Immunology & Cell Biology最新文献

T cells must reliably discriminate between foreign-derived antigens that require an adaptive immune response and nonspecific self-antigens that do not. This discrimination is highly specific to the affinity of the bond between the ligand and T-cell receptors (TCRs), and highly sensitive to the concentration of ligand. We examined the features of T-cell-mediated immunity in the context of multivalent ligand-receptor interactions between clusters of TCRs with peptide major histocompatibility complex-coated nanoparticles (NPs). Using Monte Carlo simulations of NP-T-cell surface interactions, we compared the effect of TCR clustering on the dose-response curves of bound TCRs when various NP design parameters were altered. These simulations revealed a trade-off between sensitivity and specificity, mediated by TCR clustering and NP geometry. Large TCR clusters enhance sensitivity to both NP valence and NP concentration at the expense of antigen specificity. This loss of specificity arises from two key effects of TCR clustering on NP binding: (1) steric hindrance caused by TCR proximity and NP size, leading to early saturation of bound TCRs; and (2) increased the avidity of multivalent low-affinity NPs. The combination of saturated high-affinity binding and amplified low-affinity binding resulted in impaired affinity-based discrimination. Finally, we demonstrated how kinetic proofreading (KPR) mechanisms mediated by TCR phosphorylation were able to recover specificity in models of T-cell activation. Together, these results suggest that multivalent ligand-receptor interactions promote greater sensitivity at the expense of specificity, and provide mechanistic insights into early T-cell activation that can guide the design of NPs for therapeutic applications.

Long-lasting protective immunity against sarbecoviruses is hampered by the dominance of elicited antibodies to variable parts of the Spike protein, allowing ongoing viral escape and evolution. We investigated Modified Vaccinia Ankara (MVA) vaccine candidates expressing the SARS-CoV-1 or SARS-CoV-2 Spike for their ability to induce antibodies targeting different epitopes on the SARS-CoV-2 Receptor Binding Domain (RBD), including those with wide variant conservation. We also explored the capacity of these different Spike proteins to induce broad cross-reactive or cross-neutralizing B cells against multiple variants. This revealed that the SARS-CoV-1 Spike induced distinct patterns of epitope dominance compared to the traditional SARS-CoV-2 Spike antigens. Following immune imprinting by previous exposure to ancestral SARS-CoV-2 Spike, the epitope dominance patterns induced by SARS-CoV-1 and SARS-CoV-2 vaccines still differed, with most of the germinal center response consisting of de novo recruited B cells. In addition to the de novo response, B cells with germline cross-reactivity to both antigens further increased their binding toward the most recently immunized antigen. Interestingly, we found that, while SARS-CoV-2 vaccinated animals were extremely capable of mounting an antigen-specific germinal center and plasmablast response to a booster immunization with SARS-CoV-1, SARS-CoV-2 boosters were less capable of inducing SARS-CoV-2 specific B cells following prior SARS-CoV-1 vaccination. These findings have broad implications for the implementation of vaccine strategies against emerging coronavirus variants and potential future coronavirus spillover events. The implications stemming from a fundamental directionality of immune imprinting and epitope dominance may have wider implications for noncoronavirus antigens.

This study, from the perspective of a Medical Immunology student, sought to explore and investigate the implementation of the Academic Tutor System in the teaching of Medical Immunology. The characteristics and challenges of studying Medical Immunology, as well as the limitations of conventional teaching models in this discipline, are analyzed. Additionally, the concept and theory of the Academic Tutor System and its application in the learning process of medical students are introduced in this study. Moreover, the specific implementation methods of the Academic Tutor System in Medical Immunology teaching are described, including implementation plan for the Academic Tutor System, implementation process for the Academic Tutor System and practical case analysis. Based on the findings of this study, it is concluded that the application of the Academic Tutor System benefits students' academic performance, enhances their research capabilities, and improves their overall comprehensive qualities. The vast majority of students support the implementation of the Academic Tutor System.

Public engagement is increasingly central to research, especially in biomedical fields, fostering dialogue between scientists and society, building trust and ensuring real-world relevance. However, as scientific and clinical progress accelerates, the gap between researchers and the public continues to widen, underscoring the need for deeper, more meaningful engagement. Despite the acknowledged value of public engagement for both researchers and the public, we know relatively little about academics' views on opportunities and potential barriers to participation. Using questionnaires and interviews, this study captured insights from 99 researchers and professionals across academic disciplines, career stages and geographical and cultural contexts. Respondents consistently regarded public engagement as an important and rewarding aspect of research, teaching and institutional responsibilities, with the potential to enhance public understanding, acceptance and societal impact. However, enthusiasm was tempered by persistent barriers, including academic workloads, inadequate resources and support, and a lack of formal recognition within career progression. Respondents emphasized the need for systemic reforms to enable greater participation, including tailored training, sustained funding and institutional frameworks that acknowledge and reward engagement. Overall, the findings demonstrate that while motivation for public engagement is widespread, structural and systemic challenges limit its full potential. Addressing these barriers requires coordinated action from universities, funders and policymakers to establish and embed public engagement more consistently as an integral component of academic research and higher education.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling cascade for the survival, activation, maturation, and differentiation of immune cells through interactions with cytokine receptors and transcription factors. Growing evidence indicates that autoimmune disorders are markedly affected by the JAK-STAT axis. Understanding the architecture and functions of the JAK-STAT axis has spurred the creation and authorization of a number of medications for managing autoimmune conditions in clinical settings. A mass of therapeutic agents (e.g., JAKinibs tofacitinib, baricitinib, STATinibs Stattic, FLLL32) and non-coding RNA have been used in research in preclinical experiments or/and clinical trials and demonstrate significant potential for treating autoimmune diseases. Nevertheless, concerns about these medicines' long-term safety and possible adverse consequences still exist. This narrative overview elaborates on the exact molecular underpinnings of the JAK-STAT axis, while also exploring the links among this pathway, adaptive immune cells, and autoimmune disorders. We also summarize the recently developed inhibitors of this pathway along with the present issues and future directions in the field.

Clodronate-loaded liposomes (CL liposomes) have been widely employed to deplete different macrophage subpopulations to assess their role in homeostatic, repair, regulatory, defense, autoimmune and inflammatory processes. Administration of CL liposomes, while promoting macrophage killing, can have long-term anti-inflammatory effects or cause inflammation in several mouse disease models. Therefore, the collateral effects of CL liposome treatment need to be explored when designing experiments involving macrophage depletion by CL liposomes. In this regard, the effect of a standard (high) versus low CL liposome dose on peritoneal macrophage kinetics and the structural integrity of the omentum has been investigated. High-dose clodronate treatment led to a long-lasting resMØ depletion but induced peritoneal inflammation and caused a severe and persistent omental milky spot disorganization, precluding drawing definitive conclusions on peritoneal resMØs function. In contrast, low-dose clodronate led to a transient depletion of resMØs but did not promote significant milky spot alterations or peritoneal inflammation, thus ensuring an efficient resMØ depletion in the absence of severe collateral effects, yet during a limited time window. These results have important implications for the design of experimental models aiming at addressing the role of peritoneal macrophages in peritoneal bacterial infection and tumor metastasis based on their depletion by CL liposomes.

Human invariant natural killer T cells (iNKT) play an important role in an orchestrated immune response; however, the heterogeneity of iNKT subsets is not yet fully understood. Here, we uncovered CD38 as a marker of iNKT differentiation, decoupling it from its role as a marker of activation by comparing the phenotype, cytokine profile and transcription factor expression of iNKT cell subsets in humans. Expression of CD38 on resting iNKT cells was restricted to cells that were low in well-described maturity markers such as CD161 and CCR5 and co-expressed markers associated with undifferentiated T cells (CD45RA, CCR7, CD62L). High abundance of CD38⁺ iNKT cells in human infant thymus and cord blood supported the immature nature of this subset. Functional analysis revealed that the CD38⁺ phenotype of resting iNKT cells was accompanied by diminished type 1 cytokine release, which was reflected by reduced expression of the transcription factor EOMES. Moreover, in vitro stimulation of sorted CD38⁺ and CD38⁻ iNKT cells demonstrated the distinct phenotype of cells expressing CD38 in a resting state and activation-induced CD38. These findings suggest a context-dependent role of CD38 expression on iNKT cells, distinguishing activated from resting iNKT cells where CD38 expression marks a subset of undifferentiated cells with altered functionality. Taken together, we describe a population of iNKT cells that extends the remarkable heterogeneity of the iNKT cell compartment beyond the presence of CD4⁺ and CD4⁻ subsets.

Metabolically disrupted CD8⁺ T cells drive epithelial injury in people with HIV (PWH) receiving antiretroviral therapy (ART). In colonic tissue-resident memory (TRM) CD8⁺ T cells, impaired peroxisome proliferator-activated receptor γ (PPARγ)–dependent lipid metabolism triggers aberrant lipid scavenging from epithelial cell membranes through direct cell contact, leading to epithelial apoptosis and barrier disruption.

Effective communication and public engagement are essential components of infectious disease control, yet they remain underdeveloped in the field of immunology. This review explores how immunologists and scientists can contribute to countering misinformation and improving vaccine uptake through inclusive, culturally sensitive engagement. Drawing on historical and contemporary case studies, we examine how trust, cognitive biases, and community involvement shape public responses. We highlight the importance of co-produced messaging and the role of community champions in building trust, particularly among marginalized groups. Vaccine communication is analyzed through the lens of the five Cs: confidence, complacency, convenience, communication, and context. We discuss how demographic and structural barriers, historical mistrust, and politicization of health messaging contribute to declining vaccine uptake and propose tailored strategies to address these challenges. The final section focuses on data presentation as a core foundation of public communication, emphasizing that clarity, transparency, and ethical framing are critical to public understanding. We outline principles for designing trustworthy visuals, mitigating cognitive biases, and embedding context directly within graphics to prevent misinterpretation. Participatory approaches to data communication are shown to improve comprehension and trust, especially when co-developed with affected communities. Together, these domains—engagement, vaccine communication, and data presentation—form a foundation for resilient public health responses. By integrating immunological expertise with inclusive communication strategies, scientists can play a central role in fostering informed decision making and strengthening public cooperation in future outbreaks.

Spectral flow cytometry is an advanced immunological tool that can enable comprehensive analysis of the immune system by simultaneously comparing innate and adaptive immune cells. Here, using a 40-color antibody panel, we advance our knowledge of innate-like cells by investigating chemokine receptors and maturation markers not usually assessed on these populations, examining age-related effects on these immune cell subsets. We characterize phenotypic changes of peripheral blood mononuclear cells (PBMCs) in three age groups: newborns (cord blood), adults aged 20–30 years, and adults aged > 70 years. We compare the age-related changes of innate cells, including ILCs, NK cells, monocytes, dendritic cells, and innate-like T cells, comparing them with memory T cells. We also examine subsets of CD4⁻CD8⁻ double-negative (DN) T cells and CD3⁺CD161⁺ T cells, revealing they are phenotypically similar to known subsets of innate-like T cells, and they also increase in frequency in an age-related manner. The frequencies of ILC1 increased with age, ILC2 remained stable, whereas ILC3 peaked in young adults, and were higher than cord and older adults. Notably, we identify the NK cell maturation marker, CD57, as a universal marker that defines aging populations of both innate and adaptive immune cells. This study enhances our understanding of the ontogeny of human immune cells, highlighting significant age-related changes in the frequency and phenotype of innate-like populations of immune cells.