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Seminars in Immunology

Harikesh S Wong, Ronald N Germain
The adaptive immune system continually faces unpredictable circumstances yet reproducibly counteracts invading pathogens while limiting damage to self. However, the system is dynamic in nature: many of its internal components are not fixed, but rather, fluctuate over time. This concept is exemplified by αβ T lymphocytes, which vary significantly from cell-to-cell in their spatiotemporal dynamics, antigen-binding receptors, and subcellular protein concentrations. How are reproducible immune functions achieved in the face of such variability? This design principle is known as robustness and requires the system to employ layered control schemes that both buffer and exploit different facets of cellular variation...
December 29, 2017: Seminars in Immunology
Peter J Murray
Monocytes emerging from the bone marrow are the progenitors of monocyte-derived macrophages. An essential function of monocytes is to seed tissues with sufficient macrophages to replace loss from infection and tissue damage. Recent work from diverse inflammatory and homeostatic settings has shown monocytes also possess direct protective and pathogenic activities. Thus, monocytes are not simply needed to generate macrophages, but instead contribute to the overall orchestration of immunity. Some recently described properties of monocytes are both surprising and mechanistically specific; for example, inflammatory monocytes are required for the efficacy of transferred activated cytotoxic T cells, but can have potent tissue damaging effects while patrolling monocytes are required for anti-tumor immunity in some cases, but in another example provokes resistance to chemotherapy and thereby aid tumor growth...
December 28, 2017: Seminars in Immunology
Theresa L Whiteside
Mesenchymal stem cells (MSCs) are a major component of the tumor microenvironment (TME) and play a key role in promoting tumor progression. The tumor uses exosomes to co-opt MSCs and re-program their functional profile from normally trophic to pro-tumorigenic. These tumor-derived small vesicles called "TEX" carry and deliver a cargo rich in proteins and nucleic acids to MSCs. Upon interactions with surface receptors on MSCs and uptake of the exosome cargo by MSCs, molecular, transcriptional and translational changes occur that convert MSCs into producers of factors that are necessary for tumor growth and that also alter functions of non-tumor cells in the TME...
December 27, 2017: Seminars in Immunology
Alberto Mantovani
Apparent redundancy is a recurrent theme in innate immunity in various domains including inflammatory cytokines, chemokines and pattern recognition receptors. While sharing core function, different mediators may subserve distinct functions related for instance to production and release (e.g. IL-1α versus IL-1β), predominantly local versus systemic function (e.g. PTX3 versus C-reactive protein) or fine tuning of innate and adaptive responses (chemokines). Based on hard-wired phagocyte recruitment and regulation by a wide spectrum of chemokines and conventional or atypical receptors, I argue that trafficking of phagocytic cells is a robust output of the chemokine system, resistant to genetic or environmental variation...
December 19, 2017: Seminars in Immunology
Gérard Eberl
In order to survive and reproduce, living organisms must be robust, tolerate injuries and undergo repair. Robustness in living organisms compares to robustness in human inventions, such as buildings and machines, which have to withstand occasional damage to avoid critical dysfunctions. However, the nature of robustness is fundamentally different in biology and in engineering. In living organisms, robustness is provided by homeostatic mechanisms, whereas in buildings and machines, it is provided by the redundancy of key elements...
December 16, 2017: Seminars in Immunology
Jie Zhou, Yulia Nefedova, Aihua Lei, Dmitry Gabrilovich
Neutrophils and polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) share origin and many morphological and phenotypic features. However, they have different biological role. Neutrophils are one of the major mechanisms of protection against invading pathogens, whereas PMN-MDSC have immune suppressive activity and restrict immune responses in cancer, chronic infectious disease, trauma, sepsis, and many other pathological conditions. Although in healthy adult individuals, PMN-MDSC are not or barely detectable, in patients with cancer and many other diseases they accumulate at various degree and co-exist with neutrophils...
December 15, 2017: Seminars in Immunology
Jean-Laurent Casanova, Laurent Abel
For almost any given human-tropic virus, bacterium, fungus, or parasite, the clinical outcome of primary infection is enormously variable, ranging from asymptomatic to lethal infection. This variability has long been thought to be largely determined by the germline genetics of the human host, and this is increasingly being demonstrated to be the case. The number and diversity of known inborn errors of immunity is continually increasing, and we focus here on autosomal and X-linked recessive traits underlying complete deficiencies of the encoded protein...
December 15, 2017: Seminars in Immunology
Cheng Qian, Xuetao Cao
As potent antigen-presenting cells, dendritic cells (DCs) comprise the most heterogeneous cell population with significant cellular phenotypic and functional plasticity. They form a sentinel network to modulate immune responses, since intrinsic cellular mechanisms and complex external, environmental signals endow DCs with the distinct capacity to induce protective immunity or tolerance to self. Interactions between DCs and other cells of the immune system mediate this response. This interactive response depends on DC maturation status and subtype, as well as the microenvironment of the tissue location and DC-intrinsic regulators...
December 11, 2017: Seminars in Immunology
Alain Fischer, Antonio Rausell
Advances in genomics and medicine have enabled the identification of (currently) 346 primary immunodeficiencies (PIDs) caused by mutations in 336 different genes. Most of these PIDs are monogenic conditions with Mendelian inheritance. Given this large number, it is possible to analyze the distribution of PIDs associated with infections and/or immunopathology according to the nature of the defect - even though this exercise can be challenging and arguable because of the pleiotropic nature of some gene products...
December 8, 2017: Seminars in Immunology
Matthew B Buechler, Shannon J Turley
Fibroblasts in secondary lymphoid organs, or fibroblastic reticular cells (FRC), are gate-keepers of immune responses. Here, we frame how these cells regulate immune responses via a three-part scheme in which FRC can setup, support or suppress immune responses. We also review how fibroblasts from non-lymphoid tissues influence immunity and highlight how they resemble and differ from FRC. Overall, we aim to focus attention on the emerging roles of lymphoid tissue and non-lymphoid tissue fibroblasts in control of innate and adaptive immunity...
November 30, 2017: Seminars in Immunology
Francesca Granucci, Davide Prosperi
No abstract text is available yet for this article.
December 2017: Seminars in Immunology
Tamara G Dacoba, Ana Olivera, Dolores Torres, José Crecente-Campo, María José Alonso
Nowadays, nanotechnology-based modulation of the immune system is presented as a cutting-edge strategy, which may lead to significant improvements in the treatment of severe diseases. In particular, efforts have been focused on the development of nanotechnology-based vaccines, which could be used for immunization or generation of tolerance. In this review, we highlight how different immune responses can be elicited by tuning nanosystems properties. In addition, we discuss specific formulation approaches designed for the development of anti-infectious and anti-autoimmune vaccines, as well as those intended to prevent the formation of antibodies against biologicals...
December 2017: Seminars in Immunology
Francesco Barbero, Lorenzo Russo, Michele Vitali, Jordi Piella, Ignacio Salvo, Mireya L Borrajo, Marti Busquets-Fité, Rita Grandori, Neus G Bastús, Eudald Casals, Victor Puntes
The interaction of inorganic nanoparticles and many biological fluids often withstands the formation of a Protein Corona enveloping the nanoparticle. This Protein Corona provides the biological identity to the nanoparticle that the immune system will detect. The formation of this Protein Corona depends not only on the composition of the nanoparticle, its size, shape, surface state and exposure time, but also on the type of media, nanoparticle to protein ratio and the presence of ions and other molecular species that interfere in the interaction between proteins and nanoparticles...
October 21, 2017: Seminars in Immunology
Bodduluri Haribabu
No abstract text is available yet for this article.
October 4, 2017: Seminars in Immunology
Yuanchang Liu, Joseph Hardie, Xianzhi Zhang, Vincent M Rotello
Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system...
October 3, 2017: Seminars in Immunology
L Bhatt, K Roinestad, T Van, E B Springman
The LTB4 pathway is an attractive target for therapeutic drug development. Two broad classes of drugs have been pursued: antagonists of the primary LTB4 receptors (BLT1 and BLT2) and inhibitors of LTA4 Hydrolase (LTA4H), the rate limiting enzyme in the production of LTB4. An initial wave of effort culminated in the 1990s. Over the past 15 years, a second wave of more selective drug candidates, including at least 5 BLT antagonists and 6 LTA4H inhibitors, have reached Phase 2 clinical trials. Despite the extensive efforts to discover and develop LTB4 pathway targeting drugs, only one has reached the market to date...
October 2017: Seminars in Immunology
Yoshishige Miyabe, Chie Miyabe, Andrew D Luster
Inflammatory arthritis, including rheumatoid arthritis (RA), is characterized by infiltration of inflammatory cells into the joints. Biological agents targeting TNF-α and IL-6 dramatically improve RA. However, some RA patients do not respond to current treatments and these broadly active upstream biological agents increase the risk of severe infection. Therefore, there remains a need for other effective and safe treatments for RA. Many studies have implicated that blockade of leukotriene B4 (LTB4) and its high affinity receptor BLT1 dramatically suppress arthritis in animal models...
October 2017: Seminars in Immunology
Erwin W Gelfand
For several decades, the leukotriene pathways have been implicated as playing a central role in the pathophysiology of asthma. The presence and elevation of numerous metabolites in the blood, sputum, and bronchoalveolar lavage fluid from asthmatics or experimental animals adds support to this notion. However, targeting of the leukotriene pathways has had, in general, limited success. The single exception in asthma therapy has been targeting of the cysteinyl leukotriene receptor 1, which clinically has proven effective but only in certain clinical situations...
October 2017: Seminars in Immunology
Stephanie L Brandt, C Henrique Serezani
The ability to regulate inflammatory pathways and host defense mechanisms is critical for maintaining homeostasis and responding to infections and tissue injury. While unbalanced inflammation is detrimental to the host; inadequate inflammation might not provide effective signals required to eliminate pathogens. On the other hand, aberrant inflammation could result in organ damage and impair host defense. The lipid mediator leukotriene B4 (LTB4) is a potent neutrophil chemoattractant and recently, its role as a dominant molecule that amplifies many arms of phagocyte antimicrobial effector function has been unveiled...
October 2017: Seminars in Immunology
Kazuko Saeki, Takehiko Yokomizo
Leukotriene B4 (LTB4), a lipid mediator produced from arachidonic acid, is a chemoattractant for inflammatory leukocytes. We identified two receptors for LTB4, the high-affinity receptor BLT1 and the low-affinity receptor BLT2. BLT1 is expressed in various subsets of leukocytes, and analyses of BLT1-deficient mice revealed that the LTB4/BLT1 axis enhances leukocyte recruitment to infected sites, and is involved in the elimination of pathogens. Hyperactivation of the LTB4/BLT1 axis induces acute and chronic inflammation, resulting in various inflammatory diseases...
October 2017: Seminars in Immunology
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