Review Articles in 2011

Programmed cell death of infected host cells builds up the first line of defence against viruses. Here, Mocarski and colleagues describe the tight regulation of caspase 8-dependent apoptosis and programmed necrosis and discuss how viral inhibitors of cell death may have contributed to the evolution of programmed necrosis to promote host survival.

This Review describes the dynamic interactions that occur between haematopoietic stem cells (HSCs), immune cells and their specialized niches in the bone marrow. The authors discuss how the signals provided by the niche help HSCs and immune cells to respond to injury or inflammation in peripheral tissues.

As discussed here, ubiquitylation is involved in many aspects of the immune system, including the innate immune response to pathogens, antigen presentation and the activation of the adaptive immune system. As a result, pathogens have evolved many ways to exploit this form of immune regulation.

In this Review article, the authors describe the perinatal development of intestinal and respiratory mucosal immune systems. Moreover, they discuss how environmental factors, such as the neonatal composition of commensal bacteria, can affect the maturation of mucosal immune systems, leading to the development of chronic inflammatory disorders later in life.

Understanding the molecular events that orchestrate the formation of high-affinity memory B cells will help to improve vaccination strategies. In this Review article, McHeyzer-Williams and colleagues discuss the cellular and molecular interactions that regulate commitment to B cell memory, the germinal centre reaction and the generation of memory plasma cells following antigen recall.

Cytotoxic T lymphocyte antigen 4 (CTLA4) has long been known to have an important regulatory role in the immune system; however, its mechanisms of action have been the subject of considerable debate. This article reviews the strengths and limitations of the cell-intrinsic and cell-extrinsic models that have been proposed to explain the function of CTLA4.

Infection, tissue injury and alterations in the composition of the microbiota have been implicated in the initiation of autoimmune diseases. In this Review article, Kingston Mills discusses how Toll-like receptor (TLR) signalling downstream of all these events can regulate the function of autoreactive T cells both directly and indirectly (through the activation of innate immune cells), and comments on the therapeutic implications of TLR targeting.

This Review discusses how invertebrate and vertebrate members of the PGRP family have developed an amazing variety of mechanisms to coordinate the host response to mutualistic, commensal and parasitic microorganisms.

This article provides a broad, timely review of our current understanding of MHC class I and class II antigen presentation and presents a survey of 43 experts in the field on the most important outstanding issues.

Immunologists are making good progress in unravelling the intricacies of the mononuclear phagocyte system, and this is largely due to recent technological advances. This article describes the current tools that exist for studying the origins and functions of mononuclear phagocytes and discusses the future technologies that will enable further progress in the field.

Microglia are brain-resident macrophages with a distinct origin. This Review discusses the development and function of these cells, and describes the association between the different microglial cell phenotypes and disease.

This Review describes the key transcription factors that enable the polarization of macrophages in response to the microenvironment in the context of a regulatory landscape that determines macrophage identity.

Macrophages exhibit remarkable plasticity and adopt pro- or anti-inflammatory phenotypes in response to environmental signals. This Review article by Murray and Wynn discusses the different macrophage subsets and their contribution to tissue homeostasis and disease pathogenesis.

Inflammation in adipose tissue is known to mediate insulin resistance in obesity, and macrophages are thought to have a central role in mediating this inflammatory response. But adipose tissue macrophages are not all bad: alternative activation of these cells promotes insulin sensitivity.

Monocytes serve as precursors for various tissue macrophage and dendritic cell populations and contribute to both protective and pathological immune responses. Here, the authors describe the mechanisms that are involved in mobilizing monocytes to distinct tissue sites, both during steady-state conditions and in response to infection.

Each tissue in our body contains a unique microenvironment that can differentially shape immune reactivity. In this Review article, Shiet al. describe how organ-specific factors influence natural killer cell homing and phenotype, and discuss the local molecular and cellular interactions that determine the protective or pathogenic functions of natural killer cells in the different tissues.

Haematopoietic stem cells are a rare, self-renewing population that give rise to all cells of the immune system. In this Review, the authors describe how the haematopoietic stem cell compartment is shaped by infection and inflammation, and discuss the therapeutic implications of this.

Unexpected and controversial results regarding the functional organization of the T cell synapse have been obtained from the single molecule imaging techniques that have recently become available.

Natural killer (NK) cells are traditionally considered to be innate immune players. In this Review, J. C. Sun and L. L. Lanier summarize the principles of NK cell development, homeostasis and function, and draw parallels between NK cell and CD8⁺T cell biology. From a fascinating discussion it appears that the borders between innate and adaptive immunity are not as well defined as previously thought.

This article discusses how homeostatic chemokines can shape 'cellular highways' for immune cell trafficking and lymphoid organogenesis. The authors propose that cancer cells exploit these chemokine-driven highways in order to metastasize and thrive at distant tissue sites.