CD8 T cells play a critical role in antitumor immunity. However, over time, they often become dysfunctional or exhausted and ultimately fail to control tumor growth. To effectively harness CD8 T cells for cancer immunotherapy, a detailed understanding …
The mammalian gut is a vast, diverse, and dynamic single-layer epithelial surface exposed to trillions of microbes, microbial products, and the diet. Underlying this epithelium lies the largest collection of immune cells in the body; these cells encoun…
by Hirotsugu Oda, Alessandro Annibaldi, Daniel L. Kastner and Ivona Aksentijevich
Metazoans have evolved innate antimicrobial defenses that promote cellular survival and proliferation. Countering the inevitable molecular mechanisms by which microbes sabotage these pathways, multicellular organisms rely on an alternative, perhaps mor…
by Musa M. Mhlanga, Stephanie Fanucchi, Mumin Ozturk and Maziar Divangahi
There has been an increasing effort to understand the memory responses of a complex interplay among innate, adaptive, and structural cells in peripheral organs and bone marrow. Trained immunity is coined as the de facto memory of innate immune cells an…
T lymphocytes are essential for immune responses to pathogens and tumors. Their ability to rapidly clonally expand and differentiate to effector cells following infection, and then to curb effector function following infection clearance, is fundamental…
I felt honored by the invitation to write this autobiography, although it was an arduous task to describe my journey through science: first bacterial adhesion, then cytokine function, and then immune responses in tuberculosis. Since only seven women ha…
Effective bidirectional communication between the innate and adaptive immune systems is crucial for tissue homeostasis and protective immunity against infections. The innate immune system is responsible for the early sensing of and initial response to …
For decades, scientists have relied on traditional animal models to study viral infection and the immune response. However, these models have limitations, and the search for more accurate and reliable ways to study the human-pathogen interphase has led…
by Keitaro Fukuda, Yoshihiro Ito and Masayuki Amagai
Immune responses are influenced by not only immune cells but also the tissue microenvironment where these cells reside. Recent advancements in understanding the underlying molecular mechanisms and structures of the epidermal tight junctions (TJs) and s…
by Annual Review of Immunology: Most Recent Articles
The cGAS-cGAMP-STING pathway is essential for immune defense against pathogens. Upon binding DNA, cGAS synthesizes cGAMP, which activates STING, leading to potent innate immune effector responses. However, lacking specific features to distinguish betwe…
by Annual Review of Immunology: Most Recent Articles
Catch bonds are molecular bonds that last longer under force than slip bonds, which become shorter-lived under force. Although catch bonds were initially discovered in studies of leukocyte and bacterial adhesions two decades ago, they have since been f…
by Annual Review of Immunology: Most Recent Articles
The central nervous system (CNS) has a unique set of macrophages that seed the tissue early during embryonic development. Microglia reside in the parenchyma, and border-associated macrophages are present in border regions, including the meninges, periv…
by Annual Review of Immunology: Most Recent Articles
As the site of gas exchange, the lung is critical for organismal survival. It is also subject to continual environmental insults inflicted by pathogens, particles, and toxins. Sometimes, these insults result in structural damage and the initiation of a…
by Annual Review of Immunology: Most Recent Articles
Pneumonia is an acute respiratory infection of the lower respiratory tract. The effectiveness of the host immune response determines the severity of infection, or whether pneumonia occurs at all. The lungs house both innate and adaptive immune systems,…
by Annual Review of Immunology: Most Recent Articles
Humanized mice, which carry a human hematopoietic and immune system, have greatly advanced our understanding of human immune responses and immunological diseases. These mice are created via the transplantation of human hematopoietic stem and progenitor…
by Annual Review of Immunology: Most Recent Articles
The adaptation of macrophages—the most common tissue-resident immune cells—to metabolic and microbial cues with high local variability is essential for the maintenance of organ integrity. In homeostasis, macrophages show largely predictable…
by Annual Review of Immunology: Most Recent Articles
Communication between the nervous and immune systems is evolutionarily conserved. From primitive eukaryotes to higher mammals, neuroimmune communication utilizes multiple complex and complementary mechanisms to trigger effective but balanced responses …
by Annual Review of Immunology: Most Recent Articles
Throughout biology, the pursuit of genotype-phenotype relationships has provided foundational knowledge upon which new concepts and hypotheses are built. Genetic perturbation, whether occurring naturally or in experimental settings, is the mainstay of …
by Annual Review of Immunology: Most Recent Articles
Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that recognize microbial metabolites. They are abundant in humans and conserved during mammalian evolution, which suggests that they have important nonredundant functions….
by Annual Review of Immunology: Most Recent Articles
Initially discovered for its role mediating the deleterious effects of environmental contaminants, the aryl hydrocarbon receptor (AHR) is now known to be a crucial regulator of the immune system. The expanding list of AHR ligands includes synthetic and…
by Annual Review of Immunology: Most Recent Articles
The mucosal surfaces of the body are the most vulnerable points for infection because they are lined by single or multiple layers of very active epithelial cells. The main protector of these cells is the mucus system generated by the specialized goblet…
by Annual Review of Immunology: Most Recent Articles
Prosurvival tumor necrosis factor receptor (TNFR) superfamily (TNFRSF) members on T cells, including 4-1BB, CD27, GITR, and OX40, support T cell accumulation during clonal expansion, contributing to T cell memory. During viral infection, tumor necrosis…
by Annual Review of Immunology: Most Recent Articles
The persistence of SARS-CoV-2 infections at a global level reflects the repeated emergence of variant strains encoding unique constellations of mutations. These variants have been generated principally because of a dynamic host immune landscape, the co…
by Annual Review of Immunology: Most Recent Articles
Infections have imposed strong selection pressures throughout human evolution, making the study of natural selection’s effects on immunity genes highly complementary to disease-focused research. This review discusses how ancient DNA studies, which have…
by Annual Review of Immunology: Most Recent Articles
Human Immune System (HIS) mice constructed with mature human immune cells or with human hematopoietic stem cells and thymic tissue have provided an important tool for human immunological research. In this article, we first review the different types of…
The kidneys are life-sustaining organs that are vital to removing waste from our bodies. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowl…
The liver’s unique characteristics have a profound impact on the priming and maintenance of adaptive immunity. This review delves into the cellular circuits that regulate adaptive immune responses in the liver, with a specific focus on hepatitis B viru…
T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to li…
IgE-mediated food allergy (IgE-FA) occurs due to a breakdown in immune tolerance that leads to a detrimental type 2 helper T cell (TH2) adaptive immune response. While the processes governing this loss of tolerance are incompletely understood, several …
by Susan N. Christo, Simone L. Park, Scott N. Mueller and Laura K. Mackay
Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident memory T (TRM) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against…
The immune system and the kidneys are closely related. Immune components mediate acute kidney disease and are crucial to the progression of chronic kidney disease. Beyond its pathogenic functions, the immune system supports immunological homeostasis in…
by Nicholas M. Adams, Annesa Das, Tae Jin Yun and Boris Reizis
Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and the ensuing production of type I in…
by Isaac F. López-Moyado, Myunggon Ko, Patrick G. Hogan and Anjana Rao
Ten-eleven translocation (TET) proteins are iron-dependent and α-ketoglutarate-dependent dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcyto…
by R.K. Subbarao Malireddi, Bhesh Raj Sharma and Thirumala-Devi Kanneganti
The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against …
by Zoë Steier, Esther Jeong Yoon Kim, Dominik A. Aylard and Ellen A. Robey
The choice of developing thymocytes to become CD8+ cytotoxic or CD4+ helper T cells has been intensely studied, but many of the underlying mechanisms remain to be elucidated. Recent multiomics approaches have provided much higher resolution analysis of…
Elite controllers are a heterogeneous group of people living with HIV who control viral replication without antiretroviral therapy. There is substantial evidence that at least some elite controllers are infected with replication-competent virus, thus t…
Immune checkpoint blockade (ICB) induces a remarkable and durable response in a subset of cancer patients. However, most patients exhibit either primary or acquired resistance to ICB. This resistance arises from a complex interplay of diverse dynamic m…
Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role of this cross talk for gut homeostasis and modulation of inflammatory and infectious intestinal diseases. In thi…
Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth respons…
Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit sig…
by Arnaud Mary, Renzo Mancuso and Michael T. Heneka
Alzheimer disease (AD) is the most common neurodegenerative disease, and with no efficient curative treatment available, its medical, social, and economic burdens are expected to dramatically increase. AD is historically characterized by amyloid β…
by Tadashi Takeuchi, Yumiko Nakanishi and Hiroshi Ohno
The intestine is the largest peripheral lymphoid organ in animals, including humans, and interacts with a vast array of microorganisms called the gut microbiota. Comprehending the symbiotic relationship between the gut microbiota and our immune system …
by Ainsley Lockhart, Daniel Mucida and Angelina M. Bilate
The intestinal epithelium, which segregates the highly stimulatory lumen from the underlying tissue, harbors one of the largest lymphocyte populations in the body, intestinal intraepithelial lymphocytes (IELs). IELs must balance tolerance, resistance, …
by Corey N. Miller, Michael R. Waterfield, James M. Gardner and Mark S. Anderson
The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced sin…
by Ming O. Li, Jing Zhang, Zijian Xu, Xian Zhang, Peng Li and Andrew E. Cornish
Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-…
Autoimmune diseases with B cell–directed therapeutics approved by the US Food and Drug Administration are surprisingly diverse in clinical manifestations and pathophysiology. In this review, we focus on recent clinical and mechanistic insights in…
I have spent more than the last 40 years at the University of California, San Francisco (UCSF), studying T cell receptor (TCR) signaling. I was blessed with supportive mentors, an exceptionally talented group of trainees, and wonderful collaborators an…
T follicular helper (Tfh) cells specialize in helping B cells and are therefore critical contributors to the generation of humoral immunity. Tfh cells aid immunoglobulin class-switch recombination and support the germinal center response, thereby promo…
by Robert Pick, Chen Wang, Qun Zeng, Zeynep Melis Gül and Christoph Scheiermann
Circadian rhythms of approximately 24 h have emerged as important modulators of the immune system. These oscillations are important for mounting short-term, innate immune responses, but surprisingly also long-term, adaptive immune responses. Recent dat…
by Rossana Azzoni, Olaf Perdijk, Nicola L. Harris and Benjamin J. Marsland
Barrier tissues are highly innervated by sensory and autonomic nerves that are positioned in close proximity to both stromal and immune cell populations. Together with a growing awareness of the far-reaching consequences of neuroimmune interactions, re…