Reviews & Analysis

Complement is one of the first lines of innate immune defence in the body. As reviewed here, complement regulators have a key role in keeping the complement system in check, and dysregulation of complement activation can result in pathology.

Here, Michael Cancro proposes a model to explain how B cell fate is determined by balancing signals that select B cells of suitable reactivity with signals that support survival. This balance is said to be mediated by crosstalk between the mediators downstream of the B cell receptor (BCR) and receptor for B cell-activating factor (BAFFR).

At low levels of oxygen at sites of tissue infection, innate immune cells can adapt to survive and even enhance their antimicrobial functions. Recent studies show how this is controlled by hypoxia-inducible factor (HIF) downstream of nuclear factor-κB activation.

Grant McFadden and colleagues discuss how the interferons and tumour necrosis factor can establish an intracellular antiviral state that determines the specificity of a particular virus for a specific cell type, tissue or species. Our knowledge of these antiviral cytokines can be exploited to enhance immunity against zoonotic infections and to improve the therapeutic specificity of tumour-targeted viruses.

This Review describes the recent insights gained from studies of knockout mice indicating that Rho family GTPases and their regulators transduce signals from receptors for antigen, chemokines and adhesion molecules, making them key components of lymphocyte development, activation and migration.

Understanding how memory T cells develop has important implications for vaccine design. Here,Nature Reviews Immunologyasks four leading researchers in this field their thoughts on the ontogeny and lineage relationships of memory T cells.

Elimination of early neoplastic cells by innate immune cells is an important protective measure against cancer. Here, the authors explain that this tumour surveillance is linked to stress pathways that are activated during tumorigenesis through the induction of ligands for natural killer cell receptors, particularly NKG2D.

This Review looks at how immune events in the secondary lymphoid organs can be influenced by the non-haematopoietic stromal cells that support the microarchitecture of the lymph nodes and spleen. Specialized subsets of stromal cells can provide regional control to nurture or direct the most appropriate responses to pathogens.

The more time you spend with someone, the bigger the impact that person has on you. And the same is true for lymphocytes. But what are the molecular and cellular processes that regulate intercellular contacts made by lymphocytes and how does the duration of these contacts modulate their effector functions?

This Innovation article describes recently developed assays that measure the changing physiology within maturing phagosomes and discusses how studies using these techniques have shed light on the biological functions of phagosomes and phagocytes during innate and adaptive immune responses.

Recent studies defining the structure of and signalling pathways used by receptors of the interleukin-17 family have led to interesting comparisons with the pro-inflammatory signalling pathways that are more commonly associated with innate immune receptors. Sarah Gaffen therefore suggests that T helper 17 cells might act as a bridge between innate and adaptive immunity.

Cell death has a vital role in maintaining homeostasis in the T cell pool. However, the specific roles of BIM and CD95 in the contraction phase of T cell responses has been controversial. Recent studies show that BIM and CD95 have complementary roles in this process.

Here, Teunis Geijtenbeek and Sonja Gringhuis discuss the role of the signalling pathways induced by C-type lectin receptors in determining T helper cell lineage commitment and describe how these pathways can be exploited for the development of new vaccination strategies.

To limit detection by host T cells, viruses have evolved numerous mechanisms to inhibit viral antigens being processed and presented by MHC class I molecules. As described here, studying these viral immune evasion strategies is proving useful for understanding MHC class I presentation and other cellular pathways.

Studies showing how BAFF and its closely related homologue APRIL activate their receptors and transmit growth and survival signals to B cells have shed new light on the association between BAFF and autoimmunity. This knowledge has prompted several clinical trials testing BAFF and APRIL antagonists for the treatment of autoimmune diseases and lymphomas.

In this Review, the authors discuss the central roles of the common cytokine receptor γ-chain (γ_c) family of cytokines, as well as the related cytokine TSLP, in the homeostasis, proliferation and differentiation of various T cell subsets and describe how these cytokines could be exploited for therapeutic purposes.

The activation and signalling pathways engaged by Toll-like receptors (TLRs) are determined by their localization in the cell. Here, the authors explain how generic cellular machinery involved in the compartmentalization of receptors and signalling molecules contributes to TLR function and regulation.

Exosomes can act as messengers, carrying biological information between cells. Here, the authors describe the numerous effects that exosomes have on immune cells and discuss how they might be harnessed to promote or limit immune responses for therapeutic purposes.

In this Review article, Serge Rivest discusses how microglial cells (the resident innate immune cells of the central nervous system) are activated during infection and injury, whether microglial cell activation is neurodestructive or neuroprotective, and how targeting these cells could be a therapeutic approach for the treatment of Alzheimer's disease.

Our understanding of the role of T cells in the induction of autoimmune disease in the central nervous system has progressed rapidly in recent years. Here, Joan Goverman provides us with a comprehensive overview of this field and discusses the controversies that remain.