Review Articles in 2007

The thymus is a specialized environment that controls the development of T cells. In this article, Graham Anderson and colleagues review the role of the thymic stroma in controlling T-cell development, focusing on the development and function of thymic epithelial cells.

This Review describes the journey taken by the MHC-class-I-like CD1 molecules, detailing their assembly, intracellular trafficking and loading with lipid antigens. By taking distinct routes, the different CD1-family members ensure that each intracellular compartment is surveyed for their lipid cargo.

How does a T cell recognize an allogeneic antigen? How does it compare with the conventional recognition of self antigen? Why does alloreactivity exist? Here, Paul Allen and Nathan Felix discuss these questions in the context of recent advances in our understanding of allorecognition.

Helminths infect millions of people worldwide. In this Review, William Gause and colleagues outline the current understanding of immune responses against helminth infections, focusing on results obtained in mouse models of infection withHeligmosomoides polygyrus and Schistosoma mansoni.

This Review describes the recent insights into the receptors and signalling pathways that are required for the engulfment of apoptotic cells, with particular emphasis on the 'find-me' and 'eat-me' signals expressed on apoptotic cells.

To survive a given infection, a host needs to mount a controlled immune response. Regulatory T cells are important components of the regulatory network, which benefit the host by limiting immunopathology but may also be detrimental to the host by favouring pathogen survival.

The existence of membrane rafts has been widely debated, but as discussed in this Review, recent evidence suggests that, by tethering and trapping membrane microdomains, the actin cytoskeleton has an important role in orchestrating membrane-raft dynamics during lymphocyte signalling.

The study of individuals with primary immunodeficiencies (PIDs) has helped to define mechanisms that control the development and function of the immune system. This Review focuses on recently characterized PIDs and describes the genetic defects that are associated with these disorders.

Many receptors of the immune system are composed of ligand-binding subunits combined with signalling subunits. Here, Matthew Call and Kai Wucherpfennig review recent studies on the assembly and architecture of these receptors and discuss the implications of these studies.

Ferrandon and colleagues describe the recognition of bacterial and fungal pathogens byDrosophila melanogaster,the signalling pathways that are activated and the antimicrobial peptides that are induced, highlighting parallels with the mammalian immune system.

Fluctuations in cytosolic calcium concentrations affect numerous signals involved in the development and function of B cells. Recent advances have expanded our understanding of the mechanisms involved in the regulation of cytosolic calcium concentrations and how this influences B-cell fate.

Recent advances using genetic analysis in both insects and mammals have expanded our understanding of how the immune system senses viruses and initiates immune responses against them. But what are the biochemical pathways involved and how do immune cells work together to control viral infection?

Autophagy — a cellular process for recycling, remodelling or disposing of unwanted cytoplasmic constituents — is emerging as an important pathway in innate and adaptive immunity. This Review describes its role in pathogen defence, antigen processing and presentation, T-cell homeostasis and disease.

Endothelial cells, which line the blood and lymph vessels, control the movement of proteins from the blood into the tissue. However, as discussed here, these often overlooked cells are also active participants in and regulators of the inflammatory process.

The ability of dendritic cells to drive immune responses has led researchers to target these cells in vaccination therapy. Here, the authors review the development of the field, fromex vivo loading studies to in vivotargeting using specific receptors.

Natural killer (NK) cells perform multiple functional activities, including rapid cytokine production and spontaneous cytotoxicity. James Di Santo and colleagues review the evidence that such functional heterogeneity arises from the development of diverse NK-cell subsets with unique biological roles.

To get to the site of inflammation, leukocytes must first adhere to and traverse the blood-vessel wall, events that occur in a cascade-like manner. But what are the exact steps in this cascade and what molecules are involved?

Although best known for its role in mother-to-child IgG transfer, new roles for the neonatal Fc receptor for IgG (FcRn) are emerging. Its role in regulating serum antibody half-life in adults has important implications for autoimmune diseases and antibody-based biologicals.

Recently, two key regulators of calcium influx in lymphocytes were discovered — STIM and ORAI. How this has advanced our understanding of calcium signalling in lymphocytes and the pathological consequences of disruption of this pathway are discussed in this Review.

Hedgehog signalling proteins, and in particular sonic hedgehog, have a role in T-cell development in the thymus and in peripheral T-cell activation, but, as outlined here, some aspects of their functions remain controversial.