12 results
Search Results
2. Theories of immune recognition: Is anybody right?
- Author
-
Martins, Yuri Chaves, Rosa‐Gonçalves, Pamela, and Daniel‐Ribeiro, Cláudio Tadeu
- Subjects
- *
IMMUNE recognition , *IMMUNOLOGIC memory , *B cells , *T cells , *RECOGNITION (Psychology) , *IMMUNOLOGY - Abstract
The clonal selection theory (CST) is the centrepiece of the current paradigm used to explain immune recognition and memory. Throughout the past decades, the original CST had been expanded and modified to explain new experimental evidences since its original publication by Burnet. This gave origin to new paradigms that govern experimental immunology nowadays, such as the associative recognition of antigen model and the stranger/danger signal model. However, these new theories also do not fully explain experimental findings such as natural autoimmune immunoglobulins, idiotypic networks, low and high dose tolerance, and dual‐receptor T and B cells. To make sense of these empirical data, some authors have been trying to change the paradigm of immune cognition using a systemic approach, analogies with brain processing and concepts from second‐order cybernetics. In the present paper, we review the CST and some of the theories/hypotheses derived from it, focusing on immune recognition. We point out their main weaknesses and highlight arguments made by their opponents and believers. We conclude that, until now, none of the proposed theories can fully explain the totality of immune phenomena and that a theory of everything is needed in immunology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Method for B Cell Receptor Enrichment in Malignant B Cells.
- Author
-
Bhattacharyya, Puja, Christopherson, Richard I., Skarratt, Kristen K., and Fuller, Stephen J.
- Subjects
- *
PROTEIN analysis , *RESEARCH funding , *IMMUNE system , *ANTIGENS , *MASS spectrometry , *PROTEOMICS , *B cells - Abstract
Simple Summary: The B cell receptor (BCR) is a membrane-bound protein complex that is required for the normal development of B cells. BCR signalling is also involved in the pathogenesis of B cell cancers. While there is substantial literature on genomic analyses of the BCR, there are limited proteomic studies of receptor structure and its interactions with neighbouring proteins. This is partly due to the location of the BCR in the surface-membrane lipid environment that has limited the ability to enrich the complex for proteomic analysis. Here, we report an enrichment technique that can be used for mass spectrometry analyses of the BCR from live B cells. B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. The Lung in Rheumatoid Arthritis—Friend or Enemy?
- Author
-
Anton, Maria-Luciana, Cardoneanu, Anca, Burlui, Alexandra Maria, Mihai, Ioana Ruxandra, Richter, Patricia, Bratoiu, Ioana, Macovei, Luana Andreea, and Rezus, Elena
- Subjects
- *
LUNGS , *RHEUMATOID arthritis , *CHEMOKINE receptors , *INTERSTITIAL lung diseases , *SYNOVIAL membranes , *B cells , *IMMUNE system - Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune condition frequently found in rheumatological patients that sometimes raises diagnosis and management problems. The pathogenesis of the disease is complex and involves the activation of many cells and intracellular signaling pathways, ultimately leading to the activation of the innate and acquired immune system and producing extensive tissue damage. Along with joint involvement, RA can have numerous extra-articular manifestations (EAMs), among which lung damage, especially interstitial lung disease (ILD), negatively influences the evolution and survival of these patients. Although there are more and more RA-ILD cases, the pathogenesis is incompletely understood. In terms of genetic predisposition, external environmental factors act and subsequently determine the activation of immune system cells such as macrophages, neutrophils, B and T lymphocytes, fibroblasts, and dendritic cells. These, in turn, show the ability to secrete molecules with a proinflammatory role (cytokines, chemokines, growth factors) that will produce important visceral injuries, including pulmonary changes. Currently, there is new evidence that supports the initiation of the systemic immune response at the level of pulmonary mucosa where the citrullination process occurs, whereby the autoantibodies subsequently migrate from the lung to the synovial membrane. The aim of this paper is to provide current data regarding the pathogenesis of RA-associated ILD, starting from environmental triggers and reaching the cellular, humoral, and molecular changes involved in the onset of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Role of germinal center and CD39highCD73+ B cells in the age-related tonsillar involution.
- Author
-
Pastor, Rocío, Puyssegur, Juliana, de la Guardia, M. Paula, Varón, Lindybeth Sarmiento, Beccaglia, Gladys, Spada, Nicolás, de Lima, Andrea Paes, Collado, M. Soledad, Blanco, Andrés, Scetti, Isabel Aspe, Arabolaza, M. Elena, Paoli, Bibiana, Chirdo, Fernando, and Arana, Eloísa
- Subjects
- *
B cells , *GERMINAL centers , *IMMUNOLOGIC memory , *T helper cells , *MUCOUS membranes - Abstract
Background: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results: We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. Conclusions: This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Traditional Chinese Medicine for Cancer Treatment.
- Author
-
Liu, Yangli, Fang, Cheng, Luo, Jiaojiao, Gong, Chenyuan, Wang, Lixin, and Zhu, Shiguo
- Subjects
- *
THERAPEUTIC use of antineoplastic agents , *CHINESE medicine , *VASCULAR endothelial growth factors , *TELOMERASE , *MACROPHAGES , *KILLER cells , *T cells , *CANCER patient medical care , *CELL proliferation , *APOPTOSIS , *MYELOID-derived suppressor cells , *METASTASIS , *CELL lines , *ENERGY metabolism , *TUMORS , *CARCINOGENESIS , *GENETIC mutation , *PATHOLOGIC neovascularization , *NATURAL immunity , *DENDRITIC cells , *B cells - Abstract
In recent years, due to advancements in medical conditions and the development of scientific research, the fundamental research of TCM antitumor treatments has progressed from the cellular level to the molecular and genetic levels. Previous studies have demonstrated the significant role of traditional Chinese medicine (TCM) in antitumor therapy through various mechanisms and pathways. Its mechanism of action is closely associated with cancer biology across different stages. This includes inhibiting tumor cell proliferation, blocking invasion and metastasis to surrounding tissues, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, regulating immune function, maintaining genome stability, preventing mutation, and regulating cell energy metabolism. The use of TCM for eliciting antitumor effects not only has a good therapeutic effect and low side effects, it also provides a solid theoretical basis for clinical treatment and medication. This paper reviews the mechanism of the antitumor effects of TCM based on tumor characteristics. Through our review, we found that TCM not only directly inhibits tumors, but also enhances the body's immunity, thereby indirectly inducing an antitumor effect. This function aligns with the TCM theory of "strengthening the body's resistance to eliminate pathogenic factors". Furthermore, TCM will play a significant role in tumor treatment in clinical settings. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. B cells in head and neck squamous cell carcinoma: current opinion and novel therapy.
- Author
-
Guo, Xinyue, Xu, Licheng, Nie, Luan, Zhang, Chenyu, Liu, Yaohui, Zhao, Rui, Cao, Jing, Tian, Linli, and Liu, Ming
- Subjects
- *
B cells , *SQUAMOUS cell carcinoma , *IMMUNE checkpoint inhibitors , *T cells , *TUMOR microenvironment , *RADIOTHERAPY - Abstract
Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. The Roles of Various Immune Cell Populations in Immune Response against Helminths.
- Author
-
Lekki-Jóźwiak, Janina and Bąska, Piotr
- Subjects
- *
CELL populations , *IMMUNE response , *B cells , *INNATE lymphoid cells , *HELMINTHS , *HELMINTHIASIS , *KNOWLEDGE gap theory - Abstract
Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
9. CAR-T cell therapy: Efficacy in management of cancers, adverse effects, dose-limiting toxicities and long-term follow up.
- Author
-
Elmarasi, Mohamed, Elkonaissi, Islam, Elsabagh, Ahmed Adel, Elsayed, Engy, Elsayed, Abdelrahman, Elsayed, Basant, Elmakaty, Ibrahim, and Yassin, Mohamed
- Subjects
- *
CELLULAR therapy , *CHIMERIC antigen receptors , *HEMATOLOGIC malignancies , *CYTOKINE release syndrome , *T cells , *B cells - Abstract
• CAR-T therapy offers durable remissions in refractory hematological malignancies. • Meta-analyses show significant efficacy in various hematologic cancers. • CAR T-cell therapy improves quality of life for blood cancer patients. • Encouraging results in CD22-targeting CAR T-cell therapy for B-cell malignancies. • Long-term studies reveal durable remissions but also persistent adverse effects. Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. SERS spectroscopy as a tool for the study of thiopurine drug pharmacokinetics in a model of human B leukemia cells.
- Author
-
Pagarin, Sofia, Bolognese, Anna, Fornasaro, Stefano, Franzin, Martina, Hofmann, Ute, Lucafò, Marianna, Franca, Raffaella, Schwab, Matthias, Stocco, Gabriele, Decorti, Giuliana, and Bonifacio, Alois
- Subjects
- *
SERS spectroscopy , *LIQUID chromatography-mass spectrometry , *B cells , *PHARMACOKINETICS , *CHILD patients , *CELL analysis - Abstract
Thiopurine drugs are immunomodulatory antimetabolites relevant for pediatric patients characterized by dose-dependent adverse effects such as myelosuppression and hepatotoxicity, often related to inter-individual differences, involving the activity of important enzymes at the basis of their biotransformation, such as thiopurine S-methyltransferase (TPMT). Surface Enhanced Raman Scattering (SERS) spectroscopy is emerging as a bioanalytical tool and represents a valid alternative in terms of affordable costs, shorter analysis time and easier sample preparation in comparison to the most employed methods for pharmacokinetic analysis of drugs. The aim of this study is to investigate mercaptopurine and thioguanine pharmacokinetics by SERS in cell lysates of a B-lymphoblastoid cell line (NALM-6), that did (TPMT*1) or did not (MOCK) overexpress the wild-type form of TPMT as an in vitro cellular lymphocyte model to discriminate between cells with different levels of TPMT activity on the base of the amount of thioguanosine nucleotides (TGN) metabolites formed. SERS analysis of the cell lysates was carried out using SERS substrates constituted by Ag nanoparticles deposited on paper and parallel samples were used for quantification of thiopurine nucleotides with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A direct SERS detection method has been set up that could be a tool to study thiopurine drug pharmacokinetics in in vitro cellular models to qualitatively discriminate between cells that do and do not overexpress the TPMT enzyme, as an alternative to other more laborious techniques. Results underlined decreased levels of TGN and increased levels of methylated metabolites when TPMT was overexpressed, both after mercaptopurine and thioguanine treatments. A strong positive correlation (Spearman's rank correlation coefficient rho = 0.96) exists between absolute quantification of TGMP (pmol/1 x 106 cells), obtained by LC-MS/MS, and SERS signal (intensity of TGN at 915 cm−1). In future studies, we aim to apply this method to investigate TPMT activity in pediatric patients' leukocytes. • A direct SERS method to qualitatively discriminate between cells that do and do not overexpress TPMT is discussed. • LC-MS/MS and SERS parallel analysis of cell lysate detect decreased levels of TGN when TPMT is overexpressed. • Quantification by LC-MS/MS of 12 thiopurine metabolites in human B-lymphoblastoid cell line is reported. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
11. Recent advances in the involvement of epigenetics in the pathogenesis of systemic lupus erythematosus.
- Author
-
Zhou, Hong-Yan, Luo, Qi, Sui, Hua, Du, Xiang-Ning, Zhao, Yang-Jianing, Liu, Lu, Guan, Qing, Zhou, Yue, Wen, Qing-Si, Shi, Yan, Sun, Yu, Lin, Hong-Li, and Wang, Da-Peng
- Subjects
- *
EPIGENETICS , *RNA regulation , *B cells , *NON-coding RNA , *CELLULAR control mechanisms , *AUTOIMMUNE diseases , *SYSTEMIC lupus erythematosus - Abstract
Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease that manifests as skin rash, arthritis, lymphadenopathy, and multiple organ lesions. Epigenetics, including DNA methylation, histone modification, and non-coding RNA regulation, mainly affect the function and characteristics of cells through the regulation of gene transcription or translation. Increasing evidence indicates that there are a variety of complex epigenetic effects in patients with SLE, which interfere with the differentiation and function of T, and B lymphocytes, monocytes, and neutrophils, and enhance the expression of SLE-associated pathogenic genes. This paper summarizes our currently knowledge regarding pathogenesis of SLE, and introduces current advances in the epigenetic regulation of SLE from three aspects: immune function, inflammatory response, and lupus complications. We propose that epigenetic changes could be used as potential biomarkers and therapeutic targets of SLE. • Epigenetic modifications are widely involved in the pathogenesis of SLE. • Epigenetic modifications promote and maintain continuous immune activation and chronic inflammation. • Epigenetic modifications promote and maintain continuous immune activation and chronic inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
12. A sensitive high-resolution mass spectrometry method for quantifying intact M-protein light chains in patients with multiple myeloma.
- Author
-
Muccio, Stéphane, Hirtz, Christophe, Descloux, Sandrine, Fedeli, Olivier, Macé, Sandrine, Lehmann, Sylvain, and Vialaret, Jérôme
- Subjects
- *
MULTIPLE myeloma , *BONE marrow , *IMMUNOGLOBULIN light chains , *MASS spectrometry , *B cells , *BONE marrow cells , *MONOCLONAL antibodies , *PLASMA cells - Abstract
• LC-MS offers an alternative to invasive methods in the bone marrow to measure MRD in the blood of patients with MM. • This LC-HRMS responds to two objectives: overcoming the potential interference of biotherapeutics and assessing the MRD. • Highly sensitive and specific quantification of intact M-protein light chains in patient serum was achieved. To determine the disease status and the response to treatment for patients with multiple myeloma, measuring serum M-protein levels is a widely used alternative to invasive punctures to count malignant plasma cells in the bone marrow. However, the quantification of this monoclonal antibody, which varies from patient to patient, poses significant analytical challenges. This paper describes a sensitive and specific mass spectrometry assay that addresses two objectives: to overcome the potential interference of biotherapeutics in the measurement of M-proteins, and to determine the depth of response to treatment by assessing minimal residual disease. After immunocapture of immunoglobulins and free light chains in serum, heavy and light chains were dissociated by chemical reduction and separated by liquid chromatography. M-proteins were analyzed by high-resolution mass spectrometry using a method combining a full MS scan for isotyping and identification and a targeted single ion monitoring scan for quantification. This method was able to discriminate M-protein from the therapeutic antibody in all patient samples analyzed and allowed quantification of M-protein with a LLOQ of 2.0 to 3.5 µg/ml in 5 out of 6 patients. This methodology appears to be promising for assessing minimal residual disease with sufficient sensitivity, specificity, and throughput. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.