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Current Opinion in Immunology

Gilda Varricchi, Stefania Loffredo, Maria Rosaria Galdiero, Giancarlo Marone, Leonardo Cristinziano, Francescopaolo Granata, Gianni Marone
Angiogenesis and lymphangiogenesis are distinct and complex processes requiring a finely tuned balance between stimulatory and inhibitory signals. During adulthood, angiogenesis and lymphangiogenesis are activated at sites of tumor growth, tissue injury and remodeling, and chronic inflammation. Vascular endothelial growth factors (VEGFs), angiopoietin (ANGPTs) and a multitude of additional signaling molecules play distinct roles in the modulation of angiogenesis/lymphangiogenesis. VEGFs and ANGPTs activate specific tyrosine kinase receptor (e...
May 17, 2018: Current Opinion in Immunology
Raiees Andrabi, Jinal N Bhiman, Dennis R Burton
A critical property of a prophylactic HIV vaccine is likely to be its ability to elicit broadly neutralizing antibodies (bnAbs). BnAbs typically have multiple unusual features and are generated in a fraction of HIV-infected individuals through complex pathways. Current vaccine design approaches seek to trigger rare B cell precursors and then steer affinity maturation toward bnAbs in a multi-stage multi-component immunization approach. These vaccine design strategies have been facilitated by molecular descriptions of bnAb interactions with stabilized HIV trimers, the use of an array of sophisticated approaches for immunogen design, the development of novel animal models for immunogen evaluation and advanced technologies to interrogate antibody responses...
May 15, 2018: Current Opinion in Immunology
Masatake Tanaka, Yasuko Iwakiri
The liver is the largest lymph producing organ. A significant increase in the number of hepatic lymphatic vessels, or lymphangiogenesis, has been reported in various liver diseases, including, but not limited to, cirrhosis, viral hepatitis and hepatocellular carcinoma. Despite its apparent relevance in healthy and diseased livers as these and other observations indicate, the hepatic lymphatic system has been poorly studied. With knowledge of the lymphatic system in other organs and tissues incorporated, this review article addresses the current knowledge of the hepatic lymphatic system and the potential role of lymphatic endothelial cells in the health and the disease of the liver and concludes with a brief description on future directions of the study of the hepatic lymphatic system...
May 14, 2018: Current Opinion in Immunology
Hamish Eg McWilliam, Jose A Villadangos
The major histocompatibility complex class I-related molecule MR1 is the only antigen (Ag) presenting molecule that captures and displays vitamin B-derived metabolites that are unique to a wide array of microbes. Presentation of these metabolite Ag at the cell surface activates mucosal-associated invariant T (MAIT) cells, a highly abundant innate-like T cell population, and represents a recently-described mechanism used by the mammalian immune system to sense pathogenic or commensal microbes. Our understanding of the cell biology of how MR1 accomplishes this unique task is still evolving, but recent advances are allowing a general picture to emerge...
May 10, 2018: Current Opinion in Immunology
Fabiola Osorio, Bart N Lambrecht, Sophie Janssens
The unfolded protein response (UPR) is an adaptive response meant to restore endoplasmic reticulum homeostasis in conditions of ER stress that subvert the folding capacity of the cell. Over the past few years, it has become clear that the functions of the UPR stretch far beyond their canonical role and intersect with seemingly unrelated functions such as innate immunity and antigen presentation. The aim of the present review is to dissect how the UPR interferes directly and indirectly with the major processes of MHC-I and MHC-II antigen presentation...
May 10, 2018: Current Opinion in Immunology
Taia T Wang, Stylianos Bournazos, Jeffrey V Ravetch
A critical factor in the maturation of influenza vaccine responses is the nearly inevitable binding of vaccine antigens by exiting anti-influenza IgGs. These antigen-IgG immune complexes direct the response to immunization by modulating cellular processes that determine antibody and T-cell repertoires: maturation of dendritic cells, processing and presentation of antigens to T cells, trafficking of antigens to the germinal center, and selection of B cells for antibody production. By focusing on the recent advances in the study of the immunomodulatory processes mediated by IgG immune complexes upon influenza vaccination, we discuss a pathway that is critical for modulating the breadth and potency of anti-HA antibody responses and has previously led to the development of strategies to improve influenza vaccine efficacy...
May 10, 2018: Current Opinion in Immunology
Justin M Richner, Michael S Diamond
Zika virus (ZIKV) is the most recent mosquito-transmitted virus to cause a global health crisis following its entrance into a naïve population in the Western Hemisphere. Once the ZIKV outbreak began investigators rapidly established small and large animal models of pathogenesis, developed a number candidate vaccines using different platforms, and defined mechanisms of protection. In this review, we characterize the adaptive immune response elicited by ZIKV infections and vaccines, the status of ongoing clinical trials in humans, and discuss future challenges within the field...
May 9, 2018: Current Opinion in Immunology
Hedda Wardemann, Rajagopal Murugan
Malaria is a life-threatening vector-borne disease caused by Plasmodium parasites that infect millions of people in endemic areas every year. The most advanced malaria vaccine candidate RTS,S targets the immune response against circumsporozoite protein of Plasmodium falciparum (PfCSP), the most deadly Plasmodium species in humans. PfCSP plays a fundamental role in parasite development as well as the establishment of the infection and is a molecular target of protective antibodies. However, RTS,S shows overall low efficacy and insufficient long-term protection...
May 8, 2018: Current Opinion in Immunology
Rino Rappuoli, Emmanuel Hanon
Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing...
May 8, 2018: Current Opinion in Immunology
Rachel N Cotton, Adam Shahine, Jamie Rossjohn, D Branch Moody
Peptide and lipid antigens are presented to T cells when bound to MHC or CD1 proteins, respectively. The general paradigm of T cell antigen recognition is that T cell receptors (TCRs) co-recognize an epitope comprised of the antigen and antigen presenting molecule. Here we review the latest studies in which T cells operate outside the co-recognition paradigm: TCRs can broadly contact CD1 itself, but not the carried lipid. The essential structural feature in these new mechanisms is a large 'antigen free' zone on the outer surface of certain antigen presenting molecules...
May 4, 2018: Current Opinion in Immunology
Giulietta Saletti, Thomas Gerlach, Guus F Rimmelzwaan
Currently used inactivated influenza vaccines aim at the induction of virus-neutralizing antibodies directed to the variable head domain of the viral hemagglutinin. Although these vaccines are effective against antigenically matching virus strains, they offer little protection against antigenically distinct drift variants or potentially pandemic viruses of alternative subtypes. In the last decades, the threat of novel influenza pandemics has sparked research efforts to develop vaccines that induce more broadly protective immunity...
May 4, 2018: Current Opinion in Immunology
Randy R Brutkiewicz, Laura Yunes-Medina, Jianyun Liu
Many reviews on the CD1d/NKT cell axis focus on the ability of CD1d-restricted NKT cells to serve as effector cells in a variety of disorders, be they infectious diseases, cancer or autoimmunity. In contrast, here, we discuss the ways that viruses, bacteria and tumor cells can evade the CD1d/NKT cell axis. As a result, these disease states have a better chance to establish a foothold and potentially cause problems for the subsequent adaptive immune response, as the host tries to rid itself of infections or tumors...
May 3, 2018: Current Opinion in Immunology
Sarah F Andrews, Adrian B McDermott
One hundred years ago, the 1918 H1N1 Pandemic killed 20 million people worldwide. Despite the introduction of a worldwide surveillance system, large-scale production of influenza vaccines coupled with annual vaccination schemes, influenza remains a major public health concern. Prevention of influenza on a population basis requires intimate knowledge of the interplay between the virus' ability to escape the immune response and persistent recall and regeneration of the antibody response. Here we will briefly outline the nature of the antibody response, focusing on the response to intransigent regions of the hemagglutinin (HA) and speculate on the how this data may be used to inform and ultimately develop a universal influenza vaccine...
May 3, 2018: Current Opinion in Immunology
Cassian Yee
Adoptive Cell Therapy (ACT) has enjoyed a revival in recent years with the approval of CAR T cells for the treatment of patients with B cell malignancies. Advancing the use of adoptively transferred T cells for the treatment of patients with solid tumor and other hematologic malignancies however, will require addressing numerous effector cell intrinsic as well as tumor micro environmental hurdles and exploiting a broader ACT platform that includes not only engineered CAR-T cells, but also other forms of ACT including Endogenous T Cell (ETC) and Tumor-infiltrating Lymphocyte (TIL) therapy...
May 2, 2018: Current Opinion in Immunology
Juliane Liepe, Huib Ovaa, Michele Mishto
The sequence of a large number of MHC-presented epitopes is not present as such in the original antigen because it has been re-shuffled by the proteasome or other proteases. Why do proteases throw a spanner in the works of our model of antigen tagging and immune recognition? We describe in this review what we know about the immunological relevance of post-translationally spliced epitopes and why proteases seem to have a second (dark) personality, which is keen to create new peptide bonds.
April 30, 2018: Current Opinion in Immunology
Fan Zhou, Mai-Chi Trieu, Richard Davies, Rebecca Jane Cox
Influenza virus causes contagious respiratory illness and remains a major burden on healthcare systems and the economy. Seasonal influenza vaccine is the most cost-effective way to combat the disease. However, underestimation of disease severity and controversy over vaccine safety and effectiveness hampers public confidence in vaccination. Action is needed to restore public confidence and improve vaccine uptake. Tailoring seasonal influenza vaccines according to immune responsiveness and infection/vaccination history of different populations can improve vaccine efficacy and effectiveness...
April 29, 2018: Current Opinion in Immunology
Christian W Keller, Monica Loi, Laure-Anne Ligeon, Monique Gannagé, Jan D Lünemann, Christian Münz
The macroautophagy machinery supports membrane remodeling and fusion events that lead to the engulfment of cytoplasmic constituents in autophagosomes and their degradation in lysosomes. The capacity of this machinery to regulate membrane adaptors and influence vesicle fusion with lysosomes seems to be used not only for autophagosomes, but also for endosomes. We summarize recent evidence that two aspects of endocytosis are regulated by parts of the macroautophagy machinery. These are recruitment of adaptors for the internalization of surface receptors and the fusion of phagosomes with lysosomes...
April 29, 2018: Current Opinion in Immunology
Pablo J Sáez, Juan C Sáez, Ana-María Lennon-Duménil, Pablo Vargas
Calcium ion (Ca2+ ) is an essential second messenger involved in multiple cellular and subcellular processes. Ca2+ can be released and sensed globally or locally within cells, providing complex signals of variable amplitudes and time-scales. The key function of Ca2+ in the regulation of acto-myosin contractility has provided a simple explanation for its role in the regulation of immune cell migration. However, many questions remain, including the identity of the Ca2+ stores, channels and upstream signals involved in this process...
April 28, 2018: Current Opinion in Immunology
Lucette Pelletier, Magali Savignac
Allergic asthma is a complex disease, often characterized by an inappropriate Th2 response to normally harmless allergens. Epithelial cells damaged or activated by the allergen produce IL-33, TSLP and IL-25, activating ILC2 and dendritic cells. The latter migrate into lymph nodes where they induce Th2-cell commitment. Th2 and other type 2 innate inflammatory cells trigger inflammation and airway hyper-reactivity. The toolbox consisting of the ion channels varies from one cellular type to another and depends on its activation state, offering the possibility to design novel drugs in the field of allergy...
April 25, 2018: Current Opinion in Immunology
Jan Kazenwadel, Natasha L Harvey
How are lymphatic vessels built? What are the sources of progenitor cells employed to construct lymphatic vessels during embryogenesis and in pathological situations? Are lymphatic vessels in different tissues built the same way? These questions have been highly topical and actively debated in the field of lymphangiogenesis research for more than 100 years. While embryonic veins and cells of mesenchymal origin have been recognised as sources of embryonic lymphatic endothelial cells for many years, recent advances in technology have revealed the existence of additional sources of lymphatic endothelial cells important for embryonic lymphangiogenesis...
April 25, 2018: Current Opinion in Immunology
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