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  1. Article ; Online: Imaging the immune system redux.

    Germain, Ronald N

    Immunological reviews

    2022  Volume 306, Issue 1, Page(s) 5–7

    MeSH term(s) Diagnostic Imaging ; Humans ; Immune System
    Language English
    Publishing date 2022-01-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13063
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  2. Article ; Online: Multiplex imaging in immuno-oncology.

    Zhao, Chen / Germain, Ronald N

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 10

    Abstract: Multiplex imaging has emerged as an invaluable tool for immune-oncologists and translational researchers, enabling them to examine intricate interactions among immune cells, stroma, matrix, and malignant cells within the tumor microenvironment (TME). It ... ...

    Abstract Multiplex imaging has emerged as an invaluable tool for immune-oncologists and translational researchers, enabling them to examine intricate interactions among immune cells, stroma, matrix, and malignant cells within the tumor microenvironment (TME). It holds significant promise in the quest to discover improved biomarkers for treatment stratification and identify novel therapeutic targets. Nonetheless, several challenges exist in the realms of study design, experiment optimization, and data analysis. In this review, our aim is to present an overview of the utilization of multiplex imaging in immuno-oncology studies and inform novice researchers about the fundamental principles at each stage of the imaging and analysis process.
    MeSH term(s) Humans ; Neoplasms ; Medical Oncology ; Biomarkers ; Immunotherapy/methods ; Tumor Microenvironment
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-10-29
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-006923
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  3. Article ; Online: Spatiotemporal and cell-state control of antigen presentation during tolerance and immunity.

    Hor, Jyh Liang / Germain, Ronald N

    Current opinion in immunology

    2023  Volume 84, Page(s) 102357

    Abstract: Effective adaptive immunity is rendered possible by highly organized tissue architecture and coordinated cellular crosstalk. While detailed spatiotemporal analyses of antigen presentation and adaptive immune activation in secondary lymphoid tissues have ... ...

    Abstract Effective adaptive immunity is rendered possible by highly organized tissue architecture and coordinated cellular crosstalk. While detailed spatiotemporal analyses of antigen presentation and adaptive immune activation in secondary lymphoid tissues have been a major focus of study, it is clear that antigen presentation in other tissues also plays a critical role in shaping the immune response. In this article, we concentrate on two opposing aspects of adaptive immunity: tolerance and antitumor immunity, to illustrate how a complex set of antigen presentation mechanisms contributes to maintaining a delicate balance between robust immunity and avoidance of autoimmune pathology. We emphasize the importance of how immune cell identity, state, and location collectively determine the nature of adaptive immune responses.
    MeSH term(s) Humans ; Antigen Presentation ; Adaptive Immunity ; Immune Tolerance
    Language English
    Publishing date 2023-06-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2023.102357
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  4. Article ; Online: The Cellular Determinants of Adaptive Immunity.

    Germain, Ronald N

    The New England journal of medicine

    2019  Volume 381, Issue 11, Page(s) 1083–1085

    MeSH term(s) Adaptive Immunity/physiology ; Allergy and Immunology/history ; Animals ; Awards and Prizes ; Graft Rejection/immunology ; History, 20th Century ; Humans ; Lymphocytes/immunology ; Models, Animal
    Language English
    Publishing date 2019-09-10
    Publishing country United States
    Document type Biography ; Historical Article ; Journal Article
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMcibr1909387
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  5. Article ; Online: Dynamic Multiplex Tissue Imaging in Inflammation Research.

    Uderhardt, Stefan / Neag, Georgiana / Germain, Ronald N

    Annual review of pathology

    2023  Volume 19, Page(s) 43–67

    Abstract: Inflammation is a highly dynamic process with immune cells that continuously interact with each other and parenchymal components as they migrate through tissue. The dynamic cellular responses and interaction patterns are a function of the complex tissue ... ...

    Abstract Inflammation is a highly dynamic process with immune cells that continuously interact with each other and parenchymal components as they migrate through tissue. The dynamic cellular responses and interaction patterns are a function of the complex tissue environment that cannot be fully reconstructed ex vivo, making it necessary to assess cell dynamics and changing spatial patterning in vivo. These dynamics often play out deep within tissues, requiring the optical focus to be placed far below the surface of an opaque organ. With the emergence of commercially available two-photon excitation lasers that can be combined with existing imaging systems, new avenues for imaging deep tissues over long periods of time have become available. We discuss a selected subset of studies illustrating how two-photon microscopy (2PM) has helped to relate the dynamics of immune cells to their in situ function and to understand the molecular patterns that govern their behavior in vivo. We also review some key practical aspects of 2PM methods and point out issues that can confound the results, so that readers can better evaluate the reliability of conclusions drawn using this technology.
    MeSH term(s) Humans ; Reproducibility of Results ; Inflammation
    Language English
    Publishing date 2023-09-18
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2227429-7
    ISSN 1553-4014 ; 1553-4006
    ISSN (online) 1553-4014
    ISSN 1553-4006
    DOI 10.1146/annurev-pathmechdis-070323-124158
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  6. Article ; Online: Intravital and high-content multiplex imaging of the immune system.

    Hor, Jyh Liang / Germain, Ronald N

    Trends in cell biology

    2021  Volume 32, Issue 5, Page(s) 406–420

    Abstract: Highly motile and functionally diverse immune cells orchestrate effective immune responses through complex and dynamic cooperative behavior. Multiphoton intravital microscopy (MP-IVM) presents a unique and powerful tool to study the coordinated action of ...

    Abstract Highly motile and functionally diverse immune cells orchestrate effective immune responses through complex and dynamic cooperative behavior. Multiphoton intravital microscopy (MP-IVM) presents a unique and powerful tool to study the coordinated action of immune cell interactions in situ. Here, we review the current state of intravital microscopy in deepening our understanding of the immune system and discuss its fundamental limitations. In addition, we draw insights from recent technical advances in multiplex static tissue-imaging methods and propose an approach that could enable simultaneous visualization of cellular dynamics, deep phenotyping, and transcriptional states through a new type of correlative microscopy that combines these imaging technologies with advances in complex data analysis.
    MeSH term(s) Cell Communication ; Humans ; Immune System ; Intravital Microscopy/methods ; Microscopy, Fluorescence, Multiphoton/methods
    Language English
    Publishing date 2021-12-14
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 30122-x
    ISSN 1879-3088 ; 0962-8924
    ISSN (online) 1879-3088
    ISSN 0962-8924
    DOI 10.1016/j.tcb.2021.11.007
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  7. Article ; Online: Mesoscale T cell antigen discrimination emerges from intercellular feedback.

    Wong, Harikesh S / Germain, Ronald N

    Trends in immunology

    2021  Volume 42, Issue 10, Page(s) 865–875

    Abstract: Mature T cells must distinguish between foreign and self-antigens to promote host defense while limiting autoimmunity. How such discrimination occurs reproducibly has been explored extensively regarding mechanisms regulating initial T cell activation at ... ...

    Abstract Mature T cells must distinguish between foreign and self-antigens to promote host defense while limiting autoimmunity. How such discrimination occurs reproducibly has been explored extensively regarding mechanisms regulating initial T cell activation at short time and length scales. Here, we suggest that T cells encounter a higher-level discriminatory boundary post-activation, empowering or constraining their responses over greater spatiotemporal scales. This boundary emerges from coordinated communication among at least three cell types, forming a control system governed by intercellular circuits, including negative feedback from regulatory T cells (Tregs). We propose that the nonlinearities inherent to this system can amplify subtle baseline imbalances in a single cell type's functional state, altering the threshold for productive T cell responses and autoimmune disease risk.
    MeSH term(s) Autoantigens ; Autoimmunity ; Feedback ; Lymphocyte Activation ; T-Lymphocytes, Regulatory
    Chemical Substances Autoantigens
    Language English
    Publishing date 2021-09-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2021.08.006
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  8. Article ; Online: Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.

    Germain, Ronald N

    Cold Spring Harbor perspectives in biology

    2018  Volume 10, Issue 8

    Abstract: A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters ... ...

    Abstract A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system (
    MeSH term(s) Biomedical Research/methods ; Communicable Disease Control ; Computational Biology ; Humans ; Systems Biology/methods ; Vaccines
    Chemical Substances Vaccines
    Language English
    Publishing date 2018-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a033308
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  9. Article ; Online: Tracking the T cell repertoire.

    Germain, Ronald N

    Nature reviews. Immunology

    2015  Volume 15, Issue 12, Page(s) 730

    Language English
    Publishing date 2015-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/nri3922
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  10. Book: Mechanisms of antigen processing

    Germain, Ronald N.

    (Immunological reviews ; 151)

    1996  

    Title variant antigen-processing
    Author's details [R. N. Germain ...]
    Series title Immunological reviews ; 151
    Collection
    Keywords Antigen Presentation ; Histocompatibility Antigens Class II / metabolism ; Immunogen
    Language English
    Size 148 S. : Ill., graph. Darst.
    Publisher Munksgaard
    Publishing place Copenhagen
    Publishing country Denmark
    Document type Book
    HBZ-ID HT007265091
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    Se 160 -151- verfügbar in Königswinter Königswinter

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