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The article offers information from the original research papers on T cells and helper cell metamorphosis, "T follicular helper cells differentiate from Th2 cells in response to helminth antigens," by A.G. Zaretsky et al. and "IL-4ߝproducing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells," by I.L. King and M. Mohrs that appeared in the April 20, 2009 issue of the "Journal of Experimental Medicine."

Discusses several research on the role of dendritic cells in policing the immune system. Reference to studies published in 'The Journal of Experimental Medicine'; Way by which dendritic cells contribute to the elimination of potentially harmful self-reactive T cells; Information on how tolerogenic dendritic cells might acquire antigens.

The article discusses research into the targeting of tumour necrosis factor (TNF) based on the original research paper "Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation," by M. Aouadi et al. that was published in issue 458, 2009 of "Nature." The article mentions M cells, antigens, macrophages, small interfering RNAs (siRNAs), and gene expression.

The article reports that research, published in "Immunity," has shown that machinery for endoplasmic reticulum protein retrotranslocation operates in the phagosomes of dendritic cells and is responsible for the transfer of exogenous antigens into the cytosol for cross-presentation. Cross-presentation, or the access gained by proteins within dendritic cells to cytosolic proteases, generate peptides for presentation by MHC class I molecules.

The article presents research highlights from the field of T cell memory based on the original research paper "Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow," by K. Tokoyoda et al. that was published in the May 7, 2009 issue of "Immunity." Subjects discussed include antigen-specific memory T cells in mice, immune responses, and the role of interleukin-7 (IL-7) in expressing stromal cells.

The article discusses the findings of the paper "Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma," by V. Verhasselt and colleagues. The mice experiment showed that an allergen inhaled by the mother is passed to her offspring in breast milk. The transfer of the allergen results in protection against the development of allergic airway inflammation in the progeny.

Discusses research papers that were published in the 2005 issue of "Science." "Antigen Recognition Determinants of T Cell Receptors"; "Structure of a T Cell Receptor in Complex With the Non-classical MHC T22."

Discusses two research focusing on how natural killer T (NKT) cells detect microorganisms. Recognition of bacterial glycosphingolipids by NKT cells; Antigens that activate NKT cells during microbial infections.

Discusses research being done on a network of myeloid-derived CX3C-chemokine receptor 1 dendritic cells (DC) in the lamina propria, which can sample luminal antigens. Reference to a study by J. H. Niess and colleagues, published in a 2005 issue of the "Science"; Methodology; Distribution of intestinal DC and their interactions with epithelial cells.

Discusses research being done on the mechanism of cytotoxic T lymphocyte (CTL) cross-priming with regard to antigens. Reference to a study by M. C. Wolkers, N. Brouwenstijn, A. H. Bakker, M. Toebes and T .N. Schumacher published in a 2004 issue of "Science"; Reference to a study by C.C. Norbury et al., published in a 2004 issue of "Science"; Exploration on the possible impact of the location of a CTL epitope within a peptide during cross-presentation; Investigation whether cross-priming favors proteasome substrates rather than pre-processed peptides.

Discusses research being done on the potential of CD8αα as marker of effector T cells that are destined to enter the memory pool. Reference to a study by L. T. Madakamutil and colleagues, and published in a 2004 issue of the periodical "Science"; Background on the thymic leukemia antigen.

Immune responses depend on the ability of leukocytes to move from the circulation into tissue. This is enabled by mechanisms that guide leukocytes to the right exit sites and allow them to cross the barrier of the blood vessel wall. This process is regulated by a concerted action between endothelial cells and leukocytes, whereby endothelial cells activate leukocytes and direct them to extravasation sites, and leukocytes in turn instruct endothelial cells to open a path for transmigration. This Review focuses on recently described mechanisms that control and open exit routes for leukocytes through the endothelial barrier. [ABSTRACT FROM AUTHOR]

Discusses the results of a study, which showed that tolerance to organ-specific antigens may be defective due to a failure of negative selection in the thymus. Information on the autoimmune regulator (Aire) gene; Analysis of the effects of Aire on the thymic antigen process; Lineage requirements for the expression of Aire.

The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease in the intestine. [ABSTRACT FROM AUTHOR]

Alveolar macrophages exist in a unique microenvironment and, despite historical evidence showing that they are in close contact with the respiratory epithelium, have until recently been investigated in isolation. The microenvironment of the airway lumen has a considerable influence on many aspects of alveolar macrophage phenotype, function and turnover. As the lungs adapt to environmental challenges, so too do alveolar macrophages adapt to accommodate the ever-changing needs of the tissue. In this Review, we discuss the unique characteristics of alveolar macrophages, the mechanisms that drive their adaptation and the direct and indirect influences of epithelial cells on them. We also highlight how airway luminal macrophages function as sentinels of a healthy state and how they do not respond in a pro-inflammatory manner to antigens that do not disrupt lung structure. The unique tissue location and function of alveolar macrophages distinguish them from other macrophage populations and suggest that it is important to classify macrophages according to the site that they occupy. [ABSTRACT FROM AUTHOR]

B cells are key components of the adaptive immune response. Their differentiation into either specific memory B cells or antibody-secreting plasma cells is a consequence of activation steps that involve the processing and presentation of antigens. The engagement of B cell receptors by surface-tethered antigens leads to the formation of an immunological synapse that coordinates cell signalling events and that promotes antigen uptake for presentation on MHC class II molecules. In this Review, we discuss membrane trafficking and the associated molecular mechanisms that are involved in antigen extraction and processing at the B cell synapse, and we highlight how B cells use cell polarity to coordinate the complex events that ultimately lead to efficient humoral responses. [ABSTRACT FROM AUTHOR]

The article reports that immune responses in the intestine are tightly controlled to prevent harmful attacks against commensal organisms, food proteins and self antigens. It states that dendritic cells (DCs) contribute to immune homeostasis in the intestine by constitutively generating high levels of retinoic acid. It states that patients with coeliac disease have increased levels of IL-15 in the gut mucosa.

The article offers information on two research regarding the potential of lymph node stromal cells (LNSC) to act as mediators of peripheral T cell tolerance through the expression of peripheral tissue antigens (PTA). The studies analyzed the compartment of LNSC through determining four phenotypically different cell subsets. Further, the research also examined the induction of self tolerance to specific PTAs by subsets.

The article presents abstracts on medical studies which include one on the use of reactive immunization in producing instant tumor immunity and another on autophagy induction to improve antigen presentation of the immunodominant mucobacterial antigen Ag85B for increased vaccine effectiveness.

The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. Here, we summarize recent advances in our understanding of the intracellular mechanisms of cross-presentation and discuss its role in immunity and tolerance in the context of specialization between DC subsets. Finally, we review current strategies to use cross-presentation for immunotherapy. [ABSTRACT FROM AUTHOR]

Investigations over the past two decades are revealing complexities in the regulation of the innate immune response, and how this response, in turn, controls adaptive immunity. Microbial exposure, infections and tissue damage that accompany solid-organ transplantation result in the release of pathogen- and damage-associated molecular patterns, as well as pathogen- or allograft-derived antigens. Here, we review these triggers of innate and adaptive immunity, and discuss emerging paradigms of the many ways in which infections and tissue damage might directly or indirectly affect alloreactivity and the outcome of transplanted allografts. [ABSTRACT FROM AUTHOR]

Members of the tumour necrosis factor (TNF) superfamily have been implicated in a wide range of biological functions, and their expression by cells of the immune system makes them appealing targets for immunomodulation. One common theme for TNF superfamily members is their coordinated expression at the interface between antigen-specific T cells and antigen-presenting dendritic cells and, by virtue of this expression pattern, TNF superfamily members can shape T cell immune responses. Understanding how to manipulate such functions of the TNF superfamily may allow us to tip the balance between immunity and tolerance in the context of human disease. [ABSTRACT FROM AUTHOR]

Ubiquitylation is a widely used post-translational protein modification that regulates many biological processes, including immune responses. The role of ubiquitin in immune regulation was originally uncovered through studies of antigen presentation and the nuclear factor-κB family of transcription factors, which orchestrate host defence against microorganisms. Recent studies have revealed crucial roles of ubiquitylation in many aspects of the immune system, including innate and adaptive immunity and antimicrobial autophagy. In addition, mounting evidence indicates that microbial pathogens exploit the ubiquitin pathway to evade the host immune system. Here, we review recent advances on the role of ubiquitylation in host defence and pathogen evasion. [ABSTRACT FROM AUTHOR]

The article presents several abstracts of immunology research. They include "Lymphoid reservoirs of antigen-specific memory T helper cells," "Antigen-specific immune responses to influenza vaccine in utero," and "Opposing effects of PKCϑ and WASp on symmetry breaking and relocation of the immunological synapses."

The molecular details of antigen processing and presentation by MHC class I and class II molecules have been studied extensively for almost three decades. Although the basic principles of these processes were laid out approximately 10 years ago, the recent years have revealed many details and provided new insights into their control and specificity. MHC molecules use various biochemical reactions to achieve successful presentation of antigenic fragments to the immune system. Here we present a timely evaluation of the biology of antigen presentation and a survey of issues that are considered unresolved. The continuing flow of new details into our understanding of the biology of MHC class I and class II antigen presentation builds a system involving several cell biological processes, which is discussed in this Review. [ABSTRACT FROM AUTHOR]

T cell activation depends on extracellular ligation of the T cell receptor (TCR) by peptide-MHC complexes in a synapse between the T cell and an antigen-presenting cell. The process then requires the assembly of signalling complexes between the TCR and the adaptor protein linker for activation of T cells (LAT), and subsequent filamentous actin (F-actin)-dependent TCR cluster formation. Recent progress in each of these areas, made possible by the emergence of new techniques, has forced us to rethink our assumptions and consider some radical new models. These describe the receptor interaction parameters that control T cell responses and the mechanism by which LAT is recruited to the TCR signalling machinery. This is an exciting time in T cell biology, and further innovation in imaging and genomics is likely to lead to a greater understanding of how T cells are activated. [ABSTRACT FROM AUTHOR]

As Nature Reviews Immunology reaches its 10(th) anniversary, the authors of one of the top-cited articles from each year take a trip down memory lane. We've asked them to look back on the state of research at the time their Review was published, to consider why the article has had the impact it has and to discuss the future directions of their field. This Viewpoint article provides an interesting snapshot of some of the fundamental advances in immunology over the past 10 years. Highlights include our improved understanding of Toll-like receptor signalling, and of immune regulation mediated by regulatory T cells, indoleamine 2,3-dioxygenase, myeloid-derived suppressor cells and interleukin-10. The complexities in the development and heterogeneity of macrophages, dendritic cells and T helper cells continue to engage immunologists, as do the immune processes involved in diseases such as atherosclerosis. We look forward to what the next 10 years of immunology research may bring. [ABSTRACT FROM AUTHOR]

Both jawless vertebrates, such as lampreys and hagfish, and jawed vertebrates (encompassing species as diverse as sharks and humans) have an adaptive immune system that is based on somatically diversified and clonally expressed antigen receptors. Although the molecular nature of the antigen receptors and the mechanisms of their assembly are different, recent findings suggest that the general design principles underlying the two adaptive immune systems are surprisingly similar. The identification of such commonalities promises to further our understanding of the mammalian immune system and to inspire the development of new strategies for medical interventions targeting the consequences of faulty immune functions. [ABSTRACT FROM AUTHOR]

The initiation of V(D)J recombination by the recombination activating gene 1 (RAG1) and RAG2 proteins is carefully orchestrated to ensure that antigen receptor gene assembly occurs in the appropriate cell lineage and in the proper developmental order. Here we review recent advances in our understanding of how DNA binding and cleavage by the RAG proteins are regulated by the chromatin structure and architecture of antigen receptor genes. These advances suggest novel mechanisms for both the targeting and the mistargeting of V(D)J recombination, and have implications for how these events contribute to genome instability and lymphoid malignancy. [ABSTRACT FROM AUTHOR]

Presents information on research published in "Nature" which indicated that dendritic cells can distinguish antigens taken up in the presence of Toll-like receptor ligands from those taken up in the absence of such ligands. Importance of the study in the efforts of immunologists to understand how the immune system discriminates between self- and non-self antigens; Description on how dendritic cells work during an infection.

Discusses research being done on lymphocyte signaling. Reference to a study by K. Sommer et al., published in the 2005 issue of "Immunity"; Consequences of the ligation of cell-surface antigen receptors; Functions of protein kinase Β in B cells.

Researchers working on the development of vaccines face an inherent dilemma: to maximize immunogenicity without compromising safety and tolerability. Early vaccines often induced long-lived protective immune responses, but tolerability was a major problem. Newer vaccines have very few side effects but can be of limited immunogenicity. One way to tackle this problem is to design vaccines that have all the properties of pathogens with the exception of causing disease. Key features of pathogens that can be mimicked by vaccine delivery systems are their size, shape and surface molecule organization. In addition, pathogen-associated molecular patterns can be used to induce innate immune responses that promote adaptive immunity. In this Review, we discuss the approaches currently being used to optimize the delivery of antigens and enhance vaccine efficacy. [ABSTRACT FROM AUTHOR]

In the past decade, advances in microscopic imaging methods, together with the development of genetically encoded fluorescent reporters, have made it possible to directly visualize the behaviour of cells in living tissues. At the same time, immunologists have been turning their attention from the traditional focus on responses to model antigens to a new focus on in vivo infection models. Recently, these two trends have intersected with exciting results. Here we discuss how dynamic imaging of in vivo infection has revealed fascinating and unexpected details of host-pathogen interactions at a new level of spatial and temporal resolution. [ABSTRACT FROM AUTHOR]

Deals with a research which revealed that human γδ T cells can join dendritric cells in the professional antigen-presenting cell club. Difference between γδ T cells from αβ T cells; Effects if T-cell receptor triggering on γδ T cells in human peripheral blood; Potential role for Vδ2+ T cells in antigen presentation to αβ T cells.

Discusses research being done on the control of rapamycin-resistant T cell survival and activation by PIM kinases. Reference to a study by C. J. Fox, P. S. Hammerman and C. B Thompson, published in a 2005 issue of the "Journal of Experimental Medicine"; Mediation of T-cell growth and survival following litigation of cytokine or antigen receptors; PIM kinase expression in T cells.

Presents information on a research on the ability of antigen-specific forkhead box P3-transduced T cells to control established type 1 diabetes, with reference to a study by E. Jaeckel, H. von Boehmer and M. P. Manns, published in a 2005 issue of the journal "Diabetes."

In germinal centres, somatic hypermutation and B cell selection increase antibody affinity and specificity for the immunizing antigen, but the generation of autoreactive B cells is an inevitable by-product of this process. Here, we review the evidence that aberrant selection of these autoreactive B cells can arise from abnormalities in each of the germinal centre cellular constituents--B cells, T follicular helper cells, follicular dendritic cells and tingible body macrophages--or in the supply of antigen. As the progeny of germinal centre B cells includes long-lived plasma cells, selection of autoreactive B cells can propagate long-lived autoantibody responses and cause autoimmune diseases. Elucidation of crucial molecular signals in germinal centres has led to the identification of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

The relative importance of the intrinsic and extrinsic apoptotic pathways in the control of haematopoietic cell homeostasis has been a matter of debate for many years. Cell death is omnipresent in this cellular compartment and ensures the removal of cells that are not properly equipped to assume their function as well as those that have assumed function but are no longer required. In this Review we focus on the roles of CD95 (also known as FAS) and BCL-2-interacting mediator of cell death (BIM), two major regulators of apoptosis in T cell homeostasis, with a particular emphasis on their cooperation in the shutdown of T cell responses. [ABSTRACT FROM AUTHOR]

The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. [ABSTRACT FROM AUTHOR]

Presents the results of a study on the role of the E3 ubiquitin ligase Casitas B-lineage lymphoma b (Cbl-b) in maintaining the condition of T cells despite expression from self-antigens. Factors that could contribute to the activation of Cbl-b-deficient T cells; Effect of the induction of anergy by ionomycin on calcium mobilization; Significance of the activation of T cells from Cbl-b to autoimmunity.

Presents the results of a study on the role of Toll-like receptors (TLR) in immature dendritic cells. Significance of TLR to the regulation of antigens; Background on the activation of T cells through endocytic capacity; Factors that associate TLR ligation with cell membranes.

Discusses research being done on KIR2DL3, an inhibitory natural killer-cell receptor. Reference to a study by S.I. Khakoo et al published in the 2004 issue of "Science"; Human leucocyte antigen-C1 (HLA-C1) homozygosity; Association of the KIR2DL3;HLA-C1 homozygous genotype with resolution of hepatitis C virus infection.

Focuses on a study conducted by James McCluskey, Jamie Rossjohn and colleagues on human lymphocyte antigen (HLA). Importance of HLA polymorphisms in the peptide-binding groove to the epitopes that are presented in the T cells; Overview of the study; Conclusion of the study.

Focuses on the T-cell recognition of antigen displayed by an antigen-presenting cell. Concept of the immunological synapse; Relation between antigen recognition and cytoskeletal changes; Function of Ezrin-Radixin-Moesin proteins.

Deals with the findings of a report on the method in which maternal immune system tolerate the persistence of paternal alloantigens during pregnancy. Factors which contributed to fetal evasion from immune attack; Result of the activation of natural killer cells; Expansion of maternal regulatory T-cell populations.

Focuses on the relation between antigen-specific autoreactive T-cell response on autoimmune disease. Islet-specific T cell in the peripheral blood of type 1 diabetic patients; Information on the cytokine enzyme-linked immunosorbent spot technique; Peripheral-blood mononuclear cells of patients with type 1 diabetes.

Discusses research being done on the editing of Cd1d-bound lipid antigens by endosomal lipid transfer proteins. Reference to a study by D. Zhou and colleagues published in the December 18, 2003 issue of "Science" journal; Recognition of endogenous Cd1d-bound ligands; Regulators of endosomal lipid metabolism generated by proteolysis of a precursor.

The T-cell receptor (TCR) signalling machinery is central in determining the response of a T cell (establishing immunity or tolerance) following exposure to antigen. This process is made difficult by the narrow margin of self and non-self discrimination, and by the complexity of the genetic programmes that are induced for each outcome. Recent studies have identified novel negative feedback mechanisms that are rapidly induced by TCR engagement and that have key roles in the regulation of signal triggering and propagation. In vitro and in vivo data suggest that they are important in determining ligand discrimination by the TCR and in regulating signal output in response to antigen. [ABSTRACT FROM AUTHOR]

The principal components of both MHC class I and class II antigen processing and presentation pathways are well known. In dendritic cells, these pathways are tightly regulated by Toll-like-receptor signalling and include features, such as cross-presentation, that are not seen in other cell types. However, the exact mechanisms involved in the subcellular trafficking of antigens remain poorly understood and in some cases are controversial. Recent data suggest that diverse cellular machineries, including autophagy, participate in antigen processing and presentation, although their relative contributions remain to be fully elucidated. Here, we highlight some emerging themes of antigen processing and presentation that we think merit further attention. [ABSTRACT FROM AUTHOR]

The ability to develop and sustain populations of memory T cells after infection or immunization is a hallmark of the adaptive immune response and a basis for protective vaccination against infectious disease. Technical advances that allow direct ex vivo identification and characterization of antigen-specific CD8+ T cells at various stages of the response to infection or vaccination in mouse models have fuelled efforts to characterize the factors that control memory CD8+ T-cell generation. Here, we dissect the input signals that shape the characteristics of the memory CD8+ T-cell response and discuss how manipulation of these signals has the potential to reshape CD8+ T-cell memory and improve the efficacy of vaccination. [ABSTRACT FROM AUTHOR]