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Current Opinion in Immunology

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https://www.readbyqxmd.com/read/28433952/what-chickens-might-tell-us-about-the-mhc-class-ii-system
#1
REVIEW
Aimée Parker, Jim Kaufman
Almost all knowledge about the structure and function of MHC class II molecules outside of mammals comes from work with chickens. Most of the genes implicated in the class II system are present in chickens, so it is likely that the machinery of antigen processing and peptide-loading is similar to mammals. However, there is only one isotype (lineage) of classical class II genes, with one monomorphic DR-like BLA gene and two polymorphic BLB genes, located near one DMA and two DMB genes. The DMB2 and BLB2 genes are widely expressed at high levels, whereas the DMB1 and BLB1 genes are only expressed at highest levels in spleen and intestine, suggesting the possibility of two class II systems in chickens...
April 20, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28412583/metabolic-reprograming-of-anti-tumor-immunity
#2
REVIEW
Madhusudhanan Sukumar, Rigel J Kishton, Nicholas P Restifo
Immunotherapies designed to trigger T cell destruction of tumor cells can result in sustained and complete responses in patients whose cancers were resistant to available treatment options. Evidence suggests that powering the T cell response - how T cells generate energy - plays an important role in their effectiveness. Furthermore the metabolism of T cells can be modulated to improve their anti-cancer activities. In this review, we will discuss the key metabolic properties of anti-cancer T cells, along with potential strategies to enhance immunotherapy through the modulation of T cell metabolism...
April 13, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28363157/memory-b-cells-total-recall
#3
REVIEW
Tri Giang Phan, Stuart G Tangye
Immunological memory is a cornerstone of adaptive immune responses in higher vertebrates. The remarkable ability to generate memory cells following Ag exposure, in the context of natural infection or immunization, provides long-lived protection against infectious diseases, often for the hosts' lifetime. Indeed, the generation of memory B cells and long-lived plasma cells underpins the success of most vaccines. The concept of immunological memory is not new-it was first proposed nearly 2500 years ago. While our understanding of the complexities of humoral and cell-mediated memory continues to evolve, important aspects of this process remain unresolved...
March 28, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359987/developmental-options-and-functional-plasticity-of-innate-lymphoid-cells
#4
REVIEW
Ai Ing Lim, Thomas Verrier, Christian Aj Vosshenrich, James P Di Santo
Innate lymphoid cells (ILCs) are lineage- and antigen receptor-negative lymphocytes including natural killer (NK) cells and at least three distinguishable cell subsets (ILC1, ILC2, ILC3) that rapidly produce cytokines (IFN-γ, IL-5, IL-13, IL-17A, IL-22) upon activation. As such, ILCs can act as first-line defenders in the context of infection, inflammation and cancer. Because of the strong conservation between the expression of key transcription factors that can drive signature cytokine outputs in ILCs and differentiated helper T cells, it has been proposed that ILCs represent innate counterparts of the latter...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359914/starving-for-survival-how-catabolic-metabolism-fuels-immune-function
#5
REVIEW
Maria L Balmer, Christoph Hess
Infections disturb homeostasis and often induce a switch to catabolic organismal metabolism. During catabolism, increased systemic availability of glucose, fatty acids and ketone bodies is observed, and recent evidence indicates that these metabolites might serve an immunomodulatory function. However, whereas our understanding of direct pathogen recognition by the host immune system is quite detailed, much less is known about the immunobiology of the metabolic host response to infection. In this review article we briefly discuss how pathogens induce 'dys-homeostasis' systemically, locally, and within cells, and provide examples of how such changes can shape immune-functionality during the course of an infection...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359913/obesity-altered-t-cell-metabolism-and-the-response-to-infection
#6
REVIEW
William D Green, Melinda A Beck
An epidemic of obesity over the past three decades increases the risk of chronic and infectious diseases for adults and children alike. Within the past few years, obesity has been shown to impair the adaptive immune response to infection through alterations in T cell functioning. Growing evidence suggests that perturbations in T cell metabolism drives this stunted immune response, stemming from nutrient, hormone and adipokine dysregulation in the obese. In this review, recent findings in the fields of obesity and T cell mediated immunity demonstrate a unique relationship between altered mechanisms of T cell metabolic homeostasis and plasticity of adaptive immune responses in the obese setting...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359033/regulation-of-memory-b-and-plasma-cell-differentiation
#7
REVIEW
Ryo Shinnakasu, Tomohiro Kurosaki
Memory B cell generation and antibody production result from a differentiation process that begins when the surface BCR on naïve B cells binds an antigen. How the choice between these fates is tempo-spatially regulated is still obscure, but recent advances have reinforced the concept that the combination of B cell-intrinsic heterogeneity and -extrinsic heterogeneity provided by cells such as T cells is a key determinant. As molecular regulators, the transcription factors IRF4 and Bach2, which participate in these fate choices, have been emerging...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28355576/role-of-germinal-centers-for-the-induction-of-broadly-reactive-memory-b-cells
#8
REVIEW
Yoshimasa Takahashi, Garnett Kelsoe
Virus-specific memory B cells (Bmem) play a crucial role in protecting against variant viruses. The ability to recognize these variant viruses, defined as antibody breadth, is achieved in Bmem populations by two very different pathways, germline-encoded cross-reactivity and affinity-driven, somatic evolution in germinal centers (GCs) for conserved viral epitopes. The latter class of broadly-reactive Bmem cells are not cross-reactive per se, but bind epitopes crucial for viral fitness. Although these conserved epitopes are often weakly immunogenic, the GC reaction is surprisingly permissive for the continued survival/proliferation of B cells that bind with low affinity or react to cryptic epitopes, increasing their chance of memory recruitment...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319732/an-antigen-to-remember-regulation-of-b-cell-memory-in-health-and-disease
#9
REVIEW
Aleta Pupovac, Kim L Good-Jacobson
Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM(+) MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#10
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319729/stromal-networking-cellular-connections-in-the-germinal-centre
#11
REVIEW
Alice E Denton, Michelle A Linterman
Secondary lymphoid organs are organized into distinct zones, governed by different types of mesenchymal stromal cells. These stromal cell subsets are critical for the generation of protective humoral immunity because they direct the migration of, and interaction between, multiple immune cell types to form the germinal centre. The germinal centre response generates long-lived antibody-secreting plasma cells and memory B cells which can provide long-term protection against re-infection. Stromal cell subsets mediate this response through control of immune cell trafficking, activation, localization and antigen access within the secondary lymphoid organ...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319733/plasma-cell-and-memory-b-cell-differentiation-from-the-germinal-center
#12
REVIEW
Dan Suan, Christopher Sundling, Robert Brink
Germinal centers (GCs) form in secondary lymphoid tissues in response to antigenic challenge and are the site of somatic hypermutation, generating GC B cells with increasing affinity for the inciting agent that are positively selected over time. However, it is not until GC B cells differentiate into memory B cells and plasma cells and egress from the GC back into the circulation that effective long-lived humoral immunity is conferred upon the host. Here we review what is known about the signals that initiate the transition from a GC B cell into the memory B cell and plasma cell compartments and the downstream transcriptional regulation of these processes...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319731/stimulating-cd27-to-quantitatively-and-qualitatively-shape-adaptive-immunity-to-cancer
#13
REVIEW
Timothy Nj Bullock
The capacity of the immune system to recognize and respond to tumors has been appreciated for over 100 years. However, clinical success has largely depended on the elucidation of the positive and negative regulators of effector cells after their activation via the antigen cell receptor. On the one hand, effector cells upregulate checkpoint molecules that are thought to play a role in limiting immunopathology. On the other, second and third waves of costimulation are often required to promote the expansion, survival and differentiation of effector cells...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28236750/targeting-nk-cell-checkpoints-for-cancer-immunotherapy
#14
REVIEW
Aura Muntasell, Maria C Ochoa, Luna Cordeiro, Pedro Berraondo, Ascension López-Díaz de Cerio, Mariona Cabo, Miguel López-Botet, Ignacio Melero
Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities...
February 22, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28222333/immunoprofiling-as-a-predictor-of-patient-s-response-to-cancer-therapy-promises-and-challenges
#15
REVIEW
Daniel Bethmann, Zipei Feng, Bernard A Fox
Immune cell infiltration is common to many tumors and has been recognized by pathologists for more than 100 years. The application of digital imaging and objective assessment software allowed a concise determination of the type and quantity of immune cells and their location relative to the tumor and, in the case of colon cancer, characterized overall survival better than AJCC TNM staging. Subsequently, expression of PD-L1, by 50% or more tumor cells, identified NSCLC patients with double the response rate to anti-PD-1...
February 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28208102/oncogenic-growth-factor-signaling-mediating-tumor-escape-from-cellular-immunity
#16
REVIEW
Fernando Concha-Benavente, Robert L Ferris
Unrestrained growth factor signals can promote carcinogenesis, as well as other hallmarks of cancer such as immune evasion. Our understanding of the function and complex regulation of HER family of receptors has led to the development of targeted therapeutic agents that suppress tumor growth. However, these receptors also mediate escape from recognition by the host immune system. We discuss how HER family of oncogenic receptors downregulate tumor antigen presentation and upregulate suppressive membrane-bound or soluble secreted inhibitory molecules that ultimately lead to impaired cellular immunity mediated by cytotoxic T lymphocyte (CTL) recognition...
February 13, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28192720/dendritic-cells-in-cancer-the-role-revisited
#17
REVIEW
Filippo Veglia, Dmitry I Gabrilovich
Dendritic cells (DCs) with their potent antigen presenting ability are long considered as critical factor in antitumor immunity. Despite high potential in promoting antitumor responses, tumor-associated DCs are largely defective in their functional activity and can contribute to immune suppression in cancer. In recent years existence of immune suppressive regulatory DCs in tumor microenvironment was described. Monocytic myeloid derived suppressor cells (M-MDSCs) can contribute to the pool of tumor associated DCs by differentiating to inflammatory DCs (inf-DCs), which appear to have specific phenotype and is critical component of antitumor response...
February 10, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28189879/immune-checkpoint-receptors-in-cancer-redundant-by-design
#18
REVIEW
Jing Li, Ling Ni, Chen Dong
Co-inhibitory receptors expressed on activated immune cells function to regulate T cell tolerance to self-antigens, also serving by tumor cells to escape from eradication by the host immune system. Therefore, blockade of immune checkpoint receptors (ICR) has become a promising immunotherapeutic strategy for treatment of a wide variety of cancers. However, blockade of one of the immune checkpoint receptors alone is often not sufficiently effective; co-blockade shows synergic effects in reversing immunosuppression...
February 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28160624/murine-models-of-germinal-center-derived-lymphomas
#19
REVIEW
Parham Ramezani-Rad, Robert C Rickert
The germinal center (GC) reaction is an adaptive immune response to select B cells bearing high-affinity B cell receptors (BCRs) to undergo further differentiation into antibody-producing cells or memory B cells. To drive affinity maturation, (GC) B cells undergo rounds of hypermutation and rapid proliferation, which can enhance susceptibility to malignant transformation. Lymphomas frequently originate from GC B cells, but the etiology for most lymphoma subtypes is unknown. Work in the past decade has more fully documented the mutational landscape in lymphomas, but the impact of these genomic lesions is often difficult to ascertain...
February 1, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28103497/host-microbiota-interactions-epigenomic-regulation
#20
REVIEW
Vivienne Woo, Theresa Alenghat
The coevolution of mammalian hosts and their commensal microbiota has led to the development of complex symbiotic relationships between resident microbes and mammalian cells. Epigenomic modifications enable host cells to alter gene expression without modifying the genetic code, and therefore represent potent mechanisms by which mammalian cells can transcriptionally respond, transiently or stably, to environmental cues. Advances in genome-wide approaches are accelerating our appreciation of microbial influences on host physiology, and increasing evidence highlights that epigenomics represent a level of regulation by which the host integrates and responds to microbial signals...
January 16, 2017: Current Opinion in Immunology
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