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Melanocytes are static, minimally proliferative cells. This leaves them vulnerable in vitiligo. Yet upon malignant transformation, they form vicious tumors. This profound switch in physiology is accompanied by genetic change and is driven by environmental factors. If UV exposure in younger years supports malignant transformation and melanoma formation, it can likewise impart mutations on melanocytes that reduce their viability, to initiate vitiligo. A wide variety of microbes can influence these diametrically opposed outcomes before either disease takes hold. These microbes are vehicles of change that we are only beginning to study. Once a genetic modification occurs, there is a wide variety of immune cells ready to respond. Though it does not act alone, the T cell is among the most decisive responders in this process. The same biochemical process that offered the skin protection by producing melanin can become an Achilles heel for the cell when the T cells target melanosomal enzymes or, on occasion, neoantigens. T cells are precise, determined, and consequential when they strike. Here, we probe the relationship between the microbiome and its metabolites, epithelial integrity, and the activation of T cells that target benign and malignant melanocytes in vitiligo and melanoma. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions ( DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis. [ABSTRACT FROM AUTHOR]

Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite recent advances in immunophenotyping and molecular cytogenetics, leading to a better understanding of the underlying cell biology of the prolymphocytic leukaemias, prognosis for these patients remains poor. Purine analogues and monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia although further studies are warranted. Monoclonal antibody therapy with alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia (T-PLL) but responses are still transient and further disease progression is inevitable. While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal haemoglobinuria (PNH) results from acquired mutations in the PIG-A gene of an haematopoietic stem cell, leading to defective biosynthesis of glycosylphosphatidylinositol (GPI) anchors and deficient expression of GPI-anchored proteins on the surface of the cell's progeny. Some laboratory and clinical findings have suggested genomic instability to be intrinsic in PNH; this possibility has been supported by mutation analysis of hypoxanthine-guanine phosphoribosyltransferase ( HPRT) gene abnormalities. However, the HPRT assay examines lymphocytes in peripheral blood (PB), and T cells may be related to the pathophysiology of PNH. We analysed the molecular and functional features of HPRT mutants in PB mononuclear cells from eleven PNH patients. CD8 T cells predominated in these samples; approximately half of the CD8 cells lacked GPI-anchored protein expression, while only a small proportion of CD4 cells appeared to derive from the PNH clone. The HPRT mutant frequency (Mf) in T lymphocytes from PNH patients was significantly higher than in healthy controls. The majority of the mutant T lymphocyte clones were of CD4 phenotype, and they had phenotypically normal GPI-anchored protein expression. In PNH patients, the majority of HPRT mutant clones were contained within the V β2 T cell receptor (TCR) subfamily, which was oligoclonal by complementarity-determining region three (CDR3) size analysis. Our results are more consistent with detection of uniform populations of expanded T cell clones, which presumably acquired HPRT mutations during antigen-driven cell proliferation, and not due to an increased Mf in PNH. HPRT mutant analysis does not support underlying genomic instability in PNH. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) cells express certain tumour-associated antigens (TAAs) that could serve as targets for active-specific immunotherapy. The aim of the present study was to test the MM/dendritic cell (DC) fusion as a vaccination strategy. We fused MM cells with DC to generate fusion cells (FCs) and tested their antigen presenting cell (APC) function in mixed lymphocyte reactions and cytotoxicity assays. First, the HS Sultan and SK0-007 HAT sensitive human MM cell lines and DCs generated from peripheral blood of normal donors were fused in the presence of 50% polyethylene glycol to form FCs. Next, tumour cells freshly isolated from patients were similarly fused with autologous DCs to generate FCs. The FCs demonstrated a biphenotypic profile, confirmed both by flow-cytometry and dual immunofluorescence microscopy. These FCs induced MM-specific cytotoxicity. FCs, but not MM cells or DCs alone, were potent stimulators of autologous patient T cells. More importantly, FC-primed autologous peripheral blood mononuclear cells demonstrated major histocompatibility complex-restricted MM-specific cytolysis. These studies therefore demonstrated that MM/DC FC can trigger an autologous immune response to MM cells and formed the framework for a clinical trial currently underway. [ABSTRACT FROM AUTHOR]

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, ×3; mitoxantrone 10 mg/m2/d, ×1; dexamethasone 20 mg/d, ×5; monthly cycles, ×6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50·5%, 18% and 68·5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37·5%, P = 0·03; OR: 84% vs. 47·5%, P < 0·001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0·039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0·001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0·001) and OS (67 months vs. 13 months, P < 0·001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas. [ABSTRACT FROM AUTHOR]

Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms-like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF- α. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8·5–27·2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)- γ producing CD4+ T cells and in production of IFN- γ. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells. [ABSTRACT FROM AUTHOR]

Primary intraocular lymphoma (PIOL) is a rare presentation of lymphoma that is particularly difficult to recognize. In our institution, 36 cases of PIOL were diagnosed between March 1997 and July 2002. The recognition of lymphoma cells by cytology with or without immunophenotyping on slides generated a strong suspicion of the diagnosis in 34 of 36 cases. The diagnosis was confirmed by measurement of interleukin-10 (IL-10) in the vitreous humour or aqueous humour; high levels were observed in 35 of 36 cases, all were of B-cell origin. As expected, the only case with T-cell lymphoma had a very low level of IL-10. Furthermore, IL-10 levels excluded this diagnosis in two cases that were incorrectly suspected of PIOL after cytological examination. Finally, detection of clonality by polymerase chain reaction techniques, performed in 29 cases, represented a helpful tool in diagnosing PIOL as this approach definitively confirmed the diagnosis of B- or T-cell lymphoma in 17 cases. [ABSTRACT FROM AUTHOR]

We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the ‘linker’ molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC- γ1 and PLC- γ2). Antibodies to SLP-76 and PLC- γ1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC- γ2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC- γ2 was detected in arterial endothelium). SLP-76 and PLC- γ1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC- γ1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples. [ABSTRACT FROM AUTHOR]

T-cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components of the T-cell receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four-colour flow cytometry was applied to study the surface bound molecules TCR α β, CD28, CD152 and CD154 involved in T-cell signalling and the signal transduction molecules CD3 ζ, p56lck, p59fyn, ZAP-70 and phosphatidyl-inositol-3 kinase (PI3-k) as well as the intracellular cytokines interferon- γ (IFN- γ), interleukin (IL)-4 and IL-2 as a functional read-out of non-stimulated and superantigen (staphylococcus enterotoxin B)-stimulated blood T cells of multiple myeloma (MM) patients at different stages of the disease. Multiple abnormalities were demonstrated in the CD4 and CD8 populations, both under non-stimulated and superantigen-stimulated conditions. There was a marked reduction, particular in advanced stage MM, in the proportion of CD4 and CD8 cells expressing CD28, CD152, CD3 ζ, p56lck, ZAP-70 and PI3-k. The level of intracellular T-cell cytokines (IFN- γ, IL-2 and IL-4) was normal or increased in non-stimulated cells but activation-induced cytokine production was impaired. These results illustrated profound and multiple T-cell signalling defects, from the surface and down-stream, consistent with involvement of a master T-cell function, especially in advanced stage MM. These data should be taken into consideration when developing immune-based therapeutic approaches and when applying new emerging technologies that aim to restore T-cell functions. [ABSTRACT FROM AUTHOR]

Ikaros is a Kruppel-type zinc finger protein that is essential for normal lymphocyte development and differentiation. Recently, it has been demonstrated that Ikaros is frequently inactivated in both human and mouse leukaemias/lymphomas. Although this inactivation is thought to be involved in leukaemogenesis, little is known about the molecular mechanisms that lead to neoplastic transformation. To identify the genes that may be controlled by Ikaros, we performed differential display analysis of RNAs from mouse 3T3-L1 cells that had been transfected with the Ikaros gene. Two cDNAs, the Trk-fused gene ( Tfg) and death-associated protein 3 gene ( Dap3) were upregulated in Ikaros-transfected cells. Expression of Tfg and Dap3 was consistently downregulated in radiation-induced T-cell lymphomas that exhibited defective Ikaros expression. These results suggest that Tfg and Dap3 function downstream of Ikaros and may be involved in radiation-induced lymphomagenesis. [ABSTRACT FROM AUTHOR]

Autoimmune lymphoproliferative syndrome (ALPS), is an inherited disorder characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly, accumulation of T-cell receptor (TCR)-αβ+ CD4− CD8− T cells (double-negative T cells) and autoimmunity. We investigated the incidence and nature of neutrophil and platelet antibodies in patients with ALPS. Sera from 26 patients with ALPS were tested for neutrophil antibodies by granulocyte immunofluorescence, granulocyte agglutination and monoclonal antibody immobilization assays of granulocyte antigens, and for platelet antibodies using a solid-phase antibody-detection system. Neutrophil antibodies were detected in 46% of patients with ALPS. Antibody specificity could be defined in eight of the 12 patients with neutrophil antibodies. Among these eight patients, four had antibodies directed against more than one antigen. Overall, 14 antibodies directed to specific antigens were identified: three were directed to the HNA-1a antigen of FcγRIIIb; two to the HNA-1b antigen of Fcγ-RIIIb; two to epitopes common to all FcγRIIIb molecules; four to the HNA-2a antigen of the NB1 glycoprotein; and three to neutrophil β2 integrins. Platelet antibodies were detected in 35% of patients with ALPS. No antibody specificities were identified among the platelet antibodies. There was no association between the detection of neutrophil antibodies and a history of clinical neutropenia, or between the detection of platelet antibodies and a history of clinical thromobocytopenia. Neutrophil and platelet antibodies are important markers of ALPS, but do not always cause clinical cytopenias. The specificities of neutrophil antibody were similar to those found in children with autoimmune neutropenia but without ALPS. [ABSTRACT FROM AUTHOR]

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll‐like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune‐related diseases, for example, the cGAS–STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single‐cell sequencing technologies, CAR‐T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system. [ABSTRACT FROM AUTHOR]

Aedes aegypti L. (Diptera: Culicidae) is a mosquito broadly found in tropical and temperate areas of the world. It is the main vector of dengue, chikungunya, zika and yellow fever (urban cycle), among other viruses. Aedes aegypti immatures develop in water holding containers, and frequently use artificial containers in urban settings as larval habitat. Ovitraps are artificial oviposition sites, a tool developed for mosquito population surveillance and to assess effectiveness of control measures. The preference for different oviposition substrate materials was assessed in the field, in two localities of Salta province, northern Argentina, where dengue outbreaks are frequent. The proportion of positive traps did not differ between oviposition substrates. However, higher numbers of eggs were laid in cotton fabric and velour paper, which were better than wooden paddle and blotting paper if the aim was to maximize the numbers of eggs collected. The results also evidenced that substrate preference for oviposition did not differ between geographic regions. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T‐cell (CAR‐T) therapy is becoming an effective technique for the treatment of patients with relapsed/refractory hematologic malignancies. After analyzing patients with tumor progression and sustained remission after CAR‐T cell therapy, many factors were found to be associated with the efficacy of CAR‐T therapy. This paper reviews the factors affecting the effect of CAR‐T such as tumor characteristics, tumor microenvironment and immune function of patients, CAR‐T cell structure, construction method and in vivo expansion values, lymphodepletion chemotherapy, and previous treatment, and provides a preliminary outlook on the corresponding therapeutic strategies. [ABSTRACT FROM AUTHOR]

This article focuses on abstracts of papers presented at the 32nd annual meeting of the American Society of Dermatopathology at Intercontinental Hotel, New Orleans between February 1-3, 1995. The Kveim-Siltzbach Reactions (KSR) is an important model for investigating immunologic events in granuloma formation. It has been shown that T lymphocyte predominance with oligocionality of infiltrating cells in 4 week-old KSR. Verruciform xanthoma is a rare benign condition that commonly involves the oral mucosa. Cutaneous lesions are less often observed, predominantly occurring at anogenital sites. Despite anecdotal reports of its occurrence in a variety of disease states, the etiology of this condition remains unclear.

The article presents information on abstracts of papers presented at the 29th Annual meeting of the American Society of Dermatopathology. Some of the titles are, "Histomorphometry of Dysplastic and Other Melanocytic Lesions: Correlation With Subjective grading and Flow Cytometry," by R.L. Barnhill, J.A. Bruijn, M. Berwick, M.C. Mihm, Jr., and D. Weinberg, " "Basaloid Follicular Hamartoma: Solitary and Multiple Types," by M.H. Brownstein, "CD30 Positive Plemorphic Large Cell Cutaneous T-Cells Lymphoma," by N.P. Burrows, S. Whittaker, R. Russell Jones, and others.

A list of forthcoming papers related to immunology is presented. These include "Variable influences of iodine on the T-cell recognition of a single thyroglobulin epitope," by Hong Jiang, "Triacylated lipoproteins derived from Mycoplasma pneumoniae activate NF-jB through TLR1 and TLR2," by Takashi Shimizu, and "Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and Th1/Th2 balance," by Alexander Borowsky and Kevin Kent Lloyd.

The epithelial cell adhesion molecule (Ep-CAM) is expressed on the surface of most human carcinomas, including ovarian, breast, lung, prostate and colorectal carcinoma. Ep-CAM was shown to be a valid target for monoclonal antibody-based therapies. We have investigated whether an Ep-CAM-/CD3-bispecific single-chain antibody called bscEp-CAM × CD3 is effective in tumor cell elimination within the cellular microenvironment of primary ovarian cancer tissue. The ex vivo elimination of ovarian cancer cells in tumor preparations from 21 patients was monitored by flow cytometry using Ep-CAM/CA-125 double-labeling or Ep-CAM single-labeling combined with propidium iodide uptake of cells. Methodology was established by the ovarian cancer cell line OvCAR. A total of 17 (81%) patient samples showed a dose-dependent tumor cell elimination by bscEp-CAM × CD3. High and specific tumor cell lysis was seen at bscEp-CAM × CD3 concentrations as low as 1 ng/ml, at very low effector:target ratios and in the absence of T cell costimulation. The high efficacy of the bispecific antibody may be due to the non-restricted activation of tumor-resident cytotoxic T lymphocytes. In clinical trials, the ex vivo data with the T cell-recruiting bispecific antibody bscEp-CAM × CD3 may translate into a high response rate and efficacy of tumor cell elimination. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Nanoencapsulation of living cells within artificial shells is a powerful approach for augmenting the inherent capacity of cells and enabling the acquisition of extrinsic functions. However, the current state of the field requires the development of nanoshells that can dynamically sense and adapt to environmental changes by undergoing transformations in form and composition. This paper reports the compositional transformation of an enzyme‐embedded nanoshell of Fe3+‐trimesic acid complex to an iron phosphate shell in phosphate‐containing media. The cytocompatible transformation allows the nanoshells to release functional molecules without loss of activities and biorecognition, while preserving the initial shell properties, such as cytoprotection. Demonstrations include the lysis and killing of Escherichia coli by lysozyme, and the secretion of interleukin‐2 by Jurkat T cells in response to paracrine stimulation by antibodies. This work on micrometric Transformers will benefit the creation of cell‐in‐shell nanobiohybrids that can interact with their surroundings in active and adaptive ways. [ABSTRACT FROM AUTHOR]

Background: It has been reported that programmed death‐ligand 1 (PD‐L1) is highly expressed in cells during viral infection, which helps the virus escape host immunity. However, the relationship between human papillomavirus (HPV) and PD‐L1 in condyloma acuminatum and whether they participate in immunosuppression have not been reported. In this paper, we aimed to explore the expression and significance of PD‐L1 in condyloma acuminatum. Methods: The expression of PD‐L1 in the wart of condyloma acuminatum patients and the foreskin of healthy individuals was evaluated. Lentivirus transfection was used to introduce the HPV11‐E7 gene into HaCaT cells to investigate whether HPV infection could affect the expression of PD‐L1. The successfully constructed HPV11‐E7 HaCaT cells were cocultured with Jurkat cells, and Jurkat cell apoptosis and proliferation as well as the Jurkat cell cycle were evaluated by flow cytometry and cell counting kit‐8 (CCK‐8) assays. Results: PD‐L1 was highly expressed in keratinocytes of genital warts. Through the construction of a cell model, we found that HPV11‐E7 could upregulate the expression of PD‐L1 in HaCaT cells. Furthermore, HPV11‐E7 HaCaT cells can promote the apoptosis of Jurkat cells, inhibit the proliferation of Jurkat cells and mediate the cell cycle arrest of Jurkat cells through the PD‐1/PD‐L1 signalling pathway. Conclusions: HPV infection may upregulate PD‐L1 expression in the keratinocytes of genital warts and participate in the inhibition of local T‐cell function. [ABSTRACT FROM AUTHOR]

Immune checkpoint therapy has emerged as an effective treatment option for various types of cancers. Key immune checkpoint molecules, such as cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4), programmed cell death protein 1 (PD‐1), and lymphocyte activation gene 3 (LAG‐3), have become pivotal targets in cancer immunotherapy. Antibodies designed to inhibit these molecules have demonstrated significant clinical efficacy. Nevertheless, the ability to monitor changes in the immune status of tumors and predict treatment response remains limited. Conventional methods, such as assessing lymphocytes in peripheral blood or conducting tumor biopsies, are inadequate for providing real‐time, spatial information about T‐cell distributions within heterogeneous tumors. Positron emission tomography (PET) using T‐cell specific probes represents a promising and noninvasive approach to monitor both systemic and intratumoral immune changes during treatment. This technique holds substantial clinical significance and potential utility. In this paper, we review the applications of PET probes that target immune cells in molecular imaging. [ABSTRACT FROM AUTHOR]

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]

Background: Stereotactic body radiation therapy (SBRT) is known to modulate the immune system and contribute to the generation of anti‐tumor T cells and stimulate T cell infiltration into tumors. Radiation‐induced immune suppression (RIIS) is a side effect of radiation therapy that can decrease immunological function by killing naive T cells as well as SBRT‐induced newly created effector T cells, suppressing the immune response to tumors and increasing susceptibility to infections. Purpose: RIIS varies substantially among patients and it is currently unclear what drives this variability. Models that can accurately predict RIIS in near real time based on treatment plan characteristics would allow treatment planners to maintain current protocol specific dosimetric criteria while minimizing immune suppression. In this paper, we present an algorithm to predict RIIS based on a model of circulating blood using early stage lung cancer patients treated with SBRT. Methods: This Python‐based algorithm uses DICOM data for radiation therapy treatment plans, dose maps, patient CT data sets, and organ delineations to stochastically simulate blood flow and predict the doses absorbed by circulating lymphocytes. These absorbed doses are used to predict the fraction of lymphocytes killed by a given treatment plan. Finally, the time dependence of absolute lymphocyte count (ALC) following SBRT is modeled using longitudinal blood data up to a year after treatment. This model was developed and evaluated on a cohort of 64 patients with 10‐fold cross validation. Results: Our algorithm predicted post‐treatment ALC with an average error of 0.24±0.21×109$0.24 \pm 0.21 \times {10}^9$ cells/L with 89% of the patients having a prediction error below 0.5 × 109 cells/L. The accuracy was consistent across a wide range of clinical and treatment variables. Our model is able to predict post‐treatment ALC < 0.8 (grade 2 lymphopenia), with a sensitivity of 81% and a specificity of 98%. This model has a ∼38‐s end‐to‐end prediction time of post treatment ALC. Conclusion: Our model performed well in predicting RIIS in patients treated using lung SBRT. With near‐real time model prediction time, it has the capability to be interfaced with treatment planning systems to prospectively reduce immune cell toxicity while maintaining national SBRT conformity and plan quality criteria. [ABSTRACT FROM AUTHOR]

Presents a list of forthcoming articles to be published in the "European Journal of Biochemistry". Functional and structural analysis of photosystem II core complexes from spinach with high oxygen evolution capacity; Immunosuppressive activity of bovine seminal RNase on T-cell proliferation; Fate of interleukin-6 in the rat; DNA sequence of a citrate carrier of Klebsiella pneumoniae.

Summary: Since the publication in 2017 of the revised 4th Edition of the World Health Organization (WHO) classification of haematolymphoid tumours, here referred to as WHO‐HAEM4, significant clinicopathological, immunophenotypic and molecular advances have been made in the field of lymphomas, contributing to refining the diagnostic criteria of several diseases, upgrading entities previously defined as provisional and identifying new entities. This process has resulted in two recent classification proposals of lymphoid neoplasms: the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, focusing on T‐cell lymphomas and histiocytic/dendritic cell tumours. Moreover, we update the genetic data of the various pathological entities. The main goal is to provide a tool to facilitate the work of the pathologists, haematologists and researchers involved in the diagnosis and treatment of these haematological malignancies. [ABSTRACT FROM AUTHOR]

Summary: A subset of individuals with 'primary' or 'idiopathic' immune thrombocytopenia (ITP) who fail to respond to conventional first‐ and second‐line agents or who lose responsiveness are considered to have 'refractory' disease (rITP), placing them at increased risk of bleeding and complications of intensive treatment. However, the criteria used to define the refractory state vary among studies, which complicates research and clinical investigation. Moreover, it is unclear whether rITP is simply 'more severe' ITP, or if there are specific pathogenic pathways that are more likely to result in refractory disease, and whether the presence or development of rITP can be established or anticipated based on these differences. This paper reviews potential biological features that may be associated with rITP, including genetic and epigenetic risk factors, dysregulation of T cells and cytokine networks, antibody affinity and specificity, activation of complement, impaired platelet production and alterations in platelet viability and clearance. These findings indicate the need for longitudinal studies using novel clinically available methodologies to identify and monitor pathogenic T cells, platelet antibodies and other clues to the development of refractory disease. [ABSTRACT FROM AUTHOR]

Summary: Since its first description by Evans in 1951, this syndrome has been linked to chronic immune thrombocytopenia with the concurrent or delayed onset of autoimmune haemolytic anaemia or neutropenia. For decades, the evolution of Evans syndrome (ES) has carried a poor prognosis and often resulted in chronic steroid exposure, multiple immune suppressing medications directed against T or B lymphocytes, and splenectomy. This paper presents a new view of ES based on recent advances in genomics which begin to classify patients based on their underlying molecular variants in previously described primary immune disorders. This has opened up new avenues of targeted therapy or bone marrow transplant at rather than broad long‐term immune suppression or splenectomy. Importantly, recent studies of the full lifespan of ES suggest that at least 80% of those paediatric patients will progress to various clinical or biological immunopathological manifestations with age despite the resolution of their cytopenias. Those patients merit long‐term follow‐up and monitoring in dedicated transition programs to improve outcome at the adult age. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy, represented by immune checkpoint blocking and chimeric antigen receptor (CAR) T cell therapy, has achieved promising results in clinical applications. However, it faces challenges that hinder its further development, such as limited response rates and poor tumor permeability. The efficiency of tumor immunotherapy is also closely linked to the structure and function of the immune microenvironment where the tumor resides. Recently, nanoparticle‐based tumor immune microenvironment (TIME) modulation strategies have attracted a great deal of attention in cancer immunotherapy. This is primarily due to the distinctive physical characteristics of nanoparticles, which enable them to effectively infiltrate the TIME and selectively modulate its key constituents. This paper reviews recent advances in nanoparticle engineering to improve anti‐cancer immunotherapy. Emerging nanoparticle‐based approaches for modulating immune cells, tumor stroma, cytokines and immune checkpoints are discussed, aiming to overcome current challenges in the clinic. In addition, integrating immunotherapy with various treatment modalities such as chemotherapy and photodynamic therapy can be facilitated through the utilization of nanoparticles, thereby enhancing the efficacy of cancer treatment. The future challenges and opportunities of using nanomaterials to reeducate the suppressive immune microenvironment of tumors are also discussed, with the aim of anticipating further advancements in this growing field. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a numerical and analytical study of the HIV‐1 infection of CD4+ T‐cells conformable fractional mathematical model. This model is studied analytically by Kudryashov and modified Kudryashov methods and numerically by finite difference method. A comparison between the results of the analytical and numerical methods is investigated. We also give some figures that show how accurate the solutions will be obtained from analytical and numerical methods. [ABSTRACT FROM AUTHOR]

CD25 is the alpha‐chain of the heterotrimer IL‐2 receptor. CD25 is expressed on the surface of both immune and non‐immune cells with different frequencies. For cancers, CD25 is expressed at high levels in many types of hematological malignancies, but at low levels in most solid tumors. CD25 is also highly expressed in activated circulating immune cells and regulatory T cells (Tregs). Infiltration of Tregs in the tumor microenvironment can lead to an imbalanced ratio of effector T cells (Teffs) and Tregs, which is associated with the progression of cancers. A rescued Teff/Treg cell ratio indicates an efficient anti‐tumor response to immunotherapy. CD25 as a potential target for the depletion of Tregs is critical in developing new immunotherapeutic strategies. Few articles have summarized the relationships between CD25 and tumors, or the recent progress of drugs targeting CD25. In this paper, we will discuss the structures of IL‐2 and IL‐2R, the biological function of CD25 and its important role in tumor therapy. In addition, the latest research on drugs targeting CD25 has been summarized, providing guidance for future drug development. [ABSTRACT FROM AUTHOR]

This paper is concerned with level‐dependent quasi‐birth‐death (LD‐QBD) processes, i.e., multi‐variate Markov chains with a block‐tridiagonal q$$ q $$‐matrix, and a more general class of block‐structured Markov chains, which can be seen as LD‐QBD processes with total catastrophes. Arguments from univariate birth‐death processes are combined with existing matrix‐analytic formulations to obtain sufficient conditions for these block‐structured processes to be regular, positive recurrent, and absorbed with certainty in a finite mean time. Specifically, it is our purpose to show that, as is the case for competition processes, these sufficient conditions are inherently linked to a suitably defined birth‐death process. Our results are exemplified with two Markov chain models: a study of target cells and viral dynamics and one of kinetic proof‐reading in T cell receptor signal transduction. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis involves various types of immune cells and soluble mediators, including TGF‐β and IL‐35, a recently identified heterodimeric cytokine that belongs to the IL‐12 cytokine family. However, the effect of regulatory IL‐35 may play an important role in fibrotic diseases. The aim of this paper is to explore the immunoregulatory role of IL‐35 in the development of fibrosis in interstitial lung disease (ILD). To gain a better understanding of this issue, the concentrations of IL‐35 and different profibrotic cytokines in fibrotic (F‐ILD) and non‐fibrotic (NF‐ILD) patients by ELISA were compared to that of intracellular IL‐35 and IL‐17 on CD4+ T cells stimulated in the presence of BAL or with different ratios of recombinant IL‐35 (rIL‐35) and TGF‐β (rTGF‐β), which were evaluated by flow cytometry. We observed that BAL concentration of IL‐35 was lower in F patients (p < 0.001) and was negatively correlated with concentrations of TGF‐β (p < 0.001) and IL‐17 (p < 0.001). In supplemented cell cultures, BAL from NF but not F patients enhanced the percentage of IL‐35 + CD4+ T (p < 0.001) cells and decreased the percentage of IL‐17 + CD4+ T cells (p < 0.001). The percentage of IL‐35 + CD4+ T cells correlated positively with BAL concentration of IL‐35 (p = 0.02), but correlated negatively with BAL concentrations of IL‐17 (p = 0.007) and TGF‐β (p = 0.01). After adjusting the concentrations of recombinant cytokines to establish a TGF‐β: IL‐35 ratio of 1:4, an enhanced percentage of IL‐35 + CD4+ T cells (p < 0.001) but a decreased percentage of IL‐17 + CD4+ T cells (p < 0.001) was observed. After adding recombinant IL‐35 to the BAL from F patients until a 1:4 ratio of TGF‐β: IL‐35 was reached, a significantly increased percentage of IL‐35 + CD4+ T cells (p < 0.001) and a decreased percentage of IL‐17 + CD4+ T cells (p = 0.003) was found. These results suggest that IL‐35 may induce an anti‐fibrotic response, regulating the effect of TGF‐β and the inflammatory response on CD4+ T cells. In addition, the TGF‐β: IL‐35 ratio in BAL has been shown to be a potential biomarker to predict the outcome of F patients with ILD. [ABSTRACT FROM AUTHOR]

The UVB irradiation is well known for its impact on the development of skin cancer. However, low UVB irradiation plays a protective role against various human diseases including cancer through its effect on tumor suppression. This article summarizes the key findings of the paper by Park et al., which describes a novel molecular mechanism of moderate UVB irradiation in suppressing the growth of melanoma and colorectal cancer. Key observations in this article are that moderate UVB irradiation can enhance tumor immunity by (1) increased infiltration of CD4+ and CD8+ T cells; (2) increased infiltration of CD103+ conventional type 1 dendritic cells (cDC1); and (3) a significant decrease of M2 tumor associate macrophages (TAMs) into the tumor. The authors further identified the role of Batf3 transcription factor in moderate UVB irradiation‐mediated anti‐tumor immune response. Deletion of Batf3 transcription factor reversed the tumor suppressive effect with decreased CD103+ cDC1 cell infiltration. This pre‐clinical study provides a very novel mechanistic insight into the utilization of moderate UVB irradiation for the management of melanoma and colorectal cancer. This study further provides the direction of new future research to explore moderate UVB irradiation in combination with checkpoint blockade antibodies to enhance immunotherapeutic response against various solid tumors. [ABSTRACT FROM AUTHOR]

The article titled "Correction to 'Psychological stress to ovalbumin peptide‐specific T‐cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell'" in the journal Immunology discusses a correction made to the original paper. The authors discovered that Figure 2b was unnecessary as it presented the same data as Figure 2a. Therefore, they removed Figure 2b from the paper. The correction also includes additional information about concurrent exposure to restraint stress and immune response exaggerating endoplasmic reticulum stress in type 1 regulatory T cells. The authors apologize for the error. [Extracted from the article]

Immunotherapy using immune checkpoint inhibitors (ICIs) has shown superior efficacy compared with conventional chemotherapy in certain cancer types, establishing immunotherapy as the fourth standard treatment alongside surgical intervention, chemotherapy, and radiotherapy. In cancer immunotherapy employing ICIs, CD8‐positive cytotoxic T lymphocytes are recognized as the primary effector cells. For effective clinical outcomes, it is essential that the targeted cancer cells express HLA class I molecules to present antigenic peptides derived from the tumor. However, cancer cells utilize various mechanisms to downregulate or lose HLA class I molecules from their surface, resulting in evasion from immune surveillance. Correlations between prognosis and the integrity of HLA class I molecules expressed by cancer cells have been consistently found across different types of cancer. This paper provides an overview of the regulatory mechanisms of HLA class I molecules and their role in cancer immunotherapy, with a particular emphasis on the significance of utilizing pathological tissues to evaluate HLA class I molecules expressed in cancer cells. [ABSTRACT FROM AUTHOR]

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR‐T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR‐T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR‐T cell therapy, and considers future outlooks for research development. Significance statement: The necessity and importance of chimeric antigen receptor (CAR) T cells and their therapeutic efficiency in treating diseases other than cancer, mainly cardiovascular diseases, have emerged in recent years. However, there is still room for advancement in the current models of CAR‐T cell therapy. This paper highlights the evolution and roadblocks of CAR‐T technology at different levels, from technical concerns to clinical outcomes, in an attempt to improve the therapeutic efficiency of CAR‐T cell therapy in this area. [ABSTRACT FROM AUTHOR]

Lists forthcoming papers on immunology, compiled as of November 2004. "T Cell Receptor-Induced Redistribution of Type 1 Protein Kinase A," by Wenhong Zhou and colleagues; "Phenotypic and Functional Heterogeneity of Porcine Blood Monocytes and Its Reaction with Maturation," by Sonia Chamorro and colleagues; "Purification, Characterization and Immunolocalization of Porcine Surfactant Protein D," by Tahir Razzaq and colleagues.

Objectives: This paper reviews current and emerging therapies for multiple myeloma (MM). Methods: Narrative review. Results: MM is a complex, heterogenous condition, and in recent years there has been an expansion in the number and range of treatments. Several new treatment approaches, including enhanced monoclonal antibodies, antibody‐drug conjugates, bispecific T‐cell engagers, and chimeric antigen‐T‐cell therapy are under development. Conclusions: The emergence of new treatments that aim to tackle MM‐associated immune dysfunction has led to improvements in overall survival. [ABSTRACT FROM AUTHOR]

Background: Cellular therapies using engineered T cells, haploidentical transplants, and autologous gene therapy are increasing. Specified CD3+ or high CD34+ doses are typically required for subsequent manufacturing, manipulation, or CD34+ selection. Simple, practical, and reliable lymphocyte and hematopoietic progenitor cell (HPC) collection algorithms accounting for subsequent CD34+ selection have not been published.Study Design and Methods: In this analysis of 15 haploidentical donors undergoing tandem lymphocyte and HPC collections, we validated one-step, practical prediction algorithms (Appendix S1, available as supporting information in the online version of this paper) that use conservative facility-specific collection efficiencies, CD34+ selection efficiency, and donor-specific peripheral counts to reliably achieve the target CD3+ and CD34+ product doses. These algorithms expand on our previously published work regarding predictive HPC collection algorithms.Results: Ninety-three percent of lymphocyte and 93% of CD34+ collections achieved the final target CD3+ and CD34+ product dose when our algorithm-calculated process volumes were used. Linear regression analysis of our algorithms for CD3+, preselection CD34+, and postselection CD34+ showed statistically significant models with R2 of 0.80 (root mean square error [RMSE], 31.3), 0.72 (RMSE, 385.7), and 0.56 (RMSE, 326.0), respectively, all with p values less than 0.001.Conclusion: Because achievement of CD3+ or CD34+ dose targets may be critical for safety and efficacy of cell therapies, these simple, practical, and reliable prediction algorithms for lymphocyte and HPC collections should be very useful for collection facilities. [ABSTRACT FROM AUTHOR]

The article lists forthcoming papers to be published in "Immunology," including "Dendritic Cells Modulated by Innate Immunity Improve Collagen-Induced Arthritis and Induce Treg in vivo," by Olivier Jaen, Sandrine Rullé, Natacha Bessis, Abokouo Zago, Marie-Christophe Boissier and Geraldine Falgarone; "The T-Cell Pool is Anergized in Patients with Multiple Sclerosis in Remission," by Moa E. Fransson, Lina S.E. Liljenfeldt, Jan Fagius, Thomas H. Tötterman and Angelica S.I. Loskog; and "The Mannose Receptor Binds Trichuris muris Excretory/Secretory Proteins But is Not Essential for Protective Immunity," by Matthew L. deSchoolmeester, Luisa Martinez-Pomares, Siamon Gordon and Kathryn J. Else.

The article lists forthcoming research papers related to immunology including "Tricks with tetramers: how to get the most from multimeric peptide-MHC," "Small changes in lymphocyte development and activation in mice by tissue-specific alteration of heparan sulphate" and "Alpha1 beta 1 integrin and IL-7 receptor upregulate the expression of RANKL in human T cells and enhance their osteoclastogenic function."

A list of papers and reports related to immunology is presented. They include "Studies on the interactions between C-reactive protein and complement proteins," "BMP2/4 signalling pathway components are expressed in the human thymus and inhibit early T-cell development" and "Marsupial CD1 is not orthologous to the eutherian isoforms and is a pseudogene in the opossum Monodelphis domestica."

The article presents a list of forthcoming research papers related to immunology. They include "DNA and its cationic lipid complexes induce CpG motif-dependent activation of murine dendritic cells," "Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T lymphocyte responses and antitumor immunity," and "Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40 stimulation."

A list of papers related to the field of immunology is presented. These include "Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma," by Marian Kruzel and Istvan Boldogh, "Enhancement of CD8 T-cell function through modifying surface glycoproteins in young and old mice," by Amir Sadighi Akha and Richard Miller and "Essential role of neutrophils in anti-type II collagen antibody and LPS-induced arthritis," by Daisuke Tanaka and T. Shimozato.

Lists research papers related to immunology to be published in the journal. "T Cells Homeostasis in Mice Exposed to Airborne Xenobiotics," by Nadzieja Drela, Justyna Bien, and Ewa Kozlowska; "B Cell Reconstruction by Transplantation of B220+ CD117+ B-lymphoid Progenitors Into Irradiated Mice," by Susumu Kawaguchi; "TGF-β1 Increases CXCR4 Expression, SDF-1alpha-stimulated Signaling and HIV-1 Entry in Human Monocyte-derived Macrophages," by Jeffrey Harrison.

Major histocompatibility complex (MHC) genes (referred to as human leukocyte antigen or HLA in humans) are a key component of vertebrate immune systems, coding for proteins which present antigens to T‐cells. These genes are outstanding in their degree of polymorphism, with important consequences for human and animal health. The polymorphism is thought to arise from selection pressures imposed by pathogens on MHC allomorphs, which differ in their antigen‐binding capacity. However, the existing theory has not considered MHC selection in relation to the formation of immune memory. In this paper, we argue that this omission limits our understanding of the evolution of MHC polymorphism and its role in disease. We review recent evidence that has emerged from the massive research effort related to the SARS‐CoV‐2 pandemics, and which provides new evidence for the role of MHC in shaping immune memory. We then discuss why the inclusion of immune memory within the existing theory may have non‐trivial consequence for our understanding of the evolution of MHC polymorphism. Finally, we will argue that neglecting immune memory hinders our interpretation of empirical findings, and postulate that future studies focusing on pathogen‐driven MHC selection would benefit from stratifying the available data according to the history of infection (and vaccination, if relevant). [ABSTRACT FROM AUTHOR]

CD247, which is also known as CD3ζ, CD3H, CD3Q, CD3Z, IMD25, T3Z and TCRZ, encodes CD3ζ protein, which is expressed primarily in natural killer (NK) and T cells. Since the discovery of the ζ peptide in 1986, it has been continuously investigated. In this paper, we review the composition, molecular mechanisms and regulatory factors of CD247 expression in T cells; and review the autoimmune diseases, tumours and inflammatory diseases associated with CD247, providing a detailed and comprehensive reference for further research on the mechanism of CD247 and related diseases. [ABSTRACT FROM AUTHOR]

The Immunology & Cell Biology Publication of the Year Awards recognize outstanding studies submitted by first authors who are members of the Australian & New Zealand Society for Immunology Inc. The winners for 2023 were Lukasz Kedzierski for his work on Semliki Forest virus encephalitis and Anouk von Borstel for her research on γδ T cell populations in COVID-19 patients. These papers showcase the high-quality research published in the journal and highlight important insights into immune responses and viral infections. [Extracted from the article]

A list of articles related to immunology research are presented. They include "Dose dependent modulation of CD8 and functional avidity as a result of peptide encounter," "Expression of 5-lipoxygenase (5-LOX) in T lymphocytes," and "Salmonella-induced SipB-independent cell death requires TLR4 signalling via the adapter proteins Tram and Trif."