Review Articles in 2012

Several mechanisms exist to prevent immune-mediated rejection of the allogeneic fetus. Here, Adrian Erlebacher provides an in-depth review of recent advances in our understanding of the mechanisms that control the responses of maternal T cells to antigens expressed by the conceptus.

Recent interest in identifying interferon-stimulated genes that have activity against a wide range of viruses has advanced our understanding of the IFIT and IFITM families and shown the many mechanisms by which host factors can restrict viral replication.

Thrombosis is the most frequent cause of mortality worldwide. In this Review, the authors propose that thrombosis might also have a conserved physiological role in immune defence via a process termed immunothrombosis. However, if uncontrolled, immunothrombosis facilitates pathological clot formation.

This Review describes the unique biology of the eosinophil. The authors explain how eosinophils interact with other leukocyte populations to promote protective immunity following infection. They also discuss the pathological roles of eosinophils in allergic-type diseases, such as asthma and the hypereosinophilic syndromes.

Here, the authors discuss how the T cell receptors expressed by natural killer T cells are able to recognize and respond to an array of self and foreign lipid antigens that are presented on CD1d molecules. They explain how a better understanding of these processes could be exploited for therapeutic purposes.

Inhibitor of apoptosis proteins (IAPs) contribute to innate immune responses not only through cell death control but also as essential components of pattern-recognition receptor (PRR) signalling. Here, the ubiquitin ligase activity of IAPs downstream of PRR activation is discussed, along with its therapeutic implications.

Secretory IgA is an important first-line defence mechanism that protects mucosal barrier tissues from environmental microorganisms and toxins. Here, the author discusses the pathways that lead to the generation of secretory IgA and proposes a model to describe the variable quality of IgA responses against pathogens and commensals.

This Review describes how CD8⁺T cells coordinate signals mediated by antigens, co-stimulatory molecules, pro-inflammatory cytokines and metabolic state to regulate the transcriptional programmes that determine differentiation to diverse effector and memory cell fates.

Human genetic studies associate defective A20 activity with autoimmune and autoinflammatory diseases, as well as with cancer. Here, Ma and Malynn discuss the complex mechanisms through which A20 may control immune cell activation and survival, thereby maintaining homeostasis.

This article provides a comprehensive overview of the recent advances in the development and use of humanized mice. The authors consider the remaining challenges and the potential for new advances in our understanding of human immunology through the use of these mice.

The recirculation of lymphocytes through lymph nodes and their encounter with dendritic cells is crucial for immunity. Here, the authors review the role of high endothelial venules, lymphatics and lymph node stroma in the trafficking of immune cells in lymph nodes during homeostasis.

Here, Patrick Wilson and Sarah Andrews discuss the strategies that have been used to identify rare broadly neutralizing antibodies, focusing on the recent advances in isolating such antibodies naturally generated in response to HIV and influenza virus infection or vaccination.

Dietary habits have always been associated with the robustness of the immune system. Here, the molecular links between dietary compounds and immune regulation in the intestine are discussed, with a focus on the central role of nuclear receptors.

The evolutionary 'arms race' between host restriction factors and viral antagonists has left a genetic 'signature' that can tell us much about the innate immune response to past and present viral infections.

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.

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.

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.