Review Articles in 2006

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.

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.

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.

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.

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.

Recent advances in our understanding of the mechanisms of atherosclerosis, which is an inflammatory disease that involves the formation of plaques in the arteries, indicate that the immune response can both promote and reduce disease.

Defensins are important effectors of innate immunity. Recent studies have elucidated the mechanisms of their antiviral activity, indicating that they have both direct effects on viruses and indirect effects on target cells. In addition, defensins have immunomodulatory activities.

Members of the carcinoembryonic-antigen-related cell-adhesion molecule (CEACAM) family are involved in intercellular binding interactions affecting various normal and pathogenic processes. This article provides an overview of the role of CEACAMs in immunity, focusing on the function of CEACAM1.

Studies of microbial superantigens that target B cells provide better understanding of B-cell-receptor interactions and supraclonal dysregulation. Their ability to induce tolerance that subverts host defences may provide new therapeutic approaches for the treatment of B-cell-mediated autoimmune and neoplastic diseases.

Signal-regulatory proteins (SIRPs) are members of the paired-receptor family, which regulate and fine-tune immune responses. Their rolein vivois influenced by the different affinities of the SIRPs for their ligands and by their expression levels.

With the search for an HIV vaccine still ongoing, attention is turning towards developing topical prevention strategies that prevent HIV transmission. This Review describes the rationale behind the choice of targets for such strategies and how their clinical development is progressing.