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Öğe Anti-Pneumococcal Vaccine-Induced Cellular Immune Responses in Post-Traumatic Splenectomized Individuals(Springer New York LLC, 2017) Karasartova, Djursun; Gazi, Umut; Tosun, Özgür; Güreser, Ayşe Semra; Şahiner, İbrahim Tayfun; Dolapçı, Mete; Taylan Özkan, Hikmet AyşegülSplenectomy is associated with increased risk of overwhelming post-splenectomy infections despite proper anti-pneumococcal vaccination. As most studies concentrated on vaccination-induced humoral immunity, the cellular immune responses triggered in splenectomized patients are not yet well studied. The present study aims to investigate this area as it can contribute to the development of more effective vaccination strategies.Five healthy and 14 splenectomized patients were vaccinated with pneumococcal conjugate polysaccharide vaccine (PCV) followed by pneumococcal polysaccharide vaccine according to the guidelines established by Advisory Committee on Immunization Practices. PBMC samples collected 0, 8, and 12 weeks after PCV immunization were in vitro stimulated with PCV. Levels of lymphoproliferation, T-H cell differentiation, and cytokine release were assessed by carboxyfluorescein succinimidyl ester labeling, intracellular cytokine staining, and ELISA, respectively.While T(H)1-dominated immune response was detected in both groups, asplenic individuals generated significantly lower levels of T(H)1 cells following in vitro stimulation. Similarly, levels of IFN-gamma, IL-4, and IL-17 release and lymphoproliferation were significantly lower in asplenic patients.According to our data, splenectomy negatively influences the levels of PCV-induced lymphoproliferation, T(H)1 differentiation, and cytokine release. Besides, PCV failed to induce T(H)17-dominant immune response which is crucial for protection against extracellular pathogens.Öğe Helmintoterapi(Bilimsel Tıp Yayınevi, 2017) Gazi, Umut; Taylan Özkan, Hikmet AyşegülHelmintoterapi, inflamatuvar ve otoimmün hastalıkların tedavisine yardımcı olmak amacıyla konak bağışıklık sisteminin nematodlar başta olmak üzere bazı helmintlerin kullanılmasıyla uyarılmasıdır. Ülkelerin gelişmişlik düzeyi ile sağlık profilleri arasındaki ilişki son derece karmaşıktır. Helmint infeksiyonlarının yaygın olduğu geri kalmış ülkelerde otoimmün hastalıkların prevalansı son derece düşüktür. Diğer yandan, gelişmiş ülkelerde ise otoimmün ve kronik inflamatuvar organik hastalıkların sıklığı son yüzyılda önemli ölçüde artış göstermiştir. Hijyen standartlarındaki yükselişle helmint infeksiyonlarında görülen düşüşün inflamatuvar hastalıkların çoğalmasında rolü olduğu düşünülmektedir. Bu gözlem, insan mikro ortamında bol miktarda bulunan bazı organizmaların sağlıklı bir immün sistemin gelişimi için gerekli olduğu ve bağışıklığı düzenleyici veya baskılayıcı bir etkiye sahip olduğunu iddia eden “hijyen” ve “eski dost” hipotezlerini doğurmuştur. Bu hipotezlere göre parazitler başta olmak üzere bazı organizmalara maruziyetin azalması bağışıklık kaynaklı hastalıklarda artışa neden olmuştur. Helmintler konak içindeki kalıcılıklarını sağlamak için konak bağışık yanıtını tüm yönleriyle etkileyen bir dizi immün modülatör mekanizmalar kullanmaktadırlar. Helmintlerin etkisiyle bağışık yanıttaki ana yolaklarda TH1’den TH2 fenotipine kayma olur, T düzenleyici ve B düzenleyici fenotipler artar ve inflamatuvar sitokinlerin seviyeleri azalır. Konak bağışıklığının bu geniş spektrumlu modülasyonu hem amaçlanan hem de istenmeyen sonuçlara sahiptir. Bu modülasyon sayesinde konak, parazitin oluşturduğu hasarın bastırılmasının yanı sıra allerjik, otoimmün ve inflamatuvar reaksiyonların azalmasından da faydalanır. Helmintlerin hem edinsel hem de doğuştan gelen bağışıklık sistemi üzerinde baskılayıcı ve düzenleyici etkiler göstermesi helmintlerin tedavi amaçlı kullanılması üzerine birçok araştırmaya yön vermiştir. Antihelmintik tedavinin atopik belirtileri ve inflamatuvar hastalık aktivitesini artırmanın yanında ayrıca allerji ve otoimmün hastalıklı hayvan modellerinde helmintlerin koruyucu etkisi olduğu çeşitli çalışmalarla gösterilmiştir. Hayvan deneylerinden elde edilen bu verileri takiben yapılan birçok çalışma, günümüzde hala daha bu terapinin insanda uygulanabilirliğini test etmeye ve immün modülasyonu sağlayan helmintik molekülleri tanımlamaya devam etmektedir.Öğe Immune mechanisms in human and canine demodicosis: A review(Wiley, 2019) Gazi, Umut; Taylan-Ozkan, Aysegul; Mumcuoglu, Kosta Y.Demodex mites are saprophytic parasites of the mammalian skin, mostly found in or near pilosebaceous units of hairy regions. While they can be found in healthy humans and animals without causing any clinical manifestations, they were suggested to create pathogenic symptoms when they appear in high densities under favourable conditions (ie, demodicosis). Nevertheless, their role as the primary causative agent of the pathogenic conditions in humans is debated today. Canine demodicosis, which is highly prevalent in certain dog breeds, provides a valuable tool for studying the pathogenesis of human demodicosis. Canine and human demodicosis are caused by different Demodex species, and the clinical manifestations in former could be life-threatening. Nevertheless, current literature suggests similar immune responses and immune evasion mechanisms in human and canine demodicosis; cellular immunity appeared to have a central role in protection against demodicosis, and Demodex mites were shown to influence both innate and adaptive immune response to escape immune attack. The aim of this review is to summarize the relevant literature on demodicosis obtained from studies conducted on both organisms, and draw the attention to the effect of mite-associated factors (eg, microbiota) on the different clinical manifestations displayed during human and canine demodicosis.Öğe Immune Response and its Effects on the Host during Helminthic Infections(Aves, 2020) Gazi, Umut; Ozkan, Aysegul TaylanHelminths are multicellular organisms causing chronic infections affecting nearly one-third of the global population. They are experts at immunomodulation, and pathologic outcomes are generally observed in patients with immunodeficiencies or with exaggerated levels of anti-helminth immune responses. Elimination of helminths is usually mediated by T-helper type-2 (Th2) immune responses, characterized by the induction of Immunoglobulin E (IgE) release, increase in eosinophil and mast cell levels, and elevation in the production levels of Th2 cytokines. However, the triggered mechanisms may also depend on the location of the parasite. This is because tissue invasion, an immune evasion strategy for parasites, was considered to activate more Thelper type 1 (Th1) cells in tissues. During chronic infections, immune response regulatory pathways become more influential, thereby reducing the levels of the peripheral T-cell-mediated responses against parasitic antigens. The resultant immune response is termed as modified Th2 response and is characterized by enhanced levels of anti-inflammatory cytokine production and regulatory immune cells as well as high IgG4/IgE ratios. Immunomodulation during chronic helminth infection is not limited to only parasite-specific responses. It can influence the efficiency of vaccination, host susceptibility to infections, and allergen or autoantigen responses. This review discusses anti-helminth immune responses. Moreover, it highlights current literature on the effects of chronic helminth infections on host health as well as their possible use as a treatment strategy against autoimmune, autoinflarnmatory, and allergic diseases.Öğe Importance of NK Cells in Cellular and Humoral Responses Triggered by Pneumococcus Vaccination(KARGER, 2023) Gazi, Umut; Tosun, Özgür; Derici, Mehmet Kürşat; Karasartova, Djursun; Güreser, Ayşe Semra; Taylan Özkan, Hikmet AyşegülIntroduction: Despite the success of vaccination in reducing overall rate of pneumococcal pneumonia, Streptococcus pneumoniae is still held responsible for high mortality and modality rates worldwide. Our study aimed to investigate the potential role played by NK cells in immune response generated by pneumococcal vaccination, which could contribute to the development of more effective vaccines. Methods: The study included mice with and without NK cell depletion which were immunized with pneumococcus polysaccharide-conjugated vaccine followed by pneumococcus polysaccharide vaccine (PPV). Serum samples and splenocytes were collected from mice sacrificed 4 weeks after the last PPV dose. Serum samples were used for antibody level quantification by ELISA assay, while splenocytes were treated with PPV in vitro before monitoring CD4+ T-cell subsets (TH1, TH2, and TH17) and cytokine (IFN-?, IL-4, and IL-17) secretion levels by flow cytometry and ELISA analysis, respectively. Results: Results demonstrated reduced pneumococcal IgG and TH1 cell levels due to NK cell depletion. Nevertheless, in contrast to these observations, IFN-? secretion levels after in vitro PPV-23 treatment of splenocytes did not exhibit any statistically significant difference between the two mice groups. Conclusions: The data indicate a positive contribution of NK cells to both T-cell and B-cell responses triggered against pneumococcal vaccination. Further studies are required to confirm our data and investigate the potential benefit of NK cell targeting in promoting vaccine efficacy, especially in the elderly population who continues to be affected significantly by pneumococcal pneumonia.Öğe Rozasea hastalarında demodex spp'nin araştırılması(Hitit Üniversitesi, 2019) Koşar, Nezahat; Sabancılar, Emine; Karasartova, Djursun; Güreser, Ayşe Semra; Öztekin, Aynure; Derici, M. Kürşat; Gazi, Umut; Artüz, Refika Ferda; Taylan Özkan, Hikmet Ayşegülİnsizyonel herni gelişiminde risk faktörlerinin saptanması Amaç: Rozasea, yüz bölgesinde çeşitli klinik bulgularla seyreden, değişik alt tipleri olan ve sebebi tam olarak bilinmeyen kronik enflamatuvar bir cilt hastalığıdır. Demodex spp. rozasea etyolojisinde rol oynadığı düşünülen insan derisinin zorunlu paraziti olan bir akardır. Çalışmanın amacı rozasea tanılı kadın hastalarda demodeks saptanma sıklığını ve rozasea alt tipleri ile parazitin saptanma yoğunluğu arasındaki ilişkiyi saptamaktır. Gereç ve Yöntem: T.C. Sağlık Bakanlığı Hitit Üniversitesi Erol Olçok Eğitim ve Araştırma Hastanesi Deri ve Zührevi Hastalıklar polikliniklerine Şubat-Aralık 2017 tarihleri arasında rozasea nedeniyle başvuran 27-73 yaş arasındaki 39 kadın hasta çalışmaya dahil edilmiştir. Hastalardan burun, yanak ve çene derisinden ayrı ayrı olmak üzere birer adet toplamda üç adet örnek standart yüzeyel deri biyopsisi yöntemi ile alınarak ışık mikroskobunda incelenmiştir. Bulgular: Otuz dokuz hastanın 34 (%87,2)'ünde demodeks saptanmıştır. Hastaların 14 (%35,9)'üne eritematotelenjiektatik; 25 (%64,1)'ine papülopüstüler rozasea tanısı konulmuştur. Eritematotelenjiektatik hasta grubundakilerin 11 (%78,5)'inde, papülopüstüler hasta grubundakilerin 23 (%92)'inde demodeks saptanmıştır. İki grup arasında yapılan istatistiksel analizde demodeks yoğunluğu ile rozasea alt tipi arasında anlamlı bir ilişki bulunamamıştır (p=0,276). Sonuç: Rozasea hastalarında demodeks enfestasyonun yüksek oranlarda görülmesi nedeniyle tanıda araştırılması gerektiği akıldan çıkarılmamalıdır. Ayrıca rozasea alt tiplerinde parazitin etkisini ve hastalığın etiyopatogenezini daha iyi ortaya koymak için daha fazla sayıda hasta grubu ile ilave çalışmalar yapılması faydalı olacaktır.Öğe Serological screening of West Nile virus among blood donors in northern Cyprus(Wiley, 2020) Balaman, Nagat; Gazi, Umut; Imir, Turgut; Şanlıdağ, Tamer; Ruh, Emrah; Tosun, Özgür; Özgül, Aykut; Taylan Özkan, Hikmet AyşegülBackground: West Nile virus (WNV) is a neurotropic arbovirus that can also be transmitted through blood transfusion. Even though its geographic distribution has been expanding, there has not yet been any epidemiological data on WNV in northern Cyprus. The aim of our study is to fill this gap by using donated blood samples. Methods: Samples collected from the main government hospital blood bank in Nicosia were analyzed by anti?WNV enzyme?linked immunosorbent assay (ELISA) (immunoglobulin M [IgM] and immunoglobulin G [IgG]). Seropositive samples were subjected to plaque reduction neutralization test (PRNT) for confirmation and analyzed by ELISA IgG avidity test and reverse transcription real?time polymerase chain reaction (rRT?PCR). Results: Of the 760 sera samples, 2 (0.3%) were IgM+ and 31 (4.1%) were IgG+. Neutralization activity was detected in none (0.0%) of the IgM+ and 26 (83.9%) of IgG+ donor specimens. ELISA IgG avidity test reported high avidity in 21 (67.7%) and low avidity in one (3.2%) IgG+ sample. PRNT?confirmed anti?WNV IgG+ samples exhibited only borderline (19.2%) or high avidity (80.8%) values. rRT?PCR results were negative for both IgM+ and IgG+ samples. Conclusion: Anti?WNV antibodies were detected in northern Cyprus among blood donors. The establishment of preventive measures and evaluation of the geographic extent of the WNV in northern Cyprus are highly recommended.Öğe Skin-homing T-cell responses associated with Demodex infestation and rosacea(Wiley, 2019) Gazi, Umut; Güreser, Ayşe Semra; Öztekin, Aynure; Karasartova, Djursun; Koşar Acar, Nezahat; Derici, Mehmet Kürşat; Taylan Özkan, Hikmet AyşegülAims Our aim was to investigate the skin-homing T-cell immune responses triggered in patients with Demodex infestation and/or rosacea. Methods Collected whole blood samples were divided into four groups: control subjects; nonrosacea patients with Demodex infestation (Demodex group); papulopustular rosacea (PPR) patients without Demodex infestation (Rosacea group); and PPR patients with Demodex infestation (Rosacea/Demodex group). Following ex vivo activation, skin-homing CLA+CD4+ T-cell subset levels were monitored by flow cytometry. Results When compared with control subjects, among skin-homing CD4+ T-cell subsets analysed, Demodex patients had higher T(H)9 and T-reg cell levels; Rosacea subjects displayed elevated T(H)1 cell levels; and Rosacea/Demodex patients exhibited increased frequencies of T(H)9 and T(H)22 cells. In contrast to Rosacea subjects, Rosacea/Demodex group members displayed higher T(H)2 cell levels; and when compared with Demodex groups, they had higher T(H)1 and T(H)2 but lower T-reg cell levels. Demodex group members also exhibited higher T-reg but lower T(H)1 and T(H)22 levels than Rosacea/Demodex group subjects. Conclusions The skin-homing T-cell responses associated with Demodex infestation and rosacea formation seem to influence each other. The present as well as future studies could contribute to the development of effective treatment strategies for demodicosis and rosacea.Öğe Splenektomi, OPSI ve korunma stratejileri(Refik Saydam National Public Health Agency (RSNPHA), 2019) Gazi, Umut; Karasartova, Djursun; Güreser, Ayşe SemraOne of the most important functions of the spleen, which is the largest secondary immune system of the body, is to clear blood from foreign substances by initiating an immune response against antigens carried by blood. There are abundant amounts of lymphoid tissue and cells in spleen including macrophages attacking encapsulated microorganisms and B-cells responsible for early IgM production. In the absence of the spleen, rapid antibody production against a newly encountered antigen is impaired and the bacteria can multiply rapidly. Post-splenectomy infection (OPSI) is a highly mortal disease. Although the initial symptoms of OPSI follow a mild course as in flu-like illnesses, the clinical course can quickly lead to coma and death within two days. Splenectomized patients are susceptible to develop OPSI and possess the risk for lifetime. OPSI cases are mostly caused by Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitis (N. meningitis) and Haemophilus influenzae (H. influenzae). Therefore, pneumococcal, meningococcal and Hib vaccination is recommended at least two weeks prior to splenectomy treatment, or at most two weeks after surgery if emergency splenectomy is required. Since the antibody levels decrease in individuals vaccinated over time, splenectomy patients should be re-vaccinated for every 5 years. On the other hand, antibiotic use and patient training have also an important role in the prevention of OPSI. Patients need to be informed about the OPSI risk, and need to consult their doctor before going abroad. Even though it is so important the level of patient and physician education is not required to reduce OPSI risk today. Therefore, physicians are recommended to be more active in informating their patients abbout OPSI and carefully follow up their patients. In this review, the efficacy of the strategies used to prevent OPSI will be discussed in the context of current literature, including our own laboratory and clinical study results.Öğe The effect of splenectomy on the levels of PCV-13-induced memory B- and T cells(Blackwell Publishing Ltd, 2018) Gazi, Umut; Karasartova, Djursun; Şahiner, İbrahim Tayfun; Güreser, Ayşe Semra; Tosun, Özgür; Derici, Mehmet Kürşat; Dolapçı, Mete; Taylan Özkan, Hikmet AyşegülAim: Splenectomised patients are associated with lifelong risk of fatal overwhelming post-splenectomy infection (OPSI), which is mostly caused by Streptococcus pneumoniae. Today OPSI cases can still be reported even in patients with appropriate vaccination. In our study, the levels of vaccine-specific memory B- and T cells were compared between control and splenectomised patients to enlighten the underlying reason. Materials and Methods: Five healthy and 14 post-traumatic splenectomised individuals were vaccinated with 13-valent pneumococcal conjugate vaccine (PCV-13) followed by 23-valent pneumococcal polysaccharide vaccine (PPV-23). The levels of memory B- and T cells were compared by ELISPOT analysis. Results: Splenectomised patients generated reduced levels of memory IgG B cells in response to PCV-13 vaccination, while the memory IFN-? T-cell levels were undetectable in asplenic patients. This was despite the detection of vaccine-induced memory T-cell levels in control patients, which were analysed simultaneously following the same experimental protocol. Conclusion: Our results suggest that spleen is important, but not essential, for survival and/or generation of memory IgG B cells. In contrast, it seems to be indispensable for PCV-13-specific memory TH1-cell levels. Studies enhancing the levels of vaccine-induced memory cells and further enlightening the immune responses in asplenic individuals are required to develop more effective vaccination strategies against OPSI. © 2018 John Wiley & Sons LtdÖğe The role of T reg population in pathogenesis of Crimean Congo hemorrhagic fever(Elsevier B.V., 2018) Gazi, Umut; Yapar, Derya; Karasartova, Djursun; Güreser, Ayşe Semra; Akdoğan, Özlem; Ünal, Özgür; Baykam, Nurcan; Taylan Özkan, Hikmet AyşegülCrimean-Congo hemorrhagic fever (CCHF) is a severe human infection caused by CCHF virus (CCHFV). Today, although the literature on CCHF pathogenesis is still limited, it is thought to be associated with immunosuppression in the early phase of infection followed by pro-inflammatory immune response that may lead to fatal outcomes. The aim of this study is to investigate the role of regulatory T-cells (T reg cells) in the pathogenesis of CCHFV. Peripheral blood mononuclear cell samples collected from 14 acute CCHF patients with mild disease course and 13 healthy subjects were included in this study. T reg expression and functional levels were analyzed by flow cytometry. T reg cells were identified as CD4+CD25 + CD127dim cells, and their functional levels were compared by measuring their ability to suppress CD69 and CD154 expression by activated T-cells. The flow cytometry analysis revealed that total T-cell and helper T-cell levels did not vary between the two groups. In contrast, CCHF patients displayed higher T reg cell levels but lower T reg suppressive activities when compared with control subjects. This is the first study on the involvement of T reg cells in CCHF pathogenesis. Our results indicate that even though T reg cell levels are elevated during acute phase of CCHF infection, not all generated T reg cells has immunosuppressive capacity, and therefore may not represent ‘true’ T reg cell population. Future studies on the intrinsic mechanisms responsible for the reduced T reg inhibitory activities are required for further enlightening the CCHF pathogenesis, especially in the acute phase of the disease. © 2018 Elsevier B.V.
