Seminars in Immunology最新文献

Infection with SARS-CoV-2 in humans has caused a pandemic of unprecedented dimensions. SARS-CoV-2 is primarily transmitted through respiratory droplets and targets ciliated epithelial cells in the nasal cavity, trachea, and lungs by utilizing the cellular receptor angiotensin-converting enzyme 2 (ACE2). The innate immune response, including type I and III interferons, inflammatory cytokines (IL-6, TNF-α, IL-1β), innate immune cells (monocytes, DCs, neutrophils, natural killer cells), antibodies (IgG, sIgA, neutralizing antibodies), and adaptive immune cells (B cells, CD8+ and CD4+ T cells) play pivotal roles in mitigating COVID-19 disease. Broad and durable B-cell– and T-cell immunity elicited by infection and vaccination is essential for protection against severe disease, hospitalization and death. However, the emergence of SARS-CoV-2 variants that evade neutralizing antibodies continue to jeopardize vaccine efficacy. In this review, we highlight our understanding the infection- and vaccine-mediated humoral, B and T cell responses, the durability of the immune responses, and how variants continue to threaten the efficacy of SARS-CoV-2 vaccines.

The gut microbiota is well known to possess immunomodulatory capacities, influencing a multitude of cellular signalling pathways to maintain host homeostasis. Although the formation of the immune system initiates before birth in a sterile environment, an emerging body of literature indicates that the neonatal immune system is influenced by a first wave of external stimuli that includes signals from the maternal microbiota. A second wave of stimulus begins after birth and must be tightly regulated during the neonatal period when colonization of the host occurs concomitantly with the maturation of the immune system, requiring a fine adjustment between establishing tolerance towards the commensal microbiota and preserving inflammatory responses against pathogenic invaders. Besides integrating cues from commensal microbes, the neonatal immune system must also regulate responses triggered by other environmental signals, such as dietary antigens, which become more complex with the introduction of solid food during the weaning period. This “window of opportunity” in early life is thought to be crucial for the proper development of the immune system, setting the tone of subsequent immune responses in adulthood and modulating the risk of developing chronic and metabolic inflammatory diseases. Here we review the importance of host-microbiota interactions for the development and maturation of the immune system, particularly in the early-life period, highlighting the known mechanisms involved in such communication. This discussion is focused on recent data demonstrating microbiota-mediated education of innate immune cells and its role in the development of lymphoid tissues.

Carcinogenesis in the process of long-term co-evolution of tumor cells and immune environment essentially becomes possible due to incorrect decisions made, remembered, and reproduced by the immune system at the level of clonal populations of antigen-specific T- and B-lymphocytes. Tumor-immunity interaction determines the nature of such errors and, consequently, delineates the possible ways of successful immunotherapeutic intervention. It is generally recognized that tumor-infiltrating B cells (TIL-B) can play both pro-tumor and anti-tumor roles. However, the exact mechanisms that determine the contribution of clonal B cell lineages with different specificities and functions remain largely unclear. This is due to the variability of cancer types, the molecular heterogeneity of tumor cells, and, to a large extent, the individual pattern of each immune response. Further progress requires detailed investigation of the functional properties and phenotypes of clonally heterogeneous B cells in relation to their antigenic specificities, which determine the functionality of both effector B lymphocytes and immunoglobulins produced in the tumor environment. Based on a real understanding of the role of clonal antigen-specific populations of B lymphocytes in the tumor microenvironment, we need to learn how to develop new methods of targeted immunotherapy, as well as adapt existing treatment options to the specific needs of different patients and patient subgroups. In this review, we will cover B cells functional diversity and their multifaceted roles in the tumor environment.

The integration of multi-‘omic datasets into complex systems-wide assessments has become a mainstay in immunologic investigation. This focus on high-dimensional data collection and analysis was on full display in the investigation of COVID-19, the respiratory illness resulting from infection by the novel coronavirus SARS-CoV-2. Particularly in the area of B cell biology, tremendous efforts in both cellular and serologic investigation have resulted in an increasingly detailed mapping of the coordinated effector, memory, and antibody secreting cell responses that underpin the development of humoral immunity in response to primary viral infection. Further, the rapid development and deployment of effective vaccines has allowed for the assessment of developing memory responses across a wide variety of immune contexts, including in patients with compromised immune function. The result has been a period of rapid gains in the understanding of B cell biology unrestricted to the study of COVID-19. Here, we outline the systems-level technologies that have been routinely implemented in these investigations throughout the pandemic, and discuss how their use has led to clear and applicable gains in pursuance of the amelioration of human infectious disease and beyond.