Cellular Molecular Immunology
... Контрольну групу склали 15 здорових осіб, показники яких вважалися нормальними. Рівень IL-4, IL-8 та IL-17 у сироватці крові визначали імуноферментним методом [3,7,14]. ...
... IL-17 -відомий прозапальний цитокін, надлишок якого відіграє ключову роль у розвитку аутоімунного запалення при псоріазі, ревматоїдному артриті, червоному вовчаку. Цей інтерлейкін виробляється лімфоцитами Th-17, стимулює активацію нейтрофілів і макрофагів, продукцію інтерферону-γ і фактору некрозу пухлин α; відіграє ключову роль в антибактеріальному та протигрибковому імунітеті [3,5,11]. Попередні дослі дження одностайно доводять накопичення IL-17 у сироватці крові хворих на псоріаз та in loco у хворих на червоний плоский лишай [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. ...
... Цей інтерлейкін виробляється лімфоцитами Th-17, стимулює активацію нейтрофілів і макрофагів, продукцію інтерферону-γ і фактору некрозу пухлин α; відіграє ключову роль в антибактеріальному та протигрибковому імунітеті [3,5,11]. Попередні дослі дження одностайно доводять накопичення IL-17 у сироватці крові хворих на псоріаз та in loco у хворих на червоний плоский лишай [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Наше дослі дження відповідає загальній концепції та розширює її, відводячи ключову роль IL-17 у розвитку запалення імунного комплексу при ліхеноїдних дерматозах. ...
Objective: to assess the level of interleukin‑4 (IL‑4), interleukin‑8 (IL‑8) and interleukin‑17 (IL‑17) in the serum of patients with psoriasis and lichen planus. Materials and methods: The study was performed on two groups of patients with a confirmed diagnosis of psoriasis and lichen planus. The first group consisted of 50 patients with psoriasis, including 19 female and 31 male, the average age was 41.4 years. The second group included 50 patients with lichen planus, including 22 female and 28 male, with a mean age of 41.2 years. The control group consisted of 15 healthy individuals, whose indicators were considered normal. The level of IL‑4, IL‑8 and IL‑17 in the serum was determined by enzyme-linked immunosorbent assay. Results: Our study revealed a tendency to increase of IL‑4 in patients with psoriasis and a significant decrease in this indicator by 75% in patients with lichen planus and a unidirectional increase in IL‑8 and IL‑17 in patients with psoriasis and lichen planus (by 84% and 85%, respectively, in psoriasis and by 76% and 71%, respectively, in lichen planus) compared with healthy donors. Conclusion: Deep deviations of cytokine balance in patients with lichenoid dermatoses, which had a multidirectional nature with respect to IL‑4 (tendency to increase by 16% in psoriasis and a significant decrease by 75% in lichen planus) and unidirectional nature with respect to IL‑8 and IL‑17 (increased 84% and 85%, respectively, in psoriasis and an increase of 76% and 71%, respectively, in lichen planus) have been revealed in our study.
... B and T lymphocytes mediate adaptive immunity (88). While B cells are dispensable, CD4+ T cells critically regulate hippocampal neurogenesis and behavior (89)(90)(91)(92). ...
... Tumor Necrosis Factor-a (TNF-a) coordinates the inflammatory immune response and exhibits pleiotropic effects on various cell types (123). For example, it activates neutrophils, causes muscle catabolism and, like IL1-b, induces acute phase proteins and fever (88). TNF-a is initially produced as an active transmembrane protein, serving as a precursor to the soluble form generated through processing by the TNF-a-converting enzyme (124). ...
... This interaction leads to inflammation by triggering the production of other inflammatory cytokines and chemokines, as well as cell death by apoptosis. When TNF-a interacts with the type 2 receptor (TNFR2), it may also induce apoptosis, but it can protect the cell from death as well (88,125,126). ...
Adult learning, memory, and social interaction partially depend on neurogenesis in two regions: the hippocampus and the subventricular zone. There is evidence that the immune system is important for these processes in pathological situations, but there is no review of its role in non-pathological or near-physiological conditions. Although further research is warranted in this area, some conclusions can be drawn. Intrusive LyC6hi monocytes and autoreactive CD4+ T cells have a positive impact on neurogenesis and behavior, but the latter are deleterious if specific to external antigens. Mildly activated microglia play a crucial role in promoting these processes, by eliminating apoptotic neuronal progenitors and producing low levels of interleukins, which increase if the cells are activated, leading to inhibition of neurogenesis. Chemokines are poorly studied, but progenitor cells and neurons express their receptors, which appear important for migration and maturation. The few works that jointly analyzed neurogenesis and behavior showed congruent effects of immune cells and cytokines. In conclusion, the immune system components -mostly local- seem of utmost importance for the control of behavior under non-pathological conditions.
... Рис. 2. Карта локуса ГКГС человека: HLA -лейкоцитарный антиген человека, LT -лимфотоксин, TAP -транспортер, ассоциированный с процессингом антигена, TNF -фактор некроза опухолей (Abbas et al. 2022) Современные аспекты организации молекул главного комплекса гистосовместимости… Гены ГКГС I и II классов являются наиболее полиморфными в геноме млекопитающих и человека. В популяции общее количество аллелей HLA превышает 14000, причем более чем с 3500 вариантами только для локуса HLA-B. ...
... Он нековалентно взаимодействует с доменом α3 α-цепи. Как и α3-сегмент, β2-микроглобулин структурно гомологичен Рис. 3. Структура молекулы ГКГС I класса (Abbas et al. 2022) А. В. Москалев, В. Я. Апчел, Е. А. Никитина ...
... Map of the human MHC locus. HLA -human leukocyte antigen, LT -lymphotoxin, TAP -transporter associated with antigen processing, TNF -tumor necrosis factor(Abbas et al. 2022) ...
Рассматриваются современные данные, отражающие биологические эффекты главного комплекса гистосовместимости в распознавании чужеродных антигенов и особенностях развития адаптивного иммунного ответа. Известно, что презентация антигена молекулами главного комплекса гистосовместимости инициирует развитие адаптивного иммунного ответа. Антигены для презентации либо генерируются из белков в результате клеточных трансляционных механизмов, либо транспортируются в эндоплазматический ретикулум. Распознавание антигена Т-клеточным рецептором запускает пролиферацию Т-лимфоцитов и развитие клеточно опосредованного иммунного ответа. Пептидный репертуар представляемых антигенов во многом зависит от структурных особенностей связывающего участка каждого конкретного аллельного варианта молекул главного комплекса гистосовместимости. Кроме того, пептидные редакторы — тапасин для молекул главного комплекса гистосовместимости I класса и человеческий лейкоцитарный антиген DM для II класса — способствуют отбору антигенов и их высокоаффинному связыванию. Однако не установлено, почему определенные аллельные варианты главного комплекса гистосовместимости более восприимчивы к пептидному редактированию, чем другие. После обработки пептидный репертуар, представленный молекулами главного комплекса гистосовместимости, в значительной степени зависит от структурных особенностей антиген-связывающего сайта каждого конкретного аллельного варианта главного комплекса гистосовместимости. Антигенпрезентирующие клетки, используя механизм перекрестной презентации, отбирают образцы из внеклеточной среды и представляют их молекулам главного комплекса гистосовместимости. Поэтому идентификация сайтов загрузки пептидов во время перекрестной презентации является ключевой проблемой. Мономорфная консервативная молекула MR1, в отличие от других молекул, представляет небольшие органические молекулы. Комплексы MR1-антиген распознаются инвариантным Т-клеточным рецептором. В представлении антигенов важная роль принадлежит субпопуляциям классических дендритных клеток 1-го и 2-го типов, а также плазмоцитоидных дендритных клеток, которые функционируют под контролем множественных факторов транскрипции, экспрессируемых в уникальных комбинациях.
... A surprising aspect of Th17 differentiation is that TGF-β, which is produced by many cell types and is an anti-inflammatory cytokine, promotes the development of pro-inflammatory Th17 cells when other mediators of inflammation, such as IL-6 or IL-1, are present. Th17 differentiation is inhibited by IFN-γ and IL-4; therefore, strong Th1 and Th2 responses tend to suppress Th17 development [5]. ...
... Since neutrophils are a predominant defense mechanism against many common bacteria and fungi, Th17 cells play an important role in defending against these infections. Th17 cells combat microbes by recruiting leukocytes, mainly neutrophils, to sites of infection [5]. ...
... These antagonists are not effective in inflammatory bowel disease and perhaps also in rheumatoid arthritis, so the role of Th17 cells in these diseases is unclear. Both Th1 and Th17 cells may be present in lesions in several inflammatory diseases, and both may contribute to the development and propagation of these disorders [5]. ...
Acid-base homeostasis is fundamental for the maintenance of life. Subclinical hypercortisolism (HS) is an entity that is difficult to diagnose as it does not present a noticeable symptomatological picture without advanced resources for clinical practice. The objective of this chapter is to discuss the importance of recognizing this entity and establishing differential diagnosis. Characterization of those elements is the way for provide a good clinical practice and avoid mistakes. The cortisol and other glucocorticoids which have the ability to stimulate gluconeogenesis are the target of his study. An up-to-date approach is proposed. This is a narrative review carried out between 1993 and 2024. The following databases were used: DOAJ Directory of Open Access Journals; PubMed, PubMed(Medline).
... Sitokinler, inflamatuvar ve immun yanıta katılan hücreler arasındaki sinyal iletimini ve bu hücrelerin etkinliklerini arttırmak amacıyla uyarılmış lenfositler, makrofajlar, mast hücreleri gibi bağışıklık hücrelerinin yanı sıra endotel hücreleri, fibroblastlar ve stromal hücreler gibi çeşitli hücreler tarafından sentezlenen glikoprotein veya polipeptid yapıda moleküllerdir (Abbas, Lichtman & Pillai, 2021) (Şekil 1). (Mir, Jan & Noor, 2023) kaynağından alınıp düzenlenmiştir) Hücreler, dış uyarıcılara tepki olarak sitokin sentezine başlayabilir ve uyarım sona erdiğinde bu süreç durdurulabilir. ...
... Şekil 2: Sitokinlerin etki tarzları (Kaur & Ghorai, 2022 kaynağından alınıp düzenlenmiştir) Sitokinlerin işlevleri arasında bağışıklık tepkilerini, inflamatuar yanıtları, hücre proliferasyonunu, farklılaşmasını ve apoptozu düzenlemek bulunur (Abbas, Lichtman & Pillai, 2021). Bununla birlikte, sitokin üretiminin veya sinyal iletiminin bozulması çeşitli hastalıklara neden olabilir. ...
... Bu sitokinler enflamasyonu baskılama özellikleri sayesinde otoimmun hastalıkların akut fazlarında iyileşmeyi kolaylaştırıcı moleküller olarak rol alırlar. Aynı zamanda da proinflamatuar sitokinlerin aşırı yanıtını engelleyen immünoregülatör maddelerdir (Abbas, Lichtman & Pillai, 2021). Bazı sitokinler ise (örneğin IL-6), hem pro-hem de anti-inflamatuar özelliklere sahip olabilir (Thomson & Lotze, 2003). ...
... Her ne kadar lenfositler morfolojik olarak aynı görünseler de lenfosit topluluğunda aslında fonksiyonel ve fenotipik birçok farklılık vardır. Lenfositler, lenfoid organlardaki öncüllerinden gelişir (1). T lenfositler timusta olgunlaştıkları (maturasyon) için bu şekilde adlandırılmışlardır, buna karşılık B lenfositler kemik iliğinde olgunlaşırlar. ...
... T lenfositler timusta olgunlaştıkları (maturasyon) için bu şekilde adlandırılmışlardır, buna karşılık B lenfositler kemik iliğinde olgunlaşırlar. Her T veya B lenfosit tek bir antijen için reseptör içerir ve total lenfosit topluluğu on milyonlarca ya da yüz milyonlarca antijeni tanıma yeteneğindedir (1). Antijeni tanıma, lenfosit olgunlaşması sırasında antijen reseptör genlerinin somatik yeniden düzenlenmesi ve antijen reseptörlerini oluşturmak üzere farklı gen segmentlerinin birleşmesi sırasında ortaya çıkan varyasyonlarla sağlanır (2). ...
... Kemik iliği kökenli B lenfositler, dolaşımdaki antikorlar meydana getiren humoral immünitenin efektör hücreleridir. B hücreleri dolaşımdaki periferik lenfosit popülasyonunun %10-20'sini oluşturur (1). Ayrıca kemik iliğinde ve periferik lenfoid dokuların (lenf nodülleri, dalak, tonsiller ve diğer mukozal dokular) foliküllerinde de bulunurlar. ...
Kanser, hücresel düzeyde genetik ve epigenetik değişikliklerin bir
sonucu olarak kontrolsüz hücre büyümesi ile karakterize bir hastalıktır.
Hayvanlarda kanser, veteriner hekimlikte önemli bir sağlık sorunu
olarak öne çıkar ve hem hayvanların yaşam kalitesini hem de sahiplerinin
duygusal ve mali durumunu derinden etkiler. Köpekler ve kediler gibi uzun
ömürlü evcil hayvanlarda, kanser yaşla birlikte daha sık görülen bir hastalık
haline gelmiştir. Köpeklerde lenfoma, mast hücre tümörleri, osteosarkom ve
hemangiosarkom; kedilerde ise meme tümörleri, lenfoma ve deri kanserleri
yaygın olarak görülmeye başlanmıştır. Kanserin tedavi edilmesindeki
zorluklar ve kanser türlerinin karmaşıklığı, daha etkili ve kişiselleştirilmiş
tedavi yaklaşımlarına olan ihtiyacı doğurmuştur. Bu nedenle immünoterapi,
hedefe yönelik tedaviler, gen tedavisi ve erken teşhis yöntemleri gibi yenilikçi
yaklaşımlar üzerinde yoğun çalışmalar yapılmaktadır. Kanserin önemi, yalnızca
hastalığı tedavi etmeye değil, aynı zamanda erken teşhis ve önleyici çabalarını
da kapsar. Bazı ırkların genetik yatkınlık nedeniyle belirli kanser türlerine daha
... Another avenue of investigation focuses on regulatory T cells (Tregs), which act as "peacekeepers" that quell excessive immune responses, including those that are self-reactive. Tregs also exhibit functional changes with aging; some evidence suggests that older individuals show a reduction in Treg efficacy or number, weakening the final line of defense against autoimmune reactions [Abbas et al., 2018]. On the other hand, certain data indicate that Tregs can sometimes increase 6 with age but may lose functional capacity. ...
... Once revealed, such antigens might be erroneously recognized by autoreactive T cell clones persisting in the memory pool due to incomplete central (thymic) or peripheral tolerance. Chronic inflammation itself can undermine the normal function of regulatory T cells (Tregs), thereby diminishing their capacity to restrain self-reactive clones[Abbas et al., 2018]. In turn, this sets in motion a vicious cycle: frequent infections expand memory cells, some of which may harbor autoreactive potential; these memory T cells drive inflammation and tissue damage; new antigens become accessible; and compromised Treg function fails to contain the subsequent expansion of self-targeting clones[Fulop et al., 2018]. ...
... For instance, Epstein-Barr virus (EBV) infection has been linked epidemiologically to an increased risk of developing multiple sclerosis, even though the precise mechanism (possibly involving molecular mimicry or bystander activation) remains under active investigation [Zhang et al., 2019]. Hepatitis C virus infection has been implicated in mixed cryoglobulinemia and autoimmune-like rheumatologic conditions, while Helicobacter pylori infection has shown variable associations with immune-mediated disorders such as idiopathic thrombocytopenic purpura (ITP).Although some of these examples might involve direct molecular mimicry-where pathogen-derived epitopes resemble self-antigens-many also broadly illustrate how repeated or persistent antigenic stimulation can derail immune tolerance[Abbas et al., 2018]. Our model does not delve into the molecular details of antigen mimicry or bystander activation, but it supplies a theoretical framework for understanding how frequent immunological assaults can incrementally shift equilibrium away from a naïve-dominant state.Quantifying "autoimmune risk" in a numerical simulation remains a formidable challenge. ...
As individuals grow older, their T cell repertoire progressively shifts from being dominated by naïve T lymphocytes to featuring a preponderance of memory T cells. This phenomenon-well-documented in immunological literature-is frequently attributed to repeated antigenic stimulation over the course of a lifetime, coupled with thymic involution and other age-associated changes. Although memory T cells are crucial for rapid responses to previously encountered pathogens, there is increasing interest in whether this dramatically shifted balance might predispose certain individuals to a higher risk of autoimmunity, especially when compounded by chronic stress and recurrent infections. In this article, we propose a conceptual model linking the age-related inversion of the naïve-to-memory T cell ratio to an elevated likelihood of immune dysregulation. We integrate mathematical equations to capture the dynamic interactions among key variables, present simulated data in four informative graphs, and discuss the implications and limitations of our approach. Our goal is to invite a deeper consideration of how infection history, stress-induced immune breakdowns, and the intrinsic remodeling of T cell populations with age could collectively contribute to autoimmunity.
... Sistem imun innate terdiri dari berbagai jenis sel yang berperan dalam pengenalan dan penghancuran patogen. Komponen seluler ini meliputi (Abbas, Lichtman, and Pillai 2012): 1. Makrofag Sel fagosit yang berasal dari monosit dan berfungsi untuk menelan dan menghancurkan patogen. Makrofag juga berperan dalam mempresentasikan antigen kepada sel T, sehingga menghubungkan sistem imun bawaan dengan adaptif. ...
... Gambar 5.1. Sistem Imun Adaptif melibatkan Sel T (Bellanti, Kadlec, and Escobar-Gutierrez 1994) Mekanisme sistem imun adaptif seluler melibatkan pengenalan antigen oleh sel T, yang kemudian mengaktifkan respons imun adaptif (Abbas et al. 2012). Defisiensi kerja sistem imun adaptif seluler dapat menyebabkan gangguan respons imun adaptif, sehingga meningkatkan risiko infeksi dan penyakit. ...
Buku Referensi Pengantar Imunologi menyajikan materi yang cukup lengkap, mulai dari konsep imunitas, antigen dan reseptor, sistem komplemen, sitokin, imunomodulator, hingga sistem imun innate dan adaptif. Manfaat dari buku ini adalah sebagai pondasi utama untuk mendalami keilmuan di bidang biomedik, karena memberikan pemahaman fundamental dan esensial bagi para pembaca. Buku ini dirancang secara sistematis, dimulai dari konsep imunitas, antigen imunogen, pathogen-associated molecular pattern (PAMPs), damage-associated molecular patterns (DAMPs), cell-associated pattern recognition (CAPR), sistem komplemen, sitokin, imunomodulator, sistem imun innate, antigen-presenting cell (APC), major histocompatibility complex (MHC), hingga sistem imun adaptif. Dengan mempelajari buku ini, pembaca diharapkan mampu memahami konsep dasar, jenis-jenis sistem imun beserta mekanismenya, serta molekul atau sel yang berperan dalam imunitas.
... Nötrofiller granülositler veya polimorfonükleer nötrofiller (PMN), yaygın olarak doğuştan gelen bağışıklık sistem hücreleri olup, çok loblu bir çekirdeğin (polimorfonükleer) varlığıyla tespit edilebilirler. Dolaşımdaki hücrelerin yaklaşık %50 ila %70'ini oluşturabilir (5). Nötrofil kaynaklı blastik hücrelerinde (AML) orta düzeyde CD45+ pozitifliği vardır. ...
... Bu hücreler, farklı boyalarla tespit edilebilen çok loblu çekirdeklerin ve sitoplazmik granüllerin in varlığıyla karakterize edilir. CD45dim, CD16-, HLA-DR+ özellikli olup granüler yağısı nedeniyle SSC özelliği yüksektir (5,21). ...
Flow cytometric analysis is a laboratory diagnostic method
frequently used in immune system diseases, especially
hematological malignancies. Its application area in clinical
diagnosis and research is rapidly expanding due to developing
technology. The main feature of flow cytometry is that it can
rapidly perform simultaneous, multi-parameter measurement
and characterization of thousands of cells. With flow cytometry, it
is possible to analyze cells in all body fluids, especially blood and
bone marrow, culture fluids, and even fluids obtained from tissue
samples. It is possible to monitor the vitality and developmental
stages of cellular structures with flow cytometry. In addition, it
is also possible to monitor the changes in receptor expressions
and functions on cell surfaces after cellular stimulation with
various mitogens. In flow cytometric analysis, the distribution of
different cell groups in the FS, SS and CD45 gates is examined
in the first stage. In addition to patient samples, examination of
blood and bone marrow samples from healthy individuals by flow
cytometry is an important indicator in distinguishing pathological
conditions. Depending on technological developments, the use
of flow cytometry method in clinical laboratory and research
applications requires frequent updates
... In addition, prebiotics contribute to altering the pH of the colon, modifying barrier function, enhancing mucus production, promoting the production of shortchain fatty acids, and inducing cytokine production. This direct effect of prebiotics enhances innate immunity by improving the phagocytosis process, as highlighted by Abbas et al. in 2012. The resulting higher internal acidity activates protease, leading to increased microbicidal activity (Abbas et al. 2012). ...
... This direct effect of prebiotics enhances innate immunity by improving the phagocytosis process, as highlighted by Abbas et al. in 2012. The resulting higher internal acidity activates protease, leading to increased microbicidal activity (Abbas et al. 2012). Prebiotics have a beneficial effect on gut-associated lymphoid tissue. ...
Sustainable aquaculture production is made possible by ameliorating stress, mitigating microbial infections, and preventing water quality deterioration. Diseases are one of the major concerns in intensive aquaculture systems. Frequent application of chemotherapeutics such as antimicrobials can exacerbate antibiotic resistance and will hamper environmental sustainability. Rational aquaculture advocates alternative strategies for improving the growth and immunity of cultured organisms. This includes the application of probiotics, prebiotics, immunostimulants, vaccines, phage and photodynamic therapy, and various herbal products. Among these, probiotics are found to have multiple applications in aquaculture. The application of probiotics in aquaculture improves the health of cultured organisms and the water quality of the culture system. Probiotics administered through feed (gut probiotics) are proven to promote digestion and absorption of the host organism. Furthermore, they contribute to the increased synthesis of essential nutrients such as vitamins, fatty acids, and carbohydrates, thereby augmenting the immune system of the host. Probiotics play a role in managing aquatic pathogens by generating inhibitory compounds, competing for nutrients and energy resources, contending for mucosal surface colonization, and disrupting quorum sensing. Besides, the water quality can also be improved by the administration of probiotics directly (pond probiotics) as bioaugmentors in the culture system. Microbes such as Bacillus sp., Lactobacillus sp., Lactococcus sp., Carnobacterium sp., Bifidobacterium sp., Streptomyces, Saccharomyces cerevisiae, and so on are the dominant groups reported as probiotics in aquaculture. The application of prebiotics such as inulin, oligofructose, galactooligosaccharides, mannan oligosaccharides, and so on along with probiotics is known as synbiotics and improves the activity and survival of probiotic bacteria. This chapter summarizes the diversity of probiotic and prebiotic compounds, their selection strategies, mode of action, method of administration, and individual and combined application of probiotics and prebiotics as synbiotics in aquaculture. The article also addresses the limitations, challenges, safety concerns, and prospects of probiotics and synbiotics for augmenting sustainable and eco-friendly aquaculture production.
... On the other hand, antiinflammatory nutrition aims to reduce AA levels. [15] A relationship has been observed between the AA/EPA ratio in an individual's blood and the level of latent inflammation in their organs. When the AA/EPA ratio is high, it indicates a higher concentration of AA relative to EPA, which leads to the production of higher levels of pro-inflammatory compounds. ...
... While no known drug directly reduces AA, it has been observed that only proper nutrition can achieve this. [15] The World Health Organization acknowledges that the inflammatory effects of diet play a significant role in the prevention of many non-communicable diseases, such as cardiovascular diseases, type 2 diabetes, and cancer. [17] While anti-inflammatory drugs provide therapeutic benefits in obesity and diabetes, long-term use may lead to side effects. ...
Inflammation is a critical biological response to tissue damage or infection, aimed at restoring homeostasis and initiating healing processes. Historically, inflammation was described by ancient scholars, with Celsus highlighting redness, swelling, heat, and pain, and Galen associating it with loss of function. In contemporary terms, inflammation is defined as a biological reaction to harmful stimuli, which can resolve or lead to chronic conditions if uncontrolled. Acute inflammation is vital for pathogen defense and tissue repair, but chronic inflammation is linked to cardiovascular disorders, diabetes, and autoimmune conditions. The immune system plays a key role in inflammation, with innate immunity providing a rapid response to infections, while acquired immunity offers a more specific, delayed reaction. Inflammation is regulated by mediators such as cytokines, chemokines, and prostaglandins, which facilitate immune cell migration and activation. Omega-3 polyunsaturated fatty acids have been shown to reduce inflammation by interfering with pro-inflammatory eicosanoid production and modulating gene expression. Diet plays an essential role in modulating inflammation, with anti-inflammatory diets like the Mediterranean diet showing beneficial effects in managing inflammatory markers. Conversely, Western diets rich in processed foods tend to exacerbate inflammation. Combining pharmacological approaches with anti-inflammatory dietary changes may offer a more sustainable strategy for preventing and treating inflammation-related diseases. This review aims to explore the mechanisms, impacts, and management strategies of inflammation, emphasizing its role in health and chronic disease.
... IgM antibodies, which are produced first during initial antigenic exposure, are associated with acute or earlystage infections and indicate that the immune system is encountering the antigen for the first time. Conversely, IgG antibodies are generated in a later phase, reflecting prior exposure or a secondary immune response [97,98]. Although elevated IgM levels are effective for initiating an immune response, they may not fully demonstrate the potential for long-term immunity. ...
... Although elevated IgM levels are effective for initiating an immune response, they may not fully demonstrate the potential for long-term immunity. In contrast, higher IgG levels are generally more indicative of sustained immune protection [97,98]. The observed pattern of IgM and IgG responses in our vaccine model suggests its capacity to transition from a short-term immune response to the development of immune memory, which is essential for long-term protection. ...
The global public health risk posed by Salmonella Kentucky (S. Kentucky) is rising, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans. In this study, we used a bioinformatics approach to develop a peptide-based vaccine targeting epitopes from the outer membrane proteins A, C, and F of S. Kentucky. Additionally, we employed flagellin protein (fliC) from Salmonella Typhimurium (S. Typhimurium) as an adjuvant to enhance the vaccine’s effectiveness. Through this approach, we identified 14 CD8+ and 7 CD4+ T-cell epitopes, which are predicted to be restricted by various MHC class I and MHC class II alleles. The predicted epitopes are expected to achieve a population coverage of 94.91% when used in vaccine formulations. Furthermore, we identified seven highly immunogenic linear B-cell epitopes and three conformational B-cell epitopes. These T-cell and B-cell epitopes were then linked using appropriate linkers to create a multi-epitope vaccine (MEV). To boost the immunogenicity of the peptide construct, fliC from S. Typhimurium was included at the N-terminal. The resulting MEV construct demonstrated high structural quality and favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, and 5, followed by molecular dynamic simulations, suggested that the vaccine-receptor complexes are energetically feasible, stable, and robust. Immune simulation results showed that the MEV elicited significant responses, including IgG, IgM, CD8+ T-cells, CD4+ T-cells, and various cytokines (IFN-γ, TGF-β, IL-2, IL-10, and IL-12), along with a noticeable reduction in antigen levels. Despite these promising in-silico findings, further validation through preclinical and clinical trials is required to confirm the vaccine’s efficacy and safety.
... Within mammalian and reptilian genomes, IG genes are most often localized to three primary loci: the IG heavy chain (IGH), and the kappa (IGK) and lambda (IGL) light-chain loci [37]. Each of these loci contain expanded families of variable genes (V), diversity genes (D; in IGH only), and joining genes (J) that represent templates of one of two antibody chains, the heavy chain or the light chain. ...
Despite tremendous advances in long-read sequencing, some structurally complex and repeat-rich genomic regions remain challenging to assemble. Furthermore, we lack tools to assess local assembly quality, making it hard to identify problems and assess progress. Here we develop a new approach “CloseRead” for visualizing local assembly quality and diagnosing errors using multiple metrics. We apply CloseRead to evaluate how well immunoglobulin loci, paradigmatic cases of structurally complex regions, are assembled in 74 state-of-the-art vertebrate genomes. We then show that targeted, local re-assembly can correct the specific errors identified by CloseRead, highlighting the value of an iterative approach to genome assembly.
... Spiral artery remodeling ensures the delivery of a high volume of maternal blood to the placental intervillous space, which plays an important role in human placentation. During this process, maternal-fetal immune adaptations occur to avoid an immune attack against the semi-allogenic fetus [10,11]. Maternal immune alterations are critical for successful pregnancy. ...
Hypertensive disorders of pregnancy (HDP) is assumed to be triggered by incomplete remodeling of the decidual spiral arteries. We examined the lymphocyte subsets and identified immune differences in the spiral arteries between HDP and normal pregnancies, and between remodeled and non-remodeled arteries such as the muscular artery and acute atherosis. One hundred seventy-three patients with HDP diagnosed at our hospital between 2008 and 2017 were included. Patients with a normal course of delivery and patients with premature birth after 34 weeks without pathological changes and abnormalities in the pregnancy course were included in the control group. The infiltrating lymphocytes were evaluated using immunohistochemistry. Acute atherosis was observed in 56 patients (32.4%) of all HDP patients. In patients that presented HDP with acute atherosis, the density of CD8⁺ T cells and CD4⁺ T cells was higher in the acute atherosis than those in the non-remodeled muscular artery. CD4⁺ T cells were more abundant in the non-remodeled muscular artery compared to the remodeled artery. In control patients, the density of CD4⁺ T cells was higher in the non-remodeled muscular artery than that in the remodeled artery; there was no difference in the density of CD56⁺ natural killer cells. There was no difference in the density of CD3⁺ T cells and CD56⁺ natural killer cells in the remodeled artery between patients presenting HDP with acute atherosis and control patients. These immune differences may cause changes in local cytokine balance around the spiral artery, contributing to the development of HDP.
... The expression patterns of immune-related genes, particularly TLRs and CXCRs, in MECs were evaluated over a 72-h period following bacterial infection, as illustrated in Figures 2 and 3. At 0 h, Abbas et al. [21] noted that immune defense mechanisms in mast cells begin to activate. Observations at this initial time point revealed elevated expression levels across nearly all studied genes for both bacterial species. ...
Background and Aim: Mastitis remains a major health challenge in dairy cattle, often caused by Gram-positive pathogens. Toll-like receptors (TLRs) and chemokine receptors (CXCRs) play essential roles in the innate immune response of mammary epithelial cells (MECs). However, the differential expression of these genes in response to specific mastitis-causing Bacillus spp. has not been comprehensively evaluated. This study aimed to characterize the temporal gene expression patterns of TLR and CXCR family members in murine mammary epithelial HC11 cells exposed to Bacillus cereus and Bacillus subtilis, thereby providing insights into their immunological roles in mastitis pathogenesis. Materials and Methods: HC11 cells were cultured and infected with B. cereus and B. subtilis (5 × 10⁷ colony-forming units/mL) and incubated at 37°C with 95% O2 and 5% CO2 for 48 h in RPMI 1640 medium supplemented with serum and antibiotics. Gene expression of interleukin (IL)-6, IL-8, TLR2, TLR4, IL-1 alpha (IL-1α), and CXCR1 was evaluated by quantitative real-time polymerase chain reaction at 0, 6, 12, 24, 48, and 72 h post-infection. Expression levels were normalized to glyceraldehyde-3-phosphate dehydrogenase and analyzed using ΔCt methods and Spearman correlation. Results: TLR2 exhibited a biphasic expression pattern, with early upregulation followed by suppression, while TLR4 showed higher expression in response to B. subtilis than B. cereus. IL-6 displayed prolonged expression under B. subtilis challenge but was transient under B. cereus exposure. IL-1α showed consistent expression across both bacterial challenges, suggesting its potential as a stable biomarker for mastitis susceptibility. CXCR1 exhibited delayed but sustained expression, indicative of its role in secondary neutrophil recruitment. IL-8 expression correlated with early immune activation and chemotactic signaling. Conclusion: The immune response of HC11 MECs to Gram-positive bacterial infection is gene- and pathogen-specific. TLR and CXCR genes show distinct temporal profiles, underscoring their utility in understanding epithelial-driven immune defense. These findings provide molecular insights into mastitis pathogenesis and identify IL-1α, IL-6, and CXCR1 as promising targets for genetic selection and therapeutic intervention. Keywords: Bacillus cereus, Bacillus subtilis, chemokine receptors, gene expression, HC11 cells, innate immunity, mastitis, toll-like receptors.
... Then, high-affinity B cells will exit the germinal center as plasmablasts towards the bone marrow, while B cells that fail to recognize antigens will undergo apoptosis in the light zone. 7 There are several studies that explain changes in immunity that occur as a result of the ovariectomy procedure. One of them, research by Cunningham et al. (2016) on female mice that were ovariectomized at the age of 4 (prepuberty) and 8 weeks (postpuberty). ...
Menopause is a physiological condition in women that is marked by the cessation of the menstrual cycle. Loss of estrogen levels as a powerful antioxidant can lead to oxidative stress. Several changes in the spleen that occur during menopause include increasing spleen weight, decreasing conventional dendritic cells, inhibition of the chemotactic index, lymphocyte proliferation, and natural killer cell activity, as well as an increase in the number of leukocytes, total lymphocytes, and monocytes. Red dragon fruit peel extract has estrogenic properties and is capable of being an immunomodulatory compound. Administering this extract could return the condition of the spleen to normal by reducing the number of lymph nodules and the diameter of the germinal centrum. However, the results of this research show an increasing trend. The P0 group had the smallest mean number of lymph nodules and germinal centrum diameter, namely 2.08 ± 0.81 and 320.95 ± 46.50 ?m, followed by P1 with a value of 2.97 ± 0.99 and 346.64 ± 47.15 ?m, and the largest mean gain was found in the P2 group with a value of 3.11 ± 1.06 and 432.17 ± 72.42 ?m. The increase obtained was not significant based on the One-Way ANOVA parametric test with p-value = 0.124 for the number of lymph nodules and p-value = 0.368 for germinal center diameter. Therefore, the authors did not find any significant effect of administering red dragon fruit peel extract (Hylocereus polyrhizus) on the histological appearance of the spleen in menopausal model rats.
... We therefore investigated if differences existed in IL-2 expression as a key cytokine promoting memory T cell persistence, CD158b expression as a key modulator of immune response, and T cell receptor repertoire in hospitalised and nonhospitalised cases.Interleukin-2 (IL-2) is a critical cytokine primarily produced by activated T cells, particularly CD4+ T-helper cells. It plays a central role in T cell proliferation, differentiation, and function, essential for a strong immune response (5). IL-2 promotes the expansion, survival, and effectiveness of T cells after they recognise an antigen, ensuring a sustained immune response (6). ...
SARS-CoV-2 has claimed more than 7 million lives worldwide and has been associated with prolonged inflammation, immune dysregulation and persistence of symptoms following severe infection. Understanding the T cell mediated immune response and factors impacting development and continuity of SARS-CoV-2 specific memory T cells is pivotal for developing better therapeutic and monitoring strategies for those most at risk from COVID-19. Here we present a comprehensive analysis of memory T cells in a convalescent cohort (n=20), three months post Omicron infection. Utilising flow cytometry to investigate CD4⁺CD45RO⁺ and CD8⁺CD45RO⁺ memory T cell IL-2 expression following Omicron (B.1.1.529/BA.1) peptide pool stimulation, alongside T cell receptor repertoire profiling and RNA-Seq analysis, we have identified several immunological features associated with hospitalised status. We observed that while there was no significant difference in median CD4⁺CD45RO⁺ IL-2⁺ and CD8⁺ CD45RO⁺ IL-2⁺ memory T cell count between subgroups, the hospitalised subgroup expressed significantly more IL-2 per cell following Omicron peptide pool exposure in the CD8⁺CD45RO⁺ population (p <0.03) and trended towards significance in CD4⁺CD45RO⁺ cells (p <0.06). T cell receptor repertoire analysis found that the non-hospitalised subgroup had a much higher number of circulating clonotypes, targeting a wider range of predominantly MHC-I epitopes across the SARS-CoV-2 genome. Several immunodominant epitopes, conserved between both subgroups, were observed, however hospitalised individuals were less likely to express putative HLA alleles responsible for pMHC presentation which may impact TCR affinity. We observed a bias towards shorter CDR3 segments in TCRβ repertoire analysis within the hospitalised subgroup, alongside lower rates of repertoire overlap in CDR3 sequences compared to the non-hospitalised subgroup. We found a significant proportion of TCRs targeted epitopes along the SARS-CoV-2 genome including non-structural proteins, responsible for viral replication and immune evasion. These findings highlight how the continuity of T cell based protective immunity is impacted by both the viral replication cycle of SARS-CoV-2 upon intracellular and innate immune responses, and HLA-type upon TCR affinity and clonotype formation. Our novel Epitope Target Analysis Pipeline (Epi-TAP) could prove beneficial in development of new therapeutic strategies through rapid identification of shared immunodominant epitopes across non-hospitalised and hospitalised subgroups.
... 5329). Elevated lymphocyte levels could be associated with viral infections or lymphoproliferative disorders, while lower percentages might point to stress responses or immune suppression (31). ...
This study investigates the variations in hematological parameters, including white blood cell (WBC) count, lymphocyte percentage (LYM%), granulocyte percentage (GRA%), and platelet indices, within a sample dataset. The WBC count ranged widely, with higher counts potentially indicating infection or inflammation, while lower counts suggested immune suppression or leukopenia. Lymphocyte percentages showed variability, with higher levels suggesting viral infections or lymphoproliferative disorders, and lower levels associated with stress responses or immune suppression. Granulocyte percentages also exhibited broad variation, with elevated levels linked to bacterial infections, stress, or chronic inflammation. Platelet count varied significantly, with high levels indicating thrombocytosis and low levels pointing to thrombocytopenia, which can be associated with various health conditions. Other platelet indices, including mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR), and platelet large cell count (P-LCC), displayed variations that could reflect platelet turnover, inflammation, or bone marrow disorders. Elevated MPV values typically indicate larger platelets, possibly signaling increased platelet activity or thrombocytopenia. PDW and P-LCR values also varied, suggesting altered platelet production or dysfunction. These variations highlight the need for further clinical investigation to understand the pathophysiology underlying these hematological changes. Monitoring these markers is crucial for diagnosing and managing various health conditions, such as infections, inflammation, and platelet-related disorders. The findings emphasize the importance of interpreting hematological data in conjunction with clinical evaluations for appropriate medical interventions.
... While short-lived, heterophils actively engulf, degranulate, and trap bacteria, greatly impacting the removal and clearance of the infection [30,31]. The prolonged presence of macrophages furthers this effort due to their heightened ability to respond to the various bacterial MAMPs by conducting increased phagocytic and bactericidal activities, antigen processing and presentation, and homeostatic regulation of the inflammatory response in the infected tissues [32,33]. The prominent participation of phagocytes in the response to i.d. ...
Selection for water consumption could impact broiler breeders’ immune capabilities. To assess these impacts of selection based on the water conversion ratio (WCR), three trials were conducted using broiler breeders from the modern random bred (MRB), low (L)WCR, and high (H)WCR lines. Ten- to 11-week-old male broilers received intradermal (i.d.) growing feather (GF)-pulp injections of LPS (Trial 1) or PGN (Trial 2), to assess local (GF-pulp) and systemic (blood) inflammatory responses over 24 h and 72 h p.i., respectively. Measurements included leukocyte profiles in GF-pulps and blood, GF cytokine mRNA expression and reactive oxygen species (ROS) generation, and plasma concentrations of α1-acid glycoprotein (AGP-1). In Trial 3, 14-week-old pullets were immunized by i.d. GF-pulp injection of SEV (10⁸ CFU/mL). Leukocyte profiles in the GF-pulp and blood were measured over 72 h and plasma levels of SEV-specific IgM, IgY(G), and IgA antibodies over 4 weeks p.i. Independent of the line, phagocytes infiltrated GF-pulps by 6 h post-LPS injection (p ≤ 0.05), while lymphocytes were the major leukocyte recruited in response to PGN (p ≤ 0.05). However, with both LPS and PGN, HWCR broilers were less effective in recruiting lymphocytes than MRB and LWCR broilers, which had similar lymphocyte infiltration levels. There were no line differences in GF-pulp cytokine mRNA expression and ROS generation, nor in blood leukocyte and AGP-1 concentrations, following LPS injections. Independent of the line, SEV immunization stimulated similar phagocyte recruitment profiles; however, the LWCR and MRB lines had a higher infiltration of lymphocytes (esp. B cells) than the HWCR line (p ≤ 0.05). Independent of the line, SEV immunization triggered a robust, high-quality, primary SE-specific antibody response (p ≤ 0.05). Collectively, selection for improved water efficiency in the LWCR broiler breeder lines did not negatively impact immune response capabilities to LPS, PGN, and a killed SEV.
... The success of vaccination is indicated by the ability to induce humoral immunity. Humoral immunity prevents infection by blocking the virus from entering the host cells and neutralizing the epitope of the virus [21]. The TK encoding gene, a part of KHV genome, has been used to determine KHV infection and has become a highly sensitive diagnostic tool for KHV. ...
Background: Koi Herpesvirus (KHV) infection evidently gave a serious impact to the ornamental fish industry in Indonesia. Measures have been managed to control the outbreak in local fisheries, however, the infection is somehow persistent due to presumptive broad contamination to native fishes, water body, and poor fishpond
management. This study investigated the KHV infection cases occurrence in Malang and Batu city based on pathological changes found in deceased fish followed by partial thymidine kinase (TK) encoding gene analysis. Methods: Five and two koi fish were dissected to obtain gill tissue and preserved in non-buffered 10% formalin for
histopathologic examination. Two gill tissues were performed polymerase chain reaction (PCR) and an amplicon with prominent specific band were sequenced using Sanger sequencing method. Results: The smaller fish presented lesser gills necrosis with multifocal whitish fibrinous exudate plaques and the larger fish tended to develop a vast area of necrosis. The amplicons partially covered about 410 base pairs (bp) of nucleotides of the total about 998 bp length nucleotides of TK encoding gene that matched to KHV 3 TK encoding gene sequences from NCBI Genbank. Conclusions: There was no distinct grouping of haplotypes based on KHV TK encoding gene sequences.
... Midazolam can inhibit the production of IL-2 and IL-8 and produces an immunosuppression effect. Midazolam can inhibit the activity of TNF-α [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81]. ...
Autoimmune diseases in children may be linked to genetic, environmental, and hormonal factors. It's estimated that 5% of children worldwide have at least one autoimmune condition, with many experiencing multiple autoimmune challenges. Around 80 autoimmune diseases are present. However, autoimmune diseases in children are rare. When they occur they can be challenging to diagnose and difficult to treat. Advances in our knowledge of the immune system are uncovering connections between inflammation and many different diseases. All autoimmune diseases have relapsing and remitting tendencies. Autoimmune diseases can affect almost any part of the body, though they often target connective tissues (skin, muscle and joints). Symptoms can range from fatigue and mild rashes to rare, serious side effects, like seizures. Diagnosis can be difficult, because many symptoms tend to come and go and are frequently nonspecific. They occur in different kinds of autoimmune diseases as well as other types of illnesses, like infection and cancer. Autoimmune diseases occur most often in females by a 3-to-1 margin over males. Organ-specific disorders (also called localized) focus on one organ or a specific type of tissue: Addison's disease affects the adrenal glands; Autoimmune hepatitis affects the liver; Crohn's disease affects the gastrointestinal tract; Multiple sclerosis (MS) affects the central nervous system; Type 1 diabetes affects the pancreas; Ulcerative colitis affects the gastrointestinal tract. Non-organ-specific disorders (also called systemic) cause problems throughout the body: Juvenile dermatomyositis affects the skin and muscles; Juvenile idiopathic arthritis affects the joints and sometimes the skin and lungs; Lupus affects the joints, skin, liver, kidneys, heart, brain, and other organs; Scleroderma affects the skin, joints, intestine, and sometimes the lungs. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are rare neurobehavioral disorders in children. Affected children may have a diverse array of perioperative manifestations including compulsive behavior, agitation, and abnormal movements. Intravenous anesthetics have anti-inflammatory properties, which in most septic cases are useful for patients. The anti-inflammatory effects of ketamine may be related to the suppression of TNF production by macrophage in the presence of bacteria. Propofol inhibits the phagocytosis and chemotaxis of human monocytes through GABAA receptors. Inhalational anesthetics, in a dose-dependent manner, suppress cytokine release, reduces lymphocyte proliferation, induce apoptosis of the lymphocytes, and inhibits the function of neutrophils. lnhalational anesthetics influence the endocrine response from the hypothalamus-pituitary-adrenal axis and indirectly through the secretions of hormones, such as glucocorticoids and catecholamines. Long-term administration of general anesthesia drugs, due to their effects on cytokines, can lead to disease progression in patients with immune deficiency.
... The activation and differentiation of abnormal B and T cells are crucial to SLE development. Biomarkers such as CD19 + CD20+ B cells, CD4+ T cells, and regulatory T cells (Tregs) have been linked to SLE pathogenesis and may be potential targets for treatment [32]. ...
Systemic lupus erythematosus (SLE) is an autoimmune disease that relentlessly attacks the body’s tissues, leading to widespread inflammation and consequential tissue damage in various organs, including the joints, skin, brain, lungs, kidneys, and blood vessels. While there is no known cure for this disease, it can be managed effectively through medical interventions and lifestyle modifications. It is imperative to note that SLE can significantly impact an individual’s quality of life, both in the short and long term. Diagnosing and assessing pathophysiological processes in SLE using clinical and physiological assessments alone is often inadequate. Immunological biomarkers show promise in enhancing SLE diagnosis, assessment, and management. Early detection of SLE is crucial for effective treatment. Thus, biomarkers, particularly immunological biomarkers, have emerged as a potential solution to improve the diagnosis and assessment of SLE’s pathophysiological processes. The ultimate aim is to improve disease control. This chapter comprehensively reviews immunological biomarkers for SLE diagnosis and pathophysiological aspects.
... 33 These immune cells can reach any part of the body, even though they are initially stimulated only at the vaccine injection site. 34 The spine as part of the body is no exception in this case and can also receive protection from the stimulated immune system. Some studies found different results, with no relationship between the BCG vaccination and the occurrence of TB in children. ...
Highlights: The Bacillus Calmette-Guérin (BCG) vaccination has been widely implemented in Indonesia, but cases of spinal tuberculosis (TB) in children can still be found. There are significant and moderate relationships between BCG vaccination and the occurrence of spinal TB in children. Abstract Introduction: Spinal tuberculosis (TB) is an extrapulmonary form of TB that affects the spine. The Bacillus Calmette-Guérin (BCG) vaccination program, which has been implemented to prevent TB, should have prevented this type of TB. However, cases of this disease in children can still be found. This study aimed to determine whether there was a relationship between BCG vaccination and the occurrence of spinal TB in children. Methods: This case-control analytic observational study was performed based on medical record data. The study subjects of each group, both case and control, were taken from pediatric TB patients at Dr. Soetomo General Academic Hospital, Surabaya, from 2017 to 2021. Patients with malnutrition and/or human immunodeficiency virus (HIV) infection were excluded. Statistical analyses were performed using Fisher’s exact test. Results: There were 9 patients in total within each group. Most were 12-17 years old, and the ratio of male by female was 1.25:1. There were 4 out of 9 (44%) spinal TB patients and 9 of 9 (100%) patients with no spinal TB who all received BCG vaccination. The statistical test indicated a significant (p=0.029) and moderate (C=0.527) relationship between BCG vaccination and the occurrence of spinal TB in children. Conclusion: The Bacillus Calmette-Guérin vaccination should be able to prevent the new occurrence of spinal TB in children.
... MoA of subunit vaccine is the same, unless the subunit vaccine is polysaccharide-based. The latter can induce B lymphocyte activation, differentiation, and maturation without the help of T h lymphocytes, therefore, giving a less intense immune response (Abbas et al., 2000;Baxter, 2007;Mak and Saunders, 2006;Pollard and Bijker, 2021). ...
This review examines various classes of drugs, focusing on their therapeutic and adverse effects, particularly in relation to immunostimulation. We emphasize the potential of new approach methodologies (NAMs) to study both expected and unexpected immunostimulatory effects. By evaluating the modes of action of different immunostimulatory drugs, we aim to provide insights into effectively assessing unwanted immunostimulatory responses. The review begins by exploring drugs that stimulate the immune system—including immunostimulants, monoclonal antibodies, chemotherapeutics, and nucleic acid-based drugs—to outline NAMs that could be employed to evaluate immunostimulation.
... Current understanding posits that PMNs constitute a critical first line of defense against pathogens and are vital components of the innate immune response. These cells migrate from the vascular compartment to sites of inflammation to kill or phagocytize bacteria [51], but they can also contribute to the pathogenesis of conditions characterized by disturbed tissue homeostasis, such as trauma and shock [52]. The earlier restoration of ovarian resumption in group T denotes that these animals were exposed to high estrogen levels earlier than those of group C. It is well established that estradiol stimulates vascularization of the endometrium [53,54], enhances uterine contractility [55], initiation of sexual receptivity [56], and supports sexual-specific effects on the secretory immune system [57]. ...
Olive cake was incorporated at a low inclusion rate (3.7%) into the rations of dairy cows through partial substitution of maize, and its effects on milk production, general health, and fertility traits were investigated. Multiparous purebred Holstein dairy cows (n = 148) were divided into two groups: a treated group (n = 86) and a control group (n = 62). The control ration (group C) was modified by replacing 1 kg of maize with an equal quantity of olive cake (group T). The experiment lasted from 60 days prepartum to 150 days postpartum. Electronic aids were utilized to quantify daily milk yield and detect estrus expression, while clinical and uterine examinations were performed weekly. Blood samples, uterine epithelial cells, and endometrial tissue samples were collected from a subgroup of healthy animals in both groups at specific time points. Blood samples were examined to determine the β-hydroxybutyric acid (BHBA), acute phase proteins (haptoglobin [Hpt] and serum amyloid A [SAA]), progesterone, and pregnancy-associated glycoproteins concentrations. Uterine epithelial cells were assessed for polymorphonuclear neutrophil (PMN) counts, and the expression of nine genes encoding inflammatory cytokines and immune system activation was analyzed in uterine biopsy tissue. No significant differences (p > 0.05) were observed between groups in milk yield, general morbidity, clinical endometritis, or conception rates. However, animals in group T came to estrus approximately 6 days earlier (p = 0.013) than those in group C; progesterone concentrations on day 7 of the subsequent cycle tended (p = 0.07) to be higher in group T. On day 21, BHBA concentrations were higher in group C than in group T (p < 0.05). Throughout the experiment, Hpt levels in group T were consistently lower (p < 0.001), while SAA was lower on day 7 compared to group C. From days 21 to 42 postpartum, there was a significant reduction in PMN numbers (group C p = 0.02; group T p < 0.0001), with a tendency for a greater reduction rate in group T (p = 0.08). Among the genes studied, a significant difference was revealed in the expression of the ILA1 gene, with strong correlations of gene expression in group C and weak to moderate correlations in group T. In conclusion, under the conditions of this experiment, the inclusion of olive cake into dairy cows’ rations did not affect milk production but improved certain health and fertility parameters, making olive cake a suitable alternative feedstuff for high-producing animals.
... TCD4+ and TCD8+ cells achieve this through their cytotoxic activity, the recruitment and/or priming of other immune cells and the secretion of important cytokines such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and interleukin 2 (3). Similar to memory B lymphocytes, T lymphocytes are activated on first contact with the antigen and then react on second contact by proliferating very rapidly and simultaneously producing specific effector T cells and the specific memory cell clone for subsequent contacts (4). ...
Background: The assessment of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) includes both humoral and cellular immunity. The T-cell response plays a key role in reducing the risk of developing severe forms of coronavirus disease 2019 (COVID-19). Similar to other aspects of physiology and immune system, the adaptive immune system is regulated by circadian clocks. This study aimed to determine whether cellular immunity against SARS-CoV-2 may vary throughout different times of day after COVID-19 vaccination.
Case Description: The study population consisted in four ostensibly healthy healthcare workers who received a single booster vaccination with the new bivalent BNT162b2 mRNA vaccine (Comirnaty, Pfizer/ Biontech, NY, USA) in November 2022. Blood samples were collected for three days at three different time points (9 am: T1; 2 pm: T2; 5 pm: T3). Cellular immunity was assessed using Roche Elecsys interferon-gamma (IFN-γ)-releasing assay (IGRA) SARS-CoV-2 at each time point, as IFN-γ response. The difference between the values of IFN-γ response after vaccination with BNT162b2 mRNA in the four subjects did not show a uniform and consistent trend. Even when adjusting the antigen-triggered value of interferon-γ for the value of the positive control, no uniform circadian trend appeared throughout the study period in the four subjects.
Conclusions: In this four-case series, we found no evidence of circadian variation of cellular immunity assessed with IFN-γ response after BNT162b2 mRNA bivalent vaccination. Although the measurement of cellular response against SARS-CoV-2 with IGRAs does not seem to follow a clear trend influnced by circadian bias, the large interindividual variability suggests that the timing of sampling should be standardized when multiple assessments or interindividual comparisons are needed.
... A healthy immune response may help mitigate these effects. [3] ...
The skin serves as a crucial barrier in the immune system, playing a pivotal role in protecting the body from pathogens. As the largest organ, it provides a physical and chemical barrier against infections while housing various immune cells that contribute to both innate and adaptive immunity. Keratinocytes, the primary cells of the epidermis, produce antimicrobial peptides and cytokines that enhance immune responses. Additionally, specialized immune cells, such as Langerhans cells and dermal dendritic cells, act as sentinels, capturing and presenting antigens to T cells. This interaction initiates immune responses that are essential for long-term protection. Furthermore, the skin's microbiome contributes to immune regulation and homeostasis, influencing inflammatory responses and pathogen resistance. Understanding the skin's multifaceted role in immunity is vital for developing therapeutic strategies against skin-related disorders and systemic diseases. The skin plays a fundamental role in the immune system, acting as the first line of defense against environmental threats, including pathogens, toxins, and physical injuries. As the body's largest organ, it serves both a physical barrier and a dynamic interface for immune responses. The epidermis, composed mainly of keratinocytes, produces antimicrobial peptides (AMPs) and cytokines, which are critical for early immune defense. These substances inhibit microbial growth and initiate inflammatory responses.In addition to keratinocytes, the skin contains specialized immune cells, such as Langerhans cells, dermal dendritic cells, and macrophages. Langerhans cells, located in the epidermis, play a crucial role in antigen presentation, capturing pathogens and migrating to lymph nodes to activate T cells. Dermal dendritic cells complement this function, facilitating the communication between innate and adaptive immunity
The paper presents an immunohistochemical study of greater omenta in serous borderline ovarian tumors. The role of scavenger receptors in the cells of the greater omentum in this pathology has not been sufficiently studied. Theat is why, this work is of scientific interest, and the topic under study is relevant. The purpose of the study is to analyze the expression level of scavenger receptors on macrophages in the greater omentum in serous borderline ovarian tumors. Materials and methods. The study determined the expression of scavenger receptors by immunohistochemical methods on macrophages of the greater omentum in 40 patients. The entry criteria were the presence of serous borderline ovarian tumors in the patients, surgical treatment for borderline ovarian tumors with omentectomy, as well as the age of the patients from 20 to 45 years. The exclusion criteria were severe concomitant diseases in patients. The expression of scavenger receptors on macrophages of the greater omentum was evaluated. Markers of macrophages CD91 (SR-L1), CD204 (SR-A1), CD68 (SR-D1) were studied: antibodies to macrophage markers CD91, CD204, CD68 were used. A morphometric study of the preparations was conducted. The STATISTICA 10 program (StatSoft) was used for statistical processing of the results obtained. Research results. In the study of greater omentum preparations in serous borderline ovarian tumors, when assessing the level of CD91 (SR-L1) expression, it was shown that in serous borderline tumors without implantation damage, the average CD91 expression score was lower than that in serous borderline tumors with implantation damage. The analysis of CD204 (SR-A1) expression in the greater omentum demonstrated that in serous borderline tumors without implantation lesion, the average CD204 expression score was lower than that in serous borderline tumors with implantation lesion. When assessing the expression level of CD68 (SR-D1) in the greater omentum, it was found that in serous borderline tumors without implantation lesion, the average CD68 expression score was lower compared with a serous borderline tumors with implantation lesion. Conclusions. The greater omentum participates in implementing immune reactions due to the population of macrophages expressing scavenger receptors. These cells trigger the initiation of antitumor immunity by increasing the number of CD68+, CD91+, CD204+ and have the ability to inhibit the formation of tumors dissemination.
Currently, understanding the immune response, its abnormalities, and its diagnostic possibilities is a key point in the management of patients with various diseases, from infectious to oncological ones. The aim of this review was to analyze the data presented in the current literature on immune disorders and the possibility of their laboratory diagnostics in combination with clinical manifestations. We have performed a systematic analysis of the literature presented in international databases over the last ten years. We have presented data on the possibility of diagnosing immunopathological processes due to changes in immune cells and soluble molecules involved in the pathogenesis of a wide range of diseases, as well as the determination of antibodies to detect autoimmune processes. By applying laboratory techniques such as hematology, flow cytometry, ELISA, etc., available to most clinical laboratories worldwide, clinical data on immune system dysfunction in a wide range of diseases are being collected. This process is unfortunately still very far from being completed. However, with all the diversity of accumulated knowledge, we can currently state that the pathogenesis of the vast majority of immune-mediated diseases is not yet known. At the same time, the current success in dividing immune-mediated diseases into distinct clusters based on different types of inflammatory responses that are based on the involvement of different populations of T helper cells and cytokine molecules represents significant progress. Further research in this direction seems very promising, as it allows the identification of new target cells and target molecules for both improved diagnostics and targeted therapies.
In the ever-evolving landscape of healthcare, a thorough understanding of medical sciences is essential for professionals and students alike. "Foundations and Frontiers of Medical Sciences: Comprehensive Guide to Health and Disease" offers a meticulous exploration of the core principles and advanced topics in the medical and allied health fields. Beginning with a historical overview of medical sciences, this book traces the evolution of healthcare practices and technologies. It delves into the intricacies of human anatomy and physiology, providing a detailed look at the structure and function of the body. Pathophysiology is examined to elucidate the mechanisms of disease, while medical genetics explores hereditary disorders. The book covers microbiology and immunology, focusing on the body's defense mechanisms, and pharmacology, highlighting drug actions and interactions. Clinical biochemistry is presented through the lens of biomarkers in health and disease, complemented by sections on medical imaging techniques and diagnostic pathology. Public health principles, epidemiology, and health policy are discussed to emphasize the broader context of healthcare systems and administration. The role of diet in health is detailed in nutrition science, and environmental and occupational health chapters address the impacts of surroundings and workplace safety. Mental health, rehabilitation sciences, speech and language pathology, audiology, physical and occupational therapy are explored to cover the full spectrum of patient care. Radiologic technology and medical laboratory science highlight diagnostic advancements, while clinical research methods and ethics underscore the importance of rigorous scientific inquiry. Concluding with future trends and innovations, this comprehensive guide serves as an indispensable resource for those committed to advancing their knowledge and expertise in medical sciences. Whether you are a healthcare practitioner, student, or researcher, this book aims to equip you with the foundational and cutting-edge information necessary to navigate and excel in the dynamic field of medical and allied health sciences.
Mathematical models based on regression equations are an important tool for the interpretation of data generated by the serological monitoring of poultry flocks. The present study aimed to evaluate the serological monitoring of breeders and commercial laying hens by several poultry companies, and to develop mathematical models for seven different poultry diseases. Data from serological tests for seven diseases (chicken infectious anemia, infectious bronchitis, infectious bursal disease, Newcastle disease, avian encephalomyelitis, avian metapneumovirus, and avian reovirus) were selected for analysis in this study. The variables "age of birds at the time of blood collection" was considered as the independent variable (x), while "antibody titer" was set as the dependent variable (y). Analysis of variance and coefficient of multiple determination (R²) were used to select the model with the highest capacity to adequately describe the analyzed data. Data from serological monitoring generated 166 linear and non-linear regression equations, but only 1.2% of them yielded an R²≥0.8 and more than 25 serum collections. The low number of suitable models may be related to the lack of standardization of the sample collection. In summary, serological monitoring of breeders and commercial laying hen flocks can be performed using mathematical models, but the lack of standardization of sample collections may have led to limited results.
The respiratory tract can experience inflammation if exposed to coal pollutants. The purpose of this study was to analyze IL-6 gene mRNA expression and IL-6 levels in serum formed in experimental animals given a combination of ripe Kasturi fruit pulp juice (dose 7.8 mg/kg body weight/day dissolved in 2 ml H2O), vitamin E (dose 22 mg/kg body weight/day) and DHA (dose 60 g/kg body weight/day) exposed to coal dust at 10 pm (N10S CellMicroSievesTM BioDesign Inc. of New York, USA) given 25 mg/day/m3 in 1 hour per day for 14 days. The experimental animals were grouped into 5 groups, group 1 was the control group (no coal dust exposure and no supplements), group 2 was the coal dust exposure group, group 3 was the combination of ripe kasturi fruit juice and vitamin E with coal dust exposure, group 4 was the DHA group with coal dust exposure and group 5 was the combination of ripe kasturi fruit juice, vitamin E and DHA with coal dust exposure. Coal dust exposure was carried out for 14 days. Using the post only control design method, IL-6 gene mRNA expression and serum IL-6 levels as pro-inflammatory parameters were examined. Statistical tests of homogeneity, normality and one-way anova SPSS 25.0 were performed with = 0.05. The results showed that IL-6 gene mRNA expression and IL-6 levels in serum were established in all groups. The average IL-6 gene mRNA expression obtained by group 1 was 6.486 ± 0.272, group 2 was 10.868 ± 0.258, group 3 was 8.420 ± 0.199, group 4 was 9.096 ± 0.103 and group 5 was 7.655 ± 0.121. The average serum IL-6 level obtained by group 1 was 52.21 ± 3.02 pg/ml, group 2 was 104.93 ± 2.98 pg/ml, group 3 was 80.70 ± 2.81 pg/ml, group 4 was 90.85 ± 2.36 pg/ml and group 5 was 65.81 ± 2.54 pg/ml. Statistical tests on all groups showed homogeneity and normality (p>0.05) and one-way anova and Bonferroni post hoc found p=0.000. The conclusion of this study is that IL6 gene mRNA expression and IL-6 levels have been established. In the group given a combination of ripe Kasturi fruit juice, vitamin E, and DHA with coal dust exposure for 14 years, IL-6 gene mRNA expression and IL-6 levels in serum were found to be the lowest compared to the group exposed to coal dust and the difference was statistically significant at p=0.000.
Background : T helper 1 (Th1) cell activation is an essential process for immune responses and is tightly regulated, including the prenylation of proteins critical for T cell function. Prenylation facilitates membrane association and protein function and, according to current consensus, is confined to C-terminal prenylation motifs. However, the full extent of the prenylated proteome, a broader understanding of prenylation sites, and the effects of inhibiting prenylation or blocking isoprenoid synthesis using statins remain incompletely understood. To address these gaps, we aimed to comprehensively identify and characterize protein prenylation in Th1 cells. Results : Using a click chemistry-based enrichment approach followed by mass spectrometry in primary in vitro-differentiated Th1 cells, we identified both known and novel prenylated proteins, some of which exhibited differential prenylation during Th1 cell activation, highlighting the dynamic nature of the Th1 prenylome. Characterization of these proteins revealed isoform-specific prenylation, novel C-terminal prenylation motifs, and a structural motif associated with internal prenylation. Furthermore, statin treatment influenced the Th1 prenylome, altering protein prenylation in a prenyltransferase-dependent manner, underscoring distinct enzymatic specificities and potential off-target effects. Conclusions : Our findings confirm that prenylation plays a key role in Th1 cell function, with more proteins undergoing prenylation than previously known, some of which exhibit activation-dependent changes. The identification of non-canonical prenylation events challenges current views on prenylation, expanding the repertoire of modification sites. Together, our molecular insights into protein prenylation in Th1 cells and the effects of prenyltransferase inhibition and statin treatment have important implications for therapeutic strategies targeting immune regulation.
Adaptive (Acquired) Immune System: Recognition, Effector Mechanisms, Regulation, and Activation
The immune system consists of two main branches: innate and adaptive immunity. While the innate immune system provides a rapid but non-specific defense against pathogens, the adaptive immune system develops a targeted, long-lasting immune response through T and B lymphocytes.
This section explores the adaptive immune system's key components, including antigen recognition, effector mechanisms, and immune regulation. B lymphocytes and their antibody production play a critical role in eliminating extracellular pathogens, whereas T lymphocytes, through the major histocompatibility complex (MHC), target intracellular pathogens. The unique features of adaptive immunity—specificity, diversity, memory, clonal expansion, and self-tolerance—are discussed in detail.
Cellular immunity, primarily mediated by T lymphocytes, involves cytotoxic T cells (CD8+), which eliminate infected or malignant cells, and helper T cells (CD4+), which modulate immune responses. The differentiation of CD4+ T cells into Th1, Th2, Th17, and T regulatory cells, along with their respective roles in immunity, is examined. Additionally, the activation and selection of T cells within the thymus, including positive and negative selection mechanisms, are described.
Humoral immunity, mediated by B lymphocytes, involves antibody production and antigen presentation. The activation and differentiation of B cells into plasma cells and memory B cells are explored, highlighting processes such as class switching and affinity maturation. The functions of different immunoglobulin isotypes (IgG, IgA, IgM, IgE, IgD) and their roles in pathogen defense, hypersensitivity reactions, and mucosal immunity are detailed.
Regulatory mechanisms that modulate adaptive immunity, including immune checkpoints like CTLA-4 and PD-1, are also discussed, with their implications in immune tolerance, autoimmunity, and cancer immunotherapy. Understanding the intricate interactions within the adaptive immune system provides valuable insights into vaccine development, immunodeficiencies, and targeted immunotherapies.
Keywords: Adaptive immunity, T lymphocytes, B lymphocytes, immune regulation, antigen recognition, humoral immunity, cellular immunity, immunoglobulins
Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4⁺ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection.
Breast cancer is the most common type of cancer in women and the second leading cause of death by cancer. Despite recent advances, the mortality rate remains high, underlining the need to develop new therapeutic approaches. The complex interaction between cancer cells and the tumor microenvironment (TME) is crucial in determining tumor progression, therapy response, and patient prognosis. Understanding the role of immune cells in carcinogenesis and tumor progression can help improve targeted therapeutic options, increasing the likelihood of a favorable prognosis. Therefore, this review aims to critically analyze the complex interaction between tumor cells and immune cells, emphasizing the clinical and therapeutic implications. Additionally, we explore advances in immunotherapies, with a focus on immune checkpoint inhibitors.
Sebaceous adenitis is observed in different animal species, with dogs being the most commonly diagnosed. This study aimed to report a case of sebaceous adenitis in a 5-year-old male Akita dog weighing 35.8 kg, initially presented with pruritus and alopecia on the inner ear surfaces, face, and head. Over time, signs of changes in sebaceous glands appeared in other body parts. The dog was sent to a veterinary clinic in Kamyanets-Podilsky, Ukraine. During the clinical examination, the body temperature was 38.4°C, heart rate 78 bpm, and a respiratory rate 27 breaths per minute, with no change in appetite. Clinical and dermatological methods and histopathological examination were used to detect the disease. The hair on the head was curling, and the lesions appeared on the dorsal tail, the distal front and hind legs, the groin, and the abdomen. Initially, redness and itching occurred in the affected areas, and the skin lost elasticity and became dry. The hair was stuck together with gray crusts. The diagnosis was confirmed based on pathohistological studies. An inflammatory infiltrate with migration of lymphocytes, histiocytes, neutrophils, and atrophy of sebaceous glands was diagnosed, focusing on the pathology of the dermis. Treatment included topical therapy with shampoo applied for 3-5 minutes, then rinsed and followed by Conditioner for 2 minutes, over 30 days. Omega-3 was administered orally at 1000 mg twice daily. Isotretinoin (Roaccutane®, 20 mg) was administered orally twice daily for 30 days. Moreover, Cyclosporine was dosed at 5 mg/kg once daily orally, on an empty stomach, for 30 days. During the treatment, signs of inflammation gradually disappeared, with itching and hyperemia disappearing from day 3. From day 7, desquamation and hair loss decreased, and on day 12, signs of new hair growth appeared. The areas were completely restored on day 28 of treatment. Sebaceous adenitis was found to lead to the destruction of sebaceous glands, causing scaling, hair loss, and skin inflammation, which could be a hereditary condition in Akitas. Immunomodulation and normalization of trophic processes in the skin are crucial in the treatment.
Purpose of Review
The purpose of our review was to examine the existing literature in technologies for in utero stem cell targeting. We sought to establish the qualities of candidate diseases for prenatal treatment, address the risks and benefits of this approach, and review the various technologies currently available including delivery vectors (viral and non-viral) and therapeutic modalities (antisense oligonucleotides, gene replacement, and gene editing), as well as how they are being used in the prenatal period.
Recent Findings
Prenatal somatic cell gene therapy has the potential to treat severe, early-onset congenital disorders before birth. By harnessing the benefits of the fetal environment, in utero administration of nanomedicines could be delivered at a crucial time in stem cell development before irreversible damage occurs. However, this field also represents a unique clinical situation in which it is imperative to ensure the safety of two patients: the fetus and the mother.
Summary
While further research is needed on prenatal somatic cell targeting, current literature reveals promising results for the treatment of congenital disorders during the prenatal period.
The Handbook of Immunology is a testament to the progress and promise of immunological science. As we confront challenges such as emerging infectious diseases, cancer, and chronic inflammatory conditions, the immune system remains central to our efforts to develop effective solutions. It is our hope that this handbook will serve as a trusted resource, inspiring curiosity, fostering learning, and driving innovation in the ever-expanding field of immunology.
In the evolving landscape of toxicity assessment, the surge in demand for heightened precision and environmentally conscious methodologies has become increasingly palpable. This chapter navigates the evolving landscape of hematotoxicity and immunotoxicity assessment within the realm of drug discovery. It explores advanced methodologies surpassing the limitations of traditional methods. The journey begins with a historical overview, highlighting the transformative role of flow cytometry, and unfolds the narrative of its indispensability. Imagine a scenario without flow cytometry and delve into novel approaches-DNA methylation analysis, RNA sequencing, and multiplexed immunofluorescence-each offering unique insights into immune cell profiling and drug effects on tissues. In silico predictions, leveraging artificial intelligence, and in vitro assays, including high-throughput screening for hematotoxicity, emerge as potent tools in toxicity assessment. The exploration extends to chemico-methods, ex vivo assays, and in-depth insights into in vitro hematotoxicity assays. The abstract underscores the pivotal role of omics technologies-metabolomics, genomics, transcriptomics, and proteomics-in decoding toxicogenomics. It envisions a future where a holistic approach reshapes the assessment of hematotoxicity and immunotoxicity in drug development, aligning with the transformative potential of emerging methodologies. As tradition meets innovation, this abstract provides a glimpse into the synergy propelling drug development towards precision and efficacy. Despite significant advancements, persistent challenges such as high costs and the absence of standardized databases are underscored. The chapter concludes by emphasizing the collective impact of these diverse methodologies, pushing the boundaries of our understanding of hepatotoxic and immunotoxic phenomena in the pursuit of more effective drug development.
Sel manusia tidak luput dari serangan lingkungan baik itu oleh adanya infeksi oleh virus, kerusakan DNA akibat adanya berbagai proses seperti kegagalan perbaikan DNA yang rusak, mutagen, dan karsinogen termasuk sinar UV, racun, dan bahan kimia. Berbagai serangan ini dapat menyebabkan timbulnya kanker. Berbagai karsinogen maupun mutagen dapat menyebabkan aktivasi onkogen maupun inaktivasi gen penekan tumor. Mekanisme yang terlibat mulai dari genetik, epigenetik, hingga RNA regulator. Proses karsinogenesis yang terangkum dalam hallmark of cancer memperlihatkan kompleksitas patogenesis kanker. Buku edisi ke-2 ini menampilkan berbagai temuan terbaru, termasuk update berbagai mekanisme molekuler yang membentuk hallmark of cancer. Penelitian di bidang kedokteran molekuler yang cukup pesat, berdampak positif pada penelitian di bidang kanker. Banyak temuan dihasilkan, yang diharapkan dapat bermanfaat dalam memahami kanker, mencari teknologi penapisan yang akurat dan tidak invasif, hingga menemukan terapi yang berbasis personal. Tugas kitalah sebagai peneliti dan praktisi di bidang kesehatan dan kedokteran untuk terus menggali ilmu, sehingga dapat bermanfaat untuk kesehatan terutama di bidang kanker.
Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes). This similarity can lead to cross-reactive antibodies and T-cell receptors, resulting in an immune response against autoantigens. Both commensal microbes in the human microbiome and pathogens can trigger molecular mimicry, thereby potentially contributing to the onset of ARDs.
In this review, we focus on the role of molecular mimicry in the onset of rheumatoid arthritis and systemic lupus erythematosus. Moreover, implications of molecular mimicry are also briefly discussed for ankylosing spondylitis, systemic sclerosis and myositis.
Bronchial asthma is a complex disorder that is thought to arise as a result of aberrant T-lymphocyte responses to noninfectious environmental antigens. In particular, the symptoms of asthma are closely associated with the presence of activated T-helper 2 cell (Th2) cytokine-producing cells [interleukin (IL)-4, IL-5, IL-9, and IL-13] in the airway wall. Although each of the Th2 cytokines likely contributes to the overall immune response directed against environmental antigens, a substantial body of evidence points to a singular role for IL-13 in the regulation of the allergic diathesis. Initial studies in animal models of disease provided compelling evidence that IL-13, independently of other Th2 cytokines, was both necessary and sufficient to induce all features of allergic asthma. The importance of IL-13 in allergic disorders in humans is supported by consistent associations between tissue IL-13 levels and genetic variants in the IL-13 gene with asthma and related traits. With the preponderance of evidence continuing to support a pivotal role for IL-13 in allergic disorders, attention is now turned toward understanding the mechanisms by which this cytokine may mediate the pathophysiological features of allergic disease. The emerging paradigm is that IL-13 induces features of the allergic response via a complex array of actions on resident airway cells rather than through traditional effector pathways involving eosinophils and immunoglobulin E-mediated events. In light of these recent developments, this review explores our current understanding of the singular role of IL-13 in the pathogenesis of asthma, with a particular focus on new insights into the mechanisms by which IL-13 mediates various features of asthma.