Reviews & Analysis

The immunological synapse formed between a natural killer cell and its target cell facilitates the coordinated and directional delivery of lytic granules to the cell–cell interface. Jordan Orange describes how this occurs and discusses the insights gained from studies of human genetic diseases.

Recent advances in imaging techniques have allowed researchers to 'spy' on T cells and dendritic cells (DCs) as they interact in intact lymph nodes. In this Review, Philippe Bousso discusses how these studies have provided new insights into the processes that underlie T-cell activation by DCs.

Mesenchymal stem cells (MSCs) have been used in the clinic to treat some human conditions, but what effect do they have on the immune system? This article describes the immunomodulatory properties of MSCs and discusses how these findings can be translated to the clinic.

This Review focuses on recently described regulatory mechanisms that fine-tune T-cell receptor (TCR) signalling. Such mechanisms, which are rapid and intrinsic to the TCR signalosome, may explain how the TCR can discriminate true ligands from background noise and induce an appropriate T-cell response.

The TIM (T-cell immunoglobulin domain and mucin domain) proteins are emerging as important regulators of immune responses. The recent identification of TIM-protein expression by antigen-presenting cells and new TIM-protein ligands is revealing new roles for these proteins.

The pathways of antigen processing and presentation are well known, but how do antigens gain access to MHC molecules in dendritic cells and what is the role of autophagy, endoplasmic reticulum dislocation and Toll-like receptors in these pathways?

The outcome of HIV infection is strongly influenced by the particular HLA genes expressed by the infected individual. Here, the authors draw on this association to evaluate what might constitute an effective CD8⁺T-cell response and how it might guide vaccine design.

With the identification of more disease-susceptibility genes than ever before, 2007 is thought of by many human geneticists as the year of genome-wide association studies. In this Review, the authors discuss how this powerful approach continues to reveal new information about the susceptibility and pathogenesis of several immune-mediated diseases.

By providing a global view of the host response to infection, functional genomic approaches are proving useful in deciphering complex virus–host interactions. Here, the authors reveal how such approaches are being used to better understand viral triggering and regulation of host innate immune responses.

This Review covers the recently discovered roles of WNT proteins in the regulation of haematopoietic stem-cell fate, T- and B-cell development and activation, and dendritic-cell maturation. These new immunohaematological functions of WNT proteins have implications for the development of haematological malignancies.

By sensing viral nucleic acids and producing type I interferons, plasmacytoid dendritic cells (pDCs) are key mediators of antiviral immunity. But pDCs might also contribute to autoimmune disease by responding to self nucleic acids. Here, pDC mechanisms of action and modes of regulation are reviewed.

Recent research on MALT1 (mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1), a protein essential for nuclear factor-κB (NF-κB) activation, has uncovered new mechanisms by which MALT1 can orchestrate intracellular signalling events. Here, Margot Thome highlights recent progress which characterizes how the protease and scaffolding functions of MALT1 modulate T-cell activation.

This Review describes the significant progress that has been made recently in our understanding of the immunoregulatory role of deubiquitylation. Shao-Cong Sun discusses the deubiquitylating enzymes, in particular CYLD and A20, that have been shown to modulate innate and adaptive immunity.

Regulatory T cells (T_Reg cells) have a central role in immune regulation, but how do they work? In this Review, our current understanding of the suppressive mechanisms used by T_Reg cells is described and the relative contribution of these mechanisms to T_Reg-cell function is discussed.

Type I interferons (IFNs) provide the first line of defence against viral infection. As discussed in this Review, the IFN-induced antiviral effector proteins, such as ISG15, Mx proteins, ribonuclease L and protein kinase R, are important components of this response.

A decline in T-cell immunity is a major cause of morbidity and mortality from infectious diseases in the elderly. Janko Nikolich-Žugich weighs up the relative roles of and the interplay between homeostatic factors and persistent viruses in immune senescence.

Surprisingly, and somewhat counter-intuitively, partial T-cell immunodeficiencies are commonly associated with hyper-immune dysregulation. Here, the authors review the genetic basis of such immunodeficiencies and draw on mouse models to provide a potential explanation for the coexistence of immunodeficiency and autoimmunity.

As discussed in this article, in addition to their role as haematopoietic-cell growth factors, colony-stimulating factors have broader roles in immunity, and targeting these factors might have therapeutic benefits in inflammation and autoimmunity.

A delicate balance between tolerance to commensal bacteria and immunity to pathogens occurs in the intestine. Intestinal dendritic cells have a central role in maintaining this balance and, as described here, some of the molecular pathways involved have recently been resolved.

Infection by HIV requires the virus to breach the mucosal barrier to gain access to the immune cells that it infects. But what are the immediate events that follow HIV exposure at genital mucosal sites and what are the key cells that facilitate HIV invasion?