Reviews & Analysis

This Review integrates information fromin vitro and in vivomodels of dendritic-cell (DC) development to provide an emerging, but still fragmented, picture of the pathways and precursor cells that lead to the different DC subtypes in the steady state and during inflammation.

Notch proteins are known to have crucial roles in determining cell fate during lymphoid development. But now, new research indicates that Notch signalling might also be important during T-cell activation and differentiation in the periphery, as discussed in this Review.

Fine tuning of immunity is achieved through numerous mechanisms: chemokine sequestration by non-signalling chemokine 'decoy' receptors is one example. This Review describes the chemokine decoy receptors that have evolved in both humans and viruses to elude chemokine activities and divert leukocyte recruitment.

Recent studies of the expression patterns and intracellular locations of individual SNARE proteins, which control membrane-fusion events involved in intracellular trafficking, have begun to shed light on their functions in immune responses, including the secretion of immune mediators, phagocytosis and the formation of immunological synapses.

The complement system is known to be a main part of both innate and antibody-mediated immunity. Here the emerging role of complement in the regulation of the initiation, effector and contraction phases of the T-cell response is discussed, and new perspectives in this area are revealed.

Generating an effective AIDS vaccine remains a high priority. Are we any closer to reaching this goal? How might we overcome virus variability and generate a vaccine that elicits protective humoral and cellular immune responses at mucosal surfaces as well as systemically?

Perforin is crucial for inducing the death of infected or transformed cells by cytotoxic lymphocytes. Clues to its mechanism of action and role in immune homeostasis have been gained from analysis of patients with a severe immunodeficiency disorder that is due to perforin mutations.

Toll-like receptors (TLRs) have an important role in the initiation of innate immunity following infection with protozoans. Here the activation of TLRs by protozoan components is described and TLR-based strategies to prevent or treat disease are discussed.

Antigen-specific T-cell responses are often characterized by the preferred use of certain T-cell receptors (TCRs). This Review describes when and how this might occur, with particular focus on the structural constraints that determine binding of a TCR to its ligand.

HIV has evolved ways to exploit dendritic cells to facilitate spread of the virus through the body. Dendritic cells can mediate the transfer of HIV to target CD4⁺T cells through several distinct mechanisms, as discussed in this Review.

Toll-like receptors are well known as sensors of microorganisms, but they can also sense endogenous molecules. This article describes when this might occur and how it might activate autoreactive B cells and plasmacytoid dendritic cells in systemic autoimmune disease.

Type I and type II interferons have overlapping and distinct functions in the host immune response to cancer. In this article, recent data that link interferons to the process of cancer immunoediting are reviewed, and possible therapeutic applications are considered.

How are signals initiated at the antigen receptors of T and B cells transmitted to nuclear factor-κB (NF-κB)? This Review presents a cohesive model of the activation of NF-κB, which unravels the sequence of events and the signalling machinery involved.

The importance of T helper 2 cells in asthma has long been known. Now, new evidence indicates that invariant natural killer T cells might have a distinct and crucial role in the development of asthma.

An emerging concept is that sepsis is in fact due to an impaired immune response owing to excessive apoptosis of immune cells and the immunosuppressive effect that occurs as a result of the uptake of these cells. Might the use of caspase inhibitors be of therapeutic benefit in the treatment of sepsis?

The commensal gut bacteriumBacteroides fragilismight be the key to a healthy immune system. A zwitterionic polysaccharide that is produced by this bacterium has immunomodulatory properties, and the authors suggest that this supports the 'hygiene hypothesis' at a molecular level.

An appreciation of the crosstalk between cells of the innate and the adaptive immune system is increasingly important for understanding both health and disease. As highlighted here, reciprocal regulation between natural killer cells and autoreactive T cells can influence all stages of autoimmune disease.

This Review article discusses the importance of secondary gene rearrangements in the alteration of antigen-receptor specificity by B cells and T cells, and describes how this process is facilitated by the different genomic organization of the loci that encode the two antigen-receptor chains.

Allergen-specific immunotherapy can ameliorate the symptoms of allergic diseases and has shown long-lasting benefits. Recent work discussed in this Review indicates that the beneficial effects result from immunomodulation, including a switch to IgG responses and induction of regulatory T cells.

In this Opinion article, a new model for the generation and the maintenance of memory B cells is proposed. The model involves these cells being continuously produced by the germinal centre throughout an immune response, with B cells that are produced later in the response being fitter and therefore having a survival advantage.