Reviews & Analysis

Adipose tissue produces several inflammatory mediators, including the adipocytokines adiponectin, leptin and resistin. Here, recent advances in our understanding of the role of these adipocytokines in inflammation and immunity are discussed, highlighting the importance of these mediators in obesity-associated diseases.

How does the immune system remember? The elegant system by which plasmablasts specific for 'new' pathogens compete with plasma cells specific for 'old' pathogens to gain access to survival niches ensures that the humoral immune system adapts to newly encountered antigens but does not forget those previously encountered.

Although there are numerous immune mechanisms that destroy cancer precursors, the selection of tumour cells that are poorly immunogenic and that can subvert the immune response is crucial to the development of cancer. How these processes are linked is discussed in this Review.

A discussion of structural and functional studies examining the unexpected interaction of the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) with the co-stimulatory receptor herpesvirus-entry mediator (HVEM) and their role in the regulation of many types of cell.

The sentinel lymph node (SLN) is the first node to receive lymph from a primary tumour. In this Review, the immunology of the SLN, the way in which tumour cells modulate the SLN to facilitate metastases, and possible therapies to reverse this process are discussed.

Members of the interferon-regulatory factor (IRF) family of transcription factors are known to have diverse immunoregulatory roles. This article reviews this rapidly developing field, describing how IRFs are the master regulators of immune responses mediated by both transmembrane and cytosolic pattern-recognition receptors.

To mediate their function, effector T cells must home to extralymphoid tissues. William Agace reviews how homing to certain tissues is bestowed on effector T-cell subsets and describes an important role for draining lymph nodes and tissue-derived dendritic cells in this process.

How Toll-like receptors respond to specific ligands and activate selective signalling pathways is not fully understood. This Perspective proposes a molecular mechanism, involving a series of protein conformational changes that are initiated by receptor dimerization, that might account for this specificity.

The importance of heparan sulphate, which is ubiquitously expressed as a proteoglycan, in leukocyte extravasation is often overlooked. Owing to the remarkable structural diversity of heparan sulphate proteoglycans, these molecules interact specifically with numerous proteins and participate in almost all stages of leukocyte extravasation.

How GITR (glucocorticoid-induced tumour-necrosis-factor-receptor-related protein) regulates an immune response is not clearly understood. This article proposes a model in which the interaction of GITR with its ligand co-stimulates the respective functions of both responder T cells and CD4⁺CD25⁺regulatory T cells.

The passage of transcription factors in and out of the nucleus must be regulated for their proper function. Surprisingly, regulation of nuclear trafficking among members of the signal transducer and activator of transcription (STAT) family differs, revealing specific targets for therapeutic intervention.

A new way to view the immunology of pregnancy is discussed, which takes into account the differing placental strategies used by eutherian mammals. Why some human pregnancies fail might depend on the degree of invasion of the uterus by placental trophoblast cells.

How are different memory T-cell subsets related? This is a topic of much debate; but in this article, it is suggested that the central memory and effector memory CD8⁺T cells that are generated after an acute infection are distinct cell lineages.

Somatic hypermutation (SHM) introduces mutations in the variable region of immunoglobulin genes, to generate high-affinity B-cell antigen receptors. But, as discussed in this Review, how SHM is targeted to immunoglobulin genes is a subject of intense research and debate.

Although the heterotrimeric receptors for interleukin-2 (IL-2) and IL-15 have two subunits in common, these cytokines have contrasting roles in adaptive immune responses. Understanding the biology of these cytokines and their receptors has important implications for their use as therapeutic agents.

The precise point at which haematopoietic precursors commit to being T cells is a hotly debated area. Eric Jenkinson and colleagues propose that, in the fetus, commitment occurs prethymically and Notch signalling in the thymus reaffirms rather than determines such commitment.

This article describes recent studies defining thein vivoimportance of neutrophil serine proteases in the intracellular and extracellular killing of microorganisms, as well as in the regulation of non-infectious inflammatory processes, such as the modulation of active cytokine concentrations.

This article aims to make the methodology behind the recent spate of papers reportingin situimmune-cell imaging more accessible to the reader and to highlight potential artefacts so that the reader can analyse the data more critically.

The way in which natural killer (NK) cells acquire tolerance to self is still not fully understood. Possible mechanisms involved in NK-cell self-tolerance are discussed in detail in this Review, with an emphasis on the involvement of MHC-class-I-specific receptors.

The p38 proteins are mitogen-activated protein kinases (MAPKs) that are activated by the MAPK cascade in response to pro-inflammatory cytokines and cell stresses. However, an alternative pathway of p38 activation might be particularly important in T cells and inflammatory cells.