Reviews & Analysis

Infections with HIV, hepatitis B virus and cytomegalovirus have markedly different outcomes depending on whether they are acquired during infancy or adult life. Information about the differences between antiviral immune responses in early and later life that can be gained from these examples should inform the development of new therapeutic strategies.

T cells must recognize a vast array of potential foreign peptide–MHC complexes. Comprehensive immune cover can only be provided if each T cell recognizes numerous peptides. The implications of this T cell cross-reactivity include autoimmune disease but also provide opportunities for multiple therapeutic interventions.

Forkhead box O (FOXO) transcription factors have many diverse physiological functions and regulate gene-expression programmes that are involved in immunity, metabolism and oncogenesis. This Review discusses how FOXO proteins integrate different environmental signals in order to regulate T cell differentiation and functions in a context-dependent manner.

In this Review, the authors describe how immune responses are initiated and propagated against antigens found in the central nervous system (CNS). They explain how the unique anatomy of the CNS affects immune surveillance of its tissues, and discuss the implications for autoimmune responses in the CNS.

This Review summarizes the past, current and future directions for the development of mucosal vaccines, with a particular focus on the importance of the formulation, the route of administration and the choice of adjuvant for the induction of protective mucosal immunity.

Patients with autoinflammatory diseases develop pathological tissue inflammation in the absence of any autoreactive B or T cell responses. Recent studies have shown that defective regulation of pro-inflammatory immune components or protein handling pathways can provoke such autoinflammatory attacks. This Review describes the latest findings in the field and discusses their therapeutic significance.

The development of effective antiretroviral therapies has greatly improved the disease prognosis for patients with HIV. However, the limitations of these therapies have renewed interest in developing alternative treatment strategies. Here, a group of experts from the International AIDS Society discuss the research steps that need to be taken to achieve the ultimate objective — a cure for HIV.

This Review integrates recent evidence regarding the intracellular trafficking pathways involved in cross-presentation into our understanding of the role of cross-presentation in immunity and tolerance.

Here, Joel Ernst proposes that there are distinct stages in the immune response toMycobacterium tuberculosisthat form an 'immunological life cycle'. The description of this framework can help the understanding and study of immunity to tuberculosis in humans and animal models.

Here, Paolo Casali and colleagues provide a comprehensive overview of the molecular mechanisms that drive immunoglobulin class-switch DNA recombination (CSR). They describe the signalling determinants of CSR specificity and the epigenetic modifications, transcriptional regulators and scaffold elements that direct the CSR machinery.

This Review looks at the regulation and functions of antimicrobial proteins in protecting epithelial surfaces from pathogen invasion and maintaining homeostasis with commensal microorganisms.

It is becoming increasingly clear that the activation of the innate immune system by host or microbial nucleic acids contributes to the immunogenicity of many vaccines. This article describes the receptors and signalling pathways that are involved in sensing nucleic acids and discusses the implications for current and future vaccination strategies.

Phagocytosis is an important innate defence mechanism, and there is more to this process than merely engulfing a pathogen. This Review discusses how myeloid cells integrate the various distinct signals that they receive during phagocytosis in order to promote an appropriate immune response to the threat at hand.

Ion channels and transporters, by modulating cytoplasmic concentrations of various cations, control key lymphocyte effector functions. Here, the authors review the roles of these proteins in lymphocytes and how they might interact to fine-tune cell responses.

It has long been known that infections and tissue damage can be detrimental for the survival of transplanted allografts but the underlying mechanisms that trigger both innate and adaptive immunity are only beginning to be understood and are reviewed here.

In this article, the importance of the peripheral production of complement in driving the immediate response of a transplanted organ to tissue stress and in the activation of alloreactive T cells is discussed, as well as the role of complement in antibody-mediated rejection. The authors also focus on new complement-targeted treatments for the prevention of transplant rejection.

Establishing immune tolerance in transplant recipients is essential for promoting the long-term survival of an allograft and for preventing the development of harmful graft-versus-host responses. This Review considers the clinical potential of manipulating different immunosuppressive cell populations, including regulatory T cells, B cells and macrophages, in the setting of transplantation.

Haematopoietic cell transplantation (HCT) is most frequently performed as a cancer therapy. However, more recently HCT has been used to treat patients with autoimmune diseases and to promote tolerance to other allografts. Here, the authors discuss the latest advances in HCT and the challenges still faced by researchers in the field.

Here, the authors review the most promising strategies for preventing or treating graft-versus-host disease after allogeneic haematopoietic stem cell transplantation. Approaches that target alloreactive T cells are often favoured, but those that exploit regulatory cell populations are now showing increasing success.

This article looks at the crosstalk between multipotent mesenchymal stromal cells (MSCs) and innate immunity, ranging from haematopoiesis to antimicrobial defences.