Reviews & Analysis

The relapsing-remitting form of multiple sclerosis affects around two thirds of patients with this disease. This Review discusses the roles of three key molecules — α4β1 integrin, its binding partner osteopontin and the chaperone protein αB crystallin — in the biology of relapse and remission.

With recent studies revealing the genetic determinants of multiple sclerosis, our attention must now turn to defining the function of the candidate genes in disease pathogenesis. This Review describes our progress so far and the approaches required to tease out the contribution made by multiple genetic and environmental factors.

Work in the past decade has revealed the role of neural circuits in modulating inflammatory conditions. Here, Kevin Tracey discusses the inflammatory reflex, and in particular the efferent arc of this reflex, which is known as the cholinergic anti-inflammatory pathway. In this pathway, acetylcholine activity suppresses the release of pro-inflammatory cytokines.

In this Opinion article, Betty Diamond and colleagues propose that common serum antibodies that crossreact with brain antigens might be responsible for many acquired changes or congenital impairments in cognition and behaviour in the absence of overt brain inflammation.

How should the immune system respond to a dying cell? Should it ignore it (to allow normal tissue turnover), tolerate it (to prevent autoimmunity) or respond to it (to clear pathogens or tumours)? This Review describes our current understanding of the mechanisms involved in this decision.

A dynamic face-off occurring in the vasculature between invading bacterial pathogens and the host immune system is crucial for limiting the spread of pathogens throughout the body. Recent studies visualizing these intravascular events reveal the immune mechanisms that are involved in this process and how bacteria can overcome them.

This Review discusses the importance of galectin-glycan interactions in regulating T cell survival, activation, cytokine production and regulatory functions, as well as shaping the B cell compartment. Targeting these interactions could have important therapeutic implications for inflammation, autoimmunity and cancer.

Angus Thomson and colleagues describe the consequences of mammalian target of rapamycin (mTOR) inhibition by rapamycin on dendritic cells, effector T cells and regulatory T cells. These effects make mTOR inhibition a promising immunosuppressive, but tolerance-promoting, therapeutic strategy.

Disturbances in the balance between 'good' and 'bad' bacteria that reside in the gut could underlie the development of inflammatory bowel diseases, according to the authors of this Review. They describe how a 'normal' microbiota is required for proper functioning of the immune system.

Recent studies have identified a new population of interleukin-22-producing cells in mucosal tissues that share features with both lymphoid-tissue inducer cells and natural killer cells. How are these three cell populations related and what might be the function of the new cell population?

This article looks at the dysregulation of specific B-cell subpopulations that is associated with chronic HIV infection, with a view to understanding the mechanisms of B-cell pathogenesis in HIV-associated disease and other diseases that are characterized by immune dysfunction.

Tumour necrosis factor (TNF)–TNF receptor pairs that regulate the function of effector T cells have gained prominence as therapeutic targets. Here, Michael Croft describes the biology of four such TNF–TNFR pairs and discusses the implications of targeting them during conditions of inflammation, autoimmunity and cancer.

The homeostatic roles of macrophages in tissue development and maintenance are discussed, and insights are provided into how dysregulation of these primitive functions can be subverted in chronic diseases such as cancer and obesity to contribute to pathology.

Recent studies indicate that haematopoietic progenitor cells have more plasticity with regard to lineage choice than previously appreciated. To account for this developmental plasticity, Rhodri Ceredig and colleagues propose a new model of haematopoiesis.

Viruses have long been suspected to act as triggers of autoimmune disease. This Review describes the various mechanisms that link viruses to autoimmune responses and highlights how viral infection and immune control can be dysregulated during autoimmune disease.

This Timeline article provides an overview of the discovery and proposed mechanisms of action of aluminium salts, the most widely used vaccine adjuvants. The recent progresses and outstanding controversies on how aluminium salts function as adjuvants are also discussed.

Infant and elderly humans and mice have a similar vulnerability to common pathogens as a result of the decreased quantity and persistence of antibody responses. This Review looks at the B-cell intrinsic factors and microenvironmental determinants in lymphoid tissue and bone marrow that limit protective B-cell responses in these age groups.

Memory T cells in non-lymphoid tissues provide an important early line of defence against secondary pathogen infection. In this article, the mechanisms involved in the migration, maintenance and function of memory T cells at these peripheral sites are discussed.

How the T-cell receptor translates ligand affinity to an appropriate cellular response has puzzled immunologists for decades. In this Opinion article, the authors propose a new model to explain this, which is based on the duration of receptor–ligand binding and on a 'zipper' mechanism that mediates receptor–co-receptor interactions.

Haematopoiesis is driven by complex networks of transcriptional regulators. Among them are the E and inhibitor of DNA binding (ID) proteins, which have important roles in early B- and T-cell development, as well as emerging roles in haematopoietic stem cells and other lymphoid and myeloid lineages.