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The article discusses a study by T. Enzler which provides unexpected insights into the role of the immune system in promoting or inhibiting tumour development. They suggest that the immune system rather than deleting nascent tumour cells, keeps the microbiome in balance so that pathogenic bacteria do not become dominant and cause persistent cancer-causing inflammation. They show that the function of immunosurveillance with respect to cancer initiation is to restrain pathogenic organisms.

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.

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 paper "Cathepsin K-dependent Toll-like receptor 9 signaling revealed in experimental arthritis," by M. Asagiri and colleagues. The study demonstrates the role of NC-2300, an orally active cathepsin K inhibitor, in bone resorption by osteoclasts and in mediating immune responses. The data describe a new role for cathepsin K in Toll-like receptor 9 (TLR9) signaling in response to unmethylated CpG-containing DNA and in the production of interleukin-6 (IL-6) and IL-23.

An abstract on autoimmunity from self DNA of necrotic or apoptotic cells that induced pro-inflammatory cytokine production by myeloid cells in a STING-dependent manner is presented.

The article discusses two studies published in "Nature Medicine" which describe new roles for interleukin-22 (IL-22), an IL-10-family cytokine that is mainly produced by T helper 17 (TH17) cells, in host defense at mucosal surfaces. It highlights the key findings of the papers "Interleukin-22 mediates mucosal host defense against Gram-negative bacterial pneumonia" and "Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens."

The article discusses the study which determines the crucial role of mammalian target of rapamycin (mTOR) in the blending of the signals from the three factors to determine the effector versus memory CD8+ T cells responses. The researchers involve the antigen, co-stimulation for T cell activation and cytokine stimulation to determine the result. Researchers then show that mTOR is the crucial point of integration in CD8+ T cells for signals that programme effector versus memory differentiation.

The article presents a study on thymocyte-selected CD4+ T cells. It focuses on the comparison of cytokine production from T cells isolated from wild-type mice. This research revealed that thymic selection pathway influences the effector function of CD4+ T cells and suggests investigations to address the role of thymocyte-selected D4+ T cells in immune responses.

Naive CD8(+) T cells give rise to cytotoxic T lymphocytes (CTLs), which promote the effective eradication of viruses and tumours. Although the past decades have seen enormous advances in cellular immunology, a precise understanding of the key elements that determine the specificity and magnitude of primary CTL responses has been lacking. However, recent technological advances have allowed us to more accurately identify, characterize and quantitate key determinants that define the specificity and magnitude of CD8(+) T cell-mediated immunity. This Review discusses the technical and conceptual advances that have markedly changed our understanding of the determinants of primary CTL responses. [ABSTRACT FROM AUTHOR]

The body is host to a wide variety of microbial communities from which the immune system protects us and that are important for the normal development of the immune system and for the maintenance of healthy tissues and physiological processes. Investigators have mostly focused on the bacterial members of these communities, but fungi are increasingly being recognized to have a role in defining these communities and to interact with immune cells. In this Review, we discuss what is currently known about the makeup of fungal communities in the body and the features of the immune system that are particularly important for interacting with fungi at these sites. [ABSTRACT FROM AUTHOR]

As we age, the innate immune system becomes dysregulated and is characterized by persistent inflammatory responses that involve multiple immune and non-immune cell types and that vary depending on the cell activation state and tissue context. This ageing-associated basal inflammation, particularly in humans, is thought to be induced by several factors, including the reactivation of latent viral infections and the release of endogenous damage-associated ligands of pattern recognition receptors (PRRs). Innate immune cell functions that are required to respond to pathogens or vaccines, such as cell migration and PRR signalling, are also impaired in aged individuals. This immune dysregulation may affect conditions associated with chronic inflammation, such as atherosclerosis and Alzheimer's disease. [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]

Protective responses to microorganisms involve the nonspecific but rapid defence mechanisms of the innate immune system, followed by the specific but slow defence mechanisms of the adaptive immune system. Located as sentinels at the interface between the circulation and lymphoid tissue, splenic marginal zone B cells rapidly respond to blood-borne antigens by adopting 'crossover' defensive strategies that blur the conventional boundaries of innate and adaptive immunity. This Review discusses how marginal zone B cells function as innate-like lymphocytes that mount rapid antibody responses to both T cell-dependent and T cell-independent antigens. These responses require the integration of activation signals from germline-encoded and somatically recombined receptors for microorganisms with helper signals from effector cells of the innate and adaptive immune systems. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) comprises the brain, spinal cord, optic nerves and retina, and contains post-mitotic, delicate cells. As the rigid coverings of the CNS render swelling dangerous and destructive, inflammatory reactions must be carefully controlled in CNS tissues. Nevertheless, effector immune responses that protect the host during CNS infection still occur in the CNS. Here, we describe the anatomical and cellular basis of immune surveillance in the CNS, and explain how this shapes the unique immunology of these tissues. The Review focuses principally on insights gained from the study of autoimmune responses in the CNS and to a lesser extent on models of infectious disease. Furthermore, we propose a new model to explain how antigen-specific T cell responses occur in the CNS. [ABSTRACT FROM AUTHOR]

The article focuses on the role of mitochondria, and the reactive oxygen species (ROS) that they produce, in inflammation. It states that mitochondrial ROS enhance pro-inflammatory cytokine production through the regulation of the mitogen-activated protein kinase (MAPK) pathway. It states that reducing the levels of mitochondrial ROS may be a potential therapeutic strategy for patients with TNF receptor-associated periodic syndrome (TRAPS).

The article delves into a report stressing the significance of the pro-inflammatory cytokine tumour-necrosis factor (TNF) and its receptors to the regulation of immune responses on conditions with limited immunostimulatory capacity. It highlights the relation of the involvement of TNF in immunity to the immunostimulatory properties of lymphocytic choriomeningitis virus glycoprotein. The impact of the report to the tumour progression of cancer patients treated with TNF antagonists is noted.

The vertebrate immune system has evolved in concert with a broad range of infectious agents, including ubiquitous helminth (worm) parasites. The constant pressure of helminth infections has been a powerful force in shaping not only how immunity is initiated and maintained, but also how the body self-regulates and controls untoward immune responses to minimize overall harm. In this Review, we discuss recent advances in defining the immune cell types and molecules that are mobilized in response to helminth infection. Finally, we more broadly consider how these immunological players are blended and regulated in order to accommodate persistent infection or to mount a vigorous protective response and achieve sterile immunity. [ABSTRACT FROM AUTHOR]

The innate immune system has a key role in the mammalian immune response. Recent research has demonstrated that mitochondria participate in a broad range of innate immune pathways, functioning as signalling platforms and contributing to effector responses. In addition to regulating antiviral signalling, mounting evidence suggests that mitochondria facilitate antibacterial immunity by generating reactive oxygen species and contribute to innate immune activation following cellular damage and stress. Therefore, in addition to their well-appreciated roles in cellular metabolism and programmed cell death, mitochondria appear to function as centrally positioned hubs in the innate immune system. Here, we review the emerging knowledge about the roles of mitochondria in innate immunity. [ABSTRACT FROM AUTHOR]

Natural killer T (NKT) cells are important regulatory lymphocytes that have been shown in mouse studies, to have a crucial role in promoting immunity to tumours, bacteria and viruses, and in suppressing cell-mediated autoimmunity. Many clinical studies have indicated that NKT cell deficiencies and functional defects might also contribute to similar human diseases, although there is no real consensus about the nature of the NKT cell defects or whether NKT cells could be important for the diagnosis and/or treatment of these conditions. In this Review, we describe the approaches that have been used to analyse the NKT cell populations of various patient groups, suggest new strategies to determine how (or indeed, if) NKT cell defects contribute to human disease, and discuss the prospects for using NKT cells for therapeutic benefit. [ABSTRACT FROM AUTHOR]

Cross-priming is an important mechanism to activate cytotoxic T lymphocytes (CTLs) for immune defence against viruses and tumours. Although it was discovered more than 25 years ago, we have only recently gained insight into the underlying cellular and molecular mechanisms, and we are just beginning to understand its physiological importance in health and disease. Here we summarize current concepts on the cross-talk between the immune cells involved in CTL cross-priming and on its role in antimicrobial and antitumour defence, as well as in immune-mediated diseases. [ABSTRACT FROM AUTHOR]

CD4(+) T helper (T(H)) cells have crucial roles in orchestrating adaptive immune responses. T(H)2 cells control immunity to extracellular parasites and all forms of allergic inflammatory responses. Although we understand the initiation of the T(H)2-type response in tissue culture in great detail, much less is known about T(H)2 cell induction in vivo. Here we discuss the involvement of allergen- and parasite product-mediated activation of epithelial cells, basophils and dendritic cells and the functions of the cytokines interleukin-4 (IL-4), IL-25, IL-33 and thymic stromal lymphopoietin in the initiation and amplification of T(H)2-type immune responses in vivo. [ABSTRACT FROM AUTHOR]

Understanding how thymic selection imparts self-peptide-MHC complex restriction and a high degree of self tolerance on the T cell repertoire requires a detailed description of the parameters that shape the MHC ligand repertoire of distinct thymic antigen-presenting cells and of how these cells communicate with T cells. Several recent discoveries pertaining to cortex-specific pathways of antigen processing, the heterogeneity of thymic dendritic cells and the intercellular transfer of self antigens have uncovered surprising and unique aspects of antigen presentation in the thymic microenvironment. Here, we discuss these new findings in the context of how individual thymic stromal cell types support T cell selection in a cooperative rather than a redundant manner. [ABSTRACT FROM AUTHOR]

Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease. [ABSTRACT FROM AUTHOR]

The specificity of a given virus for a cell type, tissue or species - collectively known as viral tropism - is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role of antiviral and pro-inflammatory cytokines, particularly the interferons and tumour necrosis factor, in dictating viral tropism and how these cytokine pathways can be exploited therapeutically for cancer treatment and to better counter future threats from emerging zoonotic pathogens. [ABSTRACT FROM AUTHOR]

Interleukin-17A (IL-17A), the hallmark cytokine of the newly defined T helper 17 (T(H)17) cell subset, has important roles in protecting the host against extracellular pathogens, but also promotes inflammatory pathology in autoimmune disease. IL-17A and its receptor (IL-17RA) are the founding members of a newly described family of cytokines and receptors that have unique structural features which distinguish them from other cytokine families. Research defining the signal transduction pathways induced by IL-17R family cytokines has lagged behind that of other cytokine families, but studies in the past 2 years have begun to delineate unusual functional motifs and new proximal signalling mediators used by the IL-17R family to mediate downstream events. [ABSTRACT FROM AUTHOR]

The immune system is routinely exposed to dead cells during normal cell turnover, injury and infection. Mechanisms must exist to discriminate between different forms of cell death to correctly eliminate pathogens and promote healing while avoiding responses to self, which can result in autoimmunity. However, an effective immune response against host tissue is often needed to eliminate tumours following treatment with chemotherapeutic agents that trigger tumour cell death. Consequently, a central problem in immunology is to understand how the immune system determines whether cell death is immunogenic, tolerogenic or 'silent'. [ABSTRACT FROM AUTHOR]

The immune system provides an essential defence against invading pathogens. However, bacteria have evolved numerous strategies to overcome this defence, many of which facilitate systemic dissemination of the pathogen. Nevertheless, the host has evolved many mechanisms to detect and protect against pathogens in the vasculature. Recent studies using new imaging approaches and new mouse models are revealing previously unappreciated functions of this intravascular aspect of the immune system. In this Review, we summarize recent work in this field, highlighting in vivo imaging studies that examine the behaviour of both the immune system and bacteria in the highly dynamic microvasculature. [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]

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]

Langerhans cells (LCs) are a specialized subset of dendritic cells (DCs) that populate the epidermal layer of the skin. Langerin is a lectin that serves as a valuable marker for LCs in mice and humans. In recent years, new mouse models have led to the identification of other langerin+ DC subsets that are not present in the epidermis, including a subset of DCs that is found in most non-lymphoid tissues. In this Review we describe new developments in the understanding of the biology of LCs and other langerin+ DCs and discuss the challenges that remain in identifying the role of different DC subsets in tissue immunity. [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]

Following activation, CD4+ T cells differentiate into different lineages of helper T (TH) cells that are characterized by distinct developmental regulation and biological functions. TH17 cells have recently been identified as a new lineage of effector TH cells, and they have been shown to be important in immune responses to infectious agents, as well as in various immune diseases. Over the past two to three years, there has been a rapid progress in our understanding of the differentiation programme of TH17 cells. Here, I summarize our current knowledge of the unique gene expression, cytokine-mediated regulation and transcriptional programming of TH17 cells, and provide my personal perspectives on the future studies that are required to elucidate this lineage in more detail. [ABSTRACT FROM AUTHOR]

Inflammation is a crucial element of the host response to cellular insult. Pathogen-induced inflammation includes a molecular pathway which proceeds through activation of the protease caspase-1 to the release of the inflammatory cytokines interleukin-1 (IL-1) and IL-18. Importantly, pathogens may also induce forms of cell death that have inherently pro-inflammatory features. Here, we review recent evidence demonstrating that NLR (nucleotide-binding domain, leucine-rich repeat containing) family proteins serve as a common component of both caspase-1-activated apoptotic pathways and caspase-independent necrotic pathways. Parallels are drawn between NLR protein function and the activity of structurally similar proteins involved in cell death: the apoptotic mediator APAF1 (apoptotic-protease-activating factor 1) and the plant disease resistance NBS-LRR (nucleotide-binding site leucine-rich repeats) proteins. [ABSTRACT FROM AUTHOR]

The conventional wisdom is that cell-surface receptors interact with ligands expressed on other cells to mediate cell-to-cell communication (trans interactions). Unexpectedly, it has recently been found that two classes of receptors specific for MHC class I molecules not only interact with MHC class I molecules expressed on opposing cells, but also with those on the same cell. These cis interactions are a feature of immunoreceptors that inhibit, rather than activate, cellular functions. Here, we review situations in which cis interactions have been observed, the characteristics of receptors that bind in trans and cis, and the biological roles of cis recognition. [ABSTRACT FROM AUTHOR]

Asthma and chronic obstructive pulmonary disease (COPD) are both obstructive airway diseases that involve chronic inflammation of the respiratory tract, but the type of inflammation is markedly different between these diseases, with different patterns of inflammatory cells and mediators being involved. As described in this Review, these inflammatory profiles are largely determined by the involvement of different immune cells, which orchestrate the recruitment and activation of inflammatory cells that drive the distinct patterns of structural changes in these diseases. However, it is now becoming clear that the distinction between these diseases becomes blurred in patients with severe asthma, in asthmatic subjects who smoke and during acute exacerbations. This has important implications for the development of new therapies. [ABSTRACT FROM AUTHOR]

Allergic diseases have reached epidemic proportions worldwide. An understanding of the cellular and soluble mediators that are involved in allergic inflammatory responses not only helps in understanding the mechanisms of current treatments, but is also important for the identification of new targets that are amenable to both small-molecule and biological interventions. There is now considerable optimism with regards to tackling the allergy epidemic in light of improvements in systemic and mucosal allergen-specific immunotherapy, the identification of key cytokines and their receptors that drive T-helper-2-cell polarization, a clearer understanding of the pathways of leukocyte recruitment and the signalling pathways that are involved in cell activation and mediator secretion, and new approaches to vaccine development. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are large granular lymphocytes capable of producing inflammatory cytokines and spontaneously killing malignant, infected or 'stressed' cells. These NK-cell functions are controlled by cell-surface receptors that titrate stimulatory and inhibitory signals. However, we remain puzzled about where and when NK cells develop and differentiate, and this has fuelled the debate over the diversification of the peripheral NK-cell pool: are NK cells functionally homogeneous or are there subsets with specialized effector functions? In this Review, we consider the developmental relationships and biological significance of the diverse NK-cell subsets in mice and humans, and discuss how new humanized mouse models may help to characterize them further. [ABSTRACT FROM AUTHOR]

Suppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine signalling pathways. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules positively and negatively regulate macrophage and dendritic-cell activation and are essential for T-cell development and differentiation. Evidence is also emerging of the involvement of SOCS proteins in diseases of the immune system. In this Review we bring together data from recent studies on SOCS proteins and their role in immunity, and propose a cohesive model of how cytokine signalling regulates immune-cell function. [ABSTRACT FROM AUTHOR]

The trafficking of molecules and membranes within cells is a prerequisite for all aspects of cellular immune functions, including the delivery and recycling of cell-surface proteins, secretion of immune mediators, ingestion of pathogens and activation of lymphocytes. SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor)-family members mediate membrane fusion during all steps of trafficking, and function in almost all aspects of innate and adaptive immune responses. Here, we provide an overview of the roles of SNAREs in immune cells, offering insight into one level at which precision and tight regulation are instilled on immune responses. [ABSTRACT FROM AUTHOR]

There has been much effort recently to define the role of adipocytokines, which are soluble mediators derived mainly from adipocytes (fat cells), in the interaction between adipose tissue, inflammation and immunity. The adipocytokines adiponectin and leptin have emerged as the most abundant adipocyte products, thereby redefining adipose tissue as a key component not only of the endocrine system, but also of the immune system. Indeed, as we discuss here, several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity. Other adipocytokines, such as visfatin, have only recently been identified. Understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases. [ABSTRACT FROM AUTHOR]

CD4+ T helper 1 (T(H)1) and T(H)2 cells have long been regarded as two sides of a coin in terms of adaptive immune responses. However, as I discuss here, this concept needs to be reconsidered. In particular, recent data indicate that interleukin-17 (IL-17) is produced by T(H) cells that are distinct from the traditional T(H)1- and T(H)2-cell subsets. Furthermore, the generation of these IL-17-producing CD4+ T cells from naive precursors during immune responses is not dependent on the cytokines and transcription factors that mediate T(H)1- and T(H)2-cell development. Given that IL-17 has crucial roles in regulating tissue inflammation and the development of disease in several animal models of autoimmunity, I propose that IL-17-producing CD4+ T cells represent a distinct inflammatory T(H)-cell lineage. [ABSTRACT FROM AUTHOR]

A key determinant for the survival of intracellular pathogens is their ability to subvert the cellular processes of the host to establish a compartment that allows replication. Although most microorganisms internalized by host cells are efficiently cleared following fusion with lysosomes, many pathogens have evolved mechanisms to escape this degradation. In this Review, we provide insight into the molecular processes that are targeted by pathogens that interact with the endoplasmic reticulum and thereby subvert the immune response, ensure their survival intracellularly and cause disease. We also discuss how the endoplasmic reticulum 'strikes back' and controls microbial growth. [ABSTRACT FROM AUTHOR]

Medical advances such as allogeneic transplantation can expose patients to periods of marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Control of infection will depend ultimately on the restoration of adequate antiviral immunity, and cellular immunotherapy is an attractive approach to improving immune protection. Developments in basic immunology have led to a greater understanding of the nature of protective immunity in immunocompetent donors, and this knowledge is now being used to direct immunotherapeutic protocols. Moreover, immunological techniques that have recently been developed as research tools, such as peptide-HLA tetramers and cytokine-secretion assays, have potential application for clinical use in this setting. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cells (HSCs) give rise to all blood and immune cells and are used in clinical transplantation protocols to treat a wide variety of diseases. The ability to increase the number of HSCs either in vivo or in vitro would provide new treatment options, but the amplification of HSCs has been difficult to achieve. Recent insights into the mechanisms of HSC self-renewal now make the amplification of HSCs a plausible clinical goal. This article reviews the molecular mechanisms that control HSC numbers and discusses how these can be modulated to increase the number of HSCs. Clinical applications of HSC expansion are then discussed for their potential to address the current limitations of HSC transplantation. [ABSTRACT FROM AUTHOR]

Tremendous progress has been achieved in developmental, cellular and molecular immunology in the past 20 years, largely due to studies using the mouse as a model system and the arrival of molecular genetics. Immunology is now faced with a difficult challenge. What are the functions of the individual cells and molecules in achieving immunity to infection? Renewed interest in animal models of disease has provided considerable insight in this area, but such models of infection suffer from the inherent limitation of being experimental. In humans, the complex host--environment interaction occurs in natural, as opposed to experimental, conditions. The human model is therefore an indispensable complement to animal models, as it allows an observational genetic dissection of immunity to infection. [ABSTRACT FROM AUTHOR]

Presents information on the regulation of the cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway that will enhance the ability to design rational therapeutic strategies for immune diseases. Regulation of JAK; Regulation of STAT by protein modifications; Regulation through signaling cross-talk.

Antigen presentation by both classical MHC class II molecules and the non-classical MHC class I-like molecule CD1D requires their entry into the endosomal/lysosomal compartment. Lysosomal cysteine proteases constitute an important subset of the enzymes that are present in this compartment and, here, we discuss the role of these proteases in regulating antigen presentation by both MHC class II and CD1D molecules. [ABSTRACT FROM AUTHOR]

The classical pathway of interferon-γ-dependent activation of macrophages by T helper 1 (TH1)-type responses is a well-established feature of cellular immunity to infection with intracellular pathogens, such as Mycobacterium tuberculosis and HIV. The concept of an alternative pathway of macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 has gained credence in the past decade, to account for a distinctive macrophage phenotype that is consistent with a different role in humoral immunity and repair. In this review, I assess the evidence in favour of alternative macrophage activation in the light of macrophage heterogeneity, and define its limits and relevance to a range of immune and inflammatory conditions. [ABSTRACT FROM AUTHOR]

CD8+ T cells are the main effector cells for the immune control of cytomegaloviruses. To subvert this control, human and mouse cytomegaloviruses each encode a set of immune-evasion proteins, referred to here as immunoevasins, which interfere specifically with the MHC class I pathway of antigen processing and presentation. Although the concerted action of immunoevasins prevents the presentation of certain viral peptides, other viral peptides escape this blockade conditionally or constitutively and thereby provide the molecular basis of immune surveillance by CD8+ T cells. The definition of viral antigenic peptides that are presented despite the presence of immunoevasins adds a further dimension to the prediction of protective epitopes for use in vaccines. [ABSTRACT FROM AUTHOR]

Established models of T-helper-2-cell dominance in BALB/c mice infected with Leishmania major — involving the early production of interleukin-4 by a small subset of Leishmania-specific CD4+ T cells — have been refined by accumulating evidence that this response is not sufficient and, under some circumstances, not required to promote susceptibility. In addition, more recent studies in L. major-resistant mice have revealed complexities in the mechanisms responsible for acquired immunity, which necessitate the redesign of vaccines against Leishmania and other pathogens that require sustained cell-mediated immune responses. [ABSTRACT FROM AUTHOR]