Hot off the presses! Jan 01 Nat Rev Immunol

The Jan 01 issue of the Nat Rev Immunol is now up on Pubget (About Nat Rev Immunol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Immune regulation: Immune response to tissue stress | PDF (183 KB)
  - Nat Rev Immunol 12(1):1 (2012)
  Immune activation occurs not only in response to infection, but also following physical, chemical and genotoxic tissue stress. Two recent studies by Hayday and colleagues reveal new aspects in stress-initiated immune responses (termed lymphoid stress-surveillance responses) in humans and mice.
• Mucosal immunology: Hungry for the fight | PDF (153 KB)
  - Nat Rev Immunol 12(1):2 (2012)
  Polly Matzinger and colleagues have found that intestinal epithelial cells (IECs) upregulate their expression of immune genes when the adaptive immune system fails to control the microbiota. However, this increased immune responsiveness comes at a cost — it leads to the downregulation of IEC metabolic functions.
• Viral immunity: Shelter from interferons | PDF (175 KB)
  - Nat Rev Immunol 12(1):2 (2012)
  New research has revealed a mechanism that explains how the innate immune system inhibits viral propagation but still allows the production of enough viral antigens to stimulate an effective adaptive immune response. The answer lies in a subset of macrophages that resists the antiviral effects of type I interferons (IFNs).
• Inflammation: Trauma kicks up a storm | PDF (340 KB)
  - Nat Rev Immunol 12(1):3 (2012)
  The current paradigm of the immune response to severe trauma is viewed as an early systemic inflammatory response followed by a temporary compensatory anti-inflammatory response and the suppression of adaptive immunity. It is thought that serious complications are commonly associated with a 'second hit' (for example, infection or surgical stress) during this compensatory period that results in a more severe inflammatory response.
• Regulatory T cells: Practise makes perfect | PDF (256 KB)
  - Nat Rev Immunol 12(1):4 (2012)
  In an exciting new study, Abul Abbas and colleagues report that regulatory T (TReg) cells can become more potent suppressors in response to continuous antigen exposure. The authors show that, during an autoimmune response, TReg cells proliferate, accumulate in the target tissue and promote the resolution of inflammation.
• Neuroimmunology: A CNS guard as prickly as a hedgehog | PDF (264 KB)
  - Nat Rev Immunol 12(1):4 (2012)
  Compromised function of the blood–brain barrier (BBB) and entry of activated lymphocytes into the central nervous system (CNS) are associated with the pathogenesis of neuroinflammatory diseases, such as multiple sclerosis. A recent study in Science indicates that Hedgehog signalling promotes BBB integrity and contributes to the immune-privileged state of the CNS.
• Natural killer T cells: More help for B cells | PDF (114 KB)
  - Nat Rev Immunol 12(1):5 (2012)
  Invariant natural killer T (iNKT) cells have previously been shown to provide cognate help for lipid-specific B cells. Two new studies provide further details of the long-term outcome of this help and describe a population of iNKT cells that resemble follicular helper T (TFH) cells.
• Mucosal immunology: A safety catch to prevent intestinal inflammation | PDF (149 KB)
  - Nat Rev Immunol 12(1):6 (2012)
  Constant contact with commensal microorganisms is tolerated with the help of a safety mechanism that makes the induction of T helper 17 (TH17) cells more difficult at mucosal surfaces than systemically, according to new research. A unique population of intestinal dendritic cells (DCs) increases the cytokine requirements for TH17 cell induction in the gut by tipping the balance in favour of the development of regulatory T (TReg) cells.
• Innate immunity: TLR9 mutations reveal a new level of self tolerance | PDF (197 KB)
  - Nat Rev Immunol 12(1):7 (2012)
  The activation of Toll-like receptor 9 (TLR9) by nucleic acids requires processing of the receptor by lysosomal proteases. This was thought to ensure that TLR9 responded to foreign nucleic acids in the endolysosomal compartment rather than to extracellular self DNA at the cell surface.
• Technique: New strategies for boosting immunity to pathogens and cancer | PDF (112 KB)
  - Nat Rev Immunol 12(1):6 (2012)
  There is a continued need to develop better vaccines or alternative immune-stimulating therapies. Three recent studies focus on new strategies for boosting host immunity.
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• The impact of perinatal immune development on mucosal homeostasis and chronic inflammation
  - Nat Rev Immunol 12(1):9 (2012)
  The mucosal surfaces of the gut and airways have important barrier functions and regulate the induction of immunological tolerance. The rapidly increasing incidence of chronic inflammatory disorders of these surfaces, such as inflammatory bowel disease and asthma, indicates that the immune functions of these mucosae are becoming disrupted in humans. Recent data indicate that events in prenatal and neonatal life orchestrate mucosal homeostasis. Several environmental factors promote the perinatal programming of the immune system, including colonization of the gut and airways by commensal microorganisms. These complex microbial–host interactions operate in a delicate temporal and spatial manner and have an important role in the induction of homeostatic mechanisms.
• Molecular programming of B cell memory
  - Nat Rev Immunol 12(1):24 (2012)
  The development of high-affinity B cell memory is regulated through three separable phases, each involving antigen recognition by specific B cells and cognate T helper cells. Initially, antigen-primed B cells require cognate T cell help to gain entry into the germinal centre pathway to memory. Once in the germinal centre, B cells with variant B cell receptors must access antigens and present them to germinal centre T helper cells to enter long-lived memory B cell compartments. Following antigen recall, memory B cells require T cell help to proliferate and differentiate into plasma cells. A recent surge of information — resulting from dynamic B cell imaging in vivo and the elucidation of T follicular helper cell programmes — has reshaped the conceptual landscape surrounding the generation of memory B cells. In this Review, we integrate this new information about each phase of antigen-specific B cell development to describe the newly unravelled molecular dynamics of ! memory B cell programming.
• The role of ubiquitylation in immune defence and pathogen evasion
  - Nat Rev Immunol 12(1):35 (2012)
  Ubiquitylation is a widely used post-translational protein modification that regulates many biological processes, including immune responses. The role of ubiquitin in immune regulation was originally uncovered through studies of antigen presentation and the nuclear factor-κB family of transcription factors, which orchestrate host defence against microorganisms. Recent studies have revealed crucial roles of ubiquitylation in many aspects of the immune system, including innate and adaptive immunity and antimicrobial autophagy. In addition, mounting evidence indicates that microbial pathogens exploit the ubiquitin pathway to evade the host immune system. Here, we review recent advances on the role of ubiquitylation in host defence and pathogen evasion.
• The bone marrow at the crossroads of blood and immunity
  - Nat Rev Immunol 12(1):49 (2012)
  Progenitor cells that are the basis for all blood cell production share the bone marrow with more mature elements of the adaptive immune system. Specialized niches within the bone marrow guide and, at times, constrain the development of haematopoietic stem and progenitor cells (HSPCs) and lineage-restricted immune progenitor cells. Specific niche components are organized into distinct domains to create a diversified landscape in which specialized cell differentiation or population expansion programmes proceed. Local cues that reflect the tissue and organismal state affect cellular interactions to alter the production of a range of cell types. Here, we review the organization of regulatory elements in the bone marrow and discuss how these elements provide a dynamic means for the host to modulate stem cell and adaptive immune cell responses to physiological challenges.
• Experimental mouse tumour models: what can be learnt about human cancer immunology?
  - Nat Rev Immunol 12(1):61 (2012)
  The recent demonstration that cancer immunotherapy extends patient survival has reinvigorated interest in elucidating the role of immunity in tumour pathogenesis. Experimental mouse tumour models have provided key mechanistic insights into host antitumour immune responses, and these have guided the development of novel treatment strategies. To accelerate the translation of these findings into clinical benefits, investigators need to gain a better understanding of the strengths and limitations of mouse model systems as tools for deciphering human antitumour immune responses.
• Vaccines targeting drugs of abuse: is the glass half-empty or half-full?
  - Nat Rev Immunol 12(1):67 (2012)
  The advent of vaccines targeting drugs of abuse heralded a fundamentally different approach to treating substance-related disorders. In contrast to traditional pharmacotherapies for drug abuse, vaccines act by sequestering circulating drugs and terminating the drug-induced 'high' without inducing unwanted neuromodulatory effects. Drug-targeting vaccines have entered clinical evaluation, and although these vaccines show promise from a biomedical viewpoint, the ethical and socioeconomic implications of vaccinating patients against drugs of abuse merit discussion within the scientific community.