of serum osteopontin (higher than normal in all subjects) and the severity of the brain injury, especially for prognosis: actually, the patient with the lowest level has emerged from minimal consciousness state, while the one with the highest level has died a few days after the evaluation. The lymphocyte subset was altered, with a general increase of CD4+/CD3+ ratio, but without a so strict correlation with clinical severity; the only hormone with a significant increase in the worse patients was prolactin. In fMRI we detected some responses to visual and acoustic stimuli also in vegetative states, which had no clinical response to this kind of stimulation but generally have had a better prognosis. So we conclude that osteopontin could be a good marker of neuroinflammation and relate to a worse prognosis of brain injuries; the lymphocyte alterations in these disorders are not clear, but we suspect an unbalance of CD4 towards Th2; PRL is the best endocrinological marker of brain injury severity; fMRI surely plays an important role in the detection of subclinical responses and in prognostic stratification, that is still to define with more studies and statistical analysis.

  2. Selective predisposition to bacterial infections in IRAK-4-deficient children : IRAK-4-dependent TLRs are otherwise redundant in protective immunity

    NARCIS (Netherlands)

    Ku, Cheng-Lung; von Bernuth, Horst; Picard, Capucine; Zhang, Shen-Ying; Chang, Huey-Hsuan; Yang, Kun; Chrabieh, Maya; Issekutz, Andrew C.; Cunningham, Coleen K.; Gallin, John; Holland, Steven M.; Roifman, Chaim; Ehl, Stephan; Smart, Joanne; Tang, Mimi; Barrat, Franck J.; Levy, Ofer; McDonald, Douglas; Day-Good, Noorbibi K.; Miller, Richard; Takada, Hidetoshi; Hara, Toshiro; Al-Hajjar, Sami; Al-Ghonaium, Abdulaziz; Speert, David; Sanlaville, Damien; Li, Xiaoxia; Geissmann, Frederic; Vivier, Eric; Marodi, Laszlo; Garty, Ben-Zion; Chapel, Helen; Rodriguez-Gallego, Carlos; Bossuyt, Xavier; Abel, Laurent; Puel, Anne; Casanova, Jean-Laurent

    2007-01-01

    Human interleukin ( IL) 1 receptor - associated kinase 4 ( IRAK- 4) deficiency is a recently discovered primary immunodefi ciency that impairs Toll/ IL- 1R immunity, except for the Toll- like receptor ( TLR) 3 - and TLR4 - interferon ( IFN)-alpha/beta pathways. The clinical and immunological phenoty

  3. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

    Directory of Open Access Journals (Sweden)

    Renata eToth

    2015-10-01

    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  4. Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

    Directory of Open Access Journals (Sweden)

    Irene Mavroudi

    2012-01-01

    Full Text Available Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients.

  5. Vitamin A supplementation in early life enhances the intestinal immune response of rats with gestational vitamin A deficiency by increasing the number of immune cells.

    Directory of Open Access Journals (Sweden)

    Xia Liu

    Full Text Available Vitamin A is a critical micronutrient for regulating immunity in many organisms. Our previous study demonstrated that gestational or early-life vitamin A deficiency decreases the number of immune cells in offspring. The present study aims to test whether vitamin A supplementation can restore lymphocyte pools in vitamin A-deficient rats and thereby improve the function of their intestinal mucosa; furthermore, the study aimed to identify the best time frame for vitamin A supplementation. Vitamin A-deficient pregnant rats or their offspring were administered a low-dose of vitamin A daily for 7 days starting on gestational day 14 or postnatal day 1, day 14 or day 28. Serum retinol concentrations increased significantly in all four groups that received vitamin A supplementation, as determined by high-performance liquid chromatography. The intestinal levels of secretory immunoglobulin A and polymeric immunoglobulin receptor increased significantly with lipopolysaccharide challenge in the rats that received vitamin A supplementation starting on postnatal day 1. The rats in this group had higher numbers of CD8+ intestinal intraepithelial lymphocytes, CD11C+ dendritic cells in the Peyer's patches and CD4+CD25+ T cells in the spleen compared with the vitamin A-deficient rats; flow cytometric analysis also demonstrated that vitamin A supplementation decreased the number of B cells in the mesenteric lymph nodes. Additionally, vitamin A supplementation during late gestation increased the numbers of CD8+ intestinal intraepithelial lymphocytes and decreased the numbers of B lymphocytes in the mesenteric lymph nodes. However, no significant differences in lymphocyte levels were found between the rats in the other two vitamin A supplement groups and the vitamin A-deficient group. In conclusion, the best recovery of a subset of lymphocytes in the offspring of gestational vitamin A-deficient rats and the greatest improvement in the intestinal mucosal immune

  6. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system.

    Science.gov (United States)

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C

    2016-03-03

    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C(18:1)-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C(18:1)-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C(18:1)-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C(18:1)-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C(18

  7. Immune Thrombocytopenia Resolved by Eltrombopag in a Carrier of Glucose-6-Phosphate Dehydrogenase Deficiency

    Directory of Open Access Journals (Sweden)

    Laura Scaramucci

    2016-03-01

    Full Text Available Eltrombopag, a thrombopoietin mimetic peptide, may provide excellent clinical efficacy in steroid-refractory patients with immune thrombocytopenic purpura (ITP [1,2]. Eltrombopag is generally well tolerated. However, its use in the particular setting of glucose-6-phosphate dehydrogenase (G6PD and history of acute hemolytic anemia (AHA has not been reported so far. A 51-year-old female was diagnosed as having ITP in September 2014. She was not taking any medication and her past history was negative, apart from having been diagnosed a carrier (heterozygous of G6PD deficiency (Mediterranean variant after a familial screening by molecular and biochemical methods. She presented with only slightly reduced (about 50% enzyme level, belonging to World Health Organization-defined class 3 [3,4]. In the following years, the patient experienced some episodes of AHA, which were managed at outside institutions; in particular, a severe episode of AHA, probably triggered by urinary infection and antibiotics [5], had complicated her second and last delivery. The hemolytic episodes were selflimiting and resolved without sequelae. No other causes of hemolysis were documented. When the case came to our attention, a diagnosis of ITP was made; hemolytic parameters were normal, although the G6PD enzyme concentration was not measured. Oral prednisone (1 mg/kg was given with only a transient benefit. The patient was then a candidate for elective splenectomy. However, given her extremely low platelet count, she was started in October 2014 on eltrombopag at 50 mg/day as a bridge to splenectomy. Given that, to the best of our knowledge, the use of this drug has never been reported in the particular setting of G6PD deficiency, the patient was constantly monitored. A prompt platelet increase (178x109/L was observed 1 week after the start of treatment. After she achieved the target platelet count, the dose of eltrombopag was tapered to the lowest effective dose. The patient

  8. Composition of Intestinal Microbiota in Immune-Deficient Mice Kept in Three Different Housing Conditions

    Science.gov (United States)

    Thoene-Reineke, Christa; Fischer, André; Friese, Christian; Briesemeister, Dana; Göbel, Ulf B.; Kammertoens, Thomas; Bereswill, Stefan; Heimesaat, Markus M.

    2014-01-01

    Background Abundance of commensals constituting the intestinal microbiota (IM) affects the immune system and predisposes to a variety of diseases, including intestinal infections, cancer, inflammatory and metabolic disorders. Housing conditions determine the IM and can hence influence the immune system. We analyzed how both variables affect the IM of four immune-compromized mouse lines kept under different housing conditions. Methodology/Principal Findings We investigated the IM composition in mice by quantitative 16S rRNA RT-PCR analysis of the main fecal bacterial groups (Enterobacteriaceae, enterococci, lactobacilli, bifidobacteria, Bacteroides/Prevotella (BP) spp., Clostridium leptum and coccoides groups). Mice were homozygous (HO) or heterozygous (HE) for a targeted inactivating mutation of either the IFN-γ Receptor (R), IFN-γ, Rag1 or IL-4 genes. Overall, differences in IM composition were subtle. However, in the SPF-barrier, total eubacterial loads were higher in Rag1 HE versus Rag1 HO mice as well as in IFN-γR HE versus IFN-γR HO and WT animals. Although absent in WT mice, bifidobacterial loads were higher in HO and HE IFN-γ and Rag1 as well as IL-4 HO mice. Furthermore, BP was slightly lower in HO and HE IFN-γR and IFN-γ mice as well as in IL-4 HO mice as compared to WT controls. Interestingly, IM compositions were comparable in WT mice when kept in individual ventilated cages (IVC) or open cages (OC). IFN-γ HO and HE mice, however, had higher enterobacteria and BP loads, but lacked bifidobacteria when kept in OC versus IVC, as was the case in HO and HE Rag1 mice. In addition, Rag1 HO mice harbored higher clostridial loads when housed in OC as compared to IVC. Unexpectedly, lactobacilli levels were higher in IFN-γR mice when kept in OC versus IVC. Conclusion/Significance Housing-dependent and immune-deficiency mediated changes in intestinal microbiota composition were rather subtle but may nevertheless impact immunopathology in experimental models

  9. Composition of intestinal microbiota in immune-deficient mice kept in three different housing conditions.

    Directory of Open Access Journals (Sweden)

    Christa Thoene-Reineke

    Full Text Available Abundance of commensals constituting the intestinal microbiota (IM affects the immune system and predisposes to a variety of diseases, including intestinal infections, cancer, inflammatory and metabolic disorders. Housing conditions determine the IM and can hence influence the immune system. We analyzed how both variables affect the IM of four immune-compromized mouse lines kept under different housing conditions.We investigated the IM composition in mice by quantitative 16S rRNA RT-PCR analysis of the main fecal bacterial groups (Enterobacteriaceae, enterococci, lactobacilli, bifidobacteria, Bacteroides/Prevotella (BP spp., Clostridium leptum and coccoides groups. Mice were homozygous (HO or heterozygous (HE for a targeted inactivating mutation of either the IFN-γ Receptor (R, IFN-γ, Rag1 or IL-4 genes. Overall, differences in IM composition were subtle. However, in the SPF-barrier, total eubacterial loads were higher in Rag1 HE versus Rag1 HO mice as well as in IFN-γR HE versus IFN-γR HO and WT animals. Although absent in WT mice, bifidobacterial loads were higher in HO and HE IFN-γ and Rag1 as well as IL-4 HO mice. Furthermore, BP was slightly lower in HO and HE IFN-γR and IFN-γ mice as well as in IL-4 HO mice as compared to WT controls. Interestingly, IM compositions were comparable in WT mice when kept in individual ventilated cages (IVC or open cages (OC. IFN-γ HO and HE mice, however, had higher enterobacteria and BP loads, but lacked bifidobacteria when kept in OC versus IVC, as was the case in HO and HE Rag1 mice. In addition, Rag1 HO mice harbored higher clostridial loads when housed in OC as compared to IVC. Unexpectedly, lactobacilli levels were higher in IFN-γR mice when kept in OC versus IVC.Housing-dependent and immune-deficiency mediated changes in intestinal microbiota composition were rather subtle but may nevertheless impact immunopathology in experimental models.

  10. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema.

    Science.gov (United States)

    Zuraw, Bruce L; Bernstein, Jonathan A; Lang, David M; Craig, Timothy; Dreyfus, David; Hsieh, Fred; Khan, David; Sheikh, Javed; Weldon, David; Bernstein, David I; Blessing-Moore, Joann; Cox, Linda; Nicklas, Richard A; Oppenheimer, John; Portnoy, Jay M; Randolph, Christopher R; Schuller, Diane E; Spector, Sheldon L; Tilles, Stephen A; Wallace, Dana

    2013-06-01

    These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "A focused parameter update: Hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. The Joint Task Force on Practice Parameters understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because the cost of a given test or agent is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In some instances the cost benefit of an intervention is considered relevant, and commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion

  11. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy.

    Science.gov (United States)

    Lo, Bernice; Zhang, Kejian; Lu, Wei; Zheng, Lixin; Zhang, Qian; Kanellopoulou, Chrysi; Zhang, Yu; Liu, Zhiduo; Fritz, Jill M; Marsh, Rebecca; Husami, Ammar; Kissell, Diane; Nortman, Shannon; Chaturvedi, Vijaya; Haines, Hilary; Young, Lisa R; Mo, Jun; Filipovich, Alexandra H; Bleesing, Jack J; Mustillo, Peter; Stephens, Michael; Rueda, Cesar M; Chougnet, Claire A; Hoebe, Kasper; McElwee, Joshua; Hughes, Jason D; Karakoc-Aydiner, Elif; Matthews, Helen F; Price, Susan; Su, Helen C; Rao, V Koneti; Lenardo, Michael J; Jordan, Michael B

    2015-07-24

    Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4 protein in FoxP3(+) regulatory and activated conventional T cells. In LRBA-deficient cells, inhibition of lysosome degradation with chloroquine prevented CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and control of immune responses and suggest therapies for diseases involving the CTLA4 pathway. Copyright © 2015, American Association for the Advancement of Science.

  12. Health-Related Quality of Life in Primary Immune Deficient Patients

    Directory of Open Access Journals (Sweden)

    "Habibeh Mozaffari

    2006-03-01

    Full Text Available The primary immunodeficiency (PI disorders are abnormalities in development and maturation of the immune system. Individuals with PI disease may experience frequent infections, which limit their abilities to exhibit physical and psychological well-being secondary to their illness. In this survey we compared health-related quality of life of primary immune deficient patients with healthy children. The case-control study was designed for patients with PI disease who were referred to Children Medical Center in 2004-2005. Demographic information was taken and Pediatric Quality Of Life (PEDQOL questionnaire were filled for 50 PI patients and 100 healthy children. The mean age in PI patients was 12.62± 3.65 (range from 8 to 18 years and in the control group was 11.04± 3.3 years. In PI patients 68% were male and 32% female .Most patients with PI disease had a diagnosis of common variable immunodeficiency (54% or X-linked agammaglobulinemia (24%. Patients with PI disease had great limitations in physical functioning and psychological well-being (p<0.001 and p<0.001 respectively compared with children without a chronic health condition. Patients had lower PEDQOL scores in all age groups compared with normal sample (p<0.001. Long duration of disease significantly correlated with low psychological score. (r = -3.23. P= 0.03 Children with PI disease experience poorer health related quality of life than healthy children, indicating more attention should be paid to early diagnosis and treatment of PI disease, as well as more attention to their social limitation. PI patients may need psychological consultation for better coping with their illness.

  13. Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory.

    Science.gov (United States)

    Zimmerli, Claudia; Lee, Boris P L; Palmer, Gaby; Gabay, Cem; Adams, Ralf; Aurrand-Lions, Michel; Imhof, Beat A

    2009-04-15

    We have recently shown that junctional adhesion molecule (JAM)-C-deficient mice have leukocytic pulmonary infiltrates, disturbed neutrophil homeostasis, and increased postnatal mortality. This phenotype was partially rescued when mice were housed in ventilated isolators, suggesting an inability to cope with opportunistic infections. In the present study, we further examined the adaptive immune responses in JAM-C(-/-) mice. We found that murine conventional dendritic cells express in addition to Mac-1 and CD11c also JAM-B as ligand for JAM-C. By in vitro adhesion assay, we show that murine DCs can interact with recombinant JAM-C via Mac-1. However, this interaction does not seem to be necessary for dendritic cell migration and function in vivo, even though JAM-C is highly expressed by lymphatic sinuses of lymph nodes. Nevertheless, upon immunization and boosting with a protein Ag, JAM-C-deficient mice showed decreased persistence of specific circulating Abs although the initial response was normal. Such a phenotype has also been observed in a model of Ag-induced arthritis, showing that specific IgG2a Ab titers are reduced in the serum of JAM-C(-/-) compared with wild-type mice. Taken together, these data suggest that JAM-C deficiency affects the adaptive humoral immune response against pathogens, in addition to the innate immune system.

  14. Granzyme K-deficient mice show no evidence of impaired antiviral immunity.

    Science.gov (United States)

    Joeckel, Lars T; Allison, Cody C; Pellegrini, Marc; Bird, Catherina H; Bird, Phillip I

    2017-04-21

    The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes (CTL), is controversial. It has been reported to induce perforin-mediated cell death in vitro, but is also reported to be non-cytotoxic and to operate in inflammatory processes. To elucidate the biological role of this protease, we have deleted the granzyme K gene in mice (mutant allele: Gzmk(tm1.1Pib); MGI:5636646). Gzmk (-/-) mice are healthy, anatomically normal, fecund and show normal hematopoietic development. Gzmk (-/-) mice readily recover from lymphocytic choriomeningitis virus and mouse pox Ectromelia virus infection. Ex vivo, virus-specific granzyme K-deficient CTL are indistinguishable from those of wild-type mice in apoptosis induction of target cells. These data suggest that granzyme K does not play an essential role in viral immunity or cytotoxicity. Our granzyme K knockout line completes the collection of mouse models for the human granzymes, and will further our understanding of their biological roles and relationships.Immunology and Cell Biology advance online publication, 23 May 2017; doi:10.1038/icb.2017.35.

  15. Differentiation of human embryonic stem cells after transplantation in immune-deficient mice.

    Science.gov (United States)

    Przyborski, Stefan A

    2005-10-01

    Our current knowledge of how human tissues grow and develop is limited. We need to increase our understanding of tissue formation if we are to fully realize the potential of stem cells as a source of material for research into health and disease and possible therapeutic applications. Transplanted pluripotent human embryonic stem cells (hESCs) provide a potential system to model and investigate cell differentiation in humans. hESCs transplanted into immune-deficient mice form complex teratomas consisting of a range of differentiated somatic tissues, some of which appear highly organized and resemble structures normally identified in the embryo and adult. Analysis of such tumors may provide a unique opportunity to study organogenesis and lead to novel approaches in bioengineering and the growth of functioning structures composed of a range of alternative cell types. However, little has been done to characterize the developmental potential of hESCs after transplantation. This concise review presents evidence for the ability of hESCs to differentiate in vivo and highlights some of the prominent questions that need to be addressed if transplantation is to be used as a research tool to study hESC differentiation.

  16. Dysregulated TLR3-Dependent Signaling and Innate Immune Activation in Superoxide-Deficient Macrophages From Non-Obese Diabetic Mice

    OpenAIRE

    Seleme, Maria C.; Lei, Weiqi; Burg, Ashley R.; Goh, Kah Yong; Metz, Allison; Steele, Chad; Tse, Hubert M.

    2012-01-01

    In Type 1 diabetes (T1D), reactive oxygen species (ROS) and pro-inflammatory cytokines produced by macrophages and other innate immune cells destroy pancreatic β-cells while promoting autoreactive T cell maturation. Superoxide-deficient Non-Obese Diabetic mice (NOD.Ncf1m1J) are resistant to spontaneous diabetes, revealing the integral role of ROS-signaling in T1D. Here, we evaluate the innate immune activation state of bone marrow-derived macrophages (BM-Mϕ) from NOD and NOD.Ncf1m1J mice afte...

  17. Personal and Social Predictors about Safe Sexual Behavior in Patients with Immune Deficiency Virus in Ahwaz, Iran

    Directory of Open Access Journals (Sweden)

    Shirin Hasanpoor

    2016-12-01

    Full Text Available Socio-demographic predictors about safe sex behaviours in individual suffering from immune deficiency virus (HIV had been tried to understand in this cross-sectional study. It was conducted on 120 individuals having immune deficiency virus (HIV. Collection of the data were based on socio-demographic and a safe sex behaviour questionnaire. To determine the socio-demographic the general linear model was used. Result revealed mean (SD of the total score of safe sexual behaviour among men and women was 66.5 (13.1, 62.2 (13.0 respectively and (Score limit: 0-100. Status of sexual partners, unprotected vaginal sex, drugs and alcohols, as well as employment status, were considered as predictors of safe sex behaviours. About 50 percent of the participants pose unsafe sexual practices, thus, it is advisable that the health promotion programs and HIV prevention should implement in various groups of the society.

  18. Site-specific influence of polyunsaturated fatty acids on atherosclerosis in immune incompetent LDL receptor deficient mice.

    Science.gov (United States)

    Reardon, Catherine A; Blachowicz, Lydia; Gupta, Gaorav; Lukens, John; Nissenbaum, Michael; Getz, Godfrey S

    2006-08-01

    Polyunsaturated fatty acids (PUFA) are thought to influence plasma lipid levels, atherosclerosis, and the immune system. In this study, we fed male LDL receptor deficient (LDLR(-/-)) mice and immune incompetent LDLR(-/-) RAG2(-/-) mice diets containing predominantly saturated fats (milk fat) or PUFA (safflower oil) to determine if the response to diet was influenced by immune status. Relative to milk fat diet, plasma lipid and VLDL levels in both the LDLR(-/-) and LDLR(-/-) RAG2(-/-) mice fed safflower oil diet were lower, suggesting that the primary effect of PUFA on plasma lipids was not due to its inhibition of the immune system. Neither diet nor immune status influenced hepatic triglyceride production and post-heparin lipase activity, suggesting that the differences in triglyceride levels are due to differences in rates of catabolism of triglyceride-rich lipoproteins. While both diets promoted atherogenesis, both aortic root and innominate artery atherosclerosis in LDLR(-/-) mice was less in safflower oil fed animals. In contrast, a site-specific effect of PUFA was observed in the immune incompetent LDLR(-/-) RAG2(-/-). In these mice, aortic root atherosclerosis, but not innominate artery atherosclerosis, was less in PUFA fed animal. These results suggest that PUFA and the immune system may influence innominate artery atherosclerosis by some overlapping mechanisms.

  19. The case for a national service for primary immune deficiency disorders in New Zealand.

    Science.gov (United States)

    Ameratunga, Rohan; Steele, Richard; Jordan, Anthony; Preece, Kahn; Barker, Russell; Brewerton, Maia; Lindsay, Karen; Sinclair, Jan; Storey, Peter; Woon, See-Tarn

    2016-06-10

    Primary immune deficiency disorders (PIDs) are rare conditions for which effective treatment is available. It is critical these patients are identified at an early stage to prevent unnecessary morbidity and mortality. Treatment of these disorders is expensive and expert evaluation and ongoing management by a clinical immunologist is essential. Until recently there has been a major shortage of clinical immunologists in New Zealand. While the numbers of trained immunologists have increased in recent years, most are located in Auckland. The majority of symptomatic PID patients require life-long immunoglobulin replacement. Currently there is a shortage of subcutaneous and intravenous immunoglobulin (SCIG/IVIG) in New Zealand. A recent audit by the New Zealand Blood Service (NZBS) showed that compliance with indications for SCIG/IVIG treatment was poor in District Health Boards (DHBs) without an immunology service. The NZBS audit has shown that approximately 20% of annual prescriptions for SCIG/IVIG, costing $6M, do not comply with UK or Australian guidelines. Inappropriate use may have contributed to the present shortage of SCIG/IVIG necessitating importation of the product. This is likely to have resulted in a major unnecessary financial burden to each DHB. Here we present the case for a national service responsible for the tertiary care of PID patients and oversight for immunoglobulin use for primary and non-haematological secondary immunodeficiencies. We propose that other PIDs, including hereditary angioedema, are integrated into a national PID service. Ancillary services, including the customised genetic testing service, and research are also an essential component of an integrated national PID service and are described in this review. As we show here, a hub-and-spoke model for a national service for PIDs would result in major cost savings, as well as improved patient care. It would also allow seamless transition from paediatric to adult services.

  20. Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade.

    Science.gov (United States)

    Huffaker, Thomas B; Lee, Soh-Hyun; Tang, William W; Wallace, Jared A; Alexander, Margaret; Runtsch, Marah C; Larsen, Dane K; Thompson, Jacob; Ramstead, Andrew G; Voth, Warren P; Hu, Ruozhen; Round, June L; Williams, Matthew A; O'Connell, Ryan M

    2017-09-14

    MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional knockout (KO) mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote interferon gamma (IFNγ) production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage (TAM) expression of IFNγ-inducible genes. We also found that immune checkpoint-blocking (ICB) antibodies against programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) restored antitumor immunity in miR-155 T cell-conditional KO (TCKO) mice. We noted that these ICB antibodies rescued the levels of IFNγ; expressing T cells, expression of multiple activation and effector genes expressed by tumor-infiltrating CD8+ and CD4+ T cells, and TAM activation. Moreover, the ICB approach partially restored expression of several de-repressed miR-155 targets in tumor-infiltrating, miR-155 deficient CD8+ T cells, suggesting that miR-155 and the ICB regulate overlapping pathways to promote antitumor immunity. Taken together, our findings highlight miR-155s multifaceted role in T cells in which it promotes antitumor immunity. These results suggest that the augmentation of miR-155 expression could be used to improve anticancer immunotherapies. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  1. Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity.

    Directory of Open Access Journals (Sweden)

    Timothy J Nice

    2016-06-01

    Full Text Available In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV replicates in dendritic cells (DCs and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.

  2. Zebra Fish Lacking Adaptive Immunity Acquire an Antiviral Alert State Characterized by Upregulated Gene Expression of Apoptosis, Multigene Families, and Interferon-Related Genes.

    Science.gov (United States)

    García-Valtanen, Pablo; Martínez-López, Alicia; López-Muñoz, Azucena; Bello-Perez, Melissa; Medina-Gali, Regla M; Ortega-Villaizán, María Del Mar; Varela, Monica; Figueras, Antonio; Mulero, Víctoriano; Novoa, Beatriz; Estepa, Amparo; Coll, Julio

    2017-01-01

    To investigate fish innate immunity, we have conducted organ and cell immune-related transcriptomic as well as immunohistologic analysis in mutant zebra fish (Danio rerio) lacking adaptive immunity (rag1(-/-)) at different developmental stages (egg, larvae, and adult), before and after infection with spring viremia carp virus (SVCV). The results revealed that, compared to immunocompetent zebra fish (rag1(+/+) ), rag1(-/-) acquired increased resistance to SVCV with age, correlating with elevated transcript levels of immune genes in skin/fins and lymphoid organs (head kidney and spleen). Gene sets corresponding to apoptotic functions, immune-related multigene families, and interferon-related genes were constitutively upregulated in uninfected adult rag1(-/-) zebra fish. Overexpression of activated CASPASE-3 in different tissues before and after infection with SVCV further confirmed increased apoptotic function in rag1(-/-) zebra fish. Concurrently, staining of different tissue samples with a pan-leukocyte antibody marker showed abundant leukocyte infiltrations in SVCV-infected rag1(-/-) fish, coinciding with increased transcript expression of genes related to NK-cells and macrophages, suggesting that these genes played a key role in the enhanced immune response of rag1(-/-) zebra fish to SVCV lethal infection. Overall, we present evidence that indicates that rag1(-/-) zebra fish acquire an antiviral alert state while they reach adulthood in the absence of adaptive immunity. This antiviral state was characterized by (i) a more rapid response to viral infection, which resulted in increased survival, (ii) the involvement of NK-cell- and macrophage-mediated transcript responses rather than B- and/or T-cell dependent cells, and (iii) enhanced apoptosis, described here for the first time, as well as the similar modulation of multigene family/interferon-related genes previously associated to fish that survived lethal viral infections. From this and other studies, it might

  3. Analysis of antibodies to newly described Plasmodium falciparum merozoite antigens supports MSPDBL2 as a predicted target of naturally acquired immunity

    DEFF Research Database (Denmark)

    Tetteh, Kevin K A; Osier, Faith H A; Salanti, Ali

    2013-01-01

    Prospective studies continue to identify malaria parasite genes with particular patterns of polymorphism which indicate they may be under immune selection, and the encoded proteins require investigation. Sixteen new recombinant protein reagents were designed to characterize three such polymorphic...... of these reagents by murine immunization and parasite immunofluorescence, we analyzed naturally acquired antibody responses to the antigens in two cohorts in coastal Kenya in which the parasite was endemic (Chonyi [n = 497] and Ngerenya [n = 461]). As expected, the prevalence and levels of serum antibodies...... increased with age. We then investigated correlations with subsequent risk of clinical malaria among children...

  4. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Som Gowda Nanjappa

    Full Text Available Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+ T-cell help, vaccine-induced CD8(+ T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+ T cells (Tc17 cells have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+ T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

  5. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells.

    Science.gov (United States)

    Nanjappa, Som Gowda; Heninger, Erika; Wüthrich, Marcel; Gasper, David Joseph; Klein, Bruce S

    2012-01-01

    Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+) T-cell help, vaccine-induced CD8(+) T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+) T cells (Tc17 cells) have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+) T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

  6. Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine.

    Science.gov (United States)

    Stritzelberger, J; Distel, L; Buslei, R; Fietkau, R; Putz, F

    2017-08-20

    Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. While the alkylating agent temozolomide (TMZ) has prolonged overall survival, resistance evolution represents an important clinical problem. Therefore, we studied the effectiveness of radiotherapy and CCNU in an in vitro model of acquired TMZ resistance. We studied the MGMT-methylated GBM cell line U251 and its in vitro derived TMZ-resistant subline, U251/TMZ-R. Cytotoxicity of TMZ, CCNU, and radiation was tested. Both cell lines were analyzed for MGMT promotor status and expression of mismatch repair genes (MMR). The influence of MMR inhibition by cadmium chloride (CdCl2) on the effects of both drugs was evaluated. During the resistance evolution process in vitro, U251/TMZ-R developed MMR deficiency, but MGMT status did not change. U251/TMZ-R cells were more resistant to TMZ than parental U251 cells (cell viability: 92.0% in U251/TMZ-R/69.2% in U251; p = 0.032) yet more sensitive to CCNU (56.4%/80.8%; p = 0.023). The effectiveness of radiotherapy was not reduced in the TMZ-resistant cell line. Combination of CCNU and TMZ showed promising results for both cell lines and overcame resistance. CdCl2-induced MMR deficiency increased cytotoxicity of CCNU. Our results confirm MMR deficiency as a crucial process for resistance evolution to TMZ. MMR-deficient TMZ-resistant GBM cells were particularly sensitive to CCNU and to combined CCNU/TMZ. Effectiveness of radiotherapy was preserved in TMZ-resistant cells. Consequently, CCNU might be preferentially considered as a treatment option for recurrent MGMT-methylated GBM and may even be suitable for prevention of resistance evolution in primary treatment.

  7. Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Yuanhui [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); He, Jinsheng, E-mail: jshhe@bjtu.edu.cn [College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Zheng, Xianxian [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wu, Qiang [Department of Pathology, Anhui Medical University, Hefei, Anhui, 230032 (China); Zhang, Mei; Wang, Xiaobo [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wang, Yan [Department of Pathology, Anhui Medical University, Hefei, Anhui, 230032 (China); Xie, Can; Tang, Qian; Wei, Wei [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wang, Min; Song, Jingdong; Qu, Jianguo [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); Zhang, Ying; Wang, Xin [College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); Hong, Tao [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China)

    2009-04-17

    Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection.

  8. Vpu-Deficient HIV Strains Stimulate Innate Immune Signaling Responses in Target Cells

    OpenAIRE

    Doehle, Brian P.; Chang, Kristina; Fleming, Lamar; McNevin, John; Hladik, Florian; McElrath, M. Juliana; Gale, Michael

    2012-01-01

    Acute virus infection induces a cell-intrinsic innate immune response comprising our first line of immunity to limit virus replication and spread, but viruses have developed strategies to overcome these defenses. HIV-1 is a major public health problem; however, the virus-host interactions that regulate innate immune defenses against HIV-1 are not fully defined. We have recently identified the viral protein Vpu to be a key determinant responsible for HIV-1 targeting and degradation of interfer...

  9. Hot water extracts of Chlorella vulgaris improve immune function in protein-deficient weanling mice and immune cells.

    Science.gov (United States)

    An, Hyo-Jin; Rim, Hong-Kun; Jeong, Hyun-Ja; Hong, Seung-Heon; Um, Jae-Young; Kim, Hyung-Min

    2010-12-01

    The objective of this study was to investigate the effects of hot water extracts of Chlorella vulgaris (CVE) on a deteriorated immune function through utilization of a protein-energy malnutrition (PEM) diet. Unicellular algae, C. vulgaris, were used as biological response modifier. PEM is associated with decreased host immune defense. Male C57BL/6J mice, initially four weeks old, were fed for 8 days with standard diet or a PEM diet. Mice in the PEM diet group were orally administered 0.1 g/kg and 0.15 g/kg of CVE for the following week. Nutritional parameters such as the total protein, albumin, glucose, and interferon γ (IFN-γ) were increased in blood serum of the CVE-treated group compared with the non-treated group. The mononuclear cell numbers from spleen, superficial, and mesenteric lymph node were reduced in mice fed with PEM diet, but numbers from the spleen and superficial lymph node were increased by the CVE (0.1 and 0.15 g/kg) treatment. We also investigated the effect of CVE on the production of cytokines in human T-cell line, MOLT-4 cells, and primary cultured splenocytes. The CVE treatment significantly increased the production of both interleukin (IL)-2 and IL-4 compared with the media control, but did not affect the production of IFN-γ. These results suggest that CVE may be useful in improving the immune function.

  10. Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency

    Science.gov (United States)

    Lev, A; Simon, A J; Ben-Ari, J; Takagi, D; Stauber, T; Trakhtenbrot, L; Rosenthal, E; Rechavi, G; Amariglio, N; Somech, R

    2014-01-01

    It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vβ families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient–mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (Treg) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID. PMID:24666246

  11. [Acquired angioedema with C1-INH deficiency and accompanying chronic spontaneous urticaria in a patient with chronic lymphatic B cell leukemia].

    Science.gov (United States)

    Klossowski, N; Braun, S A; von Gruben, V; Losem, C; Plewe, D; Homey, B; Meller, S

    2015-10-01

    Acquired angioedema due to C1 inhibitor deficiency (C1-INH-AAE) is characterized by recurrent edema of the subcutaneous and/or submucosal tissue without wheals and negative family history of angioedema. Here, we present the case of a patient with a chronic lymphatic B cell leukemia who suffered from both C1-INH-AAE and chronic spontaneous urticaria. Oral corticosteroids, antihistamines, and the anti-IgE antibody omalizumab were applied to treat the chronic urticaria in combination with the plasma-derived C1 esterase inhibitor concentrate Berinert® and the bradykinin B2 receptor antagonist icatibant, but the symptoms did not improved significantly. Thus, polychemotherapy targeting the slow-growing lymphoproliferative disease including rituximab was initiated, which resulted in remission of both the urticaria and the angioedema.

  12. Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.

    Science.gov (United States)

    Lev, A; Simon, A J; Ben-Ari, J; Takagi, D; Stauber, T; Trakhtenbrot, L; Rosenthal, E; Rechavi, G; Amariglio, N; Somech, R

    2014-06-01

    It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vβ families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient-mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (T(reg)) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID.

  13. AIDS (Acquired Immune Deficiency Syndrome): Views on the Administration’s Fiscal Year 1989 Public Health Service Budget

    Science.gov (United States)

    1988-06-01

    police, and providers of allied health care, such as social workers, therapists , aides, and laboratory personnel. The report emphasized that a well- 1...million is also requested for bioethics and biosafety projects. Expert Views The state and local public health officials believe that patient care...million for AIDS services and drug treatment demonstration projects, $3 million for bioethics and biosafety (unchanged from the PHS budget request), and

  14. Detection of anti-Chlamydia trachomatis Antibodies in Patients with Acquired Immune Deficiency Syndrome in Abuja, Nigeria

    Directory of Open Access Journals (Sweden)

    Izebe, K. S.

    2008-01-01

    Full Text Available Chlamydia trachomatis (CT infections are among the sexually transmitted diseases known to increase the risk for human immunodeficiency virus infection. Serum samples from 34 consenting AIDS patients which attended the Government-approved Antiretroviral Treatment (ART Facility at the National Institute for Pharmaceutical Research and Development (NIPRD, Abuja between April 2005 and March 2006 were screened by enzyme immunoassay (EIA for the presence of anti-CT antibodies using ImmunoComb® Chlamydia Bivalent IgG Test kit (Orgenics, Israel. Anti-CT antibodies were detected in ten (29.4% of the thirty-four patients tested. The detection rate was higher among the females (33.3% than the males (23.1%. Patients of the age group 31-45 years had the highest detection of anti-C. trachomatis antibodies, followed by those of age group 16-30 years. The result of the present study suggests the presence of anti-CT antibodies in AIDS patients, and reinforces the need for routine screening for anti-CT antibodies as a necessary intervention to reduce the burden of chlamydial diseases and to reduce the risk of HIV and its spread in Nigeria. The outcome of this study also provides justification for the possible inclusion of anti-chlamydial agents in the National AIDS Management Plan to treat associated C. trachomatis infections.

  15. The socioeconomic impact of human immunodeficiency virus / acquired immune deficiency syndrome in India and its relevance to eye care

    Directory of Open Access Journals (Sweden)

    Murthy GVS

    2008-01-01

    Full Text Available Human immunodeficiency virus (HIV infection is aptly called the modern day ′plague′ and has the potential to decimate people in the productive age group. On the other hand, the increasing life expectancy in developing countries spirals age-related blindness. One therefore reduces economic productivity while the other increases economic dependency. Both lead to increased expenditure of households though in different proportions. Human immunodeficiency virus and blindness are both associated with discrimination, stigma and long-term consequences. They impact the socioeconomic fabric of the affected individuals, communities and countries. The loss in productivity and the cost of support to the affected individuals are seen in both. Each is a potent problem on its own but together they spell disaster in geometric proportions rather than a simple additive effect. Strategies need to be evolved to provide solace and improve the quality of life of an HIV-positive blind individual.

  16. Investigation of perceived stigma among people living with human immunodeficiency virus/acquired immune deficiency syndrome in Henan Province, China

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    Zhen Li

    2014-12-01

    Conclusion: The level of perceived HIV stigma and discrimination among PLWHA in Henan Province is moderate and was affected by the level of education and route of infection. Special intervention should be established to address this problem.

  17. Epidemiology of Oropharyngeal Candidiasis in Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patients and CD4+ Counts

    Science.gov (United States)

    Berberi, Antoine; Noujeim, Ziad; Aoun, Georges

    2015-01-01

    Background: The present study was directed to evaluate the forms of oropharyngeal candidiasis (OPC) and their correlation with CD4+ cell counts in human immunodeficiency virus (HIV) patients. Materials and Methods: This was a descriptive and analytical cross-sectional study carried out for a 2-year period, in which quantitative data collection methods were used. 50 patients with HIV infection were evaluated. Relationship between OPC and CD4+ was investigated. Results: Five different clinical forms were noticed on examination: pseudomembranous candidiasis 20/38 (P) was the most common one (52.6%) followed by erythematous 5/38 (13.15%), angular cheilitis 5/38 (13.15%) (AC), a combination of AC and E 4/38 (10.52%) or AC, E and P 4/38 (10.52%). Candida albicans was the most frequent specie isolated in 35 cases of OPC (92%). Candida tropicalis was isolated in 2 cases (5.26%) and Candida glabrata in 1 case (2.64%). The majority of patients with OPC had cell counts 28/38 (73%) <200 cells/mm3, followed by 9/38 (23%) at CD4+ cell counts of 201-499 cells/mm3. Conclusion: Oral Candida colonization and invasive infection occur more frequently in HIV-positive patient and is significantly more common in patients with CD4+ cell counts <200 cell/mm3. PMID:25878473

  18. Neurobehavioral Consequences of HTLV-III Brain Infection and Acquired Immune Deficiency Syndrome (AIDS) Encephalopathy: A Prospective Study

    Science.gov (United States)

    1990-02-15

    0UIN) over s~x months (r=.85, p<.01). QUIN is an endogenous excitatory ncurotoxin which acts specifically at the NMDA glutamate receptors ; it wdil...response to various therapies. A small clinical trial of an NMDA receptor antagonist in seropositive patients with slowed information processing would 4...Continue on reverse itf necessary and #dentify by bNock number) FIELD GROUP SUB-GROUP RA 1, HIV, Neurology, CNS Complications, Encephalitis , 06 03

  19. Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Nylen, Susanne; Duncan, Robert; Sacks, David; Nakhasi, Hira L

    2009-08-01

    No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.

  20. Zebra Fish Lacking Adaptive Immunity Acquire an Antiviral Alert State Characterized by Upregulated Gene Expression of Apoptosis, Multigene Families, and Interferon-Related Genes

    Science.gov (United States)

    García-Valtanen, Pablo; Martínez-López, Alicia; López-Muñoz, Azucena; Bello-Perez, Melissa; Medina-Gali, Regla M.; Ortega-Villaizán, María del Mar; Varela, Monica; Figueras, Antonio; Mulero, Víctoriano; Novoa, Beatriz; Estepa, Amparo; Coll, Julio

    2017-01-01

    To investigate fish innate immunity, we have conducted organ and cell immune-related transcriptomic as well as immunohistologic analysis in mutant zebra fish (Danio rerio) lacking adaptive immunity (rag1−/−) at different developmental stages (egg, larvae, and adult), before and after infection with spring viremia carp virus (SVCV). The results revealed that, compared to immunocompetent zebra fish (rag1+/+), rag1−/− acquired increased resistance to SVCV with age, correlating with elevated transcript levels of immune genes in skin/fins and lymphoid organs (head kidney and spleen). Gene sets corresponding to apoptotic functions, immune-related multigene families, and interferon-related genes were constitutively upregulated in uninfected adult rag1−/− zebra fish. Overexpression of activated CASPASE-3 in different tissues before and after infection with SVCV further confirmed increased apoptotic function in rag1−/− zebra fish. Concurrently, staining of different tissue samples with a pan-leukocyte antibody marker showed abundant leukocyte infiltrations in SVCV-infected rag1−/− fish, coinciding with increased transcript expression of genes related to NK-cells and macrophages, suggesting that these genes played a key role in the enhanced immune response of rag1−/− zebra fish to SVCV lethal infection. Overall, we present evidence that indicates that rag1−/− zebra fish acquire an antiviral alert state while they reach adulthood in the absence of adaptive immunity. This antiviral state was characterized by (i) a more rapid response to viral infection, which resulted in increased survival, (ii) the involvement of NK-cell- and macrophage-mediated transcript responses rather than B- and/or T-cell dependent cells, and (iii) enhanced apoptosis, described here for the first time, as well as the similar modulation of multigene family/interferon-related genes previously associated to fish that survived lethal viral infections. From this and other studies

  1. Microbial Dysbiosis in Common Variable Immune Deficiencies : Evidence, Causes, and Consequences

    NARCIS (Netherlands)

    Berbers, Roos-Marijn; Nierkens, Stefan; van Laar, Jacob M.; Bogaert, Debby; Leavis, Helen L.

    2017-01-01

    Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver

  2. Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences.

    Science.gov (United States)

    Berbers, Roos-Marijn; Nierkens, Stefan; van Laar, Jacob M; Bogaert, Debby; Leavis, Helen L

    2017-03-01

    Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID. We integrate this evidence into a model describing a role for the gut microbiota in the maintenance of inflammation and immune dysregulation in CVID, and suggest research strategies to contribute to the development of new diagnostic tools and therapeutic targets.

  3. Factors of Innate and Adaptive Local Immunity in Children with Primary Deficiencies of Antibody Formation

    Directory of Open Access Journals (Sweden)

    L.I. Chernyshova

    2013-11-01

    Full Text Available In 40 children with various types of primary immunodeficiencies (PID of antibody formation we examined factors of local immunity in saliva. It is found that in the saliva of children with PID of antibody formation in comparison with immunocompetent children the concentration of factors of adaptive immunity is significantly reduced. Lack of adaptive immunity in the PID of antibody formation to some extent is compensated by increased concentrations of innate immune factors on the mucous membranes — the free Sc, as well as lactoferrin in selective immunodeficiency of IgA. At PID of antibody formation we observed increased TNF-α level in the saliva, which may indicate the persistence of local inflammation on the membranes of the respiratory tract.

  4. Effect of bacillus Calmette-Guérin vaccination on CD4+Foxp3+ T cells during acquired immune response to Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Henao-Tamayo, Marcela I; Obregón-Henao, Andres; Arnett, Kimberly; Shanley, Crystal A; Podell, Brendan; Orme, Ian M; Ordway, Diane J

    2016-04-01

    Increasing information has shown that many newly emerging strains of Mycobacterium tuberculosis, including the highly prevalent and troublesome Beijing family of strains, can potently induce the emergence of Foxp3(+)CD4 Tregs Although the significance of this is still not fully understood, we have previously provided evidence that the emergence of this population can significantly ablate the protective effect of BCG vaccination, causing progressive fatal disease in the mouse model. However, whether the purpose of this response is to control inflammation or to directly dampen the acquired immune response is still unclear. In the present study, we have shown, using both cell depletion and adoptive transfer strategies, that Tregs can have either properties. Cell depletion resulted in a rapid, but transient, decrease in the lung bacterial load, suggesting release or temporary re-expansion of effector immunity. Transfer of Tregs into Rag2(-/-)or marked congenic mice worsened the disease course and depressed cellular influx of effector T cells into the lungs. Tregs from infected donors seemed to preferentially depress the inflammatory response and granulocytic influx. In contrast, those from BCG-vaccinated and then challenged donors seemed more focused on depression of acquired immunity. These qualitative differences might be related to increasing knowledge reflecting the plasticity of the Treg response.

  5. Common variable immune deficiency associated Hodgkin’s lymphoma complicated with EBV-linked hemophagocytic lymphohistiocytosis: a case report

    Science.gov (United States)

    Malkan, Umit Yavuz; Gunes, Gursel; Aslan, Tuncay; Etgul, Sezgin; Aydin, Seda; Buyukasik, Yahya

    2015-01-01

    Hemophagocytic syndrome (HPS) is described by an increase in macrophages accountable for extensive phagocytosis of hematopoietic cells. Secondary HPS arises commonly in the presence of infections, neoplasia, autoimmune disorders and immune disorders. Here, we reported a patient with common variable immune deficiency (CVID) and Hodgkin’s lymphoma (HL) who later developed EBV linked hemophagocytic lymphohistiocytosis. 42 year old men underwent check-up because of back pain in July 2012. He had known CVID disease. In physical examination he had no lymphadenopathies however his spleen was palpable 3 cm under arcus costa. He had hypogammaglobulinemia with IgG levels around 500 mg/dl. In abdominal computed tomography (CT) multiple lymphadenopathies reaching maximum 26×17 cm size were seen so, PET-CT was performed. Involvement in thorax, abdomen, and bone was detected with maximum SUV max 11.5. He had undergone tru-cut biopsy from lymph node in November 2012 which revealed HL. Bone marrow investigation favored with mix cell type. His cytogenetic analysis was reported as 46 XY. He was considered as stage 4 disease and ABVD (Adriamycin, bleomycin, vincristine and dexamethasone). He was given six cycles of chemotherapy in May 2013 and complete remission was observed in control CT screening in July 2013. However pancytopenia evolved in August 2013. Bone marrow investigation revealed suspicious lymphohistiocytic infiltration. Treatment was planned to apply autologous stem cell transplantation (SCT) after salvage chemotherapy. Control bone marrow investigation again revealed the lymphohistiocytic aggregates with hemophagocytosis. Our patient showed 5 criteria of hemophagocytic syndrome. He had ferritin elevation (>5000 μg/dl), splenomegaly (13 cm) cytopenia, triglyceride elevation and hemophagocytosis. He had unrelated SCT transplantation however he died from transplant related toxicity. The primary and secondary immune deficiency caused by chemotherapy are the major causes

  6. Morph-specific genetic and environmental variation in innate and acquired immune response in a color polymorphic raptor.

    Science.gov (United States)

    Gangoso, Laura; Roulin, Alexandre; Ducrest, Anne-Lyse; Grande, Juan Manuel; Figuerola, Jordi

    2015-08-01

    Genetic color polymorphism is widespread in nature. There is an increasing interest in understanding the adaptive value of heritable color variation and trade-off resolution by differently colored individuals. Melanin-based pigmentation is often associated with variation in many different life history traits. These associations have recently been suggested to be the outcome of pleiotropic effects of the melanocortin system. Although pharmacological research supports that MC1R, a gene with a major role in vertebrate pigmentation, has important immunomodulatory effects, evidence regarding pleiotropy at MC1R in natural populations is still under debate. We experimentally assessed whether MC1R-based pigmentation covaries with both inflammatory and humoral immune responses in the color polymorphic Eleonora's falcon. By means of a cross-fostering experiment, we disentangled potential genetic effects from environmental effects on the covariation between coloration and immunity. Variation in both immune responses was primarily due to genetic factors via the nestlings' MC1R-related color genotype/phenotype, although environmental effects via the color morph of the foster father also had an influence. Overall, dark nestlings had lower immune responses than pale ones. The effect of the color morph of the foster father was also high, but in the opposite direction, and nestlings raised by dark eumelanic foster fathers had higher immune responses than those raised by pale foster fathers. Although we cannot completely discard alternative explanations, our results suggest that MC1R might influence immunity in this species. Morph-specific variation in immunity as well as pathogen pressure may therefore contribute to the long-term maintenance of genetic color polymorphism in natural populations.

  7. Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Leung, Wing; Neale, Geoffrey; Behm, Fred; Iyengar, Rekha; Finkelstein, David; Kastan, Michael B; Pui, Ching-Hon

    2010-06-01

    Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (alphabetaT cells and CD45RO+/RA- memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (gammadeltaT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO-/RA+ naïve T cell and less SjTREC levels in the blood, whereas the Vbeta spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole-genome scanning by SNP microarray analysis. ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  8. The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients.

    Directory of Open Access Journals (Sweden)

    Atar Lev

    Full Text Available The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2-deficient severe combined immunodeficiency (SCID patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR and the B cell receptor (BCR repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT.

  9. Vitamin A Deficiency Impairs Mucin Expression and Suppresses the Mucosal Immune Function of the Respiratory Tract in Chicks.

    Science.gov (United States)

    Fan, Xiaoxiao; Liu, Shaoqiong; Liu, Guanhua; Zhao, Jingpeng; Jiao, Hongchao; Wang, Xiaojuan; Song, Zhigang; Lin, Hai

    2015-01-01

    The chicken immune system is immature at the time of hatching. The development of the respiratory immune system after hatching is vital to young chicks. The aim of this study was to investigate the effect of dietary vitamin A supplement levels on respiratory mucin and IgA production in chicks. In this study, 120 one-day-old broiler chicks were randomly divided into 4 groups consisting of three replicates of 10 broilers and subjected to dietary vitamin A supplement levels of 0, 1,500, 6,000, or 12,000 IU/kg for seven days. Compared with control birds, vitamin A supplementation significantly increased the mucin and IgA levels in the bronchoalveolar lavage fluid (BALF) as well as the IgA level in serum. In the lungs, vitamin A supplementation downregulated TNF-α and EGFR mRNA expression. The TGF-β and MUC5AC mRNA expression levels were upregulated by vitamin A supplementation at a dose of 6,000 IU/kg, and the IL-13 mRNA expression level was increased at the 12,000 IU/kg supplement level. Vitamin A deficiency (control) significantly decreased the mRNA expression levels of MUC2, IgA, EGFR, IL-13 and TGF-β in trachea tissue. Histological section analysis revealed that the number of goblet cells in the tracheal epithelium was less in the 0 and 12,000 IU/kg vitamin A supplement groups than in the other groups. In conclusion, vitamin A deficiency suppressed the immunity of the airway by decreasing the IgA and mucin concentrations in neonatal chicks. This study suggested that a suitable level of vitamin A is essential for the secretion of IgA and mucin in the respiratory tract by regulating the gene expression of cytokines and epithelial growth factors.

  10. Effect of threonine deficiency on intestinal integrity and immune response to coccidiosis in broiler chicks

    Science.gov (United States)

    For this study, threonine (Thr) deficiency was hypothesized to exacerbate the intestinal damage induced by feed withdrawal and coccidiosis infection because of its high obligatory requirement of the gut. Two dietary Thr treatments (0.49 and 0.90%) were fed to chicks from 1-21 d of age. At 13 d of a...

  11. Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

    Science.gov (United States)

    2016-08-15

    SCID; Omenn's Syndrome; Reticular Dysgenesis; Wiskott-Aldrich Syndrome; Bare Lymphocyte Syndrome; Common Variable Immunodeficiency; Chronic Granulomatous Disease; CD40 Ligand Deficiency; Hyper IgM Syndrome; X-linked Lymphoproliferative Disease; Hemophagocytic Lymphohistiocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Langerhan's Cell Histiocytosis

  12. Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes.

    Science.gov (United States)

    Madore, Charlotte; Nadjar, Agnès; Delpech, Jean-Christophe; Sere, A; Aubert, A; Portal, Céline; Joffre, Corinne; Layé, Sophie

    2014-10-01

    Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs low dietary intake and neurodevelopmental disorders are poorly understood. Microglia, known mainly for their immune function in the injured or infected brain, have recently been demonstrated to play a pivotal role in regulating maturation of neuronal circuits during normal brain development. Disruption of this role during the perinatal period therefore could significantly contribute to psychopathologies with a neurodevelopmental neurodevelopmental component. N-3 PUFAs, essential lipids and key structural components of neuronal membrane phospholipids, are highly incorporated in cell membranes during the gestation and lactation phase. We previously showed that in a context of perinatal n-3 PUFAs deficiency, accretion of these latter is decreased and this is correlated to an alteration of endotoxin-induced inflammatory response. We thus postulated that dietary n-3 PUFAs imbalance alters the activity of microglia in the developing brain, leading to abnormal formation of neuronal networks. We first confirmed that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated that n-3 PUFAs deficiency altered microglia phenotype and motility in the post-natal developing brain. This was paralleled by an increase in pro-inflammatory cytokines expression at PND21 and to modification of neuronal plasticity-related genes expression. Overall, our findings show for the first time that a dietary n-3 PUFAs deficiency from the first day of gestation leads to the development of a pro-inflammatory condition in the central nervous system that may contribute to neurodevelopmental alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Disaccharidase deficiency.

    Science.gov (United States)

    Bayless, T M; Christopher, N L

    1969-02-01

    This review of the literature and current knowledge concerning a nutritional disorder of disaccharidase deficiency discusses the following topics: 1) a description of disorders of disaccharide digestion; 2) some historical perspective on the laboratory and bedside advances in the past 10 years that have helped define a group of these digestive disorders; 3) a classification of conditions causing disaccharide intolerance; and 4) a discussion of some of the specific clinical syndromes emphasizing nutritional consequences of these syndromes. The syndromes described include congenital lactase deficiency, acquired lactase deficiency in teenagers and adults, acquired generalized disaccharidase deficiency secondary to diffuse mucosal damage, acquired lactose intolerance secondary to alterations in the intestinal transit, sucrase-isomaltase deficiencies, and other disease associations connected with lactase deficiency such as colitis.

  14. Evaluation of a Salmonella Enteritidis vaccine and related ELISA for respective induction and assessment of acquired immunity to the vaccine and/or Echinacea purpurea in Awassi Ewes.

    Science.gov (United States)

    Barbour, Elie K; Assi, Chibli A Abou; Shaib, Houssam; Hamadeh, Shadi; Murtada, Muhammad; Mahmoud, Ghassan; Yaghmoor, Soonham; Iyer, Archana; Harakeh, Steve; Kumosani, Taha

    2015-05-05

    The aim of this study was to evaluate an experimental Salmonella Enteritidis (SE) bacterin and an indirect ELISA system to assess quantitatively the acquired immunity in Awassi ewes to the vaccine and/or Echinacea purpurea (EP) dried roots. Four treatments of the ewes were included in the experimental design, with 6 ewes/treatment. The first treatment (T1) had the controls that were non-vaccinated and non-treated with EP. The T2 ewes were only treated with EP. The T3 and T4 ewes were vaccinated at D1 (initiation of trial) and D10, while the T4 ewes were additionally administered the EP dried roots. Blood was collected from the jugular vein of all ewes at D1, D10, D21 and D45. The construction of the vaccine and the ELISA are detailed within the manuscript. The ELISA was able to detect quantitatively the significant acquired primary and secondary immunity to the vaccine in T3 and T4 ewes, compared to their low level of background immunities at initiation of the experiment (p0.05) in T1 control ewes, and in the T2 ewes that were given only the (EP) (p>0.05). Moreover, the ELISA was able to uncover the significant seroconversion of secondary immune response in T4 ewes at D21 compared to that at D10 (p<0.05), and the absence of significant seroconversion of secondary response in T3 ewes. This is the first work in literature that reports the need to supplement the vaccination by the experimental SE bacterin with daily oral intake of 250mg of EP-dried roots, effective the first vaccination day and up to 21 days, for obtaining a statistically significant seroconversion.

  15. Serine protease inhibitor 6-deficient mice have increased neutrophil immunity to Pseudomonas aeruginosa.

    Science.gov (United States)

    Zhang, Manling; Liu, Ni; Park, Sun-Mi; Wang, Yue; Byrne, Susan; Murmann, Andrea E; Bahr, Scott; Peter, Marcus E; Olson, Steven T; Belaaouaj, Abderrazzaq; Ashton-Rickardt, Philip G

    2007-10-01

    Inflammation is a localized, protective response to trauma or microbial invasion that destroys the injurious agent and the injured tissue. Neutrophil elastase (NE), a serine protease stored in the azurophil granules of polymorphonuclear neutrophils, digests microbes after phagocytosis. NE can also digest microbes extracellularly but is associated with tissue damage and inflammatory disease. In this study, we show that polymorphonuclear neutrophils from mice deficient in serine protease inhibitor 6, a weak intracellular NE inhibitor, had increased susceptibility to self-inflicted lysis because of increased NE activity. The resulting transient increase in local extracellular NE activity was within a narrow range that resulted in the clearance of Pseudomonas aeruginosa but did not damage the lung. Therefore, deficiency in a weak intracellular inhibitor of NE results in an acute inflammatory response that protects from P. aeruginosa but does not cause lung disease.

  16. Molecular pathology of mismatch repair deficient tumours with emphasis on immune escape mechanisms

    NARCIS (Netherlands)

    Dierssen, Jan Willem Frederik

    2010-01-01

    This thesis describes molecular methods to distinguish separate colon tumour entities. Furthermore, it shows that distinct immune escape mechanisms, in particular distinct mechanisms of corrupting the HLA system, are operational in subsets of colon tumours. The apparent necessity of some colon tumou

  17. Immune deficiency augments the prevalence of p53 loss of heterozygosity in spontaneous tumors but not bi-directional loss of heterozygosity in bone marrow progenitors.

    Science.gov (United States)

    Shetzer, Yoav; Napchan, Yael; Kaufman, Tom; Molchadsky, Alina; Tal, Perry; Goldfinger, Naomi; Rotter, Varda

    2017-03-15

    p53 loss of heterozygosity (LOH) is a frequent event in tumors of somatic and Li-Fraumeni syndrome patients harboring p53 mutation. Here, we focused on resolving a possible crosstalk between the immune-system and p53 LOH. Previously, we reported that p53 heterozygous bone-marrow mesenchymal progenitor cells undergo p53 LOH in-vivo. Surprisingly, the loss of either the wild-type p53 allele or mutant p53 allele was detected with a three-to-one ratio in favor of losing the mutant allele. In this study, we examined whether the immune-system can affect the LOH directionality in bone marrow progenitors. We found that mesenchymal progenitor cells derived from immune-deficient mice exhibited the same preference of losing the mutant p53 allele as immune-competent matched cells, nevertheless, these animals showed a significantly shorter tumor-free survival, indicating the possible involvement of immune surveillance in this model. Surprisingly, spontaneous tumors of p53 heterozygous immune-deficient mice exhibited a significantly higher incidence of p53 LOH compared to that observed in tumors derived of p53 heterozygous immune-competent mice. These findings indicate that the immune-system may affect the p53 LOH prevalence in spontaneous tumors. Thus suggesting that the immune-system may recognize and clear cells that underwent p53 LOH, whereas in immune-compromised mice, those cells will form tumors with shorter latency. In individuals with a competent immune-system, p53 LOH independent pathways may induce malignant transformation which requires a longer tumor latency. Moreover, this data may imply that the current immunotherapy treatment aimed at abrogating the inhibition of cellular immune checkpoints may be beneficial for LFS patients.

  18. Hematopoietic Stem Cell Transplantations for Primary Immune Deficiencies: 3 Decades of Experience From a Tertiary Medical Center.

    Science.gov (United States)

    Rousso, Sharon Z; Shamriz, Oded; Zilkha, Amir; Braun, Jacques; Averbuch, Diana; Or, Reuven; Weintraub, Michael; Revel-Vilk, Shoshana; Stepensky, Polina

    2015-07-01

    Hematopoietic stem cell transplantation (HSCT) remains the leading treatment for the majority of severe primary immune deficiency (PID). This study aims to analyze changes in outcome over time. We conducted a retrospective analysis of HSCT in children with PID in a tertiary medical center over the period of 1983 to 2012. We identified 93 children with PID with a median follow-up of 3.6 years (range, 29 d to 21.2 y) after HSCT. The 2-year survival rates after HSCT for children with severe combined immune deficiency, hemophagocytic lymphohistiocytosis/lymphoproliferative disease, Wiskott-Aldrich syndrome, granulocyte defect, and undefined PID were 65.7%±6.8%, 80%±10.3%, 83.3%±15.2%, 75%±12.5%, and 25%±21.7%, respectively. Survival was associated with year of HSCT and matching. The hazard ratio (HR) (95% CI) for HSCT done in 1983 to 1999 compared with 2000 to 2012 and for matched (related and unrelated) compared with mismatched donor were 2.14 (0.99 to 4.653) and 3.07 (1.46 to 6.4), respectively. Survival was not associated with age, sex of the recipient, underlying PID, conditioning regimen, and presence of acute graft-versus-host disease. After adjustment to the underlying PID, donor and use of fludarabine-based conditioning, the HR (95% CI) for HSCT from the year 2000 was 4.69 (range, 1.4 to 15.45). Advances in HSCT over time have improved the survival of children with PID.

  19. Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

    Energy Technology Data Exchange (ETDEWEB)

    Holásková, Ida; Elliott, Meenal; Hanson, Miranda L.; Schafer, Rosana [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV 26506 (United States)

    2012-12-01

    Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4{sup −}CD8{sup −}CD44{sup +}CD25{sup −} (DN1) thymocytes in both sexes and a decrease in the percent of CD4{sup −}CD8{sup −}CD44{sup −}CD25{sup +} (DN3) thymocytes in females. Females had an increase in the percent of splenic CD4{sup +} T cells, CD8{sup +} T cells, and CD45R/B220{sup +} B cells and a decrease in the percent of NK cells and granulocytes (Gr-1{sup +}). Males had an increase in the percent of splenic CD4{sup +} T cells and CD45R/B220{sup +} B cells and a decrease in the percent of CD8{sup +} T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed

  20. Altered Innate Immunity Confers Staphylococcus aureus resistance in O-Glycosylation Deficient Caenorhabditis elegans bus Mutants

    Science.gov (United States)

    2017-01-31

    the cuticle of Caenorhabditis elegans. Genetics 187, 141-155. 45. Gu, X. (2003). Evolution of duplicate genes versus genetic robustness against null...aureus. This work demonstrates a genetic link between O-glycosylation and expression of key components of the innate immune response...Introduction: The bus mutants were isolated in genetic screens for altered susceptibility to the nematode specific pathogen Microbacterium nematophilum

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Postmenopausal osteoporosis in rheumatoid arthritis: The estrogen deficiency-immune mechanisms link.

    Science.gov (United States)

    Sapir-Koren, Rony; Livshits, Gregory

    2017-10-01

    Rheumatoid arthritis (RA) is characterized, among other factors, by systemic bone loss, reaching ~50% prevalence of osteoporosis in postmenopausal women. This is roughly a doubled prevalence in comparison with age-matched non-RA women. Postmenopausal RA women are more likely to be sero-positive for the anti-citrullinated peptide antibody (ACPA). Our extensive review of recent scientific literature enabled us to propose several mechanisms as responsible for the accelerated bone loss in ACPA(+) RA postmenopausal women. Menopause-associated estrogen deficiency plays a major role in these pathological mechanisms, as follows. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants.

    Directory of Open Access Journals (Sweden)

    April Kaur Randhawa

    2011-08-01

    Full Text Available The development of effective immunoprophylaxis against tuberculosis (TB remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S was associated with increased BCG-induced IFN-γ in both discovery (n = 240 and validation (n = 240 cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S and TLR6_G1083C (synonymous were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2. After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the

  4. B cell-specific deficiencies in mTOR limit humoral immune responses.

    Science.gov (United States)

    Zhang, Shuling; Pruitt, Margaret; Tran, Dena; Du Bois, Wendy; Zhang, Ke; Patel, Rushi; Hoover, Shelley; Simpson, R Mark; Simmons, John; Gary, Joy; Snapper, Clifford M; Casellas, Rafael; Mock, Beverly A

    2013-08-15

    Generation of high-affinity Abs in response to Ags/infectious agents is essential for developing long-lasting immune responses. B cell maturation and Ab responses to Ag stimulation require Ig somatic hypermutation (SHM) and class-switch recombination (CSR) for high-affinity responses. Upon immunization with either the model Ag 4-hydroxy-3-nitrophenylacetyl hapten (NP) conjugated to chicken γ globulin lysine (NP-CGG) or heat-killed Streptococcus pneumoniae capsular type 14 protein (Pn14), knock-in (KI) mice hypomorphic for mTOR function had a decreased ability to form germinal centers, develop high-affinity anti-NP-specific or anti-Pn14-specific Abs, and perform SHM/CSR. Hypomorphic mTOR mice also had a high mortality (40%) compared with wild-type (WT) (0%) littermates and had lower pneumococcal surface protein A-specific Ab titers when immunized and challenged with live S. pneumoniae infection. Mice with mTOR deleted in their B cell lineage (knockout [KO]) also produced fewer splenic germinal centers and decreased high-affinity Ab responses to NP-CGG than did their WT littermates. CSR rates were lower in mTOR KI and KO mice, and pharmacologic inhibition of mTOR in WT B cells resulted in decreased rates of ex vivo CSR. RNA and protein levels of activation-induced cytidine deaminase (AID), a protein essential for SHM and CSR, were lower in B cells from both KI and B cell-specific KO mice, concomitant with increases in phosphorylated AKT and FOXO1. Rescue experiments increasing AID expression in KI B cells restored CSR levels to those in WT B cells. Thus, mTOR plays an important immunoregulatory role in the germinal center, at least partially through AID signaling, in generating high-affinity Abs.

  5. Seeding efficiency of primitive human hematopoietic cells in nonobese diabetic/severe combined immune deficiency mice: implications for stem cell frequency assessment

    NARCIS (Netherlands)

    P.B. van Hennik; A.E. de Koning (Alexandra); R.E. Ploemacher (Robert)

    1999-01-01

    textabstractNonobese diabetic/severe combined immune deficiency (NOD/SCID) mouse repopulating cells (SRC) have been proposed to represent a more primitive human stem cell subset than the cobblestone area-forming cell (CAFC) week (wk) 6 or the long-term

  6. Seeding efficiency of primitive human hematopoietic cells in nonobese diabetic/severe combined immune deficiency mice: implications for stem cell frequency assessment

    NARCIS (Netherlands)

    P.B. van Hennik; A.E. de Koning (Alexandra); R.E. Ploemacher (Robert)

    1999-01-01

    textabstractNonobese diabetic/severe combined immune deficiency (NOD/SCID) mouse repopulating cells (SRC) have been proposed to represent a more primitive human stem cell subset than the cobblestone area-forming cell (CAFC) week (wk) 6 or the long-term culture-initiatin

  7. Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence.

    Science.gov (United States)

    Strowig, Till; Chijioke, Obinna; Carrega, Paolo; Arrey, Frida; Meixlsperger, Sonja; Rämer, Patrick C; Ferlazzo, Guido; Münz, Christian

    2010-11-18

    To investigate human natural killer (NK)-cell reactivity in vivo we have reconstituted human immune system components by transplantation of human hematopoietic progenitor cells into NOD-scid IL2Rγ(null) mice. We demonstrate here that this model allows the development of all NK-cell subsets that are also found in human adult peripheral and cord blood, including NKp46(+)CD56(-) NK cells. Similar to human cord blood, NK cells from these reconstituted mice require preactivation by interleukin-15 to reach the functional competence of human adult NK cells. Mainly the terminally differentiated CD16(+) NK cells demonstrate lower reactivity without this stimulation. After preactivation, both CD16(+) and CD16(-) NK cells efficiently produce interferon-γ and degranulate in response to stimulation with NK cell-susceptible targets, including K562 erythroleukemia cells. NK-cell lines, established from reconstituted mice, demonstrate cytotoxicity against this tumor cell line. Importantly, preactivation can as well be achieved by bystander cell maturation via poly I:C stimulation in vitro and injection of this maturation stimulus in vivo. Preactivation in vivo enhances killing of human leukocyte antigen class I negative tumor cells after their adoptive transfer. These data suggest that a functional, but resting, NK-cell compartment can be established in immune-compromised mice after human hematopoietic progenitor cell transfer.

  8. Dysregulated TLR3-dependent signaling and innate immune activation in superoxide-deficient macrophages from nonobese diabetic mice.

    Science.gov (United States)

    Seleme, Maria C; Lei, Weiqi; Burg, Ashley R; Goh, Kah Yong; Metz, Allison; Steele, Chad; Tse, Hubert M

    2012-05-01

    In type 1 diabetes (T1D), reactive oxygen species (ROS) and proinflammatory cytokines produced by macrophages and other innate immune cells destroy pancreatic β cells while promoting autoreactive T cell maturation. Superoxide-deficient nonobese diabetic mice (NOD.Ncf1(m1J)) are resistant to spontaneous diabetes, revealing the integral role of ROS signaling in T1D. Here, we evaluate the innate immune activation state of bone marrow-derived macrophages (BM-Mϕ) from NOD and NOD.Ncf1(m1J) mice after poly(I:C)-induced Toll-like receptor 3 (TLR3) signaling. We show that ROS synthesis is required for efficient activation of the NF-κB signaling pathway and concomitant expression of TLR3 and the cognate adaptor molecule, TRIF. Poly(I:C)-stimulated NOD.Ncf1(m1J) BM-Mϕ exhibited a 2- and 10-fold decrease in TNF-α and IFN-β proinflammatory cytokine synthesis, respectively, in contrast to NOD BM-Mϕ. Optimal expression of IFN-α/β is not solely dependent on superoxide synthesis, but requires p47(phox) to function in a NOX-independent manner to mediate type I interferon synthesis. Interestingly, MHC-II I-A(g7) expression necessary for CD4 T cell activation is increased 2-fold relative to NOD, implicating a role for superoxide in I-A(g7) downregulation. These findings suggest that defective innate immune-pattern-recognition receptor activation and subsequent decrease in TNF-α and IFN-β proinflammatory cytokine synthesis necessary for autoreactive T cell maturation may contribute to the T1D protection observed in NOD.Ncf1(m1J) mice.

  9. Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Michelle A Favila

    2015-12-01

    Full Text Available Leishmania major infection induces robust interleukin-12 (IL12 production in human dendritic cells (hDC, ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG and other phosphoglycan-containing molecules (PGs, making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS responsible for IL12 induction.Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-, or generally deficient for all PGs, (FV1 lpg2-. Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB and Interferon Regulatory Factor (IRF mediated transcription.These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12.

  10. Nogo-receptor 1 deficiency has no influence on immune cell repertoire or function during experimental autoimmune encephalomyelitis.

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    Sara A Litwak

    Full Text Available The potential role of Nogo-66 Receptor 1 (NgR1 on immune cell phenotypes and their activation during neuroinflammatory diseases such as multiple sclerosis (MS and its animal model, experimental autoimmune encephalomyelitis (EAE, is unclear. To further understand the function of this receptor on haematopoietically-derived cells, phenotypic and functional analyses were performed using NgR1-deficient (ngr1-/- animals. Flow cytometry-based phenotypic analyses performed on blood, spleen, thymus, lymph nodes, bone marrow and central nervous-system (CNS-infiltrating blood cells revealed no immunological defects in naïve ngr1-/- animals versus wild-type littermate (WTLM controls. EAE was induced by either recombinant myelin oligodendrocyte glycoprotein (rMOG, a model in which B cells are considered to contribute pathogenically, or by MOG35-55 peptide, a B cell-independent model. We have demonstrated that in ngr1-/- mice injected with MOG35-55, a significant reduction in the severity of EAE correlated with reduced axonal damage present in the spinal cord when compared to their WTLM controls. However, despite a reduction in axonal damage observed in the CNS of ngr1-/- mice at the chronic stage of disease, no clinical differences could be attributed to a specific genotype when rMOG was used as the encephalitogen. Following MOG35-55-induction of EAE, we could not derive any major changes to the immune cell populations analyzed between ngr1-/- and WTLM mice. Collectively, these data demonstrate that NgR1 has little if any effects on the repertoire of immune cells, their activation and trafficking to the CNS.

  11. Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

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    Thorsten Peters

    2012-01-01

    Full Text Available Absence of β2 integrins (CD11/CD18 leads to leukocyte-adhesion deficiency-1 (LAD1, a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−. CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT. In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl21 acetyl chicken γ globulin (NP21-CG, even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.

  12. Feasibility of Measuring Immune Resp, Activation in Foreskin/Mucosa in HIV-, Uncircumcised High-HIV-risk MSM, Lima Peru

    Science.gov (United States)

    2015-12-10

    HIV Infections; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

  13. Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response

    DEFF Research Database (Denmark)

    Bonefeld, C. M.; Petersen, T. H.; Bandier, J.

    2016-01-01

    Background: Cellular T-helper (Th)17 infiltrates dominate skin inflammation in filaggrin-deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss-of-function mutations in the filaggrin gene...... (FLG) for increased peripheral Th17 cells is unclear. Objectives: To study whether mutations in FLG influence the frequency of peripheral Th17 cells. Methods: We studied blood samples from six adults with mutations in FLG and five controls without mutations for frequencies of cytokine-producing CD4+ T...... increased frequency of peripheral Th17 cells in FLG mutation carriers when compared with WT individuals. Mouse studies showed increased frequency of peripheral Th17 cells in adult ft/ft mice but not in 2-week-old ft/ft mice. Moreover, altered TCR Vβ-chain repertoire was found in ft/ft mice when compared...

  14. IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

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    Daniel A Rauch

    Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

  15. IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

    Science.gov (United States)

    Rauch, Daniel A; Harding, John C; Ratner, Lee

    2014-01-01

    IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL) and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/-) TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

  16. Alterations in early cytokine-mediated immune responses to Plasmodium falciparum infection in Tanzanian children with mineral element deficiencies: a cross-sectional survey

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    Jeurink Prescilla V

    2010-05-01

    Full Text Available Abstract Background Deficiencies in vitamins and mineral elements are important causes of morbidity in developing countries, possibly because they lead to defective immune responses to infection. The aim of the study was to assess the effects of mineral element deficiencies on early innate cytokine responses to Plasmodium falciparum malaria. Methods Peripheral blood mononuclear cells from 304 Tanzanian children aged 6-72 months were stimulated with P. falciparum-parasitized erythrocytes obtained from in vitro cultures. Results The results showed a significant increase by 74% in geometric mean of TNF production in malaria-infected individuals with zinc deficiency (11% to 240%; 95% CI. Iron deficiency anaemia was associated with increased TNF production in infected individuals and overall with increased IL-10 production, while magnesium deficiency induced increased production of IL-10 by 46% (13% to 144% in uninfected donors. All donors showed a response towards IL-1β production, drawing special attention for its possible protective role in early innate immune responses to malaria. Conclusions In view of these results, the findings show plasticity in cytokine profiles of mononuclear cells reacting to malaria infection under conditions of different micronutrient deficiencies. These findings lay the foundations for future inclusion of a combination of precisely selected set of micronutrients rather than single nutrients as part of malaria vaccine intervention programmes in endemic countries.

  17. Vitamin Supplementation at the Time of Immunization with a Cold-Adapted Influenza Virus Vaccine Corrects Poor Mucosal Antibody Responses in Mice Deficient for Vitamins A and D.

    Science.gov (United States)

    Surman, S L; Penkert, R R; Jones, B G; Sealy, R E; Hurwitz, J L

    2016-01-06

    Vitamin A and D deficiencies and insufficiencies are prevalent worldwide in developed and developing countries. Vitamin metabolites are functionally intertwined in that they are high-affinity ligands for related receptors of the nuclear receptor superfamily. The effects of vitamin A deficiencies (VAD) on antibody responses to respiratory virus vaccines have already been demonstrated. Of particular concern was the reduction in IgA, a first line of defense against pathogens in the respiratory tract. Here, we describe the individual and combined effects of vitamin A and D deficiencies in mice immunized with an attenuated influenza virus vaccine. Relative to VAD, vitamin D deficiency (VDD) had a limited effect, but double deficiencies for vitamins A and D (VAD+VDD) further reduced antibody responses in the respiratory tract. The administration of supplemental vitamins A and D to VAD+VDD mice at the time of vaccination restored responses in a dose-dependent manner. Results suggest that vitamin supplementation programs may be beneficial in a clinical setting to promote healthy immune responses to respiratory virus vaccines in vitamin-deficient individuals.

  18. Knowledge, attitude, and perception of disease among persons living with human immunodeficiency virus/acquired immuno deficiency syndrome: A study from a tertiary care center in North India

    Directory of Open Access Journals (Sweden)

    Mrinal Gupta

    2016-01-01

    Full Text Available Background: Although modification of behavioral practices among human immunodeficiency virus (HIV-affected patients is important in decreasing HIV disease transmission, the knowledge, attitude, and perception studies about HIV infection rarely include persons living with HIV/acquired immuno deficiency syndrome (AIDS. Aims: To assess knowledge, attitude, and perceptions of persons living with HIV/AIDS for the disease and other epidemiological aspects. Materials and Methods: One-hundred and fifty consecutive persons living with HIV/AIDS were enrolled for this questionnaire-based cross-sectional, descriptive study. Results: These 150 patients comprised 93 men and 57 women, aged between 14 and 78 (mean 37.13 years. The majority, 112 (74.67% patients were between 20 and 50 years of age and 116 (77.3% patients were either illiterate or high-school dropouts. Drivers, laborers, and self-employed comprised 69 (74.2% patients among affected males. Only 129 (86% respondents had heard about HIV/AIDS and knew about its heterosexual transmission. Ninety-eight (65.3% respondents were aware of disease transmission from infected blood or needle pricks. Interestingly, 106 (70.7% respondents were aware of the importance of using condom in preventing disease transmission. Television/radio was the most common sources of information for 135 (90% patients. Nearly, 69% respondents disfavored disclosing their disease to friends/colleagues fearing stigmatization. Conclusions: Information, education, and communication activities are imperative to educate persons living with HIV/AIDS about life-long nature of the disease, modes of its transmission, and significance of preventive measures to bridge the gaps in their knowledge. While improvement in individual economic status, education, and health services remains highly desirable, mass media can play a pivotal role in creating awareness among masses.

  19. Efeitos da deficiência de cobre, zinco e magnésio sobre o sistema imune de crianças com desnutrição grave Effects of copper, zinc and magnesium deficiency on the immune system of severely malnourished children

    Directory of Open Access Journals (Sweden)

    Érika Michelle C. de Macêdo

    2010-09-01

    studies published during the last decade were chosen. DATA SYNTHESIS: Micronutrients are essential organic compounds. Besides their regulatory function, the minerals act on the modulation of the immune response. Their deficiency may be due to inadequate intake or associated with specific diseases. When combined with malnutrition, a multimineral deficiency can cause immune dysfunction and increased susceptibility to infections, altering the effectiveness of therapeutic interventions. Copper, zinc and magnesium act as co-factors of both enzymes responsible for several metabolic activities and associated to the innate and acquired immune response. These minerals also play an important role in the maturation of lymphoid tissues and cells. Their deficiency causes neutropenia and lymphopenia, decreasing the immunocompetence. CONCLUSIONS: Deficits of serum copper, zinc and magnesium affect the function of the immune system, leading to immunosuppression. The replacement of these elements in the management of severe malnutrition, as recommended by the World Health Organization, is essential, since such changes may be reversible.

  20. Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation.

    Science.gov (United States)

    Thomé, Rodolfo; Issayama, Luidy K; Alves da Costa, Thiago; Gangi, Rosária D; Ferreira, Isadora T; Rapôso, Catarina; Lopes, Stefanie C P; da Cruz Höfling, Maria Alice; Costa, Fábio T M; Verinaud, Liana

    2014-10-01

    Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.

  1. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Aitken, R.; Coulson, P.S.; Wilson, R.A.

    1988-05-15

    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

  2. Complex regional pain syndrome treated with intravenous immunoglobulin in a patient with common variable immune deficiency.

    Science.gov (United States)

    Tachdjian, Raffi

    2013-12-01

    Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody-deficiency syndromes associated with a wide range of clinical features and a lack of defined causes in the realm of primary immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male patient with a history of longstanding complex regional pain syndrome (CRPS). His medical history included multiple sinus infections per year and several pneumonias requiring antibiotics. He has had various back surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis. Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief. Blood chemistries showed a normal white blood cell count with a normal differential, but increased erythrocyte sedimentation rate and C-reactive protein levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425 mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106), and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131 mg/dL (40-230), and IgE was 4.5 kU/L (<4.0). He only had 10 of 23 pneumococcal titers in the protective range post-vaccination. Upon treatment of the CVID with intravenous immunoglobulin, the patient's pain levels were significantly decreased and have been maintained for more than 2 years. Therefore, immunoglobulin therapy appears to have been beneficial in the treatment of the patient's symptoms of CRPS, including pain. Additional studies investigating the mechanism by which immunoglobulin therapy may reduce the inflammation and pain of CRPS are needed.

  3. Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency

    Science.gov (United States)

    Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J.; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M.; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte

    2016-01-01

    Background Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Objectives Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Methods Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. Results The linage-negative, CD127+, CD161+ lymphoid population containing T-box transcription factor, retinoic acid–related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ+RORγt+CD3− cells were identified, suggesting a role in these mucosal inflammatory states. Conclusions An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. PMID:26542033

  4. Exacerbated fatigue and motor deficits in interleukin-10-deficient mice after peripheral immune stimulation

    Science.gov (United States)

    Krzyszton, C. P.; Sparkman, N. L.; Grant, R. W.; Buchanan, J. B.; Broussard, S. R.; Woods, J.; Johnson, R. W.

    2008-01-01

    The anti-inflammatory cytokine interleukin (IL)-10 is important for regulating inflammation in the periphery and brain, but whether it protects against infection- or age-related psychomotor disturbances and fatigue is unknown. Therefore, the present study evaluated motor coordination, time to fatigue, and several central and peripheral proinflammatory cytokines in male young adult (3-mo-old) and middle-aged (12-mo-old) wild-type (IL-10+/+) and IL-10-deficient (IL-10−/−) mice after intraperitoneal injection of lipopolysaccharide (LPS) or saline. No age-related differences were observed; therefore, data from the two ages were pooled and analyzed to determine effects of genotype and treatment. LPS treatment increased IL-1β, IL-6, and TNFα mRNA in all brain areas examined in IL-10+/+ and IL-10−/− mice, but to a greater extent and for a longer time in IL-10−/− mice. Plasma IL-1β and IL-6 were increased similarly in IL-10+/+ and IL-10−/− mice 4 h after LPS but remained elevated longer in IL-10−/− mice, whereas TNFα was higher in IL-10−/− mice throughout after LPS treatment. Motor performance and motor learning in IL-10+/+ mice were not affected by LPS treatment; however, both were reduced in IL-10−/− mice treated with LPS compared with those treated with saline. Furthermore, although LPS reduced the time to fatigue in IL-10+/+ and IL-10−/− mice, the effects were exacerbated in IL-10−/− mice. Thus the increased brain and peripheral inflammation induced by LPS in IL-10−/− mice was associated with increased coordination deficits and fatigue. These data suggest that IL-10 may inhibit motor deficits and fatigue associated with peripheral infections via its anti-inflammatory effects. PMID:18650318

  5. The impaired intestinal mucosal immune system by valine deficiency for young grass carp (Ctenopharyngodon idella) is associated with decreasing immune status and regulating tight junction proteins transcript abundance in the intestine.

    Science.gov (United States)

    Luo, Jian-Bo; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu

    2014-09-01

    This study investigated the effects of dietary valine on the growth, intestinal immune response, tight junction proteins transcript abundance and gene expression of immune-related signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). Six iso-nitrogenous diets containing graded levels of valine (4.3-19.1 g kg(-)(1) diet) were fed to the fish for 8 weeks. The results showed that percentage weight gain (PWG), feed intake and feed efficiency of fish were the lowest in fish fed the valine-deficient diet (P valine deficiency decreased lysozyme, acid phosphatase activities and complement 3 content in the intestine (P valine deficiency significantly decreased transcript of Occludin, Claudin b, Claudin c, Claudin 3, and ZO-1 (P valine did not have a significant effect on expression of Claudin 12 in the intestine of grass carp (P > 0.05). In conclusion, valine deficiency decreased fish growth and intestinal immune status, as well as regulated gene expression of tight junction proteins, NF-κB P65, IκBα and TOR in the fish intestine. Based on the quadratic regression analysis of lysozyme activity or PWG, the dietary valine requirement of young grass carp (268-679 g) were established to be 14.47 g kg(-1) diet (4.82 g 100 g(-1) CP) or 14.00 g kg(-1) diet (4.77 g 100 g(-1) CP), respectively.

  6. The role of nuclear medicine in the staging and management of human immune deficiency virus infection and associated diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ankrah, Alfred O.; Sathekge, Mike [Dept. of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Pretoria (South Africa); Glaudemans, Andor W. J. M.; Klein, Hans; Dierckx, Rudi A. J. O. [University of Groningen, University Medical Centre Groningen, Groningen (Netherlands)

    2017-06-15

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  7. Poliovirus excretion among persons with primary immune deficiency disorders: summary of a seven-country study series.

    Science.gov (United States)

    Li, Li; Ivanova, Olga; Driss, Nadia; Tiongco-Recto, Marysia; da Silva, Rajiva; Shahmahmoodi, Shohreh; Sazzad, Hossain M S; Mach, Ondrej; Kahn, Anna-Lea; Sutter, Roland W

    2014-11-01

    Persons with primary immune deficiency disorders (PID), especially those disorders affecting the B-cell system, are at substantially increased risk of paralytic poliomyelitis and can excrete poliovirus chronically. However, the risk of prolonged or chronic excretion is not well characterized in developing countries. We present a summary of a country study series on poliovirus excretion among PID cases. Cases with PID from participating institutions were enrolled during the first year and after obtaining informed consent were tested for polioviruses in stool samples. Those cases excreting poliovirus were followed on a monthly basis during the second year until 2 negative stool samples were obtained. A total of 562 cases were enrolled in Bangladesh, China, Iran, Philippines, Russia, Sri Lanka, and Tunisia during 2008-2013. Of these, 17 (3%) shed poliovirus, including 2 cases with immunodeficient vaccine-derived poliovirus. Poliovirus was detected in a single sample from 5/17 (29%) cases. One case excreted for more than 6 months. None of the cases developed paralysis during the study period. Chronic polioviruses excretion remains a rare event even among individuals with PID. Nevertheless, because these individuals were not paralyzed they would have been missed by current surveillance; therefore, surveillance for polioviruses among PID should be established. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Outer membrane vesicles from flagellin-deficient Salmonella enterica serovar Typhimurium induce cross-reactive immunity and provide cross-protection against heterologous Salmonella challenge

    Science.gov (United States)

    Liu, Qiong; Liu, Qing; Yi, Jie; Liang, Kang; Hu, Bo; Zhang, Xiangmin; Curtiss, Roy; Kong, Qingke

    2016-01-01

    Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infection of multiple serotypes Salmonella. In this study, a flagellin-deficient S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein profiles and cryo-electron microscopy revealed that there were no significant differences between the wild-type and mutant OMVs, with the exception of a large amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non-flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong mucosal antibody responses in mice when administered via the intranasal route in addition to provoking higher cross-reactive immune responses against OMPs isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and intraperitoneal immunization with the non-flagellin OMVs provided efficient protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our results indicate that the flagellin-deficient OMVs may represent a new vaccine platform that could be exploited to facilitate the production of a broadly protective vaccine. PMID:27698383

  9. The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania.

    Directory of Open Access Journals (Sweden)

    Teun Bousema

    Full Text Available BACKGROUND: Naturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens are candidate transmission-blocking vaccines but little is known about the acquisition of sexual stage immunity after exposure to gametocytes, or their longevity and functionality. We conducted a longitudinal study on functional sexual stage immune responses. METHODOLOGY/PRINCIPAL FINDINGS: Parasitaemic individuals (n = 116 were recruited at a health centre in Lower Moshi, Tanzania. Patients presented with gametocytes (n = 16, developed circulating gametocytes by day 7 (n = 69 or between day 7 and 14 (n = 10 after treatment or did not develop gametocytes (n = 21. Serum samples were collected on the first day of gametocytaemia and 28 and 84 days post-enrolment (or d7, 28, 84 after enrolment from gametocyte-negative individuals. Antibody responses to sexual stage antigens Pfs230 and Pfs48/45 were detected in 20.7% (72/348 and 15.2% (53/348 of the samples, respectively, and were less prevalent than antibodies against asexual stage antigens MSP-1(19 (48.1%; 137/285 and AMA-1 (52.4%; 129/246(p<0.001. The prevalence of anti-Pfs230 (p = 0.026 and anti-Pfs48/45 antibodies (p = 0.017 increased with longer duration of gametocyte exposure and had an estimated half-life of approximately 3 months. Membrane feeding experiments demonstrated a strong association between the prevalence and concentration of Pfs230 and Pfs48/45 antibodies and transmission reducing activity (TRA, p<0.01. CONCLUSIONS/SIGNIFICANCE: In a longitudinal study, anti-Pfs230 and Pfs48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses.

  10. An Increased Risk of Osteoporosis during Acquired Immunodeficiency Syndrome

    OpenAIRE

    Annapoorna, N.; Rao, G. Venkateswara; Reddy, N S; Rambabu, P.; Rao, K.R.S.Samabasiva

    2004-01-01

    Osteoporosis is characterized by decreased bone mineral density and mechanistic imbalances of bone tissue that may result in reduced skeletal strength and an enhanced susceptibility to fractures. Osteoporosis in its most common form affects the elderly (both sexes) and all racial groups of human beings. Multiple environmental risk factors like acquired immune deficiency syndrome (AIDS) are believed to be one of the causes of osteoporosis. Recently a high incidence of osteoporosis has been obs...

  11. The role of CD4+ T cells in cell-mediated immunity to LCMV: studies in MHC class I and class II deficient mice

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Marker, O; Thomsen, Allan Randrup

    1994-01-01

    Parameters of the virus-specific T-cell response were analysed in order to dissect the contribution of CD4+ and CD8+ T cells to cell-mediated immunity to lymphocytic choriomeningitis virus. In MHC class II deficient mice, initial T-cell responsiveness was not impaired, but virus clearance...... was delayed, and virus-specific Td activity declined more rapidly. Furthermore, class I restricted Tc memory appeared to be impaired in these mice. To directly evaluate the role of CD4+ cells in virus clearance and T-cell mediated inflammation, MHC class I deficient mice were also studied. No virus......-specific CD8+ T-cell response, but our findings strongly suggest that CD4+ T cells are critical for maintaining full antiviral immunity. Furthermore, CD4+ T cells per se have a low potential for mediating virus-specific inflammation that is associated with a low degree of virus control....

  12. Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'.

    Science.gov (United States)

    Simpson, Elizabeth

    2015-04-19

    'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

  13. Regulatory T-cell depletion in the gut caused by integrin β7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity.

    Science.gov (United States)

    Zhang, H L; Zheng, Y J; Pan, Y D; Xie, C; Sun, H; Zhang, Y H; Yuan, M Y; Song, B L; Chen, J F

    2016-03-01

    Integrin α4β7 controls lymphocyte trafficking into the gut and has essential roles in inflammatory bowel disease (IBD). The α4β7-blocking antibody vedolizumab is approved for IBD treatment; however, high dose of vedolizumab aggravates colitis in a small percentage of patients. Herein, we show that integrin β7 deficiency results in colonic regulatory T (Treg) cell depletion and exacerbates dextran sulfate sodium (DSS) colitis by evoking aberrant innate immunity. In DSS-treated β7-deficient mice, the loss of colonic Treg cells induces excessive macrophage infiltration in the colon via upregulation of colonic epithelial intercellular adhesion molecule 1 and increases proinflammatory cytokine expression, thereby exacerbating DSS-induced colitis. Moreover, reconstitution of the colonic Treg cell population in β7-deficient mice suppresses aberrant innate immune response in the colon and attenuates DSS colitis. Thus, integrin α4β7 is essential for suppression of DSS colitis as it regulates the colonic Treg cell population and innate immunity.

  14. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response

    OpenAIRE

    1996-01-01

    To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, ...

  15. Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    B Akshaya Srikanth

    2012-01-01

    Full Text Available To estimate the incidence of adverse drug reactions (ADRs in Human immune deficiency virus (HIV patients on highly active antiretroviral therapy (HAART. To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%. The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52% was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm 3 with comorbid conditions.

  16. Bacillus cereus AR156 activates PAMP-triggered immunity and induces a systemic acquired resistance through a NPR1-and SA-dependent signaling pathway.

    Science.gov (United States)

    Niu, Dongdong; Wang, Xiujuan; Wang, Yanru; Song, Xiaoou; Wang, Jiansheng; Guo, Jianhua; Zhao, Hongwei

    2016-01-01

    Induced resistance responses play a potent role in plant defense system against pathogen attack. Bacillus cereus AR156 is a plant growth promoting rhizobacterium (PGPR) that installs induced systemic resistance (ISR) to Pseudomonas syringae pv. tomato (Pst) in Arabidopsis. Here, we show that AR156 leaf infiltration enhances disease resistance in Arabidopsis through the activation of a systemic acquired resistance (SAR). PR1 protein expression and reactive oxygen species (ROS) burst are strongly induced in plants treated with AR156 and inoculated with Pst than that in plants inoculated with Pst only. Moreover, AR156 can trigger SAR in jar1 or ein2 mutants, but not in the NahG transgenic and NPR1 mutant plants. Our results indicate that AR156-induced SAR depends on SA-signaling pathway and NPR1, but not JA and ET. Also, AR156-treated plants are able to rapidly activate MAPK signaling and FRK1 gene expression, which are involved in pathogen associated molecular pattern (PAMP)-triggered immunity (PTI). Altogether, our results indicate that AR156 can induce SAR by the SA-signaling pathways in an NPR1-dependent manner and involves multiple PTI components.

  17. Adiponectin administration prevents weight gain and glycemic profile changes in diet-induced obese immune deficient Rag1-/- mice lacking mature lymphocytes.

    Science.gov (United States)

    Liu, Xiaowen; Perakakis, Nikolaos; Gong, Huizhi; Chamberland, John P; Brinkoetter, Mary T; Hamnvik, Ole-Petter R; Mantzoros, Christos S

    2016-12-01

    Obesity is associated with chronic low-grade inflammation leading to insulin resistance and diabetes. Adiponectin is an adipokine that regulates inflammatory responses. The aim of our study was to investigate whether any effects of adiponectin against obesity and insulin-resistance may depend on the adaptive immune system. We treated high-fat-diet fed Rag1-/- mice lacking mature lymphocytes with adiponectin over 7weeks and investigated alterations in their metabolic outcome and inflammatory state. Adiponectin protects from weight gain despite a small compensatory stimulation of energy intake in mice lacking an adaptive immune system. Additionally, adiponectin protects from dysglycemia. Minor alterations in the macrophage phenotype, but not in the circulating cytokine levels, may contribute to the protective role of adiponectin against hyperglycemia and diabetes. Adiponectin or agents increasing adiponectin may be a promising therapeutic option against obesity and hyperglycemia in immune-deficient populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Immunity

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    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-

  19. Primary Immune Deficiency Diseases

    Science.gov (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  20. Immune Deficiency Foundation

    Science.gov (United States)

    ... informed with IDF communications Share Your Experiences Inspire others through your stories and videos Visit a Plasma Center Discover the ... to advance research and improve the quality of life of patients. Quick Links ... Reel Stories IDF ADVOCATE Newsletter IDF ePHR & PI CONNECT SCID ...

  1. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency

    NARCIS (Netherlands)

    Levi, M; Choi, G; Picavet, C; Hack, CE

    2006-01-01

    Background: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by Cl-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause co

  2. The antibody response to Plasmodium falciparum Merozoite Surface Protein 4: comparative assessment of specificity and growth inhibitory antibody activity to infection-acquired and immunization-induced epitopes

    Directory of Open Access Journals (Sweden)

    Black Casilda G

    2011-09-01

    Full Text Available Abstract Background Malaria remains a global public health challenge. It is widely believed that an effective vaccine against malaria will need to incorporate multiple antigens from the various stages of the parasite's complex life cycle. Plasmodium falciparum Merozoite Surface Protein 4 (MSP4 is a vaccine candidate that has been selected for development for inclusion in an asexual stage subunit vaccine against malaria. Methods Nine monoclonal antibodies (Mabs were produced against Escherichia coli-expressed recombinant MSP4 protein and characterized. These Mabs were used to develop an MSP4-specific competition ELISA to test the binding specificity of antibodies present in sera from naturally P. falciparum-infected individuals from a malaria endemic region of Vietnam. The Mabs were also tested for their capacity to induce P. falciparum growth inhibition in vitro and compared against polyclonal rabbit serum raised against recombinant MSP4 Results All Mabs reacted with native parasite protein and collectively recognized at least six epitopes. Four of these Mabs recognize reduction-sensitive epitopes within the epidermal growth factor-like domain found near the C-terminus of MSP4. These sera were shown to contain antibodies capable of inhibiting the binding of the six Mabs indicating infection-acquired responses to the six different epitopes of MSP4. All of the six epitopes were readily recognized by human immune sera. Competition ELISA titres varied from 20 to 640, reflecting heterogeneity in the intensity of the humoral response against the protein among different individuals. The IgG responses during acute and convalescent phases of infection were higher to epitopes in the central region than to other parts of MSP4. Immunization with full length MSP4 in Freund's adjuvant induced rabbit polyclonal antisera able to inhibit parasite growth in vitro in a manner proportionate to the antibody titre. By contrast, polyclonal antisera raised to

  3. Urokinase-type plasminogen activator deficiency has little effect on seizure susceptibility and acquired epilepsy phenotype but reduces spontaneous exploration in mice.

    Science.gov (United States)

    Rantala, J; Kemppainen, S; Ndode-Ekane, X E; Lahtinen, L; Bolkvadze, Tamuna; Gurevicius, K; Tanila, H; Pitkänen, A

    2015-01-01

    Urokinase-type plasminogen activator (uPA), a serine protease, converts plasminogen to plasmin. Activation of plasmin leads to degradation of the extracellular matrix, which is critical for tissue recovery, angiogenesis, cell migration, and axonal and synaptic plasticity. We hypothesized that uPA deficiency would cause an abnormal neurophenotype and would lead to exacerbated epileptogenesis after brain injury. Wild-type (Wt) and uPA-/- mice underwent a battery of neurologic behavioral tests evaluating general reactivity, spontaneous exploratory activity, motor coordination, pain threshold, fear and anxiety, and memory. We placed particular emphasis on the effect of uPA deficiency on seizure susceptibility, including the response to convulsants (pentylenetetrazol, kainate, or pilocarpine) and kainate-induced epileptogenesis and epilepsy. The uPA-/- mice showed no motor or sensory impairment compared with the Wt mice. Hippocampus-dependent spatial memory also remained intact. The uPA-/- mice, however, exhibited reduced exploratory activity and an enhanced response to a tone stimulus (p<0.05 compared with the Wt mice). The urokinase-type plasminogen activator deficient mice showed no increase in spontaneous or evoked epileptiform electrographic activity. Rather, the response to pilocarpine administration was reduced compared with the Wt mice (p<0.05). Also, the epileptogenesis and the epilepsy phenotype after intrahippocampal kainate injection were similar to those in the Wt mice. Taken together, uPA deficiency led to diminished interest in the environmental surroundings and enhanced emotional reactivity to unexpected aversive stimuli. Urokinase-type plasminogen activator deficiency was not associated with enhanced seizure susceptibility or worsened poststatus epilepticus epilepsy phenotype.

  4. Experimental and clinical evidence of the role of cytokines and growth factors in the pathogenesis of acquired cobalamin-deficient leukoneuropathy.

    Science.gov (United States)

    Scalabrino, Giuseppe; Veber, Daniela; Mutti, Elena

    2008-11-01

    Our experimental and clinical studies have highlighted the non-coenzyme functions of cobalamin (Cbl; vitamin B12). The neuropathy of the rat central nervous system (CNS) due to Cbl deficiency is associated with increases in CNS tissue and/or cerebrospinal fluid (CSF) levels of some neurotoxic molecules, and decreases in local and/or CSF levels of some neurotrophic molecules. The increased molecules are nerve growth factor (NGF), tumor necrosis factor (TNF)-alpha, and the soluble (s)CD40:sCD40 Ligand dyad; the decreased molecules are epidermal growth factor (EGF) and interleukin-6. The morphological lesions of the CNS white matter in Cbl-deficient (Cbl-Df) rats can be prevented to the same extent by treatments replacing Cbl or the deficient neurotrophic molecules, or treatment with agents that antagonize the excess neurotoxic molecules. Patients with neurological and/or hematological manifestations of severe Cbl deficiency also have high TNF-alpha levels and low EGF levels in CSF and serum. Cbl replacement treatment corrects cytokine and growth factor abnormalities in Cbl-Df patients and Cbl-Df rats, and so Cbl-Df CNS neuropathy is also due to an imbalance in local cytokine/growth factor networks. TNF-alpha and NGF levels are also increased in Cbl-Df rat liver, which is morphologically unaffected by Cbl deficiency. The increases in TNF-alpha and NGF levels increase nuclear factor-kappaB activity levels in both the CNS and liver, and this indirect regulation supports the idea that Cbl may modulate the expression of some cytokine/growth factor genes in rat CNS and other tissues. Finally, we have tried to harmonize our pathogenetic theory of cytokine and growth factor dysregulation with the biochemical interpretation.

  5. Complement factor I deficiency: a not so rare immune defect. Characterization of new mutations and the first large gene deletion

    Directory of Open Access Journals (Sweden)

    Alba-Domínguez María

    2012-06-01

    Full Text Available Abstract Background Complement Factor I (CFI is a serine protease with an important role in complement alternative pathway regulation. Complete factor I deficiency is strongly associated with severe infections. Approximately 30 families with this deficiency have been described worldwide. Patients and methods We have studied five new Spanish families suffering from CFI deficiency. From 19 screened people, 7 homozygous, 10 heterozygous and 2 healthy subjects were identified. Clinical, biochemical and genetic descriptions are included. Results Molecular studies demonstrated 4 novel mutations in the screened individuals; amongst them, we describe here the first great gene deletion reported in the CFI locus, which includes full exon 2 and part of the large intron 1. Conclusion CFI deficiency is possibly an underestimated defect and the eventual existence of this deficiency should be tested in those patients exhibiting low C3 and recurrent bacterial infections. We propose a simple diagnostic flowchart to help clinicians in the identification and correct diagnosis of such patients.

  6. Herpes Viral Origin of the Parsonage-Turner Syndrome: Highlighting of Serological Immune Anti-Herpes Deficiency Cured by Anti-Herpes Therapy.

    Science.gov (United States)

    Goaster, Jacqueline Le; Bourée, Patrice; Ifergan, Charles; Tangy, Frederic; Olivier, René; Haenni, Anne-Lise

    2015-01-01

    In 2012, a 50 year-old athletic male presented with weakness, pain and unilateral phrenic paralysis, followed by bilateral phrenic paralysis with deep dyspnea. In 2013, the Parsonage-Turner syndrome was diagnosed. When the patient was seen in September 2014 for the first time, he was facing phrenic neuromuscular failure, which led to the hypothesis of neurotropic herpes viruses. A control of the global serological anti-Herpes immunity to analyze his antibody (Ab) levels confirmed herpes immune genetic deficiency. An appropriate herpes chemotherapy treatment was proposed. Immediately, a spectacular recovery of the patient was observed, and after a few weeks, the respiratory function tests showed normal values. The hypothesis of the inductive role of viruses of the herpes family in the Parsonage-Turner syndrome was thus substantiated. The patient's immune deficiency covers the HSV2, HHV3, HHV4, HHV5 and HHV6 Ab levels. This led to the control of herpes in the family lineage: indeed, his daughter presented alterations of her serological herpes Ab levels.

  7. Herpes Viral Origin of the Parsonage-Turner Syndrome: Highlighting of Serological Immune Anti-Herpes Deficiency Cured by Anti-Herpes Therapy

    Directory of Open Access Journals (Sweden)

    Jacqueline Le Goaster

    2015-05-01

    Full Text Available In 2012, a 50 year-old athletic male presented with weakness, pain and unilateral phrenic paralysis, followed by bilateral phrenic paralysis with deep dyspnea. In 2013, the Parsonage-Turner syndrome was diagnosed. When the patient was seen in September 2014 for the first time, he was facing phrenic neuromuscular failure, which led to the hypothesis of neurotropic herpes viruses. A control of the global serological anti-Herpes immunity to analyze his antibody (Ab levels confirmed herpes immune genetic deficiency. An appropriate herpes chemotherapy treatment was proposed. Immediately, a spectacular recovery of the patient was observed, and after a few weeks, the respiratory function tests showed normal values. The hypothesis of the inductive role of viruses of the herpes family in the Parsonage-Turner syndrome was thus substantiated. The patient's immune deficiency covers the HSV2, HHV3, HHV4, HHV5 and HHV6 Ab levels. This led to the control of herpes in the family lineage: indeed, his daughter presented alterations of her serological herpes Ab levels.

  8. Vitamin E deficiency depressed fish growth, disease resistance, and the immunity and structural integrity of immune organs in grass carp (Ctenopharyngodon idella): Referring to NF-κB, TOR and Nrf2 signaling.

    Science.gov (United States)

    Pan, Jia-Hong; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2017-01-01

    This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E deficiency decreased lysozyme and acid phosphatase activities, complement component 3 and complement component 4 contents in the head kidney, spleen and skin of grass carp (P E deficiency down-regulated antimicrobial peptides (Hepcidin, liver-expressed antimicrobial peptide-2A, -2B, β-defensin), IL-10, TGFβ1, IκBα, TOR and S6K1 mRNA levels (P E deficiency caused oxidative damage, decreased superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione reductase (GR) activities, and down-regulated the mRNA levels of antioxidant enzymes and signaling molecules Nrf2 (P E deficiency also induced apoptosis by up-regulating capase-2, -3, -7, and -8 mRNA levels in the head kidney, spleen and skin of grass carp. In conclusion, this study indicated that dietary vitamin E deficiency depressed fish growth, impaired the immune function and disturbed the structural integrity of the head kidney, spleen and skin in grass carp, but optimal vitamin E supplementation can reverse those negative effects in fish. The optimal vitamin E requirements for young grass carp (266.39-1026.63 g) to achieve optimal growth performance and disease resistance based on the percent weight gain (PWG) and skin lesion morbidity were estimated to be 116.2 and 130.9 mg/kg diet, respectively. Meanwhile, based on immune indicator (LA activity in the head kidney) and

  9. Deficiency of dietary niacin impaired intestinal mucosal immune function via regulating intestinal NF-κB, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Feng, Lin; Li, Shun-Quan; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-02-01

    This study investigated the effects of dietary niacin on intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (255.63 ± 0.41 g) were fed six diets containing graded levels of niacin (3.95, 14.92, 24.98, 35.03, 44.97 and 55.01 mg/kg diet) for 8 weeks. Results observed that niacin deficiency decreased lysozyme (LA) and acid phosphatase (ACP) activities, and complement 3 (C3) content in the intestine (P niacin deficiency increased reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC) contents, decreased glutathione content, and copper/zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferases (GST) and glutathione reductase (GR) activities in the intestine of young grass carp (P niacin deficiency decreased mRNA levels of CuZnSOD, MnSOD, GPx, CAT, GST, GR, Claudin b, Claudin 3, Claudin c, Occludin, ZO-1, Claudin 15 and NF-E2-related factor 2 (Nrf2) (P  0.05). In conclusion, niacin deficiency decreased intestinal mucosal immune and intestinal physical function, as well as regulated mRNA levels of NF-κB P65, IκBα, IKKα, IKKβ, IKKγ, Nrf2, Keap1a, p38 MAPK and MLCK in the intestine of young grass carp. Based on the broken-line model analysis of intestinal lysozyme activity, the requirement of niacin for young grass carp (255.63 ± 0.41 g) were estimated to be 39.80 mg/kg diet.

  10. Effect of dietary phosphorus deficiency on the growth, immune function and structural integrity of head kidney, spleen and skin in young grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Chen, Kang; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2017-04-01

    This study evaluates the effects of dietary phosphorus on the growth, immune function and structural integrity (head kidney, spleen and skin) of young grass carp (Ctenopharyngodon idella) that were fed graded levels of available phosphorus (0.95-8.75 g/kg diet). Results indicated that phosphorus deficiency decreased the growth performance of young grass carp. In addition, the results first demonstrated that compared with the optimal phosphorus level, phosphorus deficiency depressed the lysozyme (LZ) and acid phosphatase (ACP) activities and the complement 3 (C3), C4 and immunoglobulin M (IgM) contents, and down-regulated the mRNA levels of antimicrobial peptides, anti-inflammatory cytokines, inhibitor of κBα (IκBα) and target of rapamycin (TOR), whereas it up-regulated pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) p65 and NF-κB p52 mRNA levels to decrease fish head kidney and spleen immune functions. Moreover, phosphorus deficiency up-regulated the mRNA levels of Kelch-like-ECH-associated protein 1a (Keap1a), Fas ligand (FasL), apoptotic protease activating factor-1 (Apaf-1), Bcl-2 associated X protein (Bax), caspase -2, -3, -7, -8 and -9, p38 mitogen-activated protein kinase (MAPK) and myosin light chain kinase (MLCK), whereas it depressed the glutathione (GSH) contents and antioxidant enzymes activities, and down-regulated the mRNA levels of antioxidant enzymes, NF-E2-related factor 2 (Nrf2), B-cell lymphoma protein-2 (Bcl-2), myeloid cell leukemia-1 (Mcl-1) and tight junction complexes to attenuate fish head kidney and spleen structural integrity. In addition, phosphorus deficiency increased skin hemorrhage and lesions morbidity. Finally, based on the percent weight gain (PWG) and the ability to combat skin hemorrhage and lesions, the dietary available phosphorus requirements for young grass carp (254.56-898.23 g) were estimated to be 4.10 and 4.13 g/kg diet, respectively. In summary, phosphorus deficiency decreases the growth

  11. 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;

    1984-01-01

    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...

  12. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses

    DEFF Research Database (Denmark)

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes

    2012-01-01

    in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii). To further evaluate the potential of this system, the concept of pre-existing inhibitory...... directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated......8 T-cell memory even in individuals with pre-existing vector immunity....

  13. Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in EGFR Mutant and ALK Positive Lung Cancers

    Science.gov (United States)

    2016-10-01

    EGFR-Mutant and ALK-Positive Lung Cancers PRINCIPAL INVESTIGATOR: Lecia Sequist MD. CONTRACTING ORGANIZATION: Massachusetts General Hospital...Intrinsic and Acquired Resistance to Targeted Therapies in EGFR-Mutant and ALK-Positive Lung Cancers 5b. GRANT NUMBER W81XWH-13-1-0227 5c. PROGRAM...submitted) have been written this year describing our findings. 15. SUBJECT TERMS BIM, apoptosis, targeted therapy, BCL-XL, kinase, EGFR, ALK, lung

  14. Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in EGFR-Mutant and ALK-Positive Lung Cancers

    Science.gov (United States)

    2016-10-01

    EGFR-Mutant and ALK-Positive Lung Cancers PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD. PhD. CONTRACTING ORGANIZATION: Massachusetts General Hospital...Acquired Resistance to 5a. CONTRACT NUMBER Targeted Therapies in EGFR-Mutant and ALK-Positive Lung Cancers 5b. GRANT NUMBER W81XWH-13-1...ALK, lung cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT

  15. Campylobacter fetus Bacteremia Revealed by Cellulitis without Gastrointestinal Symptoms in the Context of Acquired Hypogammaglobulinemia: A Report of Three Cases

    Directory of Open Access Journals (Sweden)

    Souleymane Brah

    2011-01-01

    Full Text Available Campylobacter fetus bacteremia is rare and occurs mainly in patients with immunosuppression. This infection, which often involves secondary localizations has already been reported in some primary humoral immune deficiencies. We describe three cases of severe infection due to C. fetus with cellulitis at presentation, but without any gastrointestinal symptoms, occurring in patients with acquired hypogammaglobulinemia.

  16. Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells.

    NARCIS (Netherlands)

    Dijk, M.R. van; Douradinha, B.; Franke-Fayard, B.; Heussler, V.; Dooren, M.W. van; Schaijk, B.C.L. van; Gemert, G.J.A. van; Sauerwein, R.W.; Mota, M.M.; Waters, A.P.; Janse, C.J.

    2005-01-01

    Immunization with Plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and hu

  17. LV305, a dendritic cell-targeting integration-deficient ZVex(TM)-based lentiviral vector encoding NY-ESO-1, induces potent anti-tumor immune response.

    Science.gov (United States)

    Albershardt, Tina Chang; Campbell, David James; Parsons, Andrea Jean; Slough, Megan Merrill; Ter Meulen, Jan; Berglund, Peter

    2016-01-01

    We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once with LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T cells within 14 days post-immunization and could be boosted with LV305 at least twice to recall peak-level CD8 T-cell responses. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells. Adoptive transfer of CD8 T cells, alone or together with CD4 T cells or natural killer cells, from LV305-immunized donor mice to tumor-bearing recipient mice conferred significant protection against metastatic tumor growth. Biodistribution of injected LV305 in mice was limited to the site of injection and the draining lymph node, and injected LV305 exhibited minimal excretion. Mice injected with LV305 developed little to no adverse effects, as evaluated by toxicology studies adherent to good laboratory practices. Taken together, these data support the development of LV305 as a clinical candidate for treatment against tumors expressing NY-ESO-1.

  18. LV305, a dendritic cell-targeting integration-deficient ZVexTM-based lentiviral vector encoding NY-ESO-1, induces potent anti-tumor immune response

    Science.gov (United States)

    Albershardt, Tina Chang; Campbell, David James; Parsons, Andrea Jean; Slough, Megan Merrill; ter Meulen, Jan; Berglund, Peter

    2016-01-01

    We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once with LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T cells within 14 days post-immunization and could be boosted with LV305 at least twice to recall peak-level CD8 T-cell responses. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells. Adoptive transfer of CD8 T cells, alone or together with CD4 T cells or natural killer cells, from LV305-immunized donor mice to tumor-bearing recipient mice conferred significant protection against metastatic tumor growth. Biodistribution of injected LV305 in mice was limited to the site of injection and the draining lymph node, and injected LV305 exhibited minimal excretion. Mice injected with LV305 developed little to no adverse effects, as evaluated by toxicology studies adherent to good laboratory practices. Taken together, these data support the development of LV305 as a clinical candidate for treatment against tumors expressing NY-ESO-1. PMID:27626061

  19. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    Directory of Open Access Journals (Sweden)

    Maria Abildgaard Steffensen

    Full Text Available Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii. To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  20. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    Science.gov (United States)

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes; Bassi, Maria Rosaria; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2012-01-01

    Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii). To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  1. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice.

    Directory of Open Access Journals (Sweden)

    Shen Yon Toh

    Full Text Available Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27(-/- mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs from wildtype and Fsp27(-/- mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT and white adipose tissue (WAT and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27(-/- mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27(-/-and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27(-/- mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1alpha were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27(-/- mice. Remarkably, Fsp27(-/- MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3. Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity.

  2. A novel role for APOBEC3: Susceptibility to sexual transmission of murine acquired immunodeficiency virus (mAIDS is aggravated in APOBEC3 deficient mice

    Directory of Open Access Journals (Sweden)

    Jones Philip H

    2012-06-01

    Full Text Available Abstract Background APOBEC3 proteins are host factors that restrict infection by retroviruses like HIV, MMTV, and MLV and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. Previously, we showed that APOBEC3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. In this present study, we used APOBEC3 knockout mice and their wild type counterpart to query the role of APOBEC3 in sexual transmission of LP-BM5 MLV – the etiological agent of murine AIDs (mAIDs. Results We show that mouse APOBEC3 is expressed in murine genital tract tissues and gametes and that genital tract tissue of APOBEC3-deficient mice are more susceptible to infection by LP-BM5 virus. APOBEC3 expressed in genital tract tissues most likely plays a role in decreasing virus transmission via the sexual route, since mice deficient in APOBEC3 gene have higher genitalia and seminal plasma virus load and sexually transmit the virus more efficiently to their partners compared to APOBEC3+ mice. Moreover, we show that female mice sexually infected with LP-BM5 virus transmit the virus to their off-spring in APOBEC3-dependent manner. Conclusion Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus.

  3. MiR-15a/16 deficiency enhances anti-tumor immunity of glioma-infiltrating CD8+ T cells through targeting mTOR.

    Science.gov (United States)

    Yang, Jiao; Liu, Ronghua; Deng, Yuting; Qian, Jiawen; Lu, Zhou; Wang, Yuedi; Zhang, Dan; Luo, Feifei; Chu, Yiwei

    2017-11-15

    MiR-15a/16, a miRNA cluster located at chromosome 13q14, has been reported to act as an immune regulator in inflammatory disorders besides its aberrant expression in cancers. However, little is known about its regulation in tumor-infiltrating immune cells. In our study, using an orthotropic GL261 mouse glioma model, we found that miR-15a/16 deficiency in host inhibited tumor growth and prolonged mice survival, which might be associated with the accumulation of tumor-infiltrating CD8+ T cells. More importantly, tumor-infiltrating CD8+ T cells without miR-15a/16 showed lower expression of PD-1, Tim-3 and LAG-3, and stronger secretion of IFN-γ, IL-2 and TNF-α than WT tumor-infiltrating CD8+ T cells. Also, our in vitro experiments further confirmed that miR-15a/16(-/-) CD8+ T displayed higher active phenotypes, more cytokines secretion and faster expansion, compared to WT CD8+ T cells. Mechanismly, mTOR was identified as a target gene of miR-15a/16 to negatively regulate the activation of CD8+ T cells. Taken together, these data suggest that miR-15a/16 deficiency resists the exhaustion and maintains the activation of glioma-infiltrating CD8+ T cells to alleviate glioma progression via targeting mTOR. Our findings provide evidence for the potential immunotherapy through targeting miR-15a/16 in tumor-infiltrating immune cells. © 2017 UICC.

  4. Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies

    OpenAIRE

    Brue, Thierry; Quentien, Marie-Hélène; Khetchoumian, Konstantin; Bensa, Marco; Capo-Chichi, José-Mario; Delemer, Brigitte; Balsalobre, Aurelio; Nassif, Christina; Papadimitriou, Dimitris T; Pagnier, Anne; Hasselmann, Caroline; Patry, Lysanne; Schwartzentruber, Jeremy; Souchon, Pierre-François; Takayasu, Shinobu

    2014-01-01

    Background DAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. NFKB2 mutations have recently been identified in patients with ACTH and variable immunodeficiency. A similar mutation was previously found in Nfkb2 in the immunodeficient Lym1 mouse strain, but the effect of the mutation on endocrine function was not evaluated. Methods We ascertained six unrelated DAVID syndrome families. We performed whole exome and traditional...

  5. Genetically Engineered Ascorbic acid-deficient Live Mutants of Leishmania donovani induce long lasting Protective Immunity against Visceral Leishmaniasis.

    Science.gov (United States)

    Anand, Sneha; Madhubala, Rentala

    2015-06-02

    Visceral leishmaniasis caused by Leishmania donovani is the most severe systemic form of the disease. There are still no vaccines available for humans and there are limitations associated with the current therapeutic regimens for leishmaniasis. Recently, we reported functional importance of Arabino-1, 4-lactone oxidase (ALO) enzyme from L. donovani involved in ascorbate biosynthesis pathway. In this study, we have shown that ΔALO parasites do not affect the ability of null mutants to invade visceral organs but severely impair parasite persistence beyond 16 week in BALB/c mice and hence are safe as an immunogen. Both short term (5 week) and long term (20 week) immunization with ΔALO parasites conferred sustained protection against virulent challenge in BALB/c mice, activated splenocytes and resulted in induction of pro-inflammatory cytokine response. Protection in immunized mice after challenge correlated with the stimulation of IFN-γ producing CD4(+) and CD8(+) T cells. Antigen-mediated cell immunity correlated with robust nitrite and superoxide generation, macrophage-derived oxidants critical in controlling Leishmania infection. Our data shows that live attenuated ΔALO parasites are safe, induce protective immunity and can provide sustained protection against Leishmania donovani. We further conclude that the parasites attenuated in their anti-oxidative defence mechanism can be exploited as vaccine candidates.

  6. Terapia hipolipemiante em situações especiais: síndrome de imunodeficiência adquirida Hypolipidemic therapy under special conditions: acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Pai Ching Yu

    2005-10-01

    Full Text Available Dislipidemias podem ser observadas precocemente entre pacientes com AIDS. Frequentemente, estas anormalidades lipídicas incluem HDL baixo e moderado aumento dos triglicérides sanguíneos. A terapia anti-retroviral combinada (HAART pode agravar a dislipidemia nestes pacientes, com importante aumento nos triglicérides e no LDL. Vários mecanismos são propostos para explicar a dislipidemia mista observada nestes indivíduos, incluindo diferentes etapas do metabolismo lipídico. A importância do tratamento desses distúrbios lipídicos tem se tornado evidente com o aumento da expectativa de vida e os relatos de complicações cardiovasculares nestes pacientes. Existe um estado de resistência à insulina nos pacientes com AIDS em tratamento com HAART,que apresentam lipodistrofia, hipertrigliceridemia e baixos níveis de HDL. Drogas retro-antivirais são metabolizadas pelo CYP P450 3A4 e interações com algumas estatinas, especialmente com sinvastatina podem ocorrer. O tratamento com agentes hipolipemiantes deve ser baseado no perfil lipídico e no risco de coronariopatia. Para hipertrigliceridemias, fibratos (principalmente fenofibrato ou bezafibrato devem ser as drogas de escolha, bem como as estatinas (principalmente pravastatina. Terapia combinada usando estatinas mais fibratos é recomendada para dislipidemias mistas graves e sempre sob rigoroso monitoramento de efeitos adversos.Lipid alterations can be observed early among patients with AIDS disease. Commonly, these lipid abnormalities include low HDL-C and modest increase in triglyceride plasma levels. Highly Active Anti-Retroviral Therapy (HAART in these patients may aggravate the dyslipidemia, with notable increases in triglycerides as well as in LDL-C. There are several mechanisms proposed to explain the mixed hyperlipidemia observed in these subjects, including different steps in lipid metabolism. The importance of the treatment of dyslipidemia became evident with the increased life expectancy and reports of cardiovascular complications in these individuals. There is an insulin resistance state in patients with AIDS disease under treatment with HAART, who present with lypodistrophy, hypertriglyceridemia, low levels of HDL-C. Antiretroviral drugs are metabolized by CYP P450 3A4 and interactions with some statins, especially with simvastatin are expected to occur. Treatment with lipid-lowering agents should be based on lipid profile and coronary risk. For hypertriglyceridemias, fibrates (mainly fenofibrate or bezafibrate should be the drugs of choice, as well as statins (mainly pravastatin. Combined treatment using fibrates plus statins are recommended for severe mixed hyperlipidemias under very close monitoring for adverse effects.

  7. The in vitro anti-viral potential of Setarud (IMOD™, a commercial herbal medicine with protective activity against acquired immune deficiency syndrome in clinical trials

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    Rezvan Zabihollahi

    2012-01-01

    Conclusions: Data from this study indicate that IMOD has significant anti-viral activity against HIV, HSV and MLV. Setarud could be subjected to further investigation after isolation of the constituents and determination of the toxic components.

  8. Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy

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    Lucinda Calheiros Guimarães

    Full Text Available ABSTRACT Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases; B - one or two antiretroviral drugs or HAART for less than six months (83 cases; C - HAART for six months or longer (54 cases. In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%, followed by cytomegalovirus (19.2%, Histoplasma capsulatum (6.5%, mycobacteria (5.6%, and Toxoplasma gondii (4.3%. T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV was more frequent in group A compared with groups B and C (p < 0.05; 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

  9. Immune System

    Science.gov (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...

  10. An altered immune response, but not individual cationic antimicrobial peptides, is associated with the oral attenuation of Ara4N-deficient Salmonella enterica serovar Typhimurium in mice.

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    Kristi L Strandberg

    Full Text Available Salmonella enterica serovar Typhimurium (S. Typhimurium uses two-component regulatory systems (TCRS to respond to stimuli in the local microenvironment. Upon infection, the Salmonella TCRSs PhoP-PhoQ (PhoPQ and PmrA-PmrB (PmrAB are activated by environmental signals in the intestinal lumen and within host cells. TCRS-mediated gene expression results in lipopolysaccharide (LPS modification and cationic antimicrobial peptide resistance. The PmrA-regulated pmrHFIJKLM operon mediates 4-amino-4-deoxy-L-arabinose (Ara4N production and attachment to the lipid A of LPS. A ΔpmrF S. Typhimurium strain cannot produce Ara4N, exhibits increased sensitivity to cationic antimicrobial peptide (CAMP-mediated killing, and attenuated virulence in mice upon oral infection. CAMPs are predicted to play a role in elimination of Salmonella, and may activate PhoPQ and PmrAB in vivo, which could increase bacterial resistance to host defenses. Competition experiments between wild type (WT and ΔpmrF mutant strains of S. Typhimurium indicated that selection against this mutant first occurs within the intestinal lumen early during infection. However, CRAMP and active cryptdins alone are not responsible for elimination of Ara4N-deficient bacteria in vivo. Investigation into the early immune response to ΔpmrF showed that it differed slightly from the early immune response to WT S. Typhimurium. Further investigation into the early immune response to infection of Peyer's patches suggests a role for IL-13 in the attenution of the ΔpmrF mutant strain. Thus, prominent CAMPs present in the mouse intestine are not responsible for the selection against the ΔpmrF strain in this location, but limited alterations in innate immune induction were observed that affect bacterial survival and virulence.

  11. Synergistic effects of host B7-H4 deficiency and gemcitabine treatment on tumor regression and anti-tumor T cell immunity in a mouse model.

    Science.gov (United States)

    Leung, Joanne; St-Onge, Philippe; Stagg, John; Suh, Woong-Kyung

    2017-04-01

    B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control. Given that T cell-mediated immunotherapies work best for tumors presenting tumor-associated neoantigens, we further investigated the function of host B7-H4 in the growth of a more immunogenic derivative, 4T1-12B, which is known to elicit strong anti-tumor CD8 T cell responses due to expression of a surrogate tumor-specific antigen, firefly luciferase. Notably, B7-H4 knockout hosts not only mounted greater tumor-associated anti-tumor T cell responses, but also displayed reduced tumors. Additionally, B7-H4-deficiency synergized with gemcitabine to further inhibit tumor growth, often leading to tumor eradication and the generation of protective T cell immunity. These findings imply that inhibition of host B7-H4 can enhance anti-tumor T cell immunity in immunogenic cancers, and can be combined with other anti-cancer therapies to further reduce tumor burden regardless of tumor-B7-H4 positivity.

  12. Immune Disorder HSCT Protocol

    Science.gov (United States)

    2016-11-01

    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

  13. In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

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    Tânia A Costa

    Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

  14. In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

    Directory of Open Access Journals (Sweden)

    Tânia A Costa

    Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

  15. Study of the morphological patterns and association of Epstein-Barr virus and human herpes virus 8 in acquired immunodeficiency deficiency syndrome-related reactive lymphadenopathy

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    Gujral S

    2010-10-01

    Full Text Available Aims: Study of the morphological patterns of acquired immunodeficiency syndrome (AIDS-related lymphadenopathy. Settings and Design: We retrospectively selected cases of AIDS-related benign lymphadenopathy. Cases with lymphomas, frank granulomas and necrosis were excluded. We analyzed different morphological patterns and correlated these with immunophenotypic markers along with viral markers human herpesvirus 8-latency-associated nuclear antigen (HHV8-LANA, and Epstein-Barr virus-encoded ribonucleic acid (EBER studies via in situ hybridization (EBER-ISH. Materials and Methods: We present the morphological patterns of 13 cases of human immunodeficiency virus (HIV-reactive lymph nodes and their clinical, hematological, biochemical and radiological parameters with special emphasis on the presence or absence of viral markers, including HHV8 and EBV. Results: Common patterns included follicular hyperplasia only (five cases, mixed pattern of follicular hyperplasia with burnt-out germinal centres (four cases, completely atretic follicle (two cases, folliculolysis (11 cases, dumbbell-shaped follicles (three each, progressive transformation of germinal centers (four cases, T-zone expansion (two cases, Reed Sternberg (RS cells like immunoblasts (two cases, Castleman′s-like features with lollipop-like follicles (three cases and a spindle cell prominence (one case. CD8+ T-cells were predominant in 12 cases. CD8+ T-cells were prominent in germinal centers (eight cases. Plasmablasts were seen in four cases within the perigerminal center area. Immunohistochemistry for HHV8, i.e. HHV8-LANA were negative in all cases while EBER was detected in 11 cases in the centrocyte-like B cells. Two cases of multicentric Castleman′s disease expressed EBER; however, they did not express HHV8. Conclusion: The wide spectrum of histological changes in HIV-associated lymphadenopathy requires recognition. The histological changes can mimic those of other infective

  16. Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis.

    Science.gov (United States)

    Goto, Kei; Kaneko, Yoshikatsu; Sato, Yuya; Otsuka, Tadashi; Yamamoto, Suguru; Goto, Shin; Yamamoto, Keiko; Yamamoto, Tadashi; Kawachi, Hiroshi; Madaio, Michael P; Narita, Ichiei

    2016-04-01

    Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). Sheep NTS was administered in wild-type C57BL/6J mice and food-restricted, leptin-deficient C57BL/6J-ob/ob(FR-ob/ob) mice after preimmunization with sheep IgG. The profile of mRNA expression relevant to T helper lymphocytes in the kidneys was analyzed by quantitative real-time PCR (qRT-PCR). Cultured murine glomerular podocytes and peritoneal exudate macrophages (PEMs) were used to investigate the direct effect of leptin on IL-23 or MCP-1 production by qRT-PCR. Kidney injury and macrophage infiltration were significantly attenuated in FR-ob/obmice 7 days after NTS injection. The Th17-dependent secondary immune response against deposited NTS in the glomeruli was totally impaired in FR-ob/obmice because of deteriorated IL-17 and proinflammatory cytokine production including IL-23 and MCP-1 in the kidney. IL-23 was produced in glomerular podocytes in NTN mice and cultured murine glomerular podocytes produced IL-23 under leptin stimulation. MCP-1 production in PEMs was also promoted by leptin. Induction of MCP-1 expression was observed in PEMs regardless of Ob-Rb, and the leptin signal was transduced without STAT3 phosphorylation in PEMs. Leptin deficiency impairs the secondary immune response against NTS and down-regulates IL-23 production and Th17 responses in the NTN kidney, which is accompanied by decreased MCP-1 production and macrophage infiltration in the NTN kidney.

  17. RNAi knock-down of shrimp Litopenaeus vannamei Toll gene and immune deficiency gene reveals their difference in regulating antimicrobial peptides transcription.

    Science.gov (United States)

    Hou, Fujun; He, Shulin; Liu, Yongjie; Zhu, Xiaowen; Sun, Chengbo; Liu, Xiaolin

    2014-06-01

    NF-κB dependent antimicrobial peptides (AMPs) are of critical importance in protecting insects or mammals from microorganisms infection. However, we still do not make clear signaling pathways in regulating AMPs expression in shrimps. In this study, RNAi approach was used to study differences between Toll signaling pathway and immune deficiency signaling pathway in regulating the transcription of NF-κB dependent AMPs post bacteria challenge. Results showed that the transcription level of anti-lipopolysaccharide factor was highly suppressed in Litopenaeus vannamei immune deficiency (LvIMD) silenced shrimps by gene specific dsRNA compared to Litopenaeus vannamei Toll (LvToll) silenced shrimps with or without Vibrio anguillarum and Micrococcus lysodeikticus challenge. Conversely the transcription level of penaeidin3a was significantly suppressed in LvToll silenced shrimps compared to LvIMD silenced shrimps. However, no obvious difference was found in regulating the transcription of CrustinP. Meanwhile, we found that silencing LvToll both down regulated the transcription of Dorsal and Relish while silencing LvIMD only down regulated the transcription of Relish. At last, shrimp survival experiment showed that post V. anguillarum challenge high mortality was found both in LvToll and LvIMD silenced groups while post M. lysodeikticus challenge we saw high mortality only in LvToll silenced group. Hence, we conclude that shrimp L. vannamei Toll pathway and IMD pathway might be different in regulating the transcription of NF-κB dependent AMPs and responding to bacteria challenge but not independent of each other.

  18. Fetal Hematopoietic Stem Cells Are the Canaries in the Coal Mine That Portend Later Life Immune Deficiency.

    Science.gov (United States)

    Laiosa, Michael D; Tate, Everett R

    2015-10-01

    Disorders of the blood system are a significant and growing global health concern and include a spectrum of diseases ranging from aplastic anemia and leukemias to immune suppression. This array of hematological disorders is attributed to the fact that the blood system undergoes a perpetual cycle of turn over with aged and exhausted red and white blood cells undergoing daily replacement. The foundational cells of this replenishment process are comprised of rare hematopoietic stem cells (HSCs) located in the bone marrow that possess the dual function of long-term self-renewal and multilineage differentiation. This constant turnover makes the hematopoietic system uniquely vulnerable to changes in the environment that impact multilineage differentiation, self-renewal, or both. Notably, environmental endocrine-disrupting exposures occurring during development, when HSCs are first emerging, can lead to alterations in HSC programming that impacts the blood and immune systems throughout life. In this review, we describe the process of fetal hematopoiesis and provide an overview of the intrauterine environmental and endocrine-disrupting compounds that disrupt this process. Finally, we describe research opportunities for fetal HSCs as potential sentinels of later-life blood and immune system disorders.

  19. Deficiency in Either 4E-BP1 or 4E-BP2 Augments Innate Antiviral Immune Responses

    Science.gov (United States)

    Nehdi, Atef; Sean, Polen; Linares, Izzar; Colina, Rodney; Jaramillo, Maritza; Alain, Tommy

    2014-01-01

    Genetic deletion of both 4E-BP1 and 4E-BP2 was found to protect cells against viral infections. Here we demonstrate that the individual loss of either 4E-BP1 or 4E-BP2 in mouse embryonic fibroblasts (MEFs) is sufficient to confer viral resistance. shRNA-mediated silencing of 4E-BP1 or 4E-BP2 renders MEFs resistant to viruses, and compared to wild type cells, MEFs knockout for either 4E-BP1 or 4E-BP2 exhibit enhanced translation of Irf-7 and consequently increased innate immune response to viruses. Accordingly, the replication of vesicular stomatitis virus, encephalomyocarditis virus, influenza virus and Sindbis virus is markedly suppressed in these cells. Importantly, expression of either 4E-BP1 or 4E-BP2 in double knockout or respective single knockout cells diminishes their resistance to viral infection. Our data show that loss of 4E-BP1 or 4E-BP2 potentiates innate antiviral immunity. These results provide further evidence for translational control of innate immunity and support targeting translational effectors as an antiviral strategy. PMID:25531441

  20. Combined effect of the environmental factors as ionizing radiation and a chronic iodine deficiency on the thyroid gland and the immune condition

    Energy Technology Data Exchange (ETDEWEB)

    Danyarova, L. [Department of Endocrynology, Research Institute of Cardiology and Internal Medicine, Almaty (Kazakhstan)

    2012-07-01

    The Semipalatinsk Test Site was the primary testing venue for the Soviet Union's nuclear weapons. It is located on the steppe in northeast Kazakhstan. The tragic situation of the Semipalatinsk region is an acute and chronic radiation, repeated in big and small doses and a total absence of territorial decontamination, created unique conditions for study of the long term influence of the radiation doses on the health of the population. The Semipalatinsk region of the Republic of Kazakhstan belongs also to an area of moderate and pronounced iodine deficiency. The purpose of the research is to study the prevalence of a thyroid gland pathology and the condition of a cytokine immune link that is likely to be influenced by a combine effect of ionizing radiation and a chronic iodine deficiency. 1100 people passed through the investigation and it appears that 56, 75% of them had a thyroid pathology. Thyroid gland functional condition analysis (TSH, FT3, FT4 a-TG, a-TPO) has shown the prevalence of a subclinical hypothyroidism (33%). 28, 8% resulted in the presence of antibodies to thyroglobulin and the thyroid peroxides, whereas in the areas located further to the nuclear range, the percentage was only 13, 0%

  1. Novel Combined Immune Deficiency and Radiation Sensitivity Blended Phenotype in an Adult with Biallelic Variations in ZAP70 and RNF168

    Science.gov (United States)

    Chinn, Ivan K.; Sanders, Robert P.; Stray-Pedersen, Asbjørg; Coban-Akdemir, Zeynep H.; Kim, Vy Hong-Diep; Dadi, Harjit; Roifman, Chaim M.; Quigg, Troy; Lupski, James R.; Orange, Jordan S.; Hanson, I. Celine

    2017-01-01

    With the advent of high-throughput genomic sequencing techniques, novel genetic etiologies are being uncovered for previously unexplained Mendelian phenotypes, and the underlying genetic architecture of disease is being unraveled. Although most of these “mendelizing” disease traits represent phenotypes caused by single-gene defects, a percentage of patients have blended phenotypes caused by pathogenic variants in multiple genes. We describe an adult patient with susceptibility to bacterial, herpesviral, and fungal infections. Immunologic defects included CD8+ T cell lymphopenia, decreased T cell proliferative responses to mitogens, hypogammaglobulinemia, and radiation sensitivity. Whole-exome sequencing revealed compound heterozygous variants in ZAP70. Biallelic mutations in ZAP70 are known to produce a spectrum of immune deficiency that includes the T cell abnormalities observed in this patient. Analyses for variants in genes associated with radiation sensitivity identified the presence of a homozygous RNF168 variant of unknown significance. RNF168 deficiency causes radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties syndrome and may account for the radiation sensitivity. Thus, the patient was found to have a novel blended phenotype associated with multilocus genomic variation: i.e., separate and distinct genetic defects. These findings further illustrate the clinical utility of applying genomic testing in patients with primary immunodeficiency diseases. PMID:28603521

  2. Naturally acquired immune responses to malaria vaccine candidate antigens MSP3 and GLURP in Guahibo and Piaroa indigenous communities of the Venezuelan Amazon

    DEFF Research Database (Denmark)

    Baumann, Andreas; Magris, Magda M; Urbaez, Marie-Luz;

    2012-01-01

    in two indigenous population groups in Amazonas/Venezuela. Data from the regional malaria documentation system were extracted and participants from the ethnic groups of the Guahibo (n = 180) and Piaroa (n = 295) were investigated for the presence of Plasmodium parasites and naturally acquired antibodies...

  3. As implicações sociais da deficiência auditiva adquirida em adultos Social implications of acquired hearing impairment in adults

    Directory of Open Access Journals (Sweden)

    Madalena Aparecida Silva Francelin

    2010-03-01

    Full Text Available O objetivo deste estudo foi analisar as implicações da surdez adquirida em adultos, na vida familiar, social e no trabalho, com uma abordagem qualitativa. Foram selecionadas 27 pessoas residentes em Bauru-SP, com diagnóstico de perda auditiva de manifestação súbita na faixa etária de 18 a 60 anos, matriculados no Hospital de Reabilitação de Anomalias Craniofaciais (HRAC/USP entre janeiro de 2000 e fevereiro de 2005, sendo entrevistados 16. Utilizaram-se a entrevista e a análise de conteúdo. Constatou-se: a perda auditiva ocorreu entre os 40 e 44 anos, 37,5%; 62,5% dos que perderam a audição eram do sexo masculino, 62,5% não tinham o ensino fundamental; 62,5% eram da classe Baixa Superior; 75% apresentaram perda auditiva bilateral, 18,75% de grau moderado/profundo. Dos 13 que estavam trabalhando quando perderam a audição, 30,77% pararam de trabalhar e 15,38% mudaram de profissão. Foram relatadas situações como: afastamento do trabalho, demissão a pedido e demissão pelo empregador, dificuldade de aceitação, cobranças, falta de esclarecimentos e desconhecimento dos próprios profissionais de saúde. Os dados sugerem a necessidade dos recursos de reabilitação, de apoio terapêutico, respeito e alternativas de conhecimentos.This study aimed at analyzing, by means of a qualitative approach, the implications of acquired deafness in adults with regard to family life, social life and work. Twenty-seven individuals residing in the city of Bauru, State of São Paulo, were selected. All of them had been diagnosed with hearing impairment of sudden onset at the age range of 18 to 60 years and were registered at the Hospital for Craniofacial Anomaly Rehabilitation (HRAC/USP between January 2000 and February 2005. Sixteen of such individuals were interviewed, and content analysis was used. It was found that, for 37.5% of the subjects, hearing impairment occurred between the ages of 40 and 44 years; 62.5% were males; 62.5% had not

  4. The Th17/Treg Immune Balance in Ulcerative Colitis Patients with Two Different Chinese Syndromes: Dampness-Heat in Large Intestine and Spleen and Kidney Yang Deficiency Syndrome

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    Yang Gong

    2015-01-01

    Full Text Available Objective. To investigate the Th17/Treg immune balance in the ulcerative colitis (UC patients with two Chinese syndrome: dampness-heat in large intestine (DHLI and spleen and kidney Yang deficiency (SKYD. Methods. Ninety UC patients (45 were diagnosed with DHLI and 45 with SKYD syndrome and 23 healthy people were recruited. The serumIL-17 and TGF-β1 levels of these participants were measured with ELISA; the expression of IL-17 and TGF-β 1 in colonic mucosa tissue was determined with immunohistochemistry and the percentage of Th17 and Treg in peripheral blood with flow cytometry. Results. The levels of IL-17 and Th17 were significantly higher in both DHLI and SKYD groups than in healthy control group and higher in DHLI than in SKYD group (P<0.05. The levels of TGF-β1 and Treg were significantly lower in the two UC patients groups than in healthy control group; and lower in SKYD group than in DHLI group (P<0.05. Conclusions. UC with DHLI syndrome could be characterized by the elevation of Th17 and IL-17 levels, which indicated an accentuation of inflammatory reaction; UC with SKYD syndrome could be characterized by the reduction of serum Treg and TGF-β1 levels, which represented a depression of immune tolerance.

  5. The modulation of endoplasmic reticulum stress by chemical chaperone upregulates immune negative cytokine IL-35 in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Wang, Bo; Dai, Shen; Dong, Zhaojing; Sun, Yue; Song, Xingguo; Guo, Chun; Zhu, Faliang; Wang, Qun; Zhang, Lining

    2014-01-01

    Interleukin (IL)-35 is a newly identified immune negative molecule which is secreted by CD4(+)Foxp3(+) T regulatory cells (Tregs) and contributes to their suppressive capacity. Early data have shown that IL-35 inhibits development of several autoimmune diseases. However, the role of IL-35 in atherosclerosis, a lipid-driven chronic inflammatory disease in arterial wall, remains to be investigated. Here, we found that IL-35 was involved in atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. ApoE(-/-) mice with established atherosclerotic lesion displayed a lower level of IL-35 compared to age-matched wild type C57BL/6 mice without plaque. However, IL-35 expression increased significantly in ApoE(-/-) mice with attenuated plaque. More importantly, we found that modulation of ER stress treated by chemical chaperone, 4-Phenyl butyric acid (PBA) in vivo, mainly upregulated immune negative regulating molecule IL-35, as well as IL-10 and Foxp3, accompanied by increased Tregs. However, no obvious impact on pro-inflammatory molecules such as TNF-α, IFN-γ, IL-17 and IL-23 was observed, which provides new insight into the benefit of ER stress recovery from attenuated plaque. Our results suggest that IL-35 might have a potential value for atherosclerotic therapy.

  6. Different roles of Enhanced Disease Susceptibility1 (EDS1) bound to and dissociated from Phytoalexin Deficient4 (PAD4) in Arabidopsis immunity.

    Science.gov (United States)

    Rietz, Steffen; Stamm, Anika; Malonek, Stefan; Wagner, Stephan; Becker, Dieter; Medina-Escobar, Nieves; Vlot, A Corina; Feys, Bart J; Niefind, Karsten; Parker, Jane E

    2011-07-01

    • Enhanced Disease Susceptibility1 (EDS1) is an important regulator of plant basal and receptor-triggered immunity. Arabidopsis EDS1 interacts with two related proteins, Phytoalexin Deficient4 (PAD4) and Senescence Associated Gene101 (SAG101), whose combined activities are essential for defense signaling. The different sizes and intracellular distributions of EDS1-PAD4 and EDS1-SAG101 complexes in Arabidopsis leaf tissues suggest that they perform nonredundant functions. • The nature and biological relevance of EDS1 interactions with PAD4 and SAG101 were explored using yeast three-hybrid assays, in vitro analysis of recombinant proteins purified from Escherichia coli, and characterization of Arabidopsis transgenic plants expressing an eds1 mutant (eds1(L262P) ) protein which no longer binds PAD4 but retains interaction with SAG101. • EDS1 forms molecularly distinct complexes with PAD4 or SAG101 without additional plant factors. Loss of interaction with EDS1 reduces PAD4 post-transcriptional accumulation, consistent with the EDS1 physical association stabilizing PAD4. The dissociated forms of EDS1 and PAD4 are fully competent in signaling receptor-triggered localized cell death at infection foci. By contrast, an EDS1-PAD4 complex is necessary for basal resistance involving transcriptional up-regulation of PAD4 itself and mobilization of salicylic acid defenses. • Different EDS1 and PAD4 molecular configurations have distinct and separable functions in the plant innate immune response.

  7. Iron deficiency.

    Science.gov (United States)

    Scrimshaw, N S

    1991-10-01

    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world.

  8. Transcriptomic Characterization of Innate and Acquired Immune Responses in Red-Legged Partridges (Alectoris rufa: A Resource for Immunoecology and Robustness Selection.

    Directory of Open Access Journals (Sweden)

    Natalia Sevane

    Full Text Available Present and future challenges for wild partridge populations include the resistance against possible disease transmission after restocking with captive-reared individuals, and the need to cope with the stress prompted by new dynamic and challenging scenarios. Selection of individuals with the best immune ability may be a good strategy to improve general immunity, and hence adaptation to stress. In this study, non-infectious challenges with phytohemagglutinin (PHA and sheep red blood cells allowed the classification of red-legged partridges (Alectoris rufa according to their overall immune responses (IR. Skin from the area of injection of PHA and spleen, both from animals showing extreme high and low IR, were selected to investigate the transcriptional profiles underlying the different ability to cope with pathogens and external aggressions. RNA-seq yielded 97 million raw reads from eight sequencing libraries and approximately 84% of the processed reads were mapped to the reference chicken genome. Differential expression analysis identified 1488 up- and 107 down-regulated loci in individuals with high IR versus low IR. Partridges displaying higher innate IR show an enhanced activation of host defence gene pathways complemented with a tightly controlled desensitization that facilitates the return to cellular homeostasis. These findings indicate that the immune system ability to respond to aggressions (either diseases or stress produced by environmental changes involves extensive transcriptional and post-transcriptional regulations, and expand our understanding on the molecular mechanisms of the avian immune system, opening the possibility of improving disease resistance or robustness using genome assisted selection (GAS approaches for increased IR in partridges by using genes such as AVN or BF2 as markers. This study provides the first transcriptome sequencing data of the Alectoris genus, a resource for molecular ecology that enables integration

  9. Induction of Protective Immunity to Cryptococcal Infection in Mice by a Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Rajendra Upadhya

    2016-05-01

    Full Text Available Cryptococcus neoformans is a major opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised individuals and is responsible for a large proportion of AIDS-related deaths. The fungal cell wall is an essential organelle which undergoes constant modification during various stages of growth and is critical for fungal pathogenesis. One critical component of the fungal cell wall is chitin, which in C. neoformans is predominantly deacetylated to chitosan. We previously reported that three chitin deacetylase (CDA genes have to be deleted to generate a chitosan-deficient C. neoformans strain. This cda1Δ2Δ3Δ strain was avirulent in mice, as it was rapidly cleared from the lungs of infected mice. Here, we report that clearance of the cda1Δ2Δ3Δ strain was associated with sharply spiked concentrations of proinflammatory molecules that are known to be critical mediators of the orchestration of a protective Th1-type adaptive immune response. This was followed by the selective enrichment of the Th1-type T cell population in the cda1Δ2Δ3Δ strain-infected mouse lung. Importantly, this response resulted in the development of robust protective immunity to a subsequent lethal challenge with a virulent wild-type C. neoformans strain. Moreover, protective immunity was also induced in mice vaccinated with heat-killed cda1Δ2Δ3Δ cells and was effective in multiple mouse strains. The results presented here provide a strong framework to develop the cda1Δ2Δ3Δ strain as a potential vaccine candidate for C. neoformans infection.

  10. Leucine-Rich Repeat Kinase 2 (Lrrk2) Deficiency Diminishes the Development of Experimental Autoimmune Uveitis (EAU) and the Adaptive Immune Response.

    Science.gov (United States)

    Wandu, Wambui S; Tan, Cuiyan; Ogbeifun, Osato; Vistica, Barbara P; Shi, Guangpu; Hinshaw, Samuel J H; Xie, Chengsong; Chen, Xi; Klinman, Dennis M; Cai, Huaibin; Gery, Igal

    2015-01-01

    Mutations in LRRK2 are related to certain forms of Parkinson's disease and, possibly, to the pathogenesis of Crohn's disease. In both these diseases inflammatory processes participate in the pathogenic process. LRRK2 is expressed in lymphoid cells and, interestingly, Lrrk2 (-/-) mice were reported to develop more severe experimental colitis than their wild type (WT) controls. Here, we examined the possible involvement of LRRK2 in the pathogenesis of experimental autoimmune uveitis (EAU), an animal model for human uveitis, by testing Lrrk2 (-/-) mice for their capacity to develop this experimental eye disease and related immune responses. Lrrk2 (-/-) mice and their WT controls (C57Bl/6) were immunized with interphotoreceptor retinoid-binding protein (IRBP) and compared for their development of EAU, delayed type hypersensitivity (DTH) by skin tests, production of cytokines in culture, and expression of interferon (IFN)-γ, interleukin (IL)-17 and FoxP3 by spleen cells, using flow cytometry. Peritoneal macrophages were examined for their production of cytokines/chemokines in culture following stimulation with LPS or the oligodeoxynucleotide CpG. The Lrrk2 (-/-) and WT mice were also compared for their response to bovine serum albumin (BSA). The Lrrk2 (-/-) mice developed lower levels of EAU, DTH responses and cytokine production by lymphocytes than did their WT controls. Intracellular expression of IFN-γ and IL-17, by spleen cells, and secretion of cytokines/chemokines by activated peritoneal macrophages of Lrrk2 (-/-) mice trended toward diminished levels, although variabilities were noted. The expression levels of FoxP3 by Lrrk2 (-/-) spleen cells, however, were similar to those seen in WT controls. Consistent with their low response to IRBP, Lrrk2 (-/-) mice responded to BSA less vigorously than their WT controls. Lrrk2 deficiency in mice diminished the development of EAU and the related adaptive immune responses to IRBP as compared to the WT controls.

  11. 获得性凝血因子Ⅹ缺乏症三例报告并文献复习%Acquired coagulation factor Ⅹ deficiency: three cases report and literature review

    Institute of Scientific and Technical Information of China (English)

    刘文洁; 宣旻; 薛峰; 杨仁池

    2014-01-01

    目的 加深对获得性凝血因子Ⅹ缺乏症的认识.方法 对3例获得性凝血因子Ⅹ缺乏症患者的临床资料进行分析,并复习相关文献.结果 例1,男,57岁,诊断为多发性骨髓瘤轻链型、继发性淀粉样变、获得性凝血因子Ⅹ缺乏症,表现为自发性皮肤黏膜出血,凝血因子Ⅹ活性(FⅩ∶C)1.8%,予以MP(马法兰+曲安西龙)方案联合沙利度胺及对症治疗,FⅩ∶C未见升高,因原发病进展死亡.例2,男,41岁,以颅内出血入院,FⅩ∶C 26.8%,予以补充叶酸、维生素B12、维生素K,并输注红细胞、血小板及新鲜冰冻血浆治疗,颅内出血好转.例3,女,63岁,因反复发作四肢关节出血4个月入院,FⅩ∶C 6.1%,给予凝血酶原复合物、甲泼尼龙、硫唑嘌呤、利妥昔单抗治疗,FⅩ∶C未见明显升高,关节腔出血仍反复发作.结论 获得性凝血因子Ⅹ缺乏症临床表现具有异质性,诊断依赖病史和实验室检查,治疗包括控制出血和治疗原发病,预后与患者基础疾病相关.%Objective To deepen the understanding of acquired coagulation factor Ⅹ (F Ⅹ) deficiency.Methods The clinical data of 3 patients were analyzed and related literature were reviewed.Results Case 1,a 57-year-old male,secondary to multiple myeloma and amyloidosis,was presented with spontaneous mucous hemorrhage with the level of F Ⅹ ∶ C 1.8%,which kept unchanged after chemotherapy with melphalan,glucocorticoid,and thalidomide,and died of primary disease progression.Case 2,a 41-year-old male with psoriasis,was presented with cerebral and retinal hemorrhage with the level of F Ⅹ ∶ C 26.8%.The signs of hemorrhage were alleviated after the supplement of folic acid,vitamin B12,and vitamin K,and transfusion with red blood cells,platelets,and fresh frozen plasma.Case 3,a 63-year-old female,associated with high level of lupus anticoagulant,was presented with repeated ecchymosis and haemarthrosis with the level of F Ⅹ ∶C 6.1

  12. Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to a Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Gyhrs, A; Kristensen, Kim

    1994-01-01

    Vaccination of infants with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to carrier proteins has proven protective against invasive Hib diseases in several trials. However, insufficient immunogenicity has been noted in certain populations. Therefore, studies analyzing...... factors influencing the antibody response to conjugate vaccines are needed. In this study, the response to HibCP coupled to tetanus toxoid (TT) was examined in relation to (i) priming with or coadministration of the carrier protein and (ii) the levels of passively acquired maternal TT antibodies. One...... hundred forty-four infants were vaccinated with HibCP-TT at 5 and 6 months. They were randomized into three groups that received TT as part of a diphtheria-tetanus-polio vaccine at either 6 and 7 months (group A), 5 and 6 months (group B), or 4 and 5 months (group C). Maternally acquired TT antibodies...

  13. Acquired blepharoptosis

    NARCIS (Netherlands)

    Oosterhuis, HJGH

    1996-01-01

    A review is given of the aetiology and possible treatment of acquired (non-congenital) blepharoptosis, which is a common but not specific sign of neurological disease: The diagnostic categories of upper eyelid drooping are scheduled as (a) pseudo-ptosis due to a local process or overactivity of eye

  14. Acquired blepharoptosis

    NARCIS (Netherlands)

    Oosterhuis, HJGH

    1996-01-01

    A review is given of the aetiology and possible treatment of acquired (non-congenital) blepharoptosis, which is a common but not specific sign of neurological disease: The diagnostic categories of upper eyelid drooping are scheduled as (a) pseudo-ptosis due to a local process or overactivity of eye

  15. Effects of Trauma-Hemorrhage and IL-6 Deficiency on Splenic Immune Function in a Murine Trauma Model

    Directory of Open Access Journals (Sweden)

    P. Mommsen

    2012-01-01

    Full Text Available Splenic immune function is known to be depressed following hemorrhage. The present study investigates the effects of femoral shaft fracture, isolated or in combination with hemorrhage, on early stage cytokine production capacity of splenocytes and observes the role of IL-6 under these conditions. Male IL-6 knockout (IL-6−/− and wild-type mice (WT were randomly divided into three groups: sham (S, isolated femoral fracture (Fx, and femoral fracture + volume controlled hemorrhage (TH-Fx (=6 per group. Animals were sacrificed four hours after induction of hemorrhage and fracture. Cytokine release (TNF-α, IL-6, and IL-10 of isolated and LPS-stimulated splenocytes was determined by cytometric bead array. Femoral fracture with or without hemorrhage caused a suppression of in vitro cytokine production capacity of splenocytes at an early posttraumatic stage in WT and IL-6−/−. In the absence of IL-6, the profile of splenic cytokine secretion is significantly altered, identifying this cytokine as a potential therapeutic target to modulate the posttraumatic immune response.

  16. Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Morten A; Staalsoe, Trine; Kurtzhals, Jørgen

    2002-01-01

    of immunity, as disease-causing parasites appear to be those not controlled by preexisting VSA-specific Abs. In this work we report that VSA expressed by parasites from young Ghanaian children with P. falciparum malaria were commonly and strongly recognized by plasma Abs from healthy children in the same area...... with nonsevere disease. This was not due to a higher infection multiplicity in younger patients or in patients with severe disease. Our data suggest that acquisition of VSA-specific Ab responses gradually restricts the VSA repertoire that is compatible with parasite survival in the semi-immune host. This appears...... to limit the risk of severe disease by discriminating against the expression of VSA likely to cause life-threatening complications, such as cerebral malaria and severe anemia. Such VSA seem to be preferred by parasites infecting a nonimmune host, suggesting that VSA expression and switching are not random...

  17. Kaposi Sarcoma of Childhood: Inborn or Acquired Immunodeficiency to Oncogenic HHV-8.

    Science.gov (United States)

    Jackson, Carolyn C; Dickson, Mark A; Sadjadi, Mahan; Gessain, Antoine; Abel, Laurent; Jouanguy, Emmanuelle; Casanova, Jean-Laurent

    2016-03-01

    Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single-gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV-8.

  18. Acquired Methemoglobinaemia

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    Adil Al-Lawati

    2012-05-01

    Full Text Available Acquired methemoglobinaemia is a relatively rare condition and, therefore infrequently encountered in acute medical practice. Suspicion of the condition may be triggered when the measured PaO2 is ‘out of keeping’ with the oxygen saturations that are discovered with pulse oximetry. We describe two separate cases of acquired methemoglobinaemia secondary to the recreational use of alkyl nitrites (’poppers’. The patients presented at separate times to two different teaching hospitals in London, UK. The similarity of these cases has led the authors to conclude that a raised awareness of this potentially fatal condition, and its association with a widely-available recreational drug, is necessary to ensure a correct and timely diagnosis.

  19. The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

    DEFF Research Database (Denmark)

    Kemp, M; Handman, E; Kemp, K

    1998-01-01

    . Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor...... and that these cells were the major source of interferon-gamma. The results show that Th1-like cells recognising PSA-2 are expanded during infection by L. major and that they maintain their Th1-like cytokine profile upon reactivation in vitro. Since immunity to cutaneous leishmaniasis is mediated by antigen...

  20. Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment.

    Science.gov (United States)

    Soboslay, P T; Dreweck, C M; Hoffmann, W H; Lüder, C G; Heuschkel, C; Görgen, H; Banla, M; Schulz-Key, H

    1992-09-01

    A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P less than 0.01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-1 beta, IL-2 and TNF-alpha in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-gamma) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1 beta and TNF-alpha increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-gamma did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P less than 0.01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P less than 0.01); likewise there was an absolute increase in T-helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/CD8+ cell ratio (P = 0.001). The expression of

  1. IFNγ producing CD8+ T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas

    Science.gov (United States)

    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie

    2015-01-01

    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8+ T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell surface expression of MHC-I, but MHC-I expression could be rescued by exposure of these cells to IFNγ. We show that CD8+ T cells specific for tumor antigen/MHC-I were efficient at inducing regression of the MHC-I-deficient melanoma, provided that the T cells were endowed with properties permitting their migration into the tumor and their efficient production of IFNγ. This was the case for CD8+ T cells transfected to express an active form of STAT5 (STAT5CA). The amount of IFNγ produced ex vivo from T cells present in tumors after adoptive transfer of the CD8+ T cells was correlated with an increase in surface expression of MHC-I molecules by the tumor cells. We also show that these CD8+ T cells expressed PD-1 and upregulated its ligand PDL-1 on melanoma cells within the tumor. Despite upregulation of this immunosuppressive pathway, efficient IFNγ production in the melanoma microenvironment was found associated with resistance of STAT5CA-expressing CD8+ T cells to inhibition both by PD-1/PDL-1 engagement and by TGFβ1, two main immune regulatory mechanisms hampering the efficiency of immunotherapy in patients. PMID:25949872

  2. IFNγ producing CD8(+) T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas.

    Science.gov (United States)

    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie

    2015-02-01

    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8(+) T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell surface expression of MHC-I, but MHC-I expression could be rescued by exposure of these cells to IFNγ. We show that CD8(+) T cells specific for tumor antigen/MHC-I were efficient at inducing regression of the MHC-I-deficient melanoma, provided that the T cells were endowed with properties permitting their migration into the tumor and their efficient production of IFNγ. This was the case for CD8(+) T cells transfected to express an active form of STAT5 (STAT5CA). The amount of IFNγ produced ex vivo from T cells present in tumors after adoptive transfer of the CD8(+) T cells was correlated with an increase in surface expression of MHC-I molecules by the tumor cells. We also show that these CD8(+) T cells expressed PD-1 and upregulated its ligand PDL-1 on melanoma cells within the tumor. Despite upregulation of this immunosuppressive pathway, efficient IFNγ production in the melanoma microenvironment was found associated with resistance of STAT5CA-expressing CD8(+) T cells to inhibition both by PD-1/PDL-1 engagement and by TGFβ1, two main immune regulatory mechanisms hampering the efficiency of immunotherapy in patients.

  3. Growth Hormone Deficiency

    Directory of Open Access Journals (Sweden)

    Ömer Tarım

    2010-05-01

    Full Text Available Growth hormone deficiency is the most promising entity in terms of response to therapy among the treatable causes of growth retardation. It may be due to genetic or acquired causes. It may be isolated or a part of multiple hormone deficiencies. Diagnostic criteria and therefore treatment indications are still disputed. (Journal of Current Pediatrics 2010; 8: 36-8

  4. Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes

    Directory of Open Access Journals (Sweden)

    Sean Linkes

    2010-01-01

    Full Text Available Following proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a population of such cells remained after secondary and tertiary TCR stimulation and produced cytokines upon antigenic challenge. However, when NOD blasts were induced in the presence of rIL-15, the number of antigen-experienced “CD4lo” T cells was significantly reduced. Clonal contraction, mediated in part by CD95-dependent activation-induced cell death (AICD, normally regulates the accumulation of “CD4hi” effectors. Interestingly, CD95 expression was dramatically reduced on the AICD-resistant NOD “CD4lo” T cells. Thus, while autoimmune disease has often been attributed to the engagement of robust autoimmunity, we suggest that the inability to effectively contract the immune response distinguishes benign autoimmunity from progressive autoimmune diseases that are characterized by chronic T cell-mediated inflammation.

  5. Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet

    Institute of Scientific and Technical Information of China (English)

    Hideto Kawaratani; Tatsuhiro Tsujimoto; Toshiyuld Kitazawa; Mitsuteru Kitade; Hitoshi Yoshiji; Masahito Uemura; Hiroshi Fukui

    2008-01-01

    AIM:To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α),Toll-like receptor 4 (TLR4),and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats.METHODS:Male F344 rats were fed a cholinedeficient L-amino-acid-defined (CDAA) diet.The rats were killed after 4 or 8 wk of the diet,and their livers were removed for immunohistochemical investigation and RNA extraction.The liver specimens were immunostained for TNF-α,TLR4,and CD14.The gene expressions of TNF-a,TLR4,and CD14 were determined by reverse-transcriptase polymerase chain reaction (RT-PCR).Kupffer cells were isolated from the liver by Percoll gradient centrifugation,and were then cultured to measure TNF-α production.RESULTS:The serum and liver levels of TNF-α in the CDAA-fed rats increased significantly as compared with the control group,as did the immunohistochemical values and gene expressions of TNF-α,TLR4,and CD14 with the progression of steatohepatitis.TNF-α production from the isolated Kupffer cells of the CDAAfed rats was elevated by lipopolysaccharide stimulation.CONCLUSION:The expressions of TNF-α,TLR4,and CD14 increased in the NASH model,suggesting that TLR4 and CD14-mediated endotoxin liver damage may also occur in NASH.

  6. Acquired Techniques

    DEFF Research Database (Denmark)

    Lunde Nielsen, Espen; Halse, Karianne

    2013-01-01

    Acquired Techniques - a Leap into the Archive, at Aarhus School of Architecture. In collaboration with Karianne Halse, James Martin and Mika K. Friis. Following the footsteps of past travelers this is a journey into tools and techniques of the architectural process. The workshop will focus upon...... architectural production as a conglomerate of various analogue and digital methods, and provide the basics, the tips/tricks - and how the tool themselves becomes operational for spatial/thematic investigations. Eventually, this will become a city, exhibition and phamplet inhabited by the (by...

  7. Tracing the antibody mediated acquired immunity by Foot and Mouth disease and Rift Valley Fever combined vaccine in pregnant ewes and their lambs

    Directory of Open Access Journals (Sweden)

    Wael Mossad Gamal

    2014-11-01

    Full Text Available Aim: The aim of this study was to provide adequate protection to ewes and their lambs against Foot and Mouth disease (FMD and Rift Valley Fever (RVF. Materials and Methods: A combined inactivated oil vaccine was prepared successfully. Such vaccine was found to be free from foreign contaminants, safe and potent as determined by quality control tests such as challenge protection percentage for FMD and mice ED50 for RVF. Vaccination of pregnant ewes with the prepared combined vaccine and determination of the antibody level via serum neutralization test (SNT and Enzyme Linked immune sorbent assay (ELISA in the vaccinated pregnant ewes and their lambs. Results: Vaccination of pregnant ewes revealed that these ewes exhibited high levels of specific antibodies against the included vaccine antigens (Foot and Mouth disease virus type A Iran O5, O PanAsia and SAT2/EGY/2012 and RVFV-ZH501. FMD antibodies recorded their peaks by the 10th week while those of RVF recorded their peaks by the 12th week post vaccination then all antibodies began to decrease gradually to reach their lowest protective titers for FMD by the 32nd week post vaccination and those for RVF by the 34th week post vaccination. Potency test of the prepared combined vaccine expressed as protection percentage of vaccinated sheep against target virulent FMD virus serotypes reflected a protection percentage of 80% against type O and SAT2 and 100% against A while for RVF, the mice ED50 was found to be 0.009 indicating the potency of the prepared vaccine. The antibody titer in serum and colostrum of vaccinated pregnant ewes at day of parturition (10-12 week post vaccination recorded a high titer against FMD serotype (O, serotype (A, serotype (SAT2 and against RVF. It was noticed that the colostrum antibody titers were slightly higher than those in the sera of vaccinated ewes at time of parturition. The newly born lambs from vaccinated ewes, exhibited good levels of maternal immunity against the

  8. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  9. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  10. Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women

    Science.gov (United States)

    Requena, Pilar; Rui, Edmilson; Padilla, Norma; Martínez-Espinosa, Flor E.; Castellanos, Maria Eugenia; Bôtto-Menezes, Camila; Malheiro, Adriana; Arévalo-Herrera, Myriam; Kochar, Swati; Kochar, Sanjay K.; Kochar, Dhanpat K.; Umbers, Alexandra J.; Ome-Kaius, Maria; Wangnapi, Regina; Hans, Dhiraj; Menegon, Michela; Mateo, Francesca; Sanz, Sergi; Desai, Meghna; Mayor, Alfredo; Chitnis, Chetan C.; Bardají, Azucena; Mueller, Ivo; Rogerson, Stephen; Severini, Carlo; Fernández-Becerra, Carmen; Menéndez, Clara

    2016-01-01

    P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy. Antibody responses against all antigens were detected in all populations, with PNG women presenting the highest levels overall. P. vivax infection at sample collection time was positively associated with antibody levels against PvLP1 (fold-increase: 1.60 at recruitment -first antenatal visit-) and PvLP2 (fold-increase: 1.63 at delivery), and P. falciparum co-infection was found to increase those responses (for PvLP1 at recruitment, fold-increase: 2.25). Levels of IgG against two VIR proteins at delivery were associated with higher birth weight (27 g increase per duplicating antibody levels, p<0.05). Peripheral blood mononuclear cells from PNG uninfected pregnant women had significantly higher antigen-specific IFN-γ TH1 responses (p=0.006) and secreted less pro-inflammatory cytokines TNF and IL-6 after PvLP2 stimulation than P. vivax-infected women (p<0.05). These data demonstrate that VIR antigens induce the natural acquisition of antibody and T cell memory responses that might be important in immunity to P. vivax during pregnancy in very diverse geographical settings. PMID:27711158

  11. A new mouse model of mild ornithine transcarbamylase deficiency (spf-j displays cerebral amino acid perturbations at baseline and upon systemic immune activation.

    Directory of Open Access Journals (Sweden)

    Tatyana N Tarasenko

    Full Text Available Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250 is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N. This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.

  12. Molecular mechanisms of paclitaxel and NM-3 on human gastric cancer in a severe combined immune deficiency mice orthotopic implantation model

    Institute of Scientific and Technical Information of China (English)

    Jin-Shui Zhu; Ming-Quan Song; Guo-Qiang Chen; Qin Li; Qun Sun; Qiang Zhang

    2007-01-01

    AIM: To explore the molecular mechanisms of action of paclitaxel and NM-3 on human gastric cancer in severe combined immune deficiency (SCID) mice.METHODS: Human gastric cancer cells SGC-7901 were implanted into SCID mice and mice were treated with paclitaxel and NM-3. The effects of paclitaxel and NM-3 on apoptosis of human gastric cancer cells were analyzed using flow cytometry, TUNEL assays, and DNA fragment analyses.RESULTS: Apoptosis of SGC-7901 cells was successfully induced by paclitaxel, NM-3, and the combination of paclitaxel and NM-3 24 h after injection as shown by the presence of apoptotic hypodiploid peaks on the flow cytometer before G1-S and a characteristic apoptotic band pattern in the DNA electrophoresis. The apoptotic rate detected by TUNEL assay was found to be significantly higher in the paclitaxel/NM-3 compared to the control group (38.5% ± 5.14% vs 13.2% ± 1.75%,P < 0.01).CONCLUSION: Paclitaxel in combination with NM-3 is able to induce apoptosis of the human gastric cancer cells in SCID mice effectively and synergistically.

  13. A new mouse model of mild ornithine transcarbamylase deficiency (spf-j) displays cerebral amino acid perturbations at baseline and upon systemic immune activation.

    Science.gov (United States)

    Tarasenko, Tatyana N; Rosas, Odrick R; Singh, Larry N; Kristaponis, Kara; Vernon, Hilary; McGuire, Peter J

    2015-01-01

    Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250) is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N). This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.

  14. The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901

    Science.gov (United States)

    Dvorak, Christopher C.; Cowan, Morton J.; Logan, Brent R.; Notarangelo, Luigi D.; Griffith, Linda M.; Puck, Jennifer M.; Kohn, Donald B.; Shearer, William T.; O'Reilly, Richard J.; Fleisher, Thomas A.; Pai, Sung-Yun; Hanson, I. Celine; Pulsipher, Michael A.; Fuleihan, Ramsay; Filipovich, Alexandra; Goldman, Frederick; Kapoor, Neena; Small, Trudy; Smith, Angela; Chan, Ka-Wah; Cuvelier, Geoff; Heimall, Jennifer; Knutsen, Alan; Loechelt, Brett; Moore, Theodore; Buckley, Rebecca H.

    2013-01-01

    The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92%) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92%) were treated with HCT within 1–2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes. PMID:23818196

  15. Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus—An Immunological Dilemma

    OpenAIRE

    Cristina Gluhovschi; Gheorghe Gluhovschi; Ligia Petrica; Silvia Velciov; Adrian Gluhovschi

    2015-01-01

    Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE) is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg) ...

  16. Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to a Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Gyhrs, A; Kristensen, Kim

    1994-01-01

    factors influencing the antibody response to conjugate vaccines are needed. In this study, the response to HibCP coupled to tetanus toxoid (TT) was examined in relation to (i) priming with or coadministration of the carrier protein and (ii) the levels of passively acquired maternal TT antibodies. One...... than infants with low prevaccination levels after the first (P = 0.0001) and the second (P = 0.01) doses of HibCP-TT. In contrast, active priming with TT at 4 months resulted in a threefold-higher median level of anti-HibCP (group C; 1.34 micrograms/ml) than in the unprimed group (group A; 0.......40 microgram/ml) after the first dose of HibCP-TT (P = 0.01). Coadministration of TT had no enhancing effect (group B; 0.58 microgram/ml). No significant differences between the median anti-HibCP levels were seen after the second HibCP-TT dose (6.72, 9.63, and 11.44 micrograms/ml in groups A, B, and C...

  17. Peroxisome deficiency but not the defect in ether lipid synthesis causes activation of the innate immune system and axonal loss in the central nervous system

    Directory of Open Access Journals (Sweden)

    Bottelbergs Astrid

    2012-03-01

    Full Text Available Abstract Background Mice with peroxisome deficiency in neural cells (Nestin-Pex5−/− develop a neurodegenerative phenotype leading to motor and cognitive disabilities and early death. Major pathologies at the end stage of disease include severe demyelination, axonal degeneration and neuroinflammation. We now investigated the onset and progression of these pathological processes, and their potential interrelationship. In addition, the putative role of oxidative stress, the impact of plasmalogen depletion on the neurodegenerative phenotype, and the consequences of peroxisome elimination in the postnatal period were studied. Methods Immunohistochemistry in association with gene expression analysis was performed on Nestin-Pex5−/− mice to document demyelination, axonal damage and neuroinflammation. Also Gnpat−/− mice, with selective plasmalogen deficiency and CMV-Tx-Pex5−/− mice, with tamoxifen induced generalized loss of peroxisomes were analysed. Results Activation of the innate immune system is a very early event in the pathological process in Nestin-Pex5−/− mice which evolves in chronic neuroinflammation. The complement factor C1q, one of the earliest up regulated transcripts, was expressed on neurons and oligodendrocytes but not on microglia. Transcripts of other pro- and anti-inflammatory genes and markers of phagocytotic activity were already significantly induced before detecting pathologies with immunofluorescent staining. Demyelination, macrophage activity and axonal loss co-occurred throughout the brain. As in patients with mild peroxisome biogenesis disorders who develop regressive changes, demyelination in cerebellum and brain stem preceded major myelin loss in corpus callosum of both Nestin-Pex5−/− and CMV-Tx-Pex5−/− mice. These lesions were not accompanied by generalized oxidative stress throughout the brain. Although Gnpat−/− mice displayed dysmyelination and Purkinje cell axon damage in cerebellum

  18. Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus--An Immunological Dilemma.

    Science.gov (United States)

    Gluhovschi, Cristina; Gluhovschi, Gheorghe; Petrica, Ligia; Velciov, Silvia; Gluhovschi, Adrian

    2015-01-01

    Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE) is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg) cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth) or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis) may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother's disease, is required. It is important to understand immune tolerance to grafts in transplant pathology.

  19. Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus—An Immunological Dilemma

    Directory of Open Access Journals (Sweden)

    Cristina Gluhovschi

    2015-01-01

    Full Text Available Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother’s disease, is required. It is important to understand immune tolerance to grafts in transplant pathology.

  20. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    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

  1. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901.

    Science.gov (United States)

    Dvorak, Christopher C; Cowan, Morton J; Logan, Brent R; Notarangelo, Luigi D; Griffith, Linda M; Puck, Jennifer M; Kohn, Donald B; Shearer, William T; O'Reilly, Richard J; Fleisher, Thomas A; Pai, Sung-Yun; Hanson, I Celine; Pulsipher, Michael A; Fuleihan, Ramsay; Filipovich, Alexandra; Goldman, Frederick; Kapoor, Neena; Small, Trudy; Smith, Angela; Chan, Ka-Wah; Cuvelier, Geoff; Heimall, Jennifer; Knutsen, Alan; Loechelt, Brett; Moore, Theodore; Buckley, Rebecca H

    2013-10-01

    The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.

  2. Morphometrical analysis of preantral follicular survival of VEGF-treated bovine ovarian cortex tissue following xenotransplantation in an immune deficient mouse model.

    Science.gov (United States)

    Langbeen, A; Van Ginneken, C; Fransen, E; Bosmans, E; Leroy, J L M R; Bols, P E J

    2016-05-01

    The increasing number of cancer survivors the past decades, has sparked the need for fertility preservation strategies. Due to predominantly ethical constraints, human research material is scarce. A bovine in vitro model is a valuable alternative. Therefore, the following objectives were defined: 1) to xeno-graft bovine ovarian cortex tissue in immune deficient mice as a study-model for female fertility preservation strategies; 2) to stereologically quantify vascularization in Vascular Endothelial Growth Factor (VEGF)-treated and non-treated tissue; 3) to study preantral follicular survival in situ, after xenotransplantation. Bovine ovarian tissue strips were incubated with or without VEGF prior to grafting into female, neutered BALB/c-nu mice (n=16). Non-transplanted cortical tissue was used as a control. At time zero (control), two (2 weeks) and four (4 weeks) weeks after transplantation, grafts were retrieved and assessed by von Willebrand Factor and caspase-3 immunostaining. Data were analyzed using a linear mixed model. In the VEGF+ grafts, 31% of the follicles were considered 'alive' 2 weeks after transplantation, compared to only 17% in the VEGF- grafts (P<0.05). However, no difference could be detected 4 weeks after transplantation (P=0.76) with less follicles being considered 'alive' after transplantation (22%), compared to the control (47.5%) (P<0.05). Finally, the vascular surface density was significantly less in the grafts, irrespective of the transplantation period or the use of VEGF. Although the transplantation process overall negatively influenced the number of viable follicles and vascular density, VEGF exposure prior to transplantation can favor follicle survival during a 2 weeks transplantation period.

  3. Across sectional study: the knowledge, attitude, perception, misconception and views (KAPMV) of adult family members of people living with human immune virus-HIV acquired immune deficiency syndrome-AIDS (PLWHA).

    Science.gov (United States)

    Bhagavathula, Akshaya Srikanth; Bandari, Deepak Kumar; Elnour, Asim Ahmad; Ahmad, Akram; Khan, Muhammad Umair; Baraka, Mohamed; Hamad, Farah; Shehab, Abdulla

    2015-01-01

    We intended to assess knowledge, attitude, perception, misconception and views (KAP-MV) of family members of PLWHA. A cross-sectional retrospective study conducted in Anti-retroviral centre of Mahatma Gandhi Memorial-MGM hospital, Warangal, Telangana, South-India from July to September 2014. A questionnaire containing 41 items was distributed among adult family members accompanying patients living with HIV/AIDS-PLWHA. Level of KAP-MV was categorized into poor (0-28), average (29-55) and good (56-82). Analysis was performed by Pearson's Chi square, analysis of variance and Spearman's correlation test on 41 variables using SPSS version 21 and p < 0.01. 538 questionnaires were distributed, response rate was (96 %). On knowledge scale, respondents had a mean score of 8.0 ± 1.7, attitude 5.8 ± 3.4, perception 23.4 ± 4.1, misconceptions 8.0 ± 2.1 and views 8.0 ± 3.9. The respondents mean score was 53.2 ± 9.1 (64.9 %). Overall, level of education, marital status, religious beliefs, and employment status has significant (p < 0.001) associations with KAP-MV. Knowledge was significantly correlated with respondents' attitude (r = -0.15, p < 0.001), perception (0.39; p < 0.001), and views (0.381; p < 0.001). Family members of PLWHA with less knowledge score had more negative attitude, perception and views. Level of education, marital status, religious beliefs and employment status were identified as key barriers. Interventions targeting family members of PLWHA are warranted. Practice implications are as follows: Encourage role of family members.Deploy interventions.Minimize barriers.Change misconceptions.

  4. Manganese deficiency or excess caused the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier, as regulated by NF-κB, TOR and Nrf2 signalling, in grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Jiang, Wei-Dan; Tang, Ren-Jun; Liu, Yang; Kuang, Sheng-Yao; Jiang, Jun; Wu, Pei; Zhao, Juan; Zhang, Yong-An; Tang, Ling; Tang, Wu-Neng; Zhou, Xiao-Qiu; Feng, Lin

    2015-10-01

    Intestinal mucosal immune components and mRNA levels of inflammatory cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules in young grass carp (Ctenopharyngodon idellus) under dietary manganese (Mn) deficiency or excess were investigated. Fish were fed the diets containing graded levels of Mn [3.65-27.86 mg Mn kg(-1) diet] for 8 weeks. The results demonstrated that Mn deficiency significantly decreased the lysozyme and acid phosphatase (ACP) activities, up-regulated tumour necrosis factor α (TNF-α), interleukin 8 and the signalling factor nuclear factor-κB p65, and down-regulated interleukin 10 (IL-10), transforming growth factor β1, inhibitor of signalling factors κB-α and target of rapamycin mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI). However, Mn deficiency did not change the C3 content in the PI, whereas it decreased the C3 contents in the MI and DI. Additionally, Mn depletion also resulted in significantly low mRNA levels for tight junction proteins (claudin-b, claudin-c, claudin-15, occludin and zonula occludens-1), antioxidant enzymes (MnSOD, GPx and CAT) and NF-E2-related factor-2 in the intestines of fish. Excessive Mn exhibited toxic effects similar to Mn deficiency, where optimal Mn contents reversed those indicators. In conclusion, Mn deficiency or excess causes the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier relating to NF-κB, TOR and Nrf2 signalling in grass carp. Furthermore, quadratic regression analysis at 95% maximum response of lysozyme and acid phosphatase activities in the distal intestine of young grass carp revealed the optimum dietary Mn levels to be 8.90 and 8.99 mg kg(-1) diet, respectively.

  5. Naturally-acquired humoral immune responses against the N- and C-termini of the Plasmodium vivax MSP1 protein in endemic regions of Brazil and Papua New Guinea using a multiplex assay

    Directory of Open Access Journals (Sweden)

    Alonso Pedro L

    2010-01-01

    Full Text Available Abstract Background Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. Methods Glutathione S-transferase (GST and GST-fusion proteins representing the N- terminus of the merozoite surface protein 1 of P. vivax, PvMSP1-N, and the C-terminus, PvMSP1-C, were covalently coupled to BioPlex carboxylated beads. Recombinant proteins and coupled beads were used, respectively, in ELISA and Bioplex assays using immune sera of P. vivax patients from Brazil and PNG to determine IgG and subclass responses. Concordances between the two methods in the seropositivity responses were evaluated using the Kappa statistic and the Spearman's rank correlation. Results The results using this methodology were compared with the classical microtitre enzyme-linked immnosorbent assay (ELISA, showing that the assay was sensitive, reproducible and had good concordance with ELISA; yet, further research into different statistical analyses seems desirable before claiming conclusive results exclusively based on multiplex assays. As expected, results demonstrated that PvMSP1 was immunogenic in natural infections of patients from different endemic regions of Brazil and Papua New Guinea (PNG, and that age correlated only with antibodies against the C-terminus part of the molecule. Furthermore, the IgG subclass profiles were different in these endemic regions having IgG3 predominantly recognizing PvMSP1 in Brazil and IgG1 predominantly recognizing PvMSP1 in PNG. Conclusions This study validates the use of the multiplex assay to measure naturally-acquired IgG antibodies against the merozoite surface protein 1 of P. vivax.

  6. Interventions to screen for human immune-deficiency virus among people donating blood[Protocol]%献血员人类免疫缺陷病毒(HIV)筛检措施的系统评价的研究方案

    Institute of Scientific and Technical Information of China (English)

    王莉; 刘建平; 熊玮; 邝璞; 陶铁军

    2002-01-01

    背景艾滋病(AIDS)已经成为人类目前所面临的危害最为严重的疾病之一.艾滋病病毒(HIV)主要有三个传播途径:血液、性行为和母婴垂直传播;而通过输血传播的效率更高.由于缺乏有效的HIV筛检方法或方法应用不当以及缺乏严格的管理,通过输血传播HIV的危险极为严重,特别是在一些发展中国家.自从1985年FDA批准第一个HIV试剂用于献血员筛检以来,迄今已经生产出第4代筛检试剂.最初HIV检测试剂仅用于筛检献血员,后来成为了HIV预防工作的重要方面.目前HIV筛检已被视为国家艾滋病预防和治疗策略的重要内容. 目的评价用于献血员HIV筛检所有方法的有效性,从而找出最合适的方法,以减少HIV通过输血传播的危险. 检索策略以"HIV"、"AIDS"、"screening"、"test"、"blood donor"、"blood bank"等为主题,检索了MEDLINE、CENTRAL/CCTR、AIDSLINE、EMBASE、CBM等数据库;同时检索了WHO、UNAIDS、CDC、FDA及其相关网站,并与该领域的专家和机构联系,以获得未发表的文献. 资料纳入标准纳入了所有与献血员HIV筛检方法有关的随机对照试验(RCT)、临床对照试验(CCT);同时一些观察性研究,如队列研究、病例对照研究和历史对照研究等纳入用于敏感性分析. 评价方法参照Cochrane 系统评价的原则,选择纳入的研究,并对其进行质量评价、数据提取和分析.%Background AIDS (acquired immune deficiency syndrome) has become the most devastating disease which humankind has ever encountered.Human immune-deficiency virus(HIV) is transmitted through blood, sexual behavior and mother-to-baby, with more efficient transmission through blood transfusion. HIV risk among blood transfusion was severe due to lack of effective and correctly applied screening method and rigorous management, especially in some developing countries. Since the first HIV screening reagent was approved by FDA to screen the blood in 1985

  7. 从肠黏膜免疫系统损害探讨AIDS脾虚病机%Discuss the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage

    Institute of Scientific and Technical Information of China (English)

    王春芳; 李真; 徐立然

    2012-01-01

    HIV/AIDS patients with intestinal mucosal immune system damage promoting the immunodeficiency of body and the incidence of opportunistic infections, which is consistent with the evolution of spleen deficiency pathogenesis point of view of TCM. This paper discusses the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage, and proposed strengthening the spleen to improve immune function of intestinal mucosa of AIDS.%HIV/AIDS患者肠黏膜免疫系统损害促进了机体免疫功能的缺失和机会性感染的发生,AIDS以脾虚为主的中医病机演变过程,与HIV感染所致以肠黏膜损伤为重要表现的全身免疫损伤过程相符合.文章从肠黏膜免疫系统损害角度探讨AIDS脾虚病机,提出健脾扶正以改善肠黏膜免疫功能的中医药治疗AIDS思路.

  8. Immunity decreases, antioxidant system damages and tight junction changes in the intestine of grass carp (Ctenopharyngodon idella) during folic acid deficiency: Regulation of NF-κB, Nrf2 and MLCK mRNA levels.

    Science.gov (United States)

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-04-01

    This investigation used the same growth trial as the previous study, which showed that folic acid deficiency retarded growth in young grass carp (the percent weight gain of Groups 1-6 were 102.32 ± 3.41%, 137.25 ± 10.48%, 179.78 ± 3.95%, 164.33 ± 3.21%, 143.35 ± 8.12% and 115.28 ± 2.66%) [1]. In the present study, we investigated the effects of dietary folic acid on the immune response, antioxidant status and tight junctions in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp were fed diets containing graded levels of folic acid at 0.10, 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results indicated that acid phosphatase and lysozyme activities, and the complement component 3 content in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) were decreased with folic acid deficiency (0.1 mg kg(-1)) (P Folic acid deficiency (0.1 mg kg(-1)) up-regulated interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65 (NF-κB p65), IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression, meanwhile down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in the PI, MI and DI (P folic acid deficiency decreased fish intestinal innate immune function may be partly contributed to the regulation of NF-κB p65 pathway. Moreover, the activities and corresponding gene expression of glutathione content, Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase in fish intestine were depressed by deficient folic acid diet (0.1 mg kg(-1)) (P folic acid deficiency (0.1 mg kg(-1)) down-regulated NF-E2-related factor 2 (Nrf2) gene expression, up-regulated Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression in fish intestine (P folic acid diet damaged fish intestinal antioxidant capacity partly by regulating Nrf2/Keap1 pathway

  9. WORKPLACE HUMAN IMMUNE VIRUS/ACQUIRED IMMUNO ...

    African Journals Online (AJOL)

    User

    HIV/AIDS issues and their appreciation of the impact of the pandemic would influence the quantum of resources to be ... ing on a high level of skilled labour and in an environment of high ..... The problem left to be solved is how to translate their ...

  10. Mannose Binding Lectin Deficiency and Clinical Features

    Directory of Open Access Journals (Sweden)

    Ertugrul Erken

    2013-08-01

    Full Text Available Innate immunity consists of macrophages, neutrophils, natural killer cells, mucosal immunuglobulins and the comlement system. Mannose binding lectin (MBL takes part in innate immunity through opsonisation and complement activation. MBL deficiency is associated with some infections and autoimmune disorders. However some studies indicate that MBL deficiency alone is not essential for immunity but it may intensify the clinic picture of an immune deficiency that already exists. This article refers to clincal studies related to MBL and brings up the clinical importance of MBL deficiency. [Archives Medical Review Journal 2013; 22(4.000: 565-574

  11. Deficiency of dietary niacin impaired gill immunity and antioxidant capacity, and changes its tight junction proteins via regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Li, Shun-Quan; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-08-01

    To investigate the effects of dietary niacin on gill immunity, tight junction proteins, antioxidant system and related signaling molecules mRNA expression, young grass carp (Ctenopharyngodon idella) were fed six diets containing graded levels of niacin (3.95-55.01 mg/kg diet) for 8 weeks. The study indicated that niacin deficiency decreased lysozyme and acid phosphatase activities, and complement 3 content, and caused oxidative damage that might be partly due to the decreased copper, zinc superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and reduced glutathione content in fish gills (P niacin-deficient diet group. Conversely, the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 8, interferon γ2, and interleukin 1β), signaling molecules (nuclear factor kappa B p65, IκB kinase α, IκB kinase β, IκB kinase γ, Kelch-like-ECH-associated protein 1b, myosin light chain kinase and p38 mitogen-activated protein kinase (p38 MAPK) were significantly increased (P niacin-deficient diet. Interestingly, the varying niacin levels of 3.95-55.01 mg/kg diet had no effect on the mRNA level of Kelch-like-ECH-associated protein 1a, Claudin-c and -12 in fish gills (P > 0.05). In conclusion, niacin deficiency decreased gill immunity, impaired gill antioxidant system, as well as regulated mRNA expression of gill tight junction proteins and related signaling molecules of fish.

  12. Dietary vitamin C deficiency depresses the growth, head kidney and spleen immunity and structural integrity by regulating NF-κB, TOR, Nrf2, apoptosis and MLCK signaling in young grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Xu, Hui-Jun; Jiang, Wei-Dan; Feng, Lin; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-05-01

    This study investigated the effects of dietary vitamin C on the growth, and head kidney, spleen and skin immunity, structural integrity and related signaling molecules mRNA expression levels of young grass carp (Ctenopharyngodon idella). A total of 540 grass carp (264.37 ± 0.66 g) were fed six diets with graded levels of vitamin C (2.9, 44.2, 89.1, 133.8, 179.4 and 224.5 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila and the survival rate recorded for 14 days. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) decreased lysozyme (LA) and acid phosphatase (ACP) activities, and complement 3 and complement 4 (C4) contents (P spleen), IL-12 P40, IL-15, IL-17D, nuclear factor κB p65, IκB kinases (IKKα, IKKβ, IKKγ), target of rapamycin and ribosomal protein S6 kinase 1 mRNA levels (P spleen under injection fish of A. hydrophila, suggesting that vitamin C deficiency could decrease fish head kidney and spleen immunity and cause inflammation. Meanwhile, compared with optimal vitamin C supplementation, vitamin C deficiency decreased the activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase (P spleen under injection fish of A. hydrophila, suggesting that vitamin C deficiency could decrease fish head kidney and spleen structural integrity through depression of antioxidative ability, induction of apoptosis and disruption of tight junctional complexes. In addition, except the activities of ACP and MnSOD, and mRNA expression levels of TGF-β1, Occludin and MnSOD, the effect of vitamin C on fish head kidney, spleen and skin immunity and structural integrity other indicators model are similar under infection of A. hydrophila. Finally, the vitamin C requirement for the growth performance (PWG) of young grass carp was

  13. Acquired platelet function defect

    Science.gov (United States)

    Acquired qualitative platelet disorders; Acquired disorders of platelet function ... blood clotting. Disorders that can cause problems in platelet function include: Idiopathic thrombocytopenic purpura Chronic myelogenous leukemia Multiple ...

  14. Cutting edge: FasL(+) immune cells promote resolution of fibrosis.

    Science.gov (United States)

    Wallach-Dayan, Shulamit B; Elkayam, Liron; Golan-Gerstl, Regina; Konikov, Jenya; Zisman, Philip; Dayan, Mark Richter; Arish, Nissim; Breuer, Raphael

    2015-05-01

    Immune cells, particularly those expressing the ligand of the Fas-death receptor (FasL), e.g. cytotoxic T cells, induce apoptosis in 'undesirable' self- and non-self-cells, including lung fibroblasts, thus providing a means of immune surveillance. We aimed to validate this mechanism in resolution of lung fibrosis. In particular, we elucidated whether FasL(+) immune cells possess antifibrotic capabilities by induction of FasL-dependent myofibroblast apoptosis and whether antagonists of membrane (m) and soluble (s) FasL can inhibit these capabilities. Myofibroblast interaction with immune cells and its FasL-dependency, were investigated in vitro in coculture with T cells and in vivo, following transplantation into lungs of immune-deficient syngeneic Rag-/- as well as allogeneic SCID mice, and into lungs and air pouches of FasL-deficient (gld) mice, before and after reconstitution of the mice with wild-type (wt), FasL(+) immune cells. We found that myofibroblasts from lungs resolving fibrosis undergo FasL-dependent T cell-induced apoptosis in vitro and demonstrate susceptibility to in vivo immune surveillance in lungs of reconstituted, immune- and FasL-deficient, mice. However, immune-deficient Rag-/- and SCID mice, and gld-mice with FasL-deficiency, endure the accumulation of transplanted myofibroblasts in their lungs with subsequent development of fibrosis. Concomitantly, gld mice, in contrast to chimeric FasL-deficient mice with wt immune cells, accumulated transplanted myofibroblasts in the air pouch model. In humans we found that myofibroblasts from fibrotic lungs secrete sFasL and resist T cell-induced apoptosis, whereas normal lung myofibroblasts are susceptible to apoptosis but acquire resistance upon addition of anti-s/mFasL to the coculture. Immune surveillance, particularly functional FasL(+) immune cells, may represent an important extrinsic component in myofibroblast apoptosis and serve as a barrier to fibrosis. Factors interfering with Fas/FasL-immune

  15. MINI-REVIEW: SYSTEMIC LUPUS ERYTHEMATOSUS AND DEFICIENCIES OF EARLY COMPONENTS OF THE COMPLEMENT CLASSICAL PATHWAY

    Directory of Open Access Journals (Sweden)

    Lourdes eIsaac

    2016-02-01

    Full Text Available The complement system plays an important role in the innate and acquired immune response against pathogens. It consists of more than 30 proteins found in soluble form or attached to cell membranes. Most complement proteins circulate in inactive forms and can be sequentially activated by the Classical, Alternative or Lectin Pathways. Biological functions such as opsonization, removal of apoptotic cells, adjuvant function, activation of B lymphocytes, degranulation of mast cells and basophils, solubilization and clearance of immune complex and cell lysis are dependent on complement activation. Although the activation of the complement system is important to avoid infections, it also can contribute to the inflammatory response triggered by immune complex deposition in tissues in auto-immune diseases. Paradoxically, the deficiency of early complement proteins from the Classical Pathway is strongly associated with development of systemic lupus erythematous (SLE - mainly C1q deficiency (93% and C4 deficiency (75%. The aim of this review is to focus on the deficiencies of early components of the Classical Pathway (C1q, C1r, C1s, C4, C2 proteins in SLE patients.

  16. T-cell-mediated immunity to lymphocytic choriomeningitis virus in beta2-integrin (CD18)- and ICAM-1 (CD54)-deficient mice

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Marker, O; Thomsen, Allan Randrup

    1996-01-01

    The T-cell response to lymphocytic choriomeningitis virus was studied in mice with deficient expression of beta2-integrins or ICAM-1. In such mice, the generation of virus-specific cytotoxic T lymphocytes was only slightly impaired and bystander activation was as extensive as that observed in wild...

  17. Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice

    DEFF Research Database (Denmark)

    Sorensen, G.L.; Hjelmborg, J.V.B.; Leth-Larsen, R.

    2006-01-01

    of the present study was to describe the association between serum SP-D and weight, waist circumference or BMI, and furthermore to observe body weight development in SP-D-deficient (Spd-/-) mice. As a part of the Danish population-based twin study (GEMINAKAR) on the metabolic syndrome, we analysed 1476 Danish...

  18. Absence of lactobacilli containing glycolipids with the α-galactose epitope and the enhanced fucosylation of a receptor glycolipid GA1 in the digestive tracts of immune-deficient scid mice.

    Science.gov (United States)

    Iwamori, Masao; Tanaka, Kyoko; Adachi, Shigeki; Aoki, Daisuke; Nomura, Taisei

    2015-07-01

    The Lactobacillus species in the digestive tracts of immune-deficient scid mice was distinct from that in control mice, i.e. Lactobacillus murinus in scid and L. johnsonii in control mice, according to their 16S-rRNA, indicating that a symbiotic relationship between lactobacilli and a host is established under pressure from the immune system. The caecal and colonal contents rich in L. murinus of scid mice were loose with a strong sour smell, resulting in diarrhoea, and those with L. johnsonii in control mice included abundant solid materials. Lactobacillus glycolipids were revealed to be recognized by the immune system, and by TLC-immunostaining, LacTetH-DG (Galα1-6Galα1-6Galα1-2Glcα1-3'DG) of L. johnsonii was detected in the stomach, caecum and colon of control mice, but not in those of scid ones, in which fucosylation of a receptor GA1 for L. johnsonii was enhanced more than 4-fold compared with in the control mice. Thus, structural modification of receptor glycolipids was revealed to occur in the process of establishment of a symbiotic relationship between lactobacilli and a host. LacTetH-DG was also immunogenic to human, because of the presence of natural antibodies against it, and the antibody binding to it was comparable to that of blood group- and species-related glycosphingolipids.

  19. Severe acquired anaemia in Africa: new concepts

    NARCIS (Netherlands)

    M. Boele van Hensbroek; F. Jonker; I. Bates

    2011-01-01

    Severe anaemia is common in Africa. It has a high mortality and particularly affects young children and pregnant women. Recent research provides new insights into the mechanisms and causes of severe acquired anaemia and overturns accepted dogma. Deficiencies of vitamin B12 and vitamin A, but not of

  20. Deficiency of a Disintegrin and Metalloproteinase 10 (ADAM10) on dendritic cells prevents the development of type 2 immunity and IgE production

    Science.gov (United States)

    Mice in which dendritic cells (DCs)lack ADAM10 (ADAM10DC-/-) were found to have a dramatic decrease in TH2 immunity and IgE production, as measured by both lung inflammation to house dust mite (HDM) and active systemic anaphylaxis models (ASA). With HDM, the ADAM10DC-/- had significantly less airway...

  1. Acquired hemoglobin variants and exposure to glucose-6-phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen-matched blood.

    Science.gov (United States)

    Raciti, Patricia M; Francis, Richard O; Spitalnik, Patrice F; Schwartz, Joseph; Jhang, Jeffrey S

    2013-08-01

    Red blood cell exchange (RBCEx) is frequently used in the management of patients with sickle cell disease (SCD) and acute chest syndrome or stroke, or to maintain target hemoglobin S (HbS) levels. In these settings, RBCEx is a category I or II recommendation according to guidelines on the use of therapeutic apheresis published by the American Society for Apheresis. Matching donor red blood cells (RBCs) to recipient phenotypes (e.g., C, E, K-antigen negative) can decrease the risk of alloimmunization in patients with multi-transfused SCD. However, this may select for donors with a higher prevalence of RBC disorders for which screening is not performed. This report describes a patient with SCD treated with RBCEx using five units negative for C, E, K, Fya, Fyb (prospectively matched), four of which were from donors with hemoglobin variants and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Pre-RBCEx HbS quantification by high performance liquid chromatography (HPLC) demonstrated 49.3% HbS and 2.8% hemoglobin C, presumably from transfusion of a hemoglobin C-containing RBC unit during a previous RBCEx. Post-RBCEx HPLC showed the appearance of hemoglobin G-Philadelphia. Two units were G6PD-deficient. The patient did well, but the consequences of transfusing RBC units that are G6PD-deficient and contain hemoglobin variants are unknown. Additional studies are needed to investigate effects on storage, in-vivo RBC recovery and survival, and physiological effects following transfusion of these units. Post-RBCEx HPLC can monitor RBCEx efficiency and detect the presence of abnormal transfused units.

  2. [Psychoneuroimmunology--regulation of immunity at the systemic level].

    Science.gov (United States)

    Boranić, Milivoj; Sabioncello, Ante; Gabrilovac, Jelka

    2008-01-01

    Innate and acquired immune reactions are controlled by their intrinsic regulatory mechanisms, ie. by an array of cytokines that mediate communication among cells of the immune system itself and with other cells and tissues, e. g. in areas of inflammation. In addition, the immune system is also subjected to systemic regulation by the vegetative and endocrine systems since immune cells express receptors for neurotransmitters and hormones. Neuroendocrine signals may enhance or suppress the immune reaction, accelerate or slow it, but do not affect specificity. Various stressful factors, including the psychosocial ones, affect immunity. In turn, cytokines generated by the immune system influence hormonal secretion and central nervous system, producing specific behavioral changes (the "sickness behavior") accompanying infectious and inflammatory diseases. That includes somnolence, loss of apetite, depression or anxiety and decrease of cognitive abilities, attention and memory. Local immune systems in skin and mucosa are also subjected to systemic neuroendocrine regulation and possess intrinsic neuroregulatory networks as well. These mechanisms render skin and respiratory and digestive tracts responsive to various forms of stress. Examples are neurodermitis, asthma and ulcerative colitis. In children, the immune and the neuroendocrine systems are still developing, particularly in fetal, neonatal and early infant periods, and exposure to stressful experiences at that time may result in late consequences in the form of deficient immunity or greater risks for allergic or autoimmune reactions. Recognition of the participation of neuroendocrine mechanisms in regulation of immunity helps us understand alterations and disturbances of immune reactions under the influence of stressful factors but so far has not produced reliable therapeutic implications. Psychosocial interventions involving the child and its family may be useful.

  3. Frequent respiratory tract infections in the canine model of X-linked ectodermal dysplasia are not caused by an immune deficiency

    OpenAIRE

    Casal, Margret L.; Mauldin, Elizabeth A.; Ryan, Sara; Scheidt, Jennifer L.; Kennedy, Jeffrey; Moore, Peter F.; Felsburg, Peter J.

    2005-01-01

    As in many human patients with X-linked hypohidrotic ectodermal dysplasia (XHED), XHED dogs are at an increased risk for pulmonary disorders. Localized immune system defects had been suspected previously in affected dogs because of frequent infections and unexpected deaths due to opportunistic respiratory tract infections. Experiments were designed to examine systemic and localized humoral and cellular responses, development and function of T cells, and thymic morphology. All dogs used in the...

  4. CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.

    Directory of Open Access Journals (Sweden)

    Dennis Wolf

    Full Text Available BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/- mice consumed a high fat diet (HFD for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/- mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/- mice. However, CD40L(-/- mice consuming HFD were not protected from the onset of diet-induced obesity (DIO, insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/- mice consuming a low fat diet (LFD showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.

  5. IFNγ producing CD8+ T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas

    OpenAIRE

    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie

    2015-01-01

    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8+ T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell s...

  6.  Surfactant Protein D of the Innate Immune Defence is Inversely Associated with Human Obesity and SP-D Deficiency Infers Increased Body Weight in Mice

    DEFF Research Database (Denmark)

    Sørensen, Grith Lykke; Hjelmborg, Jacob v. B.; Leth-Larsen, Rikke

    2006-01-01

    of the present study was to describe the association between serum SP-D and weight, waist circumference or BMI, and furthermore to observe body weight development in SP-D-deficient (Spd-/-) mice. As a part of the Danish population-based twin study (GEMINAKAR) on the metabolic syndrome, we analysed 1476 Danish...... twins for serum SP-D and investigated associations with weight, waist circumference and BMI by multiple regression analysis. Serum SP-D was significantly and inversely associated with weight (P = 0.001) and waist circumference in men (P

  7. Iodine Deficiency

    Science.gov (United States)

    ... 2017 By ATA | Featured , Iodine Deficiency , News Releases , Potassium Iodide (KI) | No Comments IDD NEWSLETTER – February 2017 VOLUME ... 2016 By ATA | Featured , Iodine Deficiency , News Releases , Potassium Iodide (KI) | No Comments IDD NEWSLETTER – November 2015 (PDF ...

  8. Time-course microarrays reveal early activation of the immune transcriptome in a choline-deficient mouse model of liver injury.

    Science.gov (United States)

    Mitsumoto, Koji; Watanabe, Rina; Nakao, Katsuki; Yonenaka, Hisaki; Hashimoto, Takao; Kato, Norihisa; Kumrungsee, Thanutchaporn; Yanaka, Noriyuki

    2017-09-01

    Choline-deficient diet is extensively used as a model of nonalcoholic fatty liver disease (NAFLD). In this study, we explored genes in the liver for which the expression changed in response to the choline-deficient (CD) diet. Male CD-1 mice were divided into two groups and fed a CD diet with or without 0.2% choline bitartrate for one or three weeks. Hepatic levels of choline metabolites were analyzed by using liquid chromatography mass spectrometry and hepatic gene expression profiles were examined by DNA microarray analysis. The CD diet lowered liver choline metabolites after one week and exacerbated fatty liver between one and three weeks. We identified >300 genes whose expression was significantly altered in the livers of mice after consumption of this CD diet for one week and showed that liver gene expression profiles could be classified into six distinct groups. This study showed that STAT1 and interferon-regulated genes was up-regulated after the CD diet consumption and that the Stat1 mRNA level was negatively correlated with liver phosphatidylcholine level. Stat1 mRNA expression was actually up-regulated in isolated hepatocytes from the mouse liver with the CD diet. This study provides insight into the genomic effects of the CD diet through the Stat1 expression, which might be involved in NAFLD development. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Lower limb deficient children in the Netherlands : epidemiological aspects

    NARCIS (Netherlands)

    Rijnders, LJM; Boonstra, AM; Groothoff, JW; Cornel, MC; Eisma, WH

    2000-01-01

    information on the characteristics of children with limb deficiencies and amputations in the Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency o

  10. Feeding long-chain n-3 polyunsaturated fatty acids to obese leptin receptor-deficient JCR:LA- cp rats modifies immune function and lipid-raft fatty acid composition.

    Science.gov (United States)

    Ruth, Megan R; Proctor, Spencer D; Field, Catherine J

    2009-05-01

    Dietary EPA and DHA modulate immunity and thereby may improve the aberrant immune function in obese states. To determine the effects of feeding fish oil (FO) containing EPA and DHA on splenocyte phospholipid (PL) and lipid-raft fatty acid composition, phenotypes and cytokine production, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp; n 10) were randomised to one of three nutritionally adequate diets for 3 weeks: control (Ctl, 0 % EPA+DHA); low FO (LFO, 0.8 % (w/w) EPA+DHA); high FO (HFO, 1.4 % (w/w) EPA+DHA). Lean JCR:LA-cp (+/ - or +/+) rats (n 5) were fed the Ctl diet. Obese Ctl rats had a higher proportion of n-3 PUFA in splenocyte PL than lean rats fed the same diet (P JCR:LA-cp rats. Feeding FO lowered the ex vivo inflammatory response, without altering IL-2 production from ConA-stimulated splenocytes which may occur independent of leptin signalling.

  11. Dietary pantothenic acid deficiency and excess depress the growth, intestinal mucosal immune and physical functions by regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Li, Li; Feng, Lin; Jiang, Wei-Dan; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2015-08-01

    This study investigated the effects of dietary pantothenic acid (PA) on the growth, intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of grass carp (Ctenopharyngodon idella). A total of 540 grass carp (253.44 ± 0.69 g) were fed six diets with graded levels of PA (PA1, PA15, PA30, PA45, PA60 and PA75 diets) for 8 weeks. The results indicated that compared with PA deficiency (PA1 diet) and excess (PA75 diet) groups, optimal PA supplementation increased (P TOR) mRNA expression levels in some intestinal segments; (2) reactive oxygen species, malondialdehyde and protein carbonyl contents, and Kelch-like ECH-associating protein 1a, Kelch-like ECH-associating protein 1b in the intestine; (3) Claudin 12, Claudin 15a and myosin light-chain kinase (MLCK) mRNA levels in some intestinal segments of grass carp. In conclusion, optimum PA promoted growth, intestinal mucosal immune and physical function, as well as regulated mRNA levels of signaling molecules NF-κB P65, TOR, Nrf2 and MLCK in grass carp intestine. Based on the quadratic regression analysis of PWG and intestinal lysozyme activity, the optimal PA levels in grass carp (253.44-745.25 g) were estimated to be 37.73 mg/kg and 41.38 mg/kg diet, respectively.

  12. Macrophages Subvert Adaptive Immunity to Urinary Tract Infection.

    Directory of Open Access Journals (Sweden)

    Gabriela Mora-Bau

    2015-07-01

    Full Text Available Urinary tract infection (UTI is one of the most common bacterial infections with frequent recurrence being a major medical challenge. Development of effective therapies has been impeded by the lack of knowledge of events leading to adaptive immunity. Here, we establish conclusive evidence that an adaptive immune response is generated during UTI, yet this response does not establish sterilizing immunity. To investigate the underlying deficiency, we delineated the naïve bladder immune cell compartment, identifying resident macrophages as the most populous immune cell. To evaluate their impact on the establishment of adaptive immune responses following infection, we measured bacterial clearance in mice depleted of either circulating monocytes, which give rise to macrophages, or bladder resident macrophages. Surprisingly, mice depleted of resident macrophages, prior to primary infection, exhibited a nearly 2-log reduction in bacterial burden following secondary challenge compared to untreated animals. This increased bacterial clearance, in the context of a challenge infection, was dependent on lymphocytes. Macrophages were the predominant antigen presenting cell to acquire bacteria post-infection and in their absence, bacterial uptake by dendritic cells was increased almost 2-fold. These data suggest that bacterial uptake by tissue macrophages impedes development of adaptive immune responses during UTI, revealing a novel target for enhancing host responses to bacterial infection of the bladder.

  13. Dual Effects of IL-1 Overactivity on the Immune System in a Mouse Model of Arthritis due to Deficiency of IL-1 Receptor Antagonist

    Institute of Scientific and Technical Information of China (English)

    Jian Yan; Yan Jiao; Hong Chen; Feng Jiao; Karen A.Hasty; John M.Stuart; Weikuan Gu

    2013-01-01

    Previous studies have revealed the significance of cytokine interleukin 1 (IL-1) in the onset and progression of meumatoid arthritis (RA).The precise molecular mechanisms related to IL-1 underlying RA is still elusive.We conducted a whole genome-wide transcriptomal comparison of wild-type (WT) and arthritis-prone IL-1 receptor antagonist (IL-Irn) deficient BALB/c mice to address this issue.To refine our search efforts,gene expression profiling was also performed on paired wild-type and arthritis-resis nt IL-1m deficient DBA/1 mice as internal controls when identifying causative arthritis candidate genes.Two hundred and fifteen trans dpts were found to be dysregulated greater than or equal to 2-fold in the diseased mice.The altered transcriptome in BALB/c mice revealed increased myeloid cell activities and impaired lymphocyte functionality,suggesting dual regulatory effects of IL-1 hyperactivil on immunological changes associated with arthritis development.Phase-specific gene expression changes were identified,such as early increase and late decrease of heat shock protein coding genes.Moreover,common gene expression changes were also observed,especially the upregulation of paired Ig-like receptor A (Pira) in both early and late phases of arthritis.Real-time PCR was performed to validate the expression of Pira and an intervention experiment with a major histocompatibility complex (MHC) class I inhibitor (brefeldin A) was carried out to investigate the role of suppressing Pira activity.We conclude that global pattern changes of common and distinct gene expressions may represent novel opportunities for better control of RA through early diagnosis and development of alternative therapeutic strategies.

  14. Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases)

    Science.gov (United States)

    El-Azami-El-Idrissi, Mohammed; Lakhdar-Idrissi, Mounia; Chaouki, Sanae; Atmani, Samir; Bouharrou, Abdelhak; Hida, Moustapha

    2016-01-01

    Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified. PMID:27642394

  15. Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Albert Eduardo Silva Martins

    2014-09-01

    Full Text Available Human immunodeficiency virus (HIV-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003, age greater than or equal to 35 years (p = 0.002, number of partners greater than three (p = 0.002, CD4+ lymphocyte count < 200/mm3 (p = 0.041 and alcohol abuse (p = 0.004. Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%, low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

  16. Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil.

    Science.gov (United States)

    Martins, Albert Eduardo Silva; Lucena-Silva, Norma; Garcia, Renan Gomes; Welkovic, Stefan; Barboza, Aureliana; Menezes, Maria Luiza Bezerra; Maruza, Magda; Tenório, Terezinha; Ximenes, Ricardo A A

    2014-09-01

    Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4⁺ lymphocyte count < 200/mm³ (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

  17. RELATIONSHIP BETWEEN LIPID PEROXIDATION AND RED BLOOD CELL IMMUNE FUNCTION IN PATIENTS WITH SPLEEN DEFICIENCY%脾虚患者脂质过氧化和红细胞免疫功能关系

    Institute of Scientific and Technical Information of China (English)

    章梅; 邱根全; 夏天

    2001-01-01

    Objective:To explore the effect of lipid peroxidation on red blood cell immune function in patients with spleen deficiency.Method:By the methods of TBA and red blood cell-yeast mixed flower circle,the RBC-C3b receptor rate,malonyldialdehyde(MDA) of plasma and erythrocyte membrane in patients with spleen deficiency were determined respectively.Result:The red blood cell C3b receptor rate(RBC-C3bRR)and red blood cell immune compound(RBC-IC) were lowered,but the MDA content in plasma and erythrocyte membrane were increased respectively.The relative analysis suggested that there were relationship between the RBC-C3bRR and MAD content in plasma and erythrocyte membrane.Conclusion:The lipid peroxidation lesion of red blood cell membrane had a bad effect on RBC-C3bRR.%目的:探讨脾虚患者脂质过氧化对红细胞免疫功能的影响。方法:采用红细胞酵母菌混合花环法和硫代巴比妥酸(TBA)法检测脾虚患者红细胞膜C3b受体花环率(RBC-C3bRR)、血浆及红细胞膜丙二醛(MDA)水平。结果:脾虚患者RBC-C3bRR和红细胞膜免疫复合物花环率(RBC-ICR)明显降低,血浆MDA和红细胞膜MDA明显升高;RBC-C3bRR与血浆MDA、红细胞膜MDA呈负相关,其中红细胞膜MDA和RBC-C3bRR关系更为密切。结论:红细胞膜脂质过氧化损害对RBC-C3bRR有不利影响。

  18. HIV-1 and hijacking of the host immune system: the current scenario.

    Science.gov (United States)

    Imran, Muhammad; Manzoor, Sobia; Saalim, Muhammad; Resham, Saleha; Ashraf, Javed; Javed, Aneela; Waqar, Ahmed Bilal

    2016-10-01

    Human immunodeficiency virus (HIV) infection is a major health burden across the world which leads to the development of acquired immune deficiency syndrome (AIDS). This review article discusses the prevalence of HIV, its major routes of transmission, natural immunity, and evasion from the host immune system. HIV is mostly prevalent in Sub-Saharan Africa and low income countries. It is mostly transmitted by sharing syringe needles, blood transfusion, and sexual routes. The host immune system is categorized into three main types; the innate, the adaptive, and the intrinsic immune system. Regarding the innate immune system against HIV, the key players are mucosal membrane, dendritic cells (DCs), complement system, interferon, and host Micro RNAs. The major components of the adaptive immune system exploited by HIV are T cells mainly CD4+ T cells and B cells. The intrinsic immune system confronted by HIV involves (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) APOBEC3G, tripartite motif 5-α (TRIM5a), terherin, and (SAM-domain HD-domain containing protein) SAMHD1. HIV-1 efficiently interacts with the host immune system, exploits the host machinery, successfully replicates and transmits from one cell to another. Further research is required to explore evasion strategies of HIV to develop novel therapeutic approaches against HIV.

  19. CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM Syndrome for Characterizing Immune Responses against Pathogens

    Directory of Open Access Journals (Sweden)

    Catalina Lopez-Saucedo

    2015-01-01

    Full Text Available Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria. We evaluated, compared, and characterized the humoral immune response of wild type (WT and C57-CD40L deficient (C57-CD40L−/− mice infected with Citrobacter rodentium. Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L−/− mice compared with WT. Essentially IgG1 and IgG2c levels were detectable only in WT mice. C57-CD40L−/− animals, orally inoculated with 2×109 CFU, presented several clinical manifestations since the second week of infection and eventually died. In contrast at this time point no clinical manifestations were observed among C57-CD40L−/− mice infected with 1×107 CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1×107 CFU, collected at day 14 after infection, had similar C. rodentium-specific IgM titres. Although C57-CD40L−/− animals had lower IgG and IgG2b titres than WT mice, C57-CD40L−/− mice sera displayed complement-mediated bactericidal activity against C. rodentium. C. rodentium-infected C57-CD40L−/− mice are capable of producing antibodies that are protective. C57-CD40L−/− mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens.

  20. Prolidase deficiency

    Directory of Open Access Journals (Sweden)

    Masood Qazi

    2007-01-01

    Full Text Available Prolidase deficiency is a rare inborn disorder of collagen metabolism characterized by chronic recurrent skin ulceration. A seven-year-old girl and her younger sibling with clinical features and laboratory criteria fulfilling the diagnosis of prolidase deficiency are presented in view of rarity of the condition.

  1. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.

    2009-01-01

    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. Howeve

  2. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.

    2009-01-01

    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. Howeve

  3. Acquired inflammatory demyelinating neuropathies.

    Science.gov (United States)

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  4. Iron deficiency or anemia of inflammation?

    OpenAIRE

    Nairz, Manfred; Theurl, Igor; Wolf, Dominik; Weiss, Günter

    2016-01-01

    Summary Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body’s iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear ph...

  5. Hospital-acquired pneumonia

    Science.gov (United States)

    ... tends to be more serious than other lung infections because: People in the hospital are often very sick and cannot fight off ... prevent pneumonia. Most hospitals have programs to prevent hospital-acquired infections.

  6. Acquired Cutix Laxa

    Directory of Open Access Journals (Sweden)

    Jaswal Ritu

    1999-01-01

    Full Text Available A case of acquired cutis laxa in a male is reported. The skin became loose and started hanging in folds after the patient received therapy for piles. Relevant literature is reviewed.

  7. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.

    2008-01-01

    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  8. Immune memory, immune oblivion: a lesson from Funes the memorious.

    Science.gov (United States)

    Neuman, Yair

    2007-01-01

    We commonly think of the immune system as having a memory. However, memory is always accompanied by a complementary process of oblivion. Is there immune oblivion? In this theoretical paper, I address this question and suggest that oblivion is an integral aspect of memorization. In this context, I suggest that immune memory is an orchestration of reversible and irreversible processes of biological computation through feedback loops. Drawing on the linguistic metaphor, I inquire into the implications of this idea for a better understanding of immune memory and immune deficiency among the elderly.

  9. Iodine Deficiency

    Science.gov (United States)

    ... 0 Iodine Daily Serving now recommended in Multivitamin/Mineral Supplements for Pregnant and Lactating Women By ATA | 2015 News Releases , Iodine Deficiency , News Releases , Thyroid Disease and Pregnancy | No Comments Falls Church, February 10, 2015 —The ...

  10. [Selective immunoglobulin A deficiency].

    Science.gov (United States)

    Binek, Alicja; Jarosz-Chobot, Przemysława

    2012-01-01

    Immunoglobulin class A is the main protein of the mucosal immune system. Selective immunoglobulin A deficiency (sIgAD) is the most common primary immunodeficiency in Caucasians. sIGAD is strongly associated with the certain major histocompatibility complex region. Most individuals with sIgAD are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations. Several autoimmune diseases, such as systemic lupus erythematosus, diabetes mellitus type 1, Graves disease and celiac disease, are associated with an increased prevalence of sIgAD. Screening for sIgAD in coeliac disease is essential. Patients need treatment of associated diseases. It is also known that IgA deficiency may progress into a common variable immunodeficiency (CVID). Pathogenesis and molecular mechanism involved in sIgAD should be elucidated in the future.

  11. Primary parotid B-cell lymphoma successfully treated with chemotherapy plus highly active antiretroviral therapy with prolonged survival and immune reconstitution in an acquired immunodeficiency syndrome patient: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2014-01-01

    Full Text Available Non-Hodgkin′s lymphoma (NHL is the second most common acquired immunodeficiency syndrome (AIDS-defining cancer. In this population, up to 70-80% of cases may present as extranodal location as the primary clinical manifestation of the neoplasm disease. Gastrointestinal tract is the most frequent location of AIDS-associated NHL. However, salivary gland involvement, including the parotid gland is a rare complication in human immunodeficiency virus (HIV-patients. Here, we describe a patient seropositive for the HIV, who developed a primary NHL of the parotid gland histologically classified as a high-grade diffuse large B-cell lymphoma. Patient was treated with a combination of chemotherapy plus highly active antiretroviral therapy with a good clinical, virological and immunological response and a prolonged survival, more than 5 years, without evidence of neoplasm relapse.

  12. Acquired smooth muscle hamartoma

    Directory of Open Access Journals (Sweden)

    Bari Arfan ul

    2006-01-01

    Full Text Available Smooth muscle hamartoma is an uncommon, usually congenital, cutaneous hyperplasia of the arrectores pilorum muscles. When it is acquired, it may be confused with Becker′s nevus. We report a case of this rare tumor in a 19-year-old man. The disease started several years ago as multiple small skin-colored papules that subsequently coalesced to form a large soft plaque on the back of the left shoulder. The diagnosis of acquired smooth muscle hamartoma was confirmed on histopathology. The patient was reassured about the benign nature of the lesion and was not advised any treatment.

  13. Learning to Acquire

    DEFF Research Database (Denmark)

    Henningsson, Stefan

    2015-01-01

    This paper develops a knowledge-based model of information systems (IS) integration in acquisition-based growth programs. Previous research has found important differences in the acquirers’ abilities for acquisition IS integration, and that these differences play key roles in explaining the econo...... are therefore persistent and hard to overcome for the inexperienced acquirer....

  14. Acquired cutis laxa

    Directory of Open Access Journals (Sweden)

    Musaliar S

    2003-03-01

    Full Text Available A 13-yeat-old male patient born of non consanguineous marriage with history of recurrent urticaria and angioedema for the past 2 years presented with wrinkling and laxity of the skin over the face, axilla and abdomen. Histopathology was consistent with cutis laxa. We are reporting a rare case of acquired cutis laxa due to recurrent urticaria.

  15. Acquired cutis laxa

    Directory of Open Access Journals (Sweden)

    Musaliar S

    2003-01-01

    Full Text Available A 13-yeat-old male patient born of non consanguineous marriage with history of recurrent urticaria and angioedema for the past 2 years presented with wrinkling and laxity of the skin over the face, axilla and abdomen. Histopathology was consistent with cutis laxa. We are reporting a rare case of acquired cutis laxa due to recurrent urticaria.

  16. Clinical manifestations of mannan-binding lectin deficiency

    DEFF Research Database (Denmark)

    Thiel, Steffen; Frederiksen, Pernille Dorthea; Jensenius, Jens Christian

    2006-01-01

    Mannan-binding lectin (MBL) is a plasma protein of the innate immune system with the ability to initiate antimicrobial and inflammatory actions. MBL deficiency is common. More than 10% of the general population may, depending on definition, be classified as MBL deficient, underlining the redundan...... of the immune system. Ongoing research attempt to illuminate at which conditions MBL deficiency may lead to disease. With examples, this review illustrates the diversity of results obtained so far....

  17. Cobalamin deficiency.

    Science.gov (United States)

    Herrmann, Wolfgang; Obeid, Rima

    2012-01-01

    Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor

  18. Genetics Home Reference: common variable immune deficiency

    Science.gov (United States)

    ... or Free article on PubMed Central Park JH, Resnick ES, Cunningham-Rundles C. Perspectives on common variable ... on PubMed or Free article on PubMed Central Resnick ES, Cunningham-Rundles C. The many faces of ...

  19. Primary Immune Deficiency Disease Genetics & Inheritance

    Science.gov (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  20. 健脾止泻颗粒对脾虚泄泻患儿消化吸收与 肠道局部免疫功能的影响%Effect of Jianpi Zhixie Granule on Digestion and Absorption Function and Immunity Function of Local Gut of Diarrhea Children with Spleen Deficiency

    Institute of Scientific and Technical Information of China (English)

    陈永辉

    2001-01-01

    观察脾虚泄泻患儿消化吸收与肠道局部免疫功能以及健脾止泻颗粒的作用机制。方法:对64例脾虚泄泻患儿用健脾止泻颗粒治疗,检测其治疗前后的唾液淀粉酶活性、尿D-木糖排泄率及大便SIgA,并与30例正常儿进行对照观察。结果:脾虚泄泻患儿消化吸收与肠道局部免疫功能低下,经治疗后,上述指标明显好转。结论:健脾止泻颗粒具有促进脾虚泄泻患儿消化吸收功能和提高肠道局部免疫功能的作用。%To observe the digestion and absorption function and the immunity function of the local gut of the diarrhea children with spleen deficiency and the action mechanism of Jianpi Zhixie granule.Metheods:The salivary amylase activity,urine D-xylose excretion rate and stool SIgA of 64 diarrhea children with spleen deficiency were tested before and after treatment by Jianpi Zhixie granule.Results:The digestion and absorption function and the immunity function of the local gut of the diarrhea children with spleen deficiency were lower than the normal group(30 health children).The above indices were increased markedly after treatment.Conclusion:Jianpi Zhixie granule has the functions of promoting the digestion and absorption function of the diarrhea children with spleen deficiency and improving the immunity function of the local gut.

  1. [Types of immune response in advanced suppurative peritonitis].

    Science.gov (United States)

    Borisov, A G; Savchenko, A A; Cherdantsev, D V; Zdzitovetsky, D E; Pervova, O V; Kudryavtsev, I V; Belenyuk, V D; Shapkina, V A

    to assess types of immune response in patients with advanced suppurative peritonitis and course of disease. We examined 79 patients with acute surgical abdominal diseases and injuries complicated by advanced suppurative peritonitis. Blood immunological parameters were estimated using flowing cytometry and enzyme immunoassay. It was concluded that functional parameters of immune system are very various in patients with advanced suppurative peritonitis. Cluster analysis defined 4 immune types which are determined by different state of congenital and acquired immunity. Immunodeficient and unreactive immune types are unfavorable. Immune types with activation of congenital and acquired immunity are the most favourable. This stratification personifies diagnosis and treatment of immune disorders in patients with advanced suppurative peritonitis.

  2. VLCAD deficiency

    DEFF Research Database (Denmark)

    Boneh, A; Andresen, B S; Gregersen, N

    2006-01-01

    We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood...

  3. Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes.

    Science.gov (United States)

    Acevedo, N; Mercado, D; Vergara, C; Sánchez, J; Kennedy, M W; Jiménez, S; Fernández, A M; Gutiérrez, M; Puerta, L; Caraballo, L

    2009-08-01

    The 13q33-34 region harbours a susceptibility locus to Ascaris lumbricoides, although the underlying genes are unknown. Immunoglobulin (Ig)E and IgG confer protective immunity and here we sought to investigate in an endemic population whether LIG4, TNFSF13B and IRS2 genes influence IgE and IgG levels against Ascaris and the ABA-1 allergen as a putative resistance marker. Mite-allergic asthmatic patients were analysed for potential relationships between Ascaris predisposition and allergy. One thousand and sixty-four subjects from Cartagena, Colombia, were included. Single nucleotide polymorphisms (SNPs) were genotyped using TaqMan assays. Antibody levels were measured by enzyme-linked immunosorbent assay. Linear and logistic regressions were used to model effects of genotypes on antibody levels. The GG genotype of LIG4 (rs1805388) was associated with higher IgE levels to Ascaris compared with other genotypes. TNFSF13B (rs10508198) was associated positively with IgG levels against Ascaris extract and IgE levels against ABA-1. In asthmatics, IRS2 (rs2289046) was associated with high total IgE levels. Associations held up after correction by population stratification using a set of 52 ancestry markers, age, sex and disease status. There was no association with asthma or mite sensitization. In a tropical population, LIG4 and TNFSF13B polymorphisms are associated with specific IgE and IgG to Ascaris, supporting previous linkage studies implicating the 13q33 region. Our results suggest that genes protecting against parasite infections can be different to those predisposing to asthma and atopy.

  4. Lower limb deficient children in the Netherlands: epidemiological aspects

    OpenAIRE

    Rijnders, LJM; Boonstra, AM; Groothoff, JW; Cornel, MC; Eisma, WH

    2000-01-01

    information on the characteristics of children with limb deficiencies and amputations in the Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency or amputation and male/female ratios. Data were obtained from a regional birth defects registry for the northern parr. of the Netherlands (EUROCAT-NNL) and from a national survey, inclusion criteria...

  5. Acquired methemoglobinemia in infants

    Directory of Open Access Journals (Sweden)

    Mehmet Mutlu

    2011-06-01

    Full Text Available Objective: This study aimed to determine the etiologic factors of acquired methemoglobinemia in infants younger than three months in our region. Material and Methods: This study was carried out retrospectively in infants with methemoglobinemia admitted to Karadeniz Technical University, Pediatric Clinic, during the period 2000-2009. Infants with methemoglobinemia were identified according to the medical records or ICD-10 code. Results: Nine infants with acquired methemoglobinemia (8 male, 1 female were included in the study. Seven cases were associated with the use of prilocaine for circumcision, one case with the use of prilocaine-lidocaine for local pain therapy, and one case with neonatal sepsis caused by Staphylococcus aureus.Conclusion: Prilocaine should not be used in infants less than three months of age because of the risk of methemoglobinemia. Ascorbic acid is an effective therapy if methylene blue is not obtained. It should not be forgotten that sepsis caused by S. aureus may cause methemoglobinemia in infants.

  6. Racks to acquire

    CERN Multimedia

    2004-01-01

    IT department has 25 80cm deep SCHROFF 19" racks which are no longer needed. Please contact Michel Blanc (Michel.Blanc@cern.ch, 74925 or 163223) from Monday 27th September if you are interested in acquiring some or all of these racks. Five shelf units suitable for housing up to 44 mini-tower PCs are also available. Photographs of racks and shelf units are available in the directory \\\\cern.ch\\dfs\\users\\t\\tim\\Public\\513.

  7. Acquired hypertrichosis lanuginosa

    Directory of Open Access Journals (Sweden)

    Kumar Pramod

    1993-01-01

    Full Text Available Acquired hypertirichosis lanuginose developed rapidly in a patient with no detectable malignancy. Soft, fine, downy hair growth was noticed on the face, ears, limbs and trunk. Bilaterally symmetrical vitiliginous macules were present on the ear and preauricular region. This case is reported because of its rarity, absence of any detectable malignancy and development of vitiligo, which to our knowledge has not been reported earlier.

  8. [Acquired immunodeficiency syndrome in pediatric patients].

    Science.gov (United States)

    Molina Moguel, J L; Ruiz Illezcas, R; Forsbach Sánchez, S; Carreño Alvarez, S; Picco Díaz, I

    1990-12-01

    The object of this study was to determine how many of the patients treated at the Pediatric Odontology Clinic, a branch of the Maxillo-Facial Surgery Service at the Veinte de Noviembre Regional Hospital, ISSSTE, are VIH-positive of show serious manifestations of Acquired Immuno-Deficiency Syndrome (AIDS). For such purpose, 100 pediatric patients suffering from different systemic or local diseases were evaluated, the most common being hematological alterations. Results evidenced the presence of VIH in the blood of five of the pediatric subjects, all suffering from Hemophilia.

  9. Newly appreciated roles for basophils in allergy and protective immunity.

    Science.gov (United States)

    Karasuyama, H; Obata, K; Wada, T; Tsujimura, Y; Mukai, K

    2011-09-01

    Basophils are evolutionarily conserved in many animal species, in spite of the fact that they account for basophils have an indispensable and nonredundant role in vivo, even though they show some phenotypic similarity with tissue-resident mast cells. However, their functional significance remained uncertain long after Paul Ehrlich discovered them as blood-circulating cells with basophilic granules more than 130 years ago. The study of basophils has been far behind that of mast cells, owing to the rarity of basophils and the paucity of tools for their detection and functional analysis. Recent development of novel analytical tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, has greatly advanced basophil research and illuminated previously unrecognized roles of basophils. We now appreciate that basophils and mast cells play distinct roles in immune responses. Basophils have crucial roles in the development of acute and chronic allergic responses, the protective immunity against ecto- and endoparasites, and the regulation of acquired immunity, including the augmentation of humoral memory responses and the initiation of Th2 responses. Thus, basophils are no longer the neglected minority and are key players in the immune system.

  10. Acquired hyperostosis syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Dihlmann, W.; Hering, L.; Bargon, G.W.

    1988-10-01

    Sterno-costo-clavicular hyperostosis (SCCH) is the most common manifestation of a syndrome, consisting of increased bone metabolism, mostly new bone formation and heterotopic ossification of fibrous tissue, which we have characterised as the acquired hyperostosis syndrome. In part I we discuss the terminology, radiological appearances, scintigraphy, clinical and laboratory findings, bacteriology, histology, nosology, complications, treatment and differential diagnosis of SCCH. Chronic recurrent multifocal osteomyelitis (CRMO) is regarded as a phaenotype of SCCH, depending on the age. CRMO occurs in children, adolescents and young adults, SCCH predominantly in middleaged and elderly adults.

  11. Acquired von Willebrand Syndrome

    Institute of Scientific and Technical Information of China (English)

    郭涛

    2005-01-01

    @@ Acquired von Willebrand syndrome (AvWS) is kind of bleeding disorder with laboratory findings similar to those in congenital yon Willebrand disease (vWD).AvWS doesn's have any personal or family history of bleeding, but is associated with certain diseases or abnormal conditions or drugs. Although AvWS is being stated as a rare disease, it has gained more and more attention during the past years. Not because of the severity of the disease, but it is more common than we thought and most patients don' t have a proper diagnosis.

  12. "Ready to Acquire"

    DEFF Research Database (Denmark)

    Yetton, Philip; Henningsson, Stefan; Bjørn-Andersen, Niels

    2013-01-01

    This article describes the experiences of Danisco (a global food ingredients company) as it followed a growth-by-acquisition business strategy, focusing on how a new CIO built the IT resources to ensure the IT organization was "ready to acquire." We illustrate how these IT capabilities expedited...... the IT integration following two acquisitions, one of which involved Danisco expanding the scale of its business and the other extending the scope. Based on insights gained from Danisco, we provide lessons for CIOs to realize business benefits when managing post-acquisition IT integration....

  13. Maternally acquired runt disease.

    Science.gov (United States)

    Beer, A E; Billingham, R E

    1973-01-19

    Without altering the structural integrity of the placenta by irradiation or drugs, we have shown that it is possible to immunize females both adoptively and actively against the paternally inherited transplantation antigens of their fetuses. Such immunization causes a high incidence of runt disease among the litters. Although the putative chimeric status of the affected offspring has yet to be confirmed, the results of our experiments support the thesis that runt disease is caused by the activities of "unwanted" immigrant lymphocytes from the maternal circulation. Our results suggest that immunologically activated cells are more likely to cross the placenta than normal cells and that this greater mobility may not be related to the immunologic specificity of the activated cells. Two factors may have contributed to the apparent failure of numerous previous attempts to demonstrate the capacity of transplantation immunity to affect the well-being of a fetus or, more correctly, its placenta, in the way that might be expected of a homograft. (i) Investigators were preoccupied with obtaining a classic type of rejection, in utero, analogous to the rejection of an orthotopic skin homograft. The birth of consistently healthy-looking litters, interpreted as a failure of the experiment, convinced the investigators of the efficacy of nature's solution of the homograft problem and there was no reason for them to suspect its possible limitations. Observation of the litters for several weeks might have uncovered the phenomenon of maternally induced runt disease. (ii) Most investigators resorted to hyperimmunization of the mothers. This would have facilitated the synthesis of protective isoantibodies capable of interfering with the expression of the potentially harmful cellular immune response (6). Ever since the abnormalities of runt disease were first described they have repeatedly been compared to those observed in patients with certain lymphomas (17). Various theories have been

  14. Learning-by-Being-Acquired

    DEFF Research Database (Denmark)

    Colombo, Massimo Gaetano; Moreira, Solon; Rabbiosi, Larissa

    2016-01-01

    of new teams with both inventors of the acquiring and acquired firms-and assess the impact of this integration action in the period that immediately follows the acquisition. Drawing on social identity and self-categorization theories, we argue that R&D team reorganization increases the acquired inventors......’ use of the prior stock of technological knowledge of the acquiring firm after the acquisition. Furthermore, this effect is enhanced if the focal acquired inventor has high relative innovation ability but is weakened for acquired inventors with high ingroup collaborative strength. We construct a sample...

  15. Learning-By-Being-Acquired

    DEFF Research Database (Denmark)

    Colombo, Massimo G.; Moreira, Solon; Rabbiosi, Larissa

    In this paper we study post-acquisition integration in terms of R&D team reorganization—i.e., the creation of new teams with both inventors of the acquiring and acquired firms—and assess its impact on knowledge transfer in the period that follows the acquisition. Drawing on social identity and self......-categorization theories, we argue that R&D team reorganization increases the acquired inventors’ use of the prior stock of technological knowledge of the acquiring firm after the acquisition. Furthermore, this effect is enhanced if acquired inventors have higher innovation ability relative to their acquiring peers...

  16. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  17. Nucleic Acid Immunity.

    Science.gov (United States)

    Hartmann, G

    2017-01-01

    Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to

  18. Transgenesis and reverse genetics of mosquito innate immunity.

    Science.gov (United States)

    Shin, Sang Woon; Kokoza, Vladimir A; Raikhel, Alexander S

    2003-11-01

    In recent years, mosquito molecular biology has been a scene of astounding achievements, namely the development of genetic transformation, characterization of inducible tissue-specific promoters, and acquirement of mosquito genome sequences. However, the lack of a complete genetic tool box for mosquitoes remains a serious obstacle in our ability to study essential mosquito-specific mechanisms. Unlike Drosophila, very few null mutations for mosquito genes exist. The development of reverse-genetic analyses based on RNAi and transgenic techniques will help to compensate for these deficiencies and aid in identification of critical genes in important regulatory pathways. The study of mosquito innate immunity is one example and described here. In this study, we combine mosquito transgenesis with reverse genetics. The advantage of transgenesis is the ability to establish genetically stable, dominant-negative and overexpression phenotypes. Using the blood-meal-activated vitellogenin gene (Vg) promoter, we have generated transgenic mosquitoes with blood-meal-activated, overexpressed antimicrobial peptides, Defensin A and Cecropin A. Moreover, we have recently generated a transgenic dominant-negative Relish mosquito strain, which after taking a blood meal, becomes immune-deficient to infection by Gram-negative bacteria. The latter accomplishment has opened the door to a reverse-genetic approach in mosquitoes based on transgenesis.

  19. Surgical treatment of acquired tracheocele.

    Science.gov (United States)

    Porubsky, Edward A; Gourin, Christine G

    2006-06-01

    Acquired tracheoceles are rare clinical entities that can cause a variety of chronic and recurrent aerodigestive tract symptoms. The management of acquired tracheoceles is primarily conservative, but surgical intervention may be indicated for patients with refractory symptoms. We present a case of acquired tracheocele and describe a method of successful surgical management.

  20. Recombinant B domain deleted porcine factor VIII for the treatment of bleeding episodes in adults with acquired hemophilia A.

    Science.gov (United States)

    Gomperts, Edward

    2015-08-01

    Hemophilia A is an inherited deficiency of clotting factor VIII (FVIII) often complicated by inhibitor development (CHAWI) in which neutralizing antibodies block the therapeutic benefit of replacement therapy. Inhibitors to FVIII can also be seen in an auto-immune disease known as acquired hemophilia A (AHA). 'Bypassing' therapies have been shown to provide hemostasis but dosing must be done empirically because current assays cannot measure objective markers of treatment efficacy and safety. A recombinant porcine sequence factor VIII (r-pFVIII) has been developed for the management of AHA. Preclinical, Phase I and Phase II clinical research studies in CHAWI subjects showed therapeutic potential and safety of this agent. A Phase II/III study in AHA with serious bleeding episodes shows a positive response in all subjects after administration. Based on current preclinical and clinical trial data, r-pFVIII should become the first line of treatment in the management of hemorrhage in patients with AHA.

  1. Mammalian gut immunity

    Directory of Open Access Journals (Sweden)

    Benoit Chassaing

    2014-10-01

    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.

  2. Clinical manifestation of myeloperoxidase deficiency.

    Science.gov (United States)

    Lanza, F

    1998-09-01

    Myeloperoxidase (MPO), an iron-containing heme protein localized in the azurophilic granules of neutrophil granulocytes and in the lysosomes of monocytes, is involved in the killing of several micro-organisms and foreign cells, including bacteria, fungi, viruses, red cells, and malignant and nonmalignant nucleated cells. Despite the primary role of the oxygen-dependent MPO system in the destruction of certain phagocytosed microbes, subjects with total or partial MPO deficiency generally do not have an increased frequency of infections, probably because other MPO-independent mechanism(s) for microbicidal activity compensate for the lack of MPO. Infectious diseases, especially with species of Candida, have been observed predominantly in MPO-deficient patients who also have diabetes mellitus, but the frequency of such cases is very low, less than 5% of reported MPO-deficient subjects. Evidence from a number of investigators indicates that individuals with total MPO deficiency show a high incidence of malignant tumors. Since MPO-deficient PMNs exhibit in vitro a depressed lytic action against malignant human cells, it can be speculated that the neutrophil MPO system plays a central role in the tumor surveillance of the host. However, any definitive conclusion on the association between MPO deficiency and the occurrence of cancers needs to be confirmed in further clinical studies. Clinical manifestations of this disorder depend on the nature of the defect; an acquired abnormality associated with other hematological or nonhematological diseases has been occasionally described, but the primary deficiency is the form more commonly reported. Another area of interest pertinent to MPO expression is related to the use of anti-MPO monoclonal antibodies for the lineage assignment of acute leukemic cells, the definition of FAB MO acute myeloid leukemia, the identification of biphenotypic acute leukemias, and their distinction from acute leukemia with minimal phenotypic deviation

  3. ICU-Acquired Weakness.

    Science.gov (United States)

    Jolley, Sarah E; Bunnell, Aaron E; Hough, Catherine L

    2016-11-01

    Survivorship after critical illness is an increasingly important health-care concern as ICU use continues to increase while ICU mortality is decreasing. Survivors of critical illness experience marked disability and impairments in physical and cognitive function that persist for years after their initial ICU stay. Newfound impairment is associated with increased health-care costs and use, reductions in health-related quality of life, and prolonged unemployment. Weakness, critical illness neuropathy and/or myopathy, and muscle atrophy are common in patients who are critically ill, with up to 80% of patients admitted to the ICU developing some form of neuromuscular dysfunction. ICU-acquired weakness (ICUAW) is associated with longer durations of mechanical ventilation and hospitalization, along with greater functional impairment for survivors. Although there is increasing recognition of ICUAW as a clinical entity, significant knowledge gaps exist concerning identifying patients at high risk for its development and understanding its role in long-term outcomes after critical illness. This review addresses the epidemiologic and pathophysiologic aspects of ICUAW; highlights the diagnostic challenges associated with its diagnosis in patients who are critically ill; and proposes, to our knowledge, a novel strategy for identifying ICUAW. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. Acquiring specific interpreting competence

    Directory of Open Access Journals (Sweden)

    Jana Zidar Forte

    2012-12-01

    Full Text Available In postgraduate interpreter training, the main objective of the course is to help trainees develop various competences, from linguistic, textual and cultural competence, to professional and specific interpreting competence. For simultaneous interpreting (SI, the main focus is on mastering the SI technique and strategies as well as on developing and strengthening communicative skills, which is discussed and illustrated with examples in the present paper. First, a brief overview is given of all the necessary competences of a professional interpreter with greater emphasis on specific interpreting competence for SI. In the second part of the paper, various approaches are described in terms of acquiring specific skills and strategies, specifically through a range of exercises. Besides interpreting entire speeches, practical courses should also consist of targeted exercises, which help trainees develop suitable coping strategies and mechanisms (later on almost automatisms, while at the same time "force" them to reflect on their individual learning process and interpreting performance. This provides a solid base on which trained interpreters can progress and develop their skills also after joining the professional sphere.

  5. Diabetes and risk of community-acquired Staphylococcus aureus bacteremia

    DEFF Research Database (Denmark)

    Smit, Jesper; Søgaard, Mette; Schønheyder, Henrik Carl;

    2016-01-01

    OBJECTIVE: Patients with diabetes may experience higher risk of Staphylococcus aureus bacteremia (SAB) than patients without diabetes due to decreased immunity or coexisting morbidities. We investigated the risk of community-acquired (CA) SAB in persons with and without diabetes. DESIGN: Using...

  6. Effect of Immune No. 2 on the immune reconstitution in patients with HIV/AIDS after highly active antiretroviral treatment: a randomized double blind placebo controlled clinical trial.

    Science.gov (United States)

    Wang, Jie; Li, Yong; Tang, Yan-Li; Lin, Hong-Sheng; Wu, Xin-Fang; Liu, Jie

    2013-05-01

    To observe the Immune No. 2 (2) on the immune reconstitution in patients with human immunodeficiency virus or acquired immune deficiency syndrome (HIV/AIDS) after highly active antiretroviral therapy (HAART). A randomized, double-blind, placebo-controlled clinical trial was designed. 233 patients failing immune reconstitution after HAART were randomly divided into treatment group (116 cases) and control group (117 cases), respectively using Immune No. 2 plus HAART and placebo combined with HAART for 6 months. CD4, CD45RA, CD45RO cell numbers, as well as the symptoms, signs and integral improvement rates were observed in order to evaluate the immune reconstitution efficiency. after the intervention for 1 month, the effective rate of the treatment group (18.97%, 22/116) was significantly higher than that of the control group (9.40%, 11/117) (P=0.02); 3 months after treatment, the effective rate of the treatment group (27.59%, 32/116) was no difference from that of the control group (22.22%, 26/117) (P=0.31); 6 months after treatment, the effective rate of the treatment group (34.48%, 40/116) was significantly superior to the control group (21.37%, 25/117) (P=0.02). CD4, CD45RA, CD45RO count of the treatment group was significantly higher than that of the control group (P<0.05). The total score of symptoms and signs in the treatment group was significantly lowered compared with the control group (P=0.02), and the improvement of fatigue, muscle and joint pain, pruritus and shortness of breath in the treatment group was better than the control group (P<0.05). Immune No. 2 can effectively improve the numbers of CD4 cells and its subgroups, as well as the main clinical symptoms and signs of patients after HAART, thereby promoting the immune reconstitution.

  7. Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge of Yersinia pestis CO92 in Mice

    Directory of Open Access Journals (Sweden)

    Jennifer L. Dankmeyer

    2014-01-01

    Full Text Available The current candidate vaccine against Yersinia pestis infection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host’s innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr 2, 4, and 2/4-double deficient, as well as signal adaptor protein Myd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinated Tlr4 mutant (lipopolysaccharide tolerant and Myd88-deficient mice were challenged by aerosol with Y. pestis CO92, all but one Tlr4 mutant mice survived the challenge, but no vaccinated Myd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed that Y. pestis was not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge of Y. pestis CO92 in F1-V vaccinated mice.

  8. Interactions between the immune system and bone

    OpenAIRE

    2011-01-01

    The relationship between the immune system, estrogen deficiency and bone loss is an intriguing and, as yet, unexplained challenge of the past two decades. Here we summarize the evidence that links immune cells, inflammation, cytokine production and osteoclast formation and activity with particular regard to humans.

  9. Vitamin Deficiency Anemia

    Science.gov (United States)

    ... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... at highest risk for iron-deficiency anemia. Outlook Doctors usually can successfully treat iron-deficiency anemia. Treatment ... poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency anemia, Susan got ...

  11. Immune response

    Science.gov (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 ...

  12. Role of Leptin in Immunity

    Institute of Scientific and Technical Information of China (English)

    Queenie Lai Kwan Lam; Liwei Lu

    2007-01-01

    Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis.

  13. Lower limb deficient children in The Netherlands: epidemiological aspects.

    Science.gov (United States)

    Rijnders, L J; Boonstra, A M; Groothoff, J W; Cornel, M C; Eisma, W H

    2000-04-01

    Information on the characteristics of children with limb deficiencies and amputations in The Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency or amputation and male/female ratios. Data were obtained from a regional birth defects registry for the northern part of The Netherlands (EUROCAT-NNL) and from a national survey. Inclusion criteria for the selection of the EUROCAT data were: children/foetuses with lower leg deficiencies born in 1981-1986. Inclusion criteria for the survey data were: children aged 1-18 years with congenital deficiencies or acquired amputations of the leg, excluding toe deficiencies/amputations. Both the regional birth defects registry and the national survey only yielded small numbers of children, which limits the validity of the authors' findings. The Eurocat data show a prevalence of lower leg deficiencies at birth of 2.07/10,000. Fifty-five (55) children/foetuses were included in the present study. The male/female ratio was 1:1. Of the live-born children, 30% also had defects of the upper limbs, while 38% had bilateral lower limb deficiencies. The national survey included 89 children, of whom 73% had congenital deficiencies, while the others had undergone amputations: of which 37% were due to malignancies, 29% to traumata, 13% to infections and 21% to other pathology. The male/female ratio was 7:3 for the children with congenital deficiencies versus 6:4 for the children with acquired amputations. In the group of congenital deficiencies, fibula deficiency was most frequently seen (36%), while in the group with acquired amputations trans-femoral amputation, knee disarticulation and trans-tibial amputation were seen with equal frequency (21%). In 40% of the children with congenital deficiency and in 8% of the children with acquired amputations the arm was also affected. Both legs were

  14. Malaria transmission model for different levels of acquired immunity and temperature-dependent parameters (vector Modelo de transmissão de malária em diferentes níveis de imunidade e de parâmetros temperatura-dependentes (vetor

    Directory of Open Access Journals (Sweden)

    Hyun M Yang

    2000-06-01

    Full Text Available OBJECTIVE: Describe the overall transmission of malaria through a compartmental model, considering the human host and mosquito vector. METHODS: A mathematical model was developed based on the following parameters: human host immunity, assuming the existence of acquired immunity and immunological memory, which boosts the protective response upon reinfection; mosquito vector, taking into account that the average period of development from egg to adult mosquito and the extrinsic incubation period of parasites (transformation of infected but non-infectious mosquitoes into infectious mosquitoes are dependent on the ambient temperature. RESULTS: The steady state equilibrium values obtained with the model allowed the calculation of the basic reproduction ratio in terms of the model's parameters. CONCLUSIONS: The model allowed the calculation of the basic reproduction ratio, one of the most important epidemiological variables.OBJETIVO: Propõe-se um modelo compartimental para descrever a transmissão de malária, levando em consideração duas populações envolvidas: o hospedeiro humano e o vetor mosquito. MÉTODOS: Desenvolveu-se um modelo matemático baseado nas seguintes características: em relação ao hospedeiro humano, assumiu-se a existência de imunidade adquirida e de memória imunológica que, em uma reinfecção, leva ao reforço da resposta imune; em relação ao vetor mosquito, levou-se em consideração que o período médio de desenvolvimento desde ovo até mosquito adulto e o período de incubação extrínseco de parasitas (transformação de mosquitos infectados mas não-infecciosos em mosquitos infecciosos são dependentes de temperatura ambiente. RESULTADOS: Foram obtidos os valores do equilíbrio no estado estacionário do modelo proposto. Da análise da estabilidade dos pontos de equilíbrio, foi determinada a razão de reprodutibilidade basal. CONCLUSÕES: Foi obtida uma variável epidemiológica importante, a razão de

  15. Defence mechanisms and immune evasion in the interplay between the humane immune system and Plasmodium falciparum

    DEFF Research Database (Denmark)

    Theander, T G

    1992-01-01

    Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when......) Immune recognition is hampered by the extraordinary diversity of antigen phenotypes in the parasite population. 3) Immune regulation is obstructed by immune suppression. During P. falciparum malaria such suppression is characterized by a profoundly diminished in vitro proliferative response to malaria...

  16. Immunity to Diphtheria in Haemodialysis Patients

    OpenAIRE

    Abdolreza S. Jahromi; Mortaza Pourahmd; Sara Azhdari; Gita Manshoori; Abdolhossain Madani; Seyed H. Moosavy

    2011-01-01

    Problem statement: The incidence of infectious diseases is increased in patients with chronic renal failure. Chronic renal failure severely influences the immune functions of the host. Diphtheria is of great epidemiological concern. Although mainly observed during childhood, unvaccinated adults and relatively immunocompromised patients are at increased risk for acquiring diphtheria. Approach: To evaluate the anti-Diphtheria immunity level in southern Iranian patients ...

  17. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations

    Science.gov (United States)

    Qian, Bingjun; Shen, Shanqi; Zhang, Jianhua

    2017-01-01

    The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

  18. Trained immunity: A program of innate immune memory in health and disease.

    Science.gov (United States)

    Netea, Mihai G; Joosten, Leo A B; Latz, Eicke; Mills, Kingston H G; Natoli, Gioacchino; Stunnenberg, Hendrik G; O'Neill, Luke A J; Xavier, Ramnik J

    2016-04-22

    The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity, as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed "trained immunity" or "innate immune memory." Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, new therapeutic strategies for the treatment of immune deficiency states, and modulation of exaggerated inflammation in autoinflammatory diseases. Copyright © 2016, American Association for the Advancement of Science.

  19. Single Nutrients and Immunity

    Science.gov (United States)

    1982-02-01

    allergic Proc 198140:344. encephalomyelitis. J Nutr 1975105:288-300. 198. Rice C, Hudig D. Redelman D, Mendelsohn J, 180. Weston PG. Johnston PV...Pediatr 1978;93:71-3. AE. Defect of cell-mediated immunity in patients 272. Weston WL, Huff JC, Humbert JR, et al. Zinc with iron-deficiency anaemia...Methylmercuy: ogy. Hagerstown Md: Harper & Row, 1980:155-97. effect on serum enzymes and humoral antibody. J 385. Ota DM. Copeland EM. Dudrick SJ, et al. The

  20. Carnitine Deficiency and Pregnancy

    OpenAIRE

    Anouk de Bruyn; Yves Jacquemyn; Kristof Kinget; François Eyskens

    2015-01-01

    We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, su...

  1. The immune system and the impact of zinc during aging

    Directory of Open Access Journals (Sweden)

    Haase Hajo

    2009-06-01

    Full Text Available Abstract The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.

  2. Acquired ichthyosis with hoffman's syndrome

    Directory of Open Access Journals (Sweden)

    Sathyanarayana B

    2003-01-01

    Full Text Available A middle aged man presented with features of acquired ichthyosis with Hoffman's syndrome. Laboratory tests support hypothyodism. Myoedema and hypertrophy of muscles were present. Patient was previously treated for Pellagra.

  3. In vivo anti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune deficiency

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To develop a fusion vaccine of esophageal carcinoma cells and dendritic cells (DC) and observe its protective and therapeutic effect against esophageal carcinoma cell line 109 (EC109). METHODS: The fusion vaccine was produced by fusing traditional polyethyleneglycol (PEG), inducing cytokine, sorting CD34+ magnetic microbead marker and magnetic cell system (MACS). The liver, spleen and lung were pathologically tested after injection of the fusion vaccine. To study the therapeutic and protective effect of the fusion vaccine against tumor EC109, mice were divided immune group and therapeutic group. The immune group was divided into P, E, D and ED subgroups, immunized by phosphate buffered solution (PBS), inactivated EC109,DC and the fusion vaccine respectively, and attacked by EC109 cells. The tumor size, weight, latent period and mouse survival period were recorded and statistically analyzed. The therapeutic group was divided into four subgroups: P, inactivated EC109,D and ED subgroups, which were attacked by EC109 and then treated with PBS, inactivated EC109,DC,and EC109-DC respectively. Pathology and flow cytometry were also used to study the therapeutic effect of the fusion vaccine against EC109 cells. RESULTS: Flow cytometry showed that the expression of folate receptor (FR), EC109, D Cs (D) in human nasopharyngeal carcinoma cell line (HNE1) (B) was 78.21%,89.50%,and 0.18%,respectively.The fusion cells were highly expressed. No tumor was found in the spleen, lung and liver after injection of the fusion vaccine. Human IgG was tested in peripheral blood lymphocytes (PBL). In the immune group, the latent period was longer in EC109-DC subgroup than in other subgroups, while the tumor size and weight were also smaller than those in ED subgroup. In the therapeutic group, the tumor size and weight were smaller in ED subgroup than in P, inactivated EC109 and DC subgroups. CONCLUSION: Fusion cells are highly expressed not only in FR but also in CD80.The fusion

  4. Biochemical Principles and Functional Aspects of Pipecolic Acid Biosynthesis in Plant Immunity1[OPEN

    Science.gov (United States)

    Kim, Denis; Schreiber, Stefan; Zeier, Tatyana; Schuck, Stefan; Reichel-Deland, Vanessa

    2017-01-01

    The nonprotein amino acid pipecolic acid (Pip) regulates plant systemic acquired resistance and basal immunity to bacterial pathogen infection. In Arabidopsis (Arabidopsis thaliana), the lysine (Lys) aminotransferase AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) mediates the pathogen-induced accumulation of Pip in inoculated and distal leaf tissue. Here, we show that ALD1 transfers the α-amino group of l-Lys to acceptor oxoacids. Combined mass spectrometric and infrared spectroscopic analyses of in vitro assays and plant extracts indicate that the final product of the ALD1-catalyzed reaction is enaminic 2,3-dehydropipecolic acid (DP), whose formation involves consecutive transamination, cyclization, and isomerization steps. Besides l-Lys, recombinant ALD1 transaminates l-methionine, l-leucine, diaminopimelate, and several other amino acids to generate oxoacids or derived products in vitro. However, detailed in planta analyses suggest that the biosynthesis of 2,3-DP from l-Lys is the major in vivo function of ALD1. Since ald1 mutant plants are able to convert exogenous 2,3-DP into Pip, their Pip deficiency relies on the inability to form the 2,3-DP intermediate. The Arabidopsis reductase ornithine cyclodeaminase/μ-crystallin, alias SYSTEMIC ACQUIRED RESISTANCE-DEFICIENT4 (SARD4), converts ALD1-generated 2,3-DP into Pip in vitro. SARD4 significantly contributes to the production of Pip in pathogen-inoculated leaves but is not the exclusive reducing enzyme involved in Pip biosynthesis. Functional SARD4 is required for proper basal immunity to the bacterial pathogen Pseudomonas syringae. Although SARD4 knockout plants show greatly reduced accumulation of Pip in leaves distal to P. syringae inoculation, they display a considerable systemic acquired resistance response. This suggests a triggering function of locally accumulating Pip for systemic resistance induction. PMID:28330936

  5. Immune System

    NARCIS (Netherlands)

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

    2013-01-01

    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. Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid.

    Science.gov (United States)

    Zheng, Xiao-Yu; Zhou, Mian; Yoo, Heejin; Pruneda-Paz, Jose L; Spivey, Natalie Weaver; Kay, Steve A; Dong, Xinnian

    2015-07-28

    The plant hormone salicylic acid (SA) is essential for local defense and systemic acquired resistance (SAR). When plants, such as Arabidopsis, are challenged by different pathogens, an increase in SA biosynthesis generally occurs through transcriptional induction of the key synthetic enzyme isochorismate synthase 1 (ICS1). However, the regulatory mechanism for this induction is poorly understood. Using a yeast one-hybrid screen, we identified two transcription factors (TFs), NTM1-like 9 (NTL9) and CCA1 hiking expedition (CHE), as activators of ICS1 during specific immune responses. NTL9 is essential for inducing ICS1 and two other SA synthesis-related genes, phytoalexin-deficient 4 (PAD4) and enhanced disease susceptibility 1 (EDS1), in guard cells that form stomata. Stomata can quickly close upon challenge to block pathogen entry. This stomatal immunity requires ICS1 and the SA signaling pathway. In the ntl9 mutant, this response is defective and can be rescued by exogenous application of SA, indicating that NTL9-mediated SA synthesis is essential for stomatal immunity. CHE, the second identified TF, is a central circadian clock oscillator and is required not only for the daily oscillation in SA levels but also for the pathogen-induced SA synthesis in systemic tissues during SAR. CHE may also regulate ICS1 through the known transcription activators calmodulin binding protein 60g (CBP60g) and systemic acquired resistance deficient 1 (SARD1) because induction of these TF genes is compromised in the che-2 mutant. Our study shows that SA biosynthesis is regulated by multiple TFs in a spatial and temporal manner and therefore fills a gap in the signal transduction pathway between pathogen recognition and SA production.

  7. The epidemiology of global micronutrient deficiencies.

    Science.gov (United States)

    Bailey, Regan L; West, Keith P; Black, Robert E

    2015-01-01

    Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions.

  8. Characterization of a Pipecolic Acid Biosynthesis Pathway Required for Systemic Acquired Resistance.

    Science.gov (United States)

    Ding, Pingtao; Rekhter, Dmitrij; Ding, Yuli; Feussner, Kirstin; Busta, Lucas; Haroth, Sven; Xu, Shaohua; Li, Xin; Jetter, Reinhard; Feussner, Ivo; Zhang, Yuelin

    2016-10-01

    Systemic acquired resistance (SAR) is an immune response induced in the distal parts of plants following defense activation in local tissue. Pipecolic acid (Pip) accumulation orchestrates SAR and local resistance responses. Here, we report the identification and characterization of SAR-DEFICIENT4 (SARD4), which encodes a critical enzyme for Pip biosynthesis in Arabidopsis thaliana Loss of function of SARD4 leads to reduced Pip levels and accumulation of a Pip precursor, Δ(1)-piperideine-2-carboxylic acid (P2C). In Escherichia coli, expression of the aminotransferase ALD1 leads to production of P2C and addition of SARD4 results in Pip production, suggesting that a Pip biosynthesis pathway can be reconstituted in bacteria by coexpression of ALD1 and SARD4. In vitro experiments showed that ALD1 can use l-lysine as a substrate to produce P2C and P2C is converted to Pip by SARD4. Analysis of sard4 mutant plants showed that SARD4 is required for SAR as well as enhanced pathogen resistance conditioned by overexpression of the SAR regulator FLAVIN-DEPENDENT MONOOXYGENASE1. Compared with the wild type, pathogen-induced Pip accumulation is only modestly reduced in the local tissue of sard4 mutant plants, but it is below detection in distal leaves, suggesting that Pip is synthesized in systemic tissue by SARD4-mediated reduction of P2C and biosynthesis of Pip in systemic tissue contributes to SAR establishment.

  9. Battlefield Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome

    Science.gov (United States)

    2014-10-01

    Award Number: W81XWH-10-2-0138 TITLE: "Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome." PRINCIPAL...Orthopaedic Implant Outcome." 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nadim James Hallab, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER 5f...battlefield injuries resulting in increased exposure to metal may sensitize individuals and lead to excessive immune responses to orthopedic implants

  10. Somatically acquired structural genetic differences

    DEFF Research Database (Denmark)

    Magaard Koldby, Kristina; Nygaard, Marianne; Christensen, Kaare;

    2016-01-01

    Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested t...... with age.European Journal of Human Genetics advance online publication, 20 April 2016; doi:10.1038/ejhg.2016.34.......Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested...... that they may accumulate in elderly individuals. To further explore the presence and the age-related acquisition of somatic structural variants in the human genome, we investigated CNVs acquired over a period of 10 years in 86 elderly Danish twins as well as CNV discordances between co-twins of 18 monozygotic...

  11. The immune response to Trypanoplasma borreli: kinetics of immune gene expression and polyclonal lymphocyte activation

    NARCIS (Netherlands)

    Saeij, J.P.J.; Vries, de B.J.; Wiegertjes, G.F.

    2003-01-01

    Although Trypanoplasma borreli induces the production of non-specific antibodies, survival of infection is associated with the production of T. borreli specific antibodies, able to lyse this parasite in the presence of complement. During the lag phase of this acquired immune response, innate immune

  12. The decreased growth performance and impaired immune function and structural integrity by dietary iron deficiency or excess are associated with TOR, NF-κB, p38MAPK, Nrf2 and MLCK signaling in head kidney, spleen and skin of grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Guo, Yan-Lin; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Zhou, Xiao-Qiu; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Feng, Lin

    2017-06-01

    This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days. Then, a challenge test was conducted by infection of Aeromonas hydrophila for 14 days. The results firstly showed that compared with optimal iron level, iron deficiency decreased lysozyme (LZ) and acid phosphatase (ACP) activities, complement 3 (C3), C4 and immunoglobulin M (IgM) contents and down-regulated the mRNA levels of antibacterial peptides, anti-inflammatory cytokines, inhibitor of κBα (IκBα), target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1), whereas up-regulated the mRNA levels of pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) p65, IκB kinases β (IKKβ) and eIF4E-binding protein (4E-BP) in head kidney and spleen of young grass carp (P integrity in head kidney and spleen of fish. Thirdly, iron deficiency increased skin hemorrhage and lesion morbidity, and impaired immune function and structural integrity in skin of fish. Fourthly, iron excess decreased growth and impaired the immune function and structural integrity in head kidney, spleen and skin of fish. Besides, in young grass carp, based on PWG and ability against skin hemorrhage and lesion, the efficacy of ferrous fumarate relative to ferrous sulfate was 140.32% and 126.48%, respectively, and the iron requirements based on PWG, ability against skin hemorrhage and lesion, ACP activities and MDA contents in head kidney and spleen were estimated to be 75.65, 87.03, 79.74, 78.93, 83.17 and 82.14 mg/kg diet (based on ferrous fumarate), respectively

  13. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000408.htm Familial lipoprotein lipase deficiency To use the sharing features on this page, please enable JavaScript. Familial lipoprotein lipase deficiency is a group of rare genetic ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video— ... treatment. For more information about living with and managing iron-deficiency anemia, go to the Health Topics ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  16. Folate-deficiency anemia

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000551.htm Folate-deficiency anemia To use the sharing features on this page, please enable JavaScript. Folate-deficiency anemia is a decrease in red blood cells (anemia) ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... severity of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in a hospital, blood ... With and Managing Iron-Deficiency Anemia 05/18/2011 This video— ...