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Current Opinion in Immunology

Philipp Georg, Leif E Sander
Pattern recognition receptors (PRRs) control elemental functions of antigen presenting cells (APCs) and critically shape adaptive immune responses. Wielding a natural adjuvanticity, live attenuated vaccines elicit exceptionally efficient and durable immunity. Commonly used vaccine adjuvants target individual PRRs or bolster the immunogenicity of vaccines via indirect mechanisms of inflammation. Here, we review the impact of innate sensors on immune responses to live attenuated vaccines and commonly used vaccine adjuvants, with a focus on human vaccine responses...
April 9, 2019: Current Opinion in Immunology
Nicole L Sullivan, Christiane S Eberhardt, Andreas Wieland, Kalpit A Vora, Bali Pulendran, Rafi Ahmed
Zostavax is a live-attenuated varicella zoster virus (VZV) vaccine recommended for use in adults >50 years of age to prevent shingles. The main risk factor for the development of shingles is age, which correlates with decreasing cell-mediated immunity. These data suggest a predominant role of T cell immunity in controlling VZV latency. However, other components of the immune system may also contribute. In this review, we will discuss how the immune system responds to Zostavax, focusing on recent studies examining innate immunity, transcriptomics, metabolomics, cellular, and humoral immunity...
April 7, 2019: Current Opinion in Immunology
Kouji Kobiyama, Ryosuke Saigusa, Klaus Ley
Atherosclerosis is a chronic inflammatory disease that causes most heart attacks and strokes, making it the biggest killer in the world. Although cholesterol-lowering drugs have dramatically reduced these major adverse cardiovascular events, there remains a high residual risk called inflammatory risk. Atherosclerosis has an autoimmune component that can be manipulated by immunologic approaches including vaccination. Vaccination is attractive, because it is antigen-specific, does not impair host defense, and provides long-term protection...
March 28, 2019: Current Opinion in Immunology
Hideki Ueno
Elucidating the immune mechanism by which seasonal influenza vaccines induce a protective immune response is of great importance to gain insights into the design of next-generation vaccines conferring more effective and long-lasting immune protection. Recent studies have established that T follicular helper (Tfh) cells play a major role for the generation of antibody response following influenza vaccination. Yet, the evidence is gained largely through the analysis of blood samples, and our knowledge on the role of Tfh cells in influenza vaccination is still largely limited to the generation of antigen-specific plasmablasts...
March 25, 2019: Current Opinion in Immunology
Ahmed M Fahmy, Jonathan Boulais, Michel Desjardins, Diana Matheoud
Parkinson's disease (PD) is caused by the progressive loss of dopaminergic neurons and afflicts millions of people world-wide. The current treatments address only the late motor symptoms, with no cure or preventive therapeutic approaches. The contribution of dysfunctional immune mechanisms in PD has been clearly established, with an emphasis on neuroinflammation and microglial cell activation. Recent studies have widened the involvement of the immune system in this disease by clearly showing the engagement of adaptive immunity and antigen presentation processes, directly regulated by PD-related proteins, raising the question whether PD is an autoimmune disease...
March 21, 2019: Current Opinion in Immunology
Aleksey Chudnovskiy, Giulia Pasqual, Gabriel D Victora
Antigen presentation is the key first step in the establishment of an antigen-specific T cell response. Among professional antigen presenting cells (APCs), dendritic cells (DCs) are the major population responsible for the priming of both CD4+ and CD8+ naïve T cells. This priming requires physical interaction between the DC and the T cell; during which signals are exchanged that determine both the magnitude and the quality of the ensuing response. The nature of these signals varies widely depending on the nature of the antigen, the anatomical site in which they take place, and the phenotype of the antigen-presenting DC, making the study of the dynamics, microanatomical distribution and phenotypic variation of DCs a key part of our understanding of adaptive immunity...
March 15, 2019: Current Opinion in Immunology
Jinsheng Wen, Sujan Shresta
Zika and the four serotypes of dengue are closely related flaviviruses that share a high degree of structural and sequence homology and co-circulate in many regions of the world. Here, we review recent studies investigating antigenic cross-reactivity between the two viruses. We discuss the pathogenic and protective roles of cross-reactive anti-viral antibody and T cell responses, respectively, in modulating the outcome of secondary dengue or Zika infection. Based on recent findings and increased incidence of severe disease in seronegative recipients of the first dengue vaccine to be licensed, we propose that the time has come to focus on developing pan-flavivirus vaccines that protect against Zika and four dengue serotypes by eliciting protective cross-reactive T cell responses while concomitantly reducing production of cross-reactive antibodies that can exacerbate disease...
March 15, 2019: Current Opinion in Immunology
Thiago A Patente, Leonard R Pelgrom, Bart Everts
Dendritic cells (DCs) are professional antigen-presenting cells that play a crucial role in the priming and differentiation of CD4+ T cells into several distinct subsets including effector T helper (Th) 1, Th17 and Th2 cells, as well as regulatory T cells (Tregs). It is becoming increasingly clear that cellular metabolism shapes the functional properties of DCs. Specifically, the ability of DCs to drive polarization of different Th cell subsets may be orchestrated by the engagement of distinct metabolic pathways...
March 12, 2019: Current Opinion in Immunology
Mary M Tomayko, David Allman
In many ways, memory B cells represent the ultimate outcome of humoral immunity. Many of these cells express exceptionally high affinity antigen-specific B cell receptors for antigen, and these cells are a critical source of the long-lived plasma cells that secrete protective serum antibodies to protect against secondary exposure to pathogens and other life-threatening antigens. Evidence is now emerging that not all memory B cells are created via the same cellular pathways and molecular events. Similarly, it is becoming clear that different memory B cells can take on different functions, with some producing IgM rather than IgG antibodies upon reactivation, and others preferentially producing plasma cells rather than additional waves of memory B cells...
March 9, 2019: Current Opinion in Immunology
Sandra Cathrine Abel Nielsen, Scott Dexter Boyd
The human immune system changes dramatically with age, and early life exposures to pathogens and environmental antigens begin the formation of immune memory which influences subsequent responses later in life. To study infant immunity, sample-sparing experimental methods that extract maximal data from small samples of blood or other tissues are needed; fortunately, recent developments in high-throughput sequencing and multiplexed labeling and measurement of markers on cells are well-suited to these tasks. Here, we review some recent studies of infant immune responses to infectious disease, highlighting similarities and differences between infants and adults, and identifying important questions for future research...
February 27, 2019: Current Opinion in Immunology
Elisa Corsiero, Francesca Romana Delvecchio, Michele Bombardieri, Costantino Pitzalis
Tertiary lymphoid organs named also tertiary lymphoid structures (TLS) often occur at sites of autoimmune inflammation, organ transplantation and cancer. Although the mechanisms for their formation/function are not entirely understood, it is known that TLS can display features of active germinal centres supporting the proliferation and differentiation of (auto)-reactive B cells. In this Review, we discuss current knowledge on TLS-associated B cells with particular reference on how within diseased tissues these structures are linked to either deleterious or protective outcomes in patients and the potential for therapeutic targeting of TLS through novel drugs...
February 21, 2019: Current Opinion in Immunology
Arpita Myles, Ignacio Sanz, Michael P Cancro
T-bet+ B cells have emerged as a key component of the humoral immune response in both infections and autoimmune disorders, with many of their phenotypic and functional attributes conserved between mice and humans. They are protective (infections) and pathogenic (autoimmunity), although the associated commonalities and differences remain unclear. Heterogeneity within this pool, in terms of origin, fate and function may underlie these divergent roles. Their significance is context-dependent- they may constitute a persistent effector memory cell pool, or products of recent primary responses...
February 19, 2019: Current Opinion in Immunology
Christoph Thomas, Robert Tampé
Major histocompatibility complex class I (MHC I) molecules present peptides on the surface of most nucleated cells and allow the immune system to detect and eliminate infected or malignantly transformed cells. The peptides are derived from endogenous proteins by proteasomal degradation or aberrant translation, and are translocated from the cytosol into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP), a central component of the peptide-loading complex (PLC). The peptides are subsequently processed by ER-resident aminopeptidases (ERAP1/2) and loaded onto MHC I...
February 14, 2019: Current Opinion in Immunology
Priscillia Perrin, Marlieke Lm Jongsma, Jacques Neefjes, Ilana Berlin
Antigen-presenting cells (APCs) capture and present pathogens to T cells, thus arousing adaptive immune responses geared at the elimination of these invaders. In APCs, pathogens acquired from the extracellular space intersect with MHC class II (MHC-II) molecules in the endolysosomal system, where processing and loading of antigenic peptides occur. The resulting complexes can then be directed to the cell surface for recognition by T cells. To achieve this, the endosomal pathway of APCs must undergo dramatic rearrangements upon pathogen encounter...
February 6, 2019: Current Opinion in Immunology
Teng Zuo, Avneesh Gautam, Duane R Wesemann
B cell immunoglobulin (Ig) repertoire composition shapes immune responses. The generation of Ig diversity begins with Ig variable region exon assembly from gene segments, random inter-segment junction sequence diversity, and combinations of Ig heavy and light chain. This generates vast preemptive sequence freedom in early developing B lineage cell Ig genes that can anticipate a great diversity of threats. This freedom is met with large restrictions that ultimately define the naïve (i.e. preimmune) Ig repertoire...
January 25, 2019: Current Opinion in Immunology
Fauna L Smith, Nicole Baumgarth
B-1 cells represent an innate-like early-developing B cell population, whose existence as an independent lymphocyte subset has been questioned in the past. Recent molecular and lineage tracing studies have not only confirmed their unique origins and differentiation paths, they have also provided a rationale for their distinctive functionalities compared to conventional B cells. This review summarizes our current understanding of B-1 cell development, and the activation events that regulate B-1 cell responses to self and foreign antigens...
January 24, 2019: Current Opinion in Immunology
Feidi Chen, Thaddeus S Stappenbeck
Numerous scientific disciplines, including immunology, are now positioned to fully realize the potential of the intestinal microbiome to modulate a wide array of basic processes. Increasingly, microbiota-derived metabolites are being recognized for mediating these effects. Coupled with advances in large scale sequencing and mass spectrometry, research into the microbiota and their metabolites has entered into an era of rapid discovery. Here, we review recent studies that have shown how-specific metabolic products of the microbiome alter properties of the innate immune system that in turn modulate response to infection and immunity...
January 21, 2019: Current Opinion in Immunology
Nicolas Manel, James P Di Santo
No abstract text is available yet for this article.
February 2019: Current Opinion in Immunology
Steven D Scoville, Aharon G Freud, Michael A Caligiuri
Innate lymphoid cells (ILCs) are critical to effective immune surveillance against pathogens, have malignant counterparts, and contribute to disease. Thus, it is important to understand ILC development. All ILCs are derived from the common lymphoid progenitor cell; however, the exact mechanisms and signals that initiate their divergence from T cells, B cells and one and other are incompletely understood. Evidence now supports a stepwise developmental process that includes distinct cellular intermediates, progressively narrowed differentiation, and some plasticity...
December 19, 2018: Current Opinion in Immunology
Christoph Sn Klose, David Artis
The cardinal signs of inflammation suggest a close connection between the nervous system and the immune system. However, the cellular and molecular basis of these interactions remains incompletely defined. Recent research has demonstrated that tissue-resident innate lymphoid cells (ILCs) obtain neuronal signals, particularly at mucosal barriers, where ILCs regulate tissue homeostasis. New developments in our understanding of neuronal regulation of ILCs provide insight into how immune responses in tissues are precisely targeted, spatially regulated, and how ILCs sense environmental changes and disturbance of tissue homeostasis...
December 7, 2018: Current Opinion in Immunology
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