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The article discusses papers which show that signals derived from basophils and eosinophils are directly involved in the induction of T helper 2 (TH2)-cell responses. It highlights the findings in "A mechanism for the initiation of allergen-induced T helper type 2 responses," by C.L. Sokol and colleagues, and "Eosinophil-derived neurotoxin acts as an alarm to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses," by D. Yang and colleagues.

The article discusses research being done on thymic epithelial cells (TEC). It references separate studies by S. W. Rossi, W. E. Jenkinson, G. Anderson and E. J. Jenkinson and C. C. Bleul et al, published in 2006 issues of "Nature." The complementary papers identify bipotent progenitors that can give rise to both cortical and medullary TEC in embryonic, as well as neonatal, mice.

Cells digest portions of their interiors in a process known as autophagy to recycle nutrients, remodel and dispose of unwanted cytoplasmic constituents. This ancient pathway, conserved from yeast to humans, is now emerging as a central player in the immunological control of bacterial, parasitic and viral infections. The process of autophagy may degrade intracellular pathogens, deliver endogenous antigens to MHC-class-II-loading compartments, direct viral nucleic acids to Toll-like receptors and regulate T-cell homeostasis. This Review describes the mechanisms of autophagy and highlights recent advances relevant to the role of autophagy in innate and adaptive immunity. [ABSTRACT FROM AUTHOR]

The article discusses the important roles of E proteins in maintaining two key checkpoints in the development of thymocyte. These developments are the transition from double negative 3 (DN3) to double positive (DP) cells and from DP to CD8 single positive (SP) cells. The four E proteins are E12, E47, E2-2 and HEB. The study showed that partial or complete loss of E47 in DN3 thymocytes resulted in a substantial loss of chromatin accessibility at the TCRβlocus.

The article presents a medical research in Great Britain on the alternative pathways of T-cell development. It is said that the recent report of immunity revealed the common need for signalling through the signalling lymphocytic activation molecule (SLAM) family of receptors. However, the studies featured in the paper helped define pathways of T-cell selection on haematopoietic cells and indicate an important role for SLAM receptor signalling in these alternative pathways of T-cell development.

Discusses research being done on the role of lipopolysaccharide (LPS) and peptidoglycan in activating the immune-deficiency (IMD) pathway. Reference to a study by T. Kaneko and colleagues published in a 2004 issue of "Immunity"; Capability of re-extracted Escherichia coli LPS and Gram-negative peptidoglycan to induce the IMD pathway in cultured cells; Observation on the immunostimulatory results of digested peptidoglycan contaminants in the LPS preparation in the IMD pathway.

Presents studies on the role of cellular protein as a viral inhibitor and the importance of virion infectivity factor in overcoming antiviral strategy. Background on the cellular protein; Investigation on whether protein acted on RNA or DNA; Analysis of guanine to adenine changes in HIV-1 genes.

The article provides information on a research which shows that the Th 17-cell lineage can shift from the production of interleukin-17 to interferon-y in a time of immune response. It is implied that this finding suggests an evolutionary method to maximize pathogen clearance and minimize host damage.

The article presents a study which identifies the expression of the signature T helper 1 cell-associated cytokine interferonϒ-regulated at the level of chromatin CD4+T[H] cells. It has been identified that eight conserved non-coding sequences within 57 kilobases upstream or downstream of the gene are identified as potential regulatory elements. Moreover, the regulatory enhanced gene has acted mainly as boundary elements.

The innate immune system is central for the maintenance of tissue homeostasis and quickly responds to local or systemic perturbations by pathogenic or sterile insults. This rapid response must be metabolically supported to allow cell migration and proliferation and to enable efficient production of cytokines and lipid mediators. This Review focuses on the role of mammalian target of rapamycin (mTOR) in controlling and shaping the effector responses of innate immune cells. mTOR reconfigures cellular metabolism and regulates translation, cytokine responses, antigen presentation, macrophage polarization and cell migration. The mTOR network emerges as an integrative rheostat that couples cellular activation to the environmental and intracellular nutritional status to dictate and optimize the inflammatory response. A detailed understanding of how mTOR metabolically coordinates effector responses by myeloid cells will provide important insights into immunity in health and disease. [ABSTRACT FROM AUTHOR]

Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular pathways that control the development, trafficking and degranulation of eosinophils have improved our understanding of the immunomodulatory functions of these cells and their roles in promoting homeostasis. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of different diseases, including asthma and primary hypereosinophilic syndromes, and have also provided us with a more complete appreciation of the activities of these cells during parasitic infection. [ABSTRACT FROM AUTHOR]

Microglia - resident myeloid-lineage cells in the brain and the spinal cord parenchyma - function in the maintenance of normal tissue homeostasis. Microglia also act as sentinels of infection and injury, and participate in both innate and adaptive immune responses in the central nervous system. Microglia can become activated and/or dysregulated in the context of neurodegenerative disease and cancer, and thereby contribute to disease severity. Here, we discuss recent studies that provide new insights into the origin and phenotypes of microglia in health and disease. [ABSTRACT FROM AUTHOR]

Stimulation of almost all mammalian cell types leads to the release of cellular ATP and autocrine feedback through a diverse array of purinergic receptors. Depending on the types of purinergic receptors that are involved, autocrine signalling can promote or inhibit cell activation and fine-tune functional responses. Recent work has shown that autocrine signalling is an important checkpoint in immune cell activation and allows immune cells to adjust their functional responses based on the extracellular cues provided by their environment. This Review focuses on the roles of autocrine purinergic signalling in the regulation of both innate and adaptive immune responses and discusses the potential of targeting purinergic receptors for treating immune-mediated disease. [ABSTRACT FROM AUTHOR]

The behaviour of T cells is not fixed in the germ line, but is highly adaptable depending on experiences encountered during a T cell's life. To understand how different T cell subsets arise and how prior signalling input regulates subsequent T cell behaviour, approaches are required that couple a given T cell state to signals received by the cell, or by one of its ancestors, at earlier times. Here we describe recently developed technologies that have been used to determine the kinship of different T cell subsets and their prior functional characteristics. Furthermore, we discuss the potential value of new technologies that would allow assessment of T cell migration patterns and prior signalling events. [ABSTRACT FROM AUTHOR]

When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the mononuclear phagocyte system and to give their opinion on the importance of defining these cells for future research. [ABSTRACT FROM AUTHOR]

Mammalian microRNAs (miRNAs) have recently been identified as important regulators of gene expression, and they function by repressing specific target genes at the post-transcriptional level. Now, studies of miRNAs are resolving some unsolved issues in immunology. Recent studies have shown that miRNAs have unique expression profiles in cells of the innate and adaptive immune systems and have pivotal roles in the regulation of both cell development and function. Furthermore, when miRNAs are aberrantly expressed they can contribute to pathological conditions involving the immune system, such as cancer and autoimmunity; they have also been shown to be useful as diagnostic and prognostic indicators of disease type and severity. This Review discusses recent advances in our understanding of both the intended functions of miRNAs in managing immune cell biology and their pathological roles when their expression is dysregulated. [ABSTRACT FROM AUTHOR]

A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A crucial aspect of this response is a failure to resolve inflammation, which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can trigger atherothrombotic vascular disease, the leading cause of death in industrialized societies. In this Review I provide an overview of these concepts, with a focus on macrophage death and defective apoptotic cell clearance, and discuss new therapeutic strategies designed to boost inflammation resolution in atherosclerosis. [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.

Presents research which proves that the strength of the signal transmitted by the T-cell receptor (TCR) is the key determinant in the αβ/γδ lineage-fate decision. Role of T-cell receptor in αβ/γδ lineage commitment; Results of the experiment done in the study;Difference between γδ TCR thymocytes and pre-TCR thymocytes.

Presents information on a research on the conversion of T-cell autoreactivity into overt autoimmune disease through Toll-like receptor engagement, with reference to a study by K. S. Lang et al., published in a 2005 issue of the journal "Nature Medicine."

Presents information on a research on the regulation of T cell receptor β allelic exclusion at a level beyond accessibility, with reference to a study by A. Jackson, H. D. Kondilis, B. Khor, B. P. Sleckman and M. S. Krangel, published in a 2005 issue of the journal "Nature Immunology."

The complement system is important for cellular integrity and tissue homeostasis. Complement activation mediates the removal of microorganisms and the clearance of modified self cells, such as apoptotic cells. Complement regulators control the spontaneously activated complement cascade and any disturbances in this delicate balance can result in damage to tissues and in autoimmune disease. Therefore, insights into the mechanisms of complement regulation are crucial for understanding disease pathology and for enabling the development of diagnostic tools and therapies for complement-associated diseases. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor (HIF) is an important transcriptional regulator of cell metabolism and the adaptation to cellular stress caused by oxygen deficiency (hypoxia). Phagocytic cells have an essential role in innate immune defence against pathogens and this is a battle that takes place mainly in the hypoxic microenvironments of infected tissues. It has now become clear that HIF promotes the bactericidal activities of phagocytic cells and supports the innate immune functions of dendritic cells, mast cells and epithelial cells. In response to microbial pathogens, HIF expression is upregulated through pathways involving the key immune response regulator nuclear factor-kappaB, highlighting an interdependence of the innate immune and hypoxic responses to infection and tissue damage. In turn, HIF-driven innate immune responses have important consequences for both the pathogen and the host, such that the tissue microenvironment fundamentally influences susceptibility to infectious disease. [ABSTRACT FROM AUTHOR]

Many models of haematopoiesis dictate that haematopoietic stem cells make an early and irrevocable choice between lymphoid and myeloid cell fates. However, recent data show that intermediate progenitors have both lymphoid and myeloid potential, thereby refuting early theories and leading to a lack of consensus in the field. In this Opinion article we present a simple pairwise relationships model of cell fate determination that does not depend on the underlying developmental branch points that in other models dictate a preferred route (or routes) to a particular cell fate. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit. [ABSTRACT FROM AUTHOR]

Many advances in our understanding of the molecules that regulate the development, differentiation and function of T cells have been made over the past few years. One important regulator of T-cell differentiation is the transcription factor GATA-binding protein 3 (GATA3). Although the main function of GATA3 is to act as a master transcription factor for the differentiation of T helper 2 (T(H)2) cells, new research has helped to uncover crucial functions of GATA3 in T cells that go beyond T(H)2-cell differentiation and that are important at earlier stages of haematopoietic and lymphoid-cell development. This Review focuses on the functions of GATA3 from early thymocyte development to effector T-cell differentiation. In addition, we discuss the interactions between GATA3 and other transcription factors and signalling pathways, and highlight the functional significance of the GATA3 protein structure. [ABSTRACT FROM AUTHOR]

Over the past 20 years great progress has been made in defining most of the key signalling pathways that functionally regulate immune cells. Recently, it has become clear that scaffold proteins have a crucial role in regulating many of these signalling cascades. By binding two or more components of a signalling pathway, scaffold proteins can help to localize signalling molecules to a specific part of the cell or to enhance the efficacy of a signalling pathway. Scaffold proteins can also affect the thresholds and the dynamics of signalling reactions by coordinating positive and negative feedback signals. In this Review, we focus on recent progress in the understanding of the function of scaffold proteins in immune cells. [ABSTRACT FROM AUTHOR]

Discusses research being done on mature dendritic cells (DC). Reference to a study by M. Zhang et al, which appeared in a 2004 issue of "Nature Immunology"; Role of endothelial-like splenic stromal cells in the induction of mature DC proliferation; Main distinguishing characteristic of DC phenotype in vitro.

Discusses several research being done on the migration of thymocytes in the thymus. Reference to the studies by A. Missitz et al and H.T. Petrie published in the 2004 issue of "Journal of Experimental Medicine"; Factors that express CC-chemokine receptor 7; Anatomical localization of the double-negative cells.

Focuses on a study which revealed that crucial differences between naive and memory T cells in terms of the formation and duration of immunological synapses might be responsible. Information on immunological synapse; Methodology used in the study; Conclusion of the study.

Discusses research being done on the responses of mast cells. Reference to a study by S. Yamasaki which was published in the 2004 issue of the journal "Blood"; Effect of the activation of extracellular-signal-regulated kinase; Role of IgE in mast-cell degranulation or survival.

Focuses on the antiviral immunity in Drosophila and mosquito cells provided by the production of small interfering RNA from double-stranded RNA. Function of the B2 protein nodavirus flock house virus; Activation of an RNA interference-mediated antiviral response by nodamura virus infection of mosquito cells; Function of the RNA interference on RNA silencing in invertebrate cells.

Discusses the findings of studies on the role of interleukin-7 in the generation and maintenance of CD4+ memory. Methodology of the studies; Dependency of effector-memory transition on interleukin-7 signalling; Importance of interluekin-7 to central memory and effector memory cells.

Although often encoding fewer than a dozen genes, RNA viruses can overcome host antiviral responses and wreak havoc on the cells they infect. Some manage to evade host antiviral defences, whereas others elicit an aberrant or disproportional immune response. Both scenarios can result in the disruption of intracellular signalling pathways and significant pathology in the host. Systems-biology approaches are increasingly being used to study the processes of viral triggering and regulation of host immune responses. By providing a global and integrated view of cellular events, these approaches are beginning to unravel some of the complexities of virus-host interactions and provide new insights into how RNA viruses cause disease. [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]

Phagocytosis, the engulfment of material by cells, is a highly conserved process that arose before the development of multicellularity. Phagocytes have a key role in embryogenesis and also guard the portals of potential pathogen entry. They discriminate between diverse particles through the array of receptors expressed on their surface. In higher species, arguably the most sophisticated function of phagocytes is the processing and presentation of antigens derived from internalized material to stimulate lymphocytes and long-lived specific immunity. Central to these processes is the generation of a phagosome, the organelle that forms around internalized material. As we discuss in this Review, over the past two decades important insights into phagocytosis have been gleaned from studies in the model organism Drosophila melanogaster. [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]

MicroRNAs (miRNAs) are an abundant class of evolutionarily conserved small non-coding RNAs that are thought to control gene expression by targeting mRNAs for degradation or translational repression. Emerging evidence suggests that miRNA-mediated gene regulation represents a fundamental layer of genetic programmes at the post-transcriptional level and has diverse functional roles in animals. Here, we provide an overview of the mechanisms by which miRNAs regulate gene expression, with specific focus on the role of miRNAs in regulating the development of immune cells and in modulating innate and adaptive immune responses. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies. [ABSTRACT FROM AUTHOR]

Assesses the existence of self-reactive antibodies that is a potential problem with respect to the development of autoimmune disease. Process by which antibodies are generated; Approaches in eliminating self-reactive antibodies; Characteristics of B cells used to generate antibodies.

Presents news briefs on cell studies as of July 2003. Importance of caspases in cell proliferation; Role of raft proteins in B-cell receptor signaling; Influence of mast cells in inducing intestinal permeability.

Offers information on the mechanics of signaling pathways selection in natural killer (NK) cells. Activation of NK cells; Influence of immunoreceptor tyrosine-based activation motif on NK cell cytotoxicity; Physiological transport of NK cells.

Investigates the potential involvement of CD3[sup-]CD4[sup+] cells in an immune response of antigen-specific CD4[sup+] T helper cells. Role of dendritic cells in T cell responses; Expression of the cells; Physiological presence of the cells; Details on CD antigens.

Discusses research being done on lung antigen-presenting cells. Reference to a study by S.L. Constant and colleagues published in the 'Journal of Clinical Investigation'; Process of the preferential priming of protein antigens; Antigen-presenting cells in the lungs.

Important insights have recently been gained in our understanding of how host immune responses mediate resistance to parasitic helminths and control associated pathological responses. Although similar cells and cytokines are evoked in response to infection by helminths as diverse as nematodes and schistosomes, the components of the response that mediate protection are dependent on the particular parasite. In this Review, we examine recent findings regarding the mechanisms of protection in helminth infections that have been elucidated in murine models and discuss the implications of these findings in terms of future therapies. [ABSTRACT FROM AUTHOR]

B-lymphocyte-induced maturation protein 1 (BLIMP1) is a transcriptional repressor, and its importance in controlling the terminal differentiation of antibody-secreting cells (ASCs) is well established. However, as we discuss in this Progress article, it has now become evident that the ASC programme consists of a discrete BLIMP1-independent initiation phase, followed by a second step in which BLIMP1 is absolutely required for the differentiation of fully mature ASCs. In addition, an important role for BLIMP1 in maintaining the homeostasis of effector T cells is emerging, suggesting intriguing parallels between the control of effector-cell fates in both B and T cells. [ABSTRACT FROM AUTHOR]

The clearance of apoptotic cells by phagocytes is an integral component of normal life, and defects in this process can have significant implications for self tolerance and autoimmunity. Recent studies have provided new insights into the engulfment process, including how phagocytes seek apoptotic cells, how they recognize and ingest these targets and how they maintain cellular homeostasis after the 'meal'. Several new factors that regulate engulfment have been identified, whereas the roles of some of the older players require revision. This Review focuses on these recent developments and attempts to highlight some of the important questions in this field. [ABSTRACT FROM AUTHOR]

CD1d-dependent natural killer T (NKT) cells are a unique T-cell subset with the ability to regulate the immune system in response to a broad range of diseases. That low NKT-cell numbers are associated with many different disease states in mice and humans, combined with the fact that NKT-cell numbers vary widely between individuals, makes it crucial to understand how these cells develop and how their numbers are maintained. Here, we review the current state of knowledge of NKT-cell development and attempt to highlight the most important questions in this field. [ABSTRACT FROM AUTHOR]

Discusses research on PIM-1 phosphorylates and its enhancement of NFAT-dependent transcription. Regulation of PIM-1 expression during T-cell activation; Role of PIM-1 kinase in signalling for NFAT activation; Implications of the study findings for the mechanism of PIM-1.

Somatic hypermutation (SHM) introduces mutations in the variable region of immunoglobulin genes at a rate of ∼10−3 mutations per base pair per cell division, which is 106-fold higher than the spontaneous mutation rate in somatic cells. To ensure genomic integrity, SHM needs to be targeted specifically to immunoglobulin genes. The rare mistargeting of SHM can result in mutations and translocations in oncogenes, and is thought to contribute to the development of B-cell malignancies. Despite years of intensive investigation, the mechanism of SHM targeting is still unclear. We review and attempt to reconcile the numerous and sometimes conflicting studies on the targeting of SHM to immunoglobulin loci, and highlight areas that hold promise for further investigation. [ABSTRACT FROM AUTHOR]