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Immunological Reviews

Andrea J Sant, Anthony T DiPiazza, Jennifer L Nayak, Ajitanuj Rattan, Katherine A Richards
CD4 T cells convey a number of discrete functions to protective immunity to influenza, a complexity that distinguishes this arm of adaptive immunity from B cells and CD8 T cells. Although the most well recognized function of CD4 T cells is provision of help for antibody production, CD4 T cells are important in many aspects of protective immunity. Our studies have revealed that viral antigen specificity is a key determinant of CD4 T cell function, as illustrated both by mouse models of infection and human vaccine responses, a factor whose importance is due at least in part to events in viral antigen handling...
July 2018: Immunological Reviews
Sandra C A Nielsen, Scott D Boyd
The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane-bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies...
July 2018: Immunological Reviews
Patrick C Wilson, Sarah Cobey
No abstract text is available yet for this article.
July 2018: Immunological Reviews
Kim L Good-Jacobson
The vast majority of vaccines exploit antibody memory to induce lasting immunity. Memory B cells are generated during the initial response to infection, but persist long after the infection has cleared. Immune memory success relies on its adaptability: in response to different pathogens, variants of a single pathogen, and in balancing persistence with reactivation and plasma cell differentiation. This is likely achieved by producing a B cell memory population that is highly diverse, and recent work has highlighted the importance of memory B cell subsets in mediating the dichotomous roles of the population...
July 2018: Immunological Reviews
Katharina Imkeller, Hedda Wardemann
A hallmark of the adaptive immune system is the specificity of B cell and T cell responses. Mechanistically, this feature relies on the fact that the two genes that encode B cell and T cell antigen receptors are not germline encoded and instead are assembled from a large number of small gene segments during lymphocyte development. The underlying somatic gene recombination process can generate a quasi-unlimited repertoire of antigen receptors. The high degree of diversity is essential to guarantee recognition of nearly any antigenic structure to protect from the large variety of potential invading pathogens and to keep the balance with commensals...
July 2018: Immunological Reviews
Stefan A Schattgen, Paul G Thomas
Over the last several decades, novel populations of unconventional T cells have been identified; defined by an invariant (or nearly invariant) T cell receptor (TCR) with a fixed specificity to non-canonical antigens and major histocompatibility (MHC) molecules, they form large, functionally monoclonal populations tasked with surveying for their specific antigens. With residence in both lymphoid and non-lymphoid tissues coupled with their ability to rapidly produce a spectrum of cytokines and effector molecules, the unconventional T cells are poised as some of the first responders to infection/damage and are thought to provide critical coverage before more focused, conventional T cell responses are mobilized...
July 2018: Immunological Reviews
Branden J Olson, Frederick A Matsen
Probabilistic modeling is fundamental to the statistical analysis of complex data. In addition to forming a coherent description of the data-generating process, probabilistic models enable parameter inference about given datasets. This procedure is well developed in the Bayesian perspective, in which one infers probability distributions describing to what extent various possible parameters agree with the data. In this paper, we motivate and review probabilistic modeling for adaptive immune receptor repertoire data then describe progress and prospects for future work, from germline haplotyping to adaptive immune system deployment across tissues...
July 2018: Immunological Reviews
Christopher M Tipton, Jennifer R Hom, Christopher F Fucile, Alexander F Rosenberg, Inaki Sanz
Understanding antibody repertoires and in particular, the properties and fates of B cells expressing potentially pathogenic antibodies is critical to define the mechanisms underlying multiple immunological diseases including autoimmune and allergic conditions as well as transplant rejection. Moreover, an integrated knowledge of the antibody repertoires expressed by B cells and plasma cells (PC) of different functional properties and longevity is essential to develop new therapeutic strategies, better biomarkers for disease segmentation, and new assays to measure restoration of B-cell tolerance or, at least, of normal B-cell homeostasis...
July 2018: Immunological Reviews
Mohamed Khass, Andre M Vale, Peter D Burrows, Harry W Schroeder
Although at first glance the diversity of the immunoglobulin repertoire appears random, there are a number of mechanisms that act to constrain diversity. For example, key mechanisms controlling the diversity of the third complementarity determining region of the immunoglobulin heavy chain (CDR-H3) include natural selection of germline diversity (DH ) gene segment sequence and somatic selection upon passage through successive B-cell developmental checkpoints. To test the role of DH gene segment sequence, we generated a panel of mice limited to the use of a single germline or frameshifted DH gene segment...
July 2018: Immunological Reviews
Yuval Elhanati, Zachary Sethna, Curtis G Callan, Thierry Mora, Aleksandra M Walczak
Despite the extreme diversity of T-cell repertoires, many identical T-cell receptor (TCR) sequences are found in a large number of individual mice and humans. These widely shared sequences, often referred to as "public," have been suggested to be over-represented due to their potential immune functionality or their ease of generation by V(D)J recombination. Here, we show that even for large cohorts, the observed degree of sharing of TCR sequences between individuals is well predicted by a model accounting for the known quantitative statistical biases in the generation process, together with a simple model of thymic selection...
July 2018: Immunological Reviews
Joel Finney, Chen-Hao Yeh, Garnett Kelsoe, Masayuki Kuraoka
Germinal centers (GCs) are the primary sites of antibody affinity maturation, sites where B-cell antigen-receptor (BCR) genes rapidly acquire mutations and are selected for increasing affinity for antigen. This process of hypermutation and affinity-driven selection results in the clonal expansion of B cells expressing mutated BCRs and acts to hone the antibody repertoire for greater avidity and specificity. Remarkably, whereas the process of affinity maturation has been confirmed in a number of laboratories, models for how affinity maturation in GCs operates are largely from studies of genetically restricted B-cell populations competing for a single hapten epitope...
July 2018: Immunological Reviews
Deborah Dunn-Walters, Catherine Townsend, Emma Sinclair, Alex Stewart
The human immunoglobulin repertoire is a hugely diverse set of sequences that are formed by processes of gene rearrangement, heavy and light chain gene assortment, class switching and somatic hypermutation. Early B cell development produces diverse IgM and IgD B cell receptors on the B cell surface, resulting in a repertoire that can bind many foreign antigens but which has had self-reactive B cells removed. Later antigen-dependent development processes adjust the antigen affinity of the receptor by somatic hypermutation...
July 2018: Immunological Reviews
Brian D Corrie, Nishanth Marthandan, Bojan Zimonja, Jerome Jaglale, Yang Zhou, Emily Barr, Nicole Knoetze, Frances M W Breden, Scott Christley, Jamie K Scott, Lindsay G Cowell, Felix Breden
Next-generation sequencing allows the characterization of the adaptive immune receptor repertoire (AIRR) in exquisite detail. These large-scale AIRR-seq data sets have rapidly become critical to vaccine development, understanding the immune response in autoimmune and infectious disease, and monitoring novel therapeutics against cancer. However, at present there is no easy way to compare these AIRR-seq data sets across studies and institutions. The ability to combine and compare information for different disease conditions will greatly enhance the value of AIRR-seq data for improving biomedical research and patient care...
July 2018: Immunological Reviews
Jae-Ho Cho, Jonathan Sprent
After selection in the thymus, the post-thymic T cell compartments comprise heterogenous subsets of naive and memory T cells that make continuous T cell receptor (TCR) contact with self-ligands bound to major histocompatibility complex (MHC) molecules. T cell recognition of self-MHC ligands elicits covert TCR signaling and is particularly important for controlling survival of naive T cells. Such tonic TCR signaling is tightly controlled and maintains the cells in a quiescent state to avoid autoimmunity. Here, we review how naive and memory T cells are differentially tuned and wired for TCR sensitivity to self and foreign ligands...
May 2018: Immunological Reviews
Paul Klenerman
Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to "exhaustion" the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T-cell population structure which maintains functionality and size...
May 2018: Immunological Reviews
Maike Hofmann, Dominik Wieland, Hanspeter Pircher, Robert Thimme
Memory CD8+ T cells are essential in orchestrating protection from re-infection. Hallmarks of virus-specific memory CD8+ T cells are the capacity to mount recall responses with rapid induction of effector cell function and antigen-independent survival. Growing evidence reveals that even chronic infection does not preclude virus-specific CD8+ T-cell memory formation. However, whether this kind of CD8+ T-cell memory that is established during chronic infection is indeed functional and provides protection from re-infection is still unclear...
May 2018: Immunological Reviews
Dirk Homann, Ross M Kedl
No abstract text is available yet for this article.
May 2018: Immunological Reviews
Benjamin Gourbal, Silvain Pinaud, Gerold J M Beckers, Jos W M Van Der Meer, Uwe Conrath, Mihai G Netea
Over the last decades, there was increasing evidence for the presence of innate immune memory in living organisms. In this review, we compare the innate immune memory of various organisms with a focus on phylogenetics. We discuss the acquisition and molecular basis of immune memory and we describe the innate immune memory paradigm and its role in host defense during evolution. The molecular characterization of innate immunological memory in diverse organisms and host-parasite systems reconciles mechanisms with phenomena and paves the way to molecular comprehension of innate immune memory...
May 2018: Immunological Reviews
Kilian Schober, Veit R Buchholz, Dirk H Busch
During infections and cancer, the composition of the T-cell receptor (TCR) repertoire of antigen-specific CD8+ T cells changes over time. TCR avidity is thought to be a major driver of this process, thereby interacting with several additional regulators of T-cell responses to form a composite immune response architecture. Infections with latent viruses, such as cytomegalovirus (CMV), can lead to large T-cell responses characterized by an oligoclonal TCR repertoire. Here, we review the current status of experimental studies and theoretical models of TCR repertoire evolution during CMV infection...
May 2018: Immunological Reviews
Itziar Martinez-Gonzalez, Maryam Ghaedi, Catherine A Steer, Laura Mathä, Eric Vivier, Fumio Takei
Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as macrophages, also termed "trained immunity" and more recently to epithelial stem cells. In this review, we discuss the mechanisms underlying memory generation on ILC2s and speculate about their potential role in human allergic diseases, such as asthma. Moreover, we examine the relevance of the spontaneous ILC2 activation in the lung during the neonatal period in order to efficiently respond to stimuli later in life...
May 2018: Immunological Reviews
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