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Genetics and pathogenesis of multiple sclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple sclerosis (MS) is an idiopathic autoimmune neurodegenerative disease. Like many common diseases, MS has a genetic component; however, as with most complex diseases, the genetic architecture may be influenced by heterogeneity, incomplete penetrance, polygenic inheritance, and environmental factors. This clinically complex disease has provided great challenges for geneticists over the years. Although the first consistent genetic association to MS (with HLA-DR*1501) was discovered more than 30 years ago, lack of consistently replicated genetic results has plagued the scientific community. New study design methods...
Source: Seminars in Immunology - September 20, 2009 Category: Allergy & Immunology Authors: Zuvich RL, McCauley JL, Pericak-Vance MA, Haines JL Tags: Semin Immunol Source Type: journals

The many faces of CD40: Multiple roles in normal immunity and disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19713124 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - August 24, 2009 Category: Allergy & Immunology Authors: Bishop DG Tags: Semin Immunol Source Type: journals

Innate immunity: The connection with inflammation and disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19699108 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - August 18, 2009 Category: Allergy & Immunology Authors: Girardin SE, Philpott DJ Tags: Semin Immunol Source Type: journals

The Janus faces of CD40 in cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD40 is a TNF receptor family member that is widely recognized for its prominent role in immune regulation and homeostasis. Expression of CD40 is not restricted to normal lymphoid cells but is also evident in the majority of haemopoietic and epithelial malignancies where it has been implicated in oncogenic events. Accumulating evidence, however, suggests that the CD40 pathway can be exploited for cancer therapy by virtue of its ability to stimulate the host anti-tumor immune response, normalize the tumor microenvironment and directly suppress the growth of CD40-positive tumors. Here, we provide an overview of the multi...
Source: Seminars in Immunology - July 29, 2009 Category: Allergy & Immunology Authors: Loskog AS, Eliopoulos AG Tags: Semin Immunol Source Type: journals

Epithelial cells as immune effector cells: The role of CD40.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Through the expression of inflammatory mediators and immune-related molecules, epithelial cells function as immune effector cells in a wide variety of tissues; the expression of the CD40 receptor on these cells contributes this role. Engagement of CD40 activates epithelial cells and results in their release of pro- and anti-inflammatory mediators as well as pro-fibrotic molecules. As such, epithelial CD40 has been implicated in the pathogenesis of inflammatory disorders, generation of self-tolerance, and rejection of allografts. PMID: 19628407 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - July 20, 2009 Category: Allergy & Immunology Authors: Dugger K, Lowder TW, Tucker TA, Schwiebert LM Tags: Semin Immunol Source Type: journals

CD40 and the immune response to parasitic infections.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The interaction between CD40 and CD154 regulates many aspects of cellular and humoral immunity. The CD40-CD154 pathway is important for resistance against a variety of parasites. Studies done with these pathogens have provided important insight into the various mechanisms by which this pathway enhances host protection, mechanisms by which pathogens subvert CD40 signaling, conditions in which the CD40-CD154 pathway promotes disease and on modulation of this pathway for immunotherapy. PMID: 19616968 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - July 16, 2009 Category: Allergy & Immunology Authors: Subauste CS Tags: Semin Immunol Source Type: journals

The immunobiology of CD154-CD40-TRAF interactions in atherosclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atherosclerosis is a chronic disease of the large arteries that is responsible for the majority of cardiovascular events. In its pathogenesis, the immune system plays a pivotal role. The effectuation of the immune response through interactions between immune cells that is mediated by co-stimulatory molecules, determine atherosclerosis severity. This review will highlight the role of one of the most powerful co-stimulatory dyads, the CD154 (also known as CD40 ligand, CD40L)-CD40 dyad, in atherosclerosis. Its cell-type specific actions, signal transduction cascades and its therapeutic potentials will be discussed. PM...
Source: Seminars in Immunology - July 15, 2009 Category: Allergy & Immunology Authors: Engel D, Seijkens T, Poggi M, Sanati M, Thevissen L, Beckers L, Wijnands E, Lievens D, Lutgens E Tags: Semin Immunol Source Type: journals

CD40 and autoimmunity: The dark side of a great activator.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD40 is a tumor necrosis factor receptor superfamily member expressed by immune and non-immune cells. CD40:CD154 interactions mediate T-dependent B cell responses and efficient T cell priming. Thus, CD40 is a likely candidate to play roles in autoimmune diseases in which activated T and B cells cause pathology. Diseases in which CD40 plays a pathogenic role include autoimmune thyroiditis, type 1 diabetes, inflammatory bowel disease, psoriasis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. This review discusses the role of CD40:CD154 interaction in human and mouse autoimmunity, human polymo...
Source: Seminars in Immunology - July 9, 2009 Category: Allergy & Immunology Authors: Peters AL, Stunz LL, Bishop GA Tags: Semin Immunol Source Type: journals

Genome-wide association studies in type 1 diabetes, inflammatory bowel disease and other immune-mediated disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genome-wide association studies have delivered on the promise of uncovering genetic determinants of complex disease. In this review, we provide a summary of recent advances in the identification of multiple variants associated with autoimmune-mediated disorders; specifically type 1 diabetes and inflammatory bowel disease. Sixteen loci, all replicated in independent samples, have now been uncovered for type 1 diabetes and in excess of 40 for inflammatory bowel disease. The next steps are to identify the true causal variants underlying evidence of disease association and to leverage this information to improve diagnosis,...
Source: Seminars in Immunology - June 29, 2009 Category: Allergy & Immunology Authors: Hakonarson H, Grant SF Tags: Semin Immunol Source Type: journals

Macrophage CD40 signaling: A pivotal regulator of disease protection and pathogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Macrophages reside in all tissues as resident populations and as immigrants recruited in response to tissue injury, inflammation or pathogen invasion. Under normal conditions, macrophages contribute to tissue homeostasis and provide innate immune surveillance. Both macrophages and their progenitors, bone marrow-derived monocytes, constitutively express the tumor necrosis factor receptor superfamily member, CD40, and are capable of a robust response to CD40 ligation resulting in the induction or enhancement of expression of genes with a predominantly pro-inflammatory function. CD40 signaling in macrophages in the contex...
Source: Seminars in Immunology - June 17, 2009 Category: Allergy & Immunology Authors: Suttles J, Stout RD Tags: Semin Immunol Source Type: journals

Functional roles for T cell CD40 in infection and autoimmune disease: The role of CD40 in lymphocyte homeostasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD40 stimulation on monocytes/macrophages, dendritic cells, and B-lymphocytes has been the subject of much study. It is well recognized that activation of CD40 on antigen presenting cells by its ligand, CD154, expressed on T-lymphocytes, contributes to the pro-inflammatory response necessary for eradication of infection, yet pathological in autoimmunity. However, there is evidence that CD40 is also expressed on T-lymphocytes and can act as a costimulatory molecule. While the exact role of CD40 on CD8 T cells remains controversial, it does appear to contribute to the adaptive immune response against infection. CD40 on C...
Source: Seminars in Immunology - June 15, 2009 Category: Allergy & Immunology Authors: Munroe ME Tags: Semin Immunol Source Type: journals

NLR-mediated control of inflammasome assembly in the host response against bacterial pathogens.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The host response against diverse bacterial pathogens involves activation of specialized immune cells and elaboration of pro-inflammatory cytokines that help to coordinate appropriate host defense. Members of the interleukin-1 (IL-1) cytokine family, IL-1beta and IL-18, are central players in this process. Extracellular release of the mature, active form of these cytokines requires their processing by the cysteine protease caspase-1, which therefore serves as a key regulator of the inflammatory response. In addition to its role in secretion of pro-inflammatory cytokines, caspase-1 is also required for a form of cell de...
Source: Seminars in Immunology - June 15, 2009 Category: Allergy & Immunology Authors: Brodsky IE, Monack D Tags: Semin Immunol Source Type: journals

RIG-I-like receptors: Sensing and responding to RNA virus infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Viral and microbial pathogens contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). RNA virus infection is also detected through TLR-independent mechanisms. Early viral replicative intermediates are detected by two recently characterized cystolic viral RNA receptors-RIG-I and MDA-5. Both are DExDH/box RNA helicases, and RIG-I specifically recognizes 5'-triphosphate containing viral RNA and transmits signals that induce type I interferon-mediated host immunity against virus infection. In this review, we will focu...
Source: Seminars in Immunology - June 15, 2009 Category: Allergy & Immunology Authors: Nakhaei P, Genin P, Civas A, Hiscott J Tags: Semin Immunol Source Type: journals

The role of mitochondria in cellular defense against microbial infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria have been long recognized for their key role in the modulation of cell death pathways. Thus, it is therefore not surprising that this organelle represents a recurrent target for pathogenic microbes, aiming to manipulate the fate of the infected host cell. More recently, mitochondria have been shown to serve as a crucial platform for innate immune signaling, as illustrated by the identification of MAVS (also known as IPS-1, VISA and Cardif), NLRX1 and STING as mitochondrial proteins. This review discusses the tight interplay between microbial infection, innate immune signaling and mitochondria. PMID: 19...
Source: Seminars in Immunology - June 14, 2009 Category: Allergy & Immunology Authors: Arnoult D, Carneiro L, Tattoli I, Girardin SE Tags: Semin Immunol Source Type: journals

The role of CD40 and CD154/CD40L in dendritic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this review, we focus on the function of CD40-CD40L (CD154) interactions in the regulation of dendritic cell (DC)-T cell and DC-B cell crosstalk. In addition, we examine differences and similarities between the CD40 signaling pathway in DCs and other innate immune cell receptors, and how these pathways integrate DC functions. As research into DC vaccines and immunotherapies progresses, further understanding of CD40 and DC function will advance the applicability of DCs in immunotherapy for human diseases. PMID: 19524453 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - June 10, 2009 Category: Allergy & Immunology Authors: Ma DY, Clark EA Tags: Semin Immunol Source Type: journals

Modulation of adaptive immunity with Toll-like receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The discovery of Toll-like receptors (TLRs), and their role in sensing infections represents one of the most seminal advances in immunology in recent years. It is now clear that TLRs play a fundamental role in innate recognition of microbes, and stimulate and tune the quality of the adaptive immune response. However, major knowledge gaps remain in our understanding of how TLRs regulate the development and persistence of T- and B-cell memory. Here, we review our current understanding of how TLR-signaling shapes the adaptive immune response, and highlight unanswered questions, the solution of which will be imperative in ...
Source: Seminars in Immunology - June 4, 2009 Category: Allergy & Immunology Authors: Manicassamy S, Pulendran B Tags: Semin Immunol Source Type: journals

Autophagy as an emerging dimension to adaptive and innate immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autophagy is an evolutionary conserved cellular process during which cytoplasmic material is engulfed in double membrane vacuoles that then fuse with lysosomes, ultimately degrading their cargo. Emerging evidence, however, now suggests that autophagy can form part of our innate and adaptive immune defense programs. Recent studies have identified pattern recognition molecules as mediators of this process and shown that intracellular pathogens can interact with and even manipulate autophagy. Recent translational evidence has also implicated autophagy in the pathogenesis of several immune-mediated diseases, including Croh...
Source: Seminars in Immunology - June 4, 2009 Category: Allergy & Immunology Authors: Hussey S, Travassos LH, Jones NL Tags: Semin Immunol Source Type: journals

The NLRP3 inflammasome: A sensor of immune danger signals.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The innate immune system senses danger signals via evolutionary conserved receptors. The nucleotide-binding domain leucine-rich repeat containing receptor (NLR) family is a group of intracellular receptors that drive a wide variety of inflammatory responses. A number of the NLR family members can form inflammasomes, which are multiprotein complexes that can activate caspase-1 and ultimately lead to the processing and secretion of interleukin (IL)-1beta, IL-18 and IL-33. One of the best-studied members of the NLR family is NLRP3 for which a number of divergent activators have recently been described. These and other stu...
Source: Seminars in Immunology - June 3, 2009 Category: Allergy & Immunology Authors: Cassel SL, Joly S, Sutterwala FS Tags: Semin Immunol Source Type: journals

The innate immune response to DNA.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
As a component of all living cells and microbes, it is not surprising that organisms have evolved mechanisms to detect foreign or aberrant DNA and trigger an innate immune response. TLR9 is an endosomal membrane bound receptor that is widely studied and the best understood DNA sensor. However, the existence of TLR9-independent DNA sensing pathways have been recognized for many years. Recently, novel cytosolic DNA sensors have been uncovered that include ZBP1 or DNA-dependent activator of interferon-regulatory factors (DAI) and a DNA sensing inflammasome consisting of the HIN200 protein, absent in melanoma 2 (AIM2). In ...
Source: Seminars in Immunology - June 1, 2009 Category: Allergy & Immunology Authors: Vilaysane A, Muruve DA Tags: Semin Immunol Source Type: journals

Skin immune surveillance by T cells--a new order?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although studies of the skin have provided fundamental models for innate and adaptive immune surveillance of body surfaces, there remains relatively little understanding of the role that epithelial cells play in sensing infection and/or organ dysfunction, and the pathways available to them to communicate with local and systemic immune cells. In particular, evidence is emerging for a novel stress response initiated by local lymphocytes, rather than dendritic cells, and based on their recognition of epithelial stress-induced antigens. Its consequences are to sustain tissue integrity by providing immunoprotection and nove...
Source: Seminars in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Strid J, Tigelaar RE, Hayday AC Tags: Semin Immunol Source Type: journals

Barrier immunity and IL-17.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD4+ T(H)17 cells display a featured role in barrier immunity. This effector population of T cells is important for clearance of microorganisms but can also promote autoimmunity at barrier sites. Recent work has indicated that these effector cells share a pathway with CD4+ regulatory T cells (T(R) cells) that also have a critical function in barrier protection and immune regulation. The development and function of T(H)17 cells, and their relationship with T(R) cells are discussed. PMID: 19386512 [PubMed - in process] (Source: Seminars in Immunology)
Source: Seminars in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Marks BR, Craft J Tags: Semin Immunol Source Type: journals

Intestinal T cells: facing the mucosal immune dilemma with synergy and diversity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The epithelium of the gastrointestinal tract, which represents the greatest body surface area exposed to the outside environment, is confronted with a plethora of foreign and potentially harmful antigens. Consequently, the immune system of the gut faces the daunting task of distinguishing harmless dietary proteins and commensal bacteria from potentially dangerous pathogens, and of then responding accordingly. Mucosal T cells play a central role in maintaining barrier function and controlling the delicate balance between immune activation and immune tolerance. This review will focus on the unique features of mucosal T c...
Source: Seminars in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: van Wijk F, Cheroutre H Tags: Semin Immunol Source Type: journals

Barrier immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19446471 [PubMed - in process] (Source: Seminars in Immunology)
Source: Seminars in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Hayday AC, Spencer J Tags: Semin Immunol Source Type: journals

Innate immune sensing and activation of cell surface Toll-like receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The expansion of sensing function by cell surface Toll-like receptors (TLRs) has grown to include not only more diverse viral, bacterial, fungal and protozoan surface components, but also a plethora of endogenous molecules arising from host cell and tissue damage as well as the inflammatory response itself. This flexibility in recognition is accommodated not only by physical and structural features of the TLRs themselves, but also by additional innate immune receptors, soluble molecules and subcellular trafficking mechanisms. These events have begun to reveal a remarkable plasticity and complexity within this critical ...
Source: Seminars in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Tapping RI Tags: Semin Immunol Source Type: journals

IL-2 and its high-affinity receptor: Genetic control of immunoregulation and autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type 1 diabetes (T1D) is an organ-specific autoimmune disease featured by destruction of the insulin producing beta-cells of the pancreas by autoreactive T-lymphocytes. Putative environmental triggers conspire with a constellation of genetic elements scattered throughout the genome to elicit a multifactorial autoimmune response involving virtually every cell type of the immune system against pancreatic beta-cells. Recent highly powered genome-wide association studies have confirmed and identified fifteen chromosomal regions harboring several candidate T1D-associated gene loci. Here, we summarize what we know about the ...
Source: Seminars in Immunology - May 13, 2009 Category: Allergy & Immunology Authors: Wang J, Wicker LS, Santamaria P Tags: Semin Immunol Source Type: journals

Genetics and pathogenesis of coeliac disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Coeliac disease is a common complex disease caused by a dietary intolerance to wheat gluten. Susceptibility is determined by both environmental and genetic factors. Coeliac disease results from complex interactions between the innate immune system, an adaptive T and B cell response and the mucosal barrier where inflammation is ultimately manifested. Genetic variants within the HLA region are well established, while variants outside of the HLA region have recently been identified. These variants are beginning to enhance our understanding of the immunology of the condition. This review focuses on the immunological pathog...
Source: Seminars in Immunology - May 12, 2009 Category: Allergy & Immunology Authors: Heap GA, van Heel DA Tags: Semin Immunol Source Type: journals

Unraveling the genetics of complex diseases: Susceptibility genes for rheumatoid arthritis and psoriasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Talk of numerous genetic risk factors for rheumatoid arthritis (RA) and psoriasis has been percolating for years, but with the exception of the human leukocyte antigen (HLA) region, none have been definitively identified. Recently the results of multiple, well powered, genetic case-control studies have begun to appear providing convincing statistical evidence for at least ten non-HLA related risk genes or loci (C5/TRAF1, CD40, CTLA4, KIF5A/PIP4K2C, MMEL1/TNFRSF14, PADI4, PRKCQ, PTPN22, STAT4, and TNFAIP3/OLIG3) for RA and six (IL12B, IL13, IL23R, STAT2/IL23A, TNFAIP3, and TNIP1) for psoriasis. These initial, novel find...
Source: Seminars in Immunology - May 12, 2009 Category: Allergy & Immunology Authors: Li Y, Begovich AB Tags: Semin Immunol Source Type: journals

T cell memory.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19298945 [PubMed - in process] (Source: Seminars in Immunology)
Source: Seminars in Immunology - March 24, 2009 Category: Allergy & Immunology Authors: Schoenberger SP Tags: Semin Immunol Source Type: journals

Biochemical signaling pathways for memory T cell recall.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Memory T cells exhibit low activation thresholds and rapid effector responses following antigen stimulation, contrasting naive T cells with high activation thresholds and no effector responses. Signaling mechanisms for the distinct properties of naive and memory T cells remain poorly understood. Here, I will discuss new results on signal transduction in naive and memory T cells that suggest proximal control of activation threshold and a distinct biochemical pathway to rapid recall. The signaling and transcriptional pathways controlling immediate effector function in memory T cells closely resemble pathways for rapid ef...
Source: Seminars in Immunology - March 24, 2009 Category: Allergy & Immunology Authors: Farber DL Tags: Semin Immunol Source Type: journals

CD4 memory T cells: What are they and what can they do?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Immunological memory provides the basis for successful vaccines. It is important to understand the properties of memory cells. There is much known about the phenotype and functions of memory CD8 T cells, less about memory B cells, while CD4 memory T cells have proved difficult to study. Differences in the types of memory CD4 cells studied and the difficulties of tracking the small number of cells have led to conflicting and unclear results. Here we discuss the different systems used to study CD4 memory cells and ask whether, and in what circumstances, memory CD4 cells could provide protection against infections. PM...
Source: Seminars in Immunology - March 6, 2009 Category: Allergy & Immunology Authors: Macleod MK, Clambey ET, Kappler JW, Marrack P Tags: Semin Immunol Source Type: journals

Critical role of the Polycomb and Trithorax complexes in the maintenance of CD4 T cell memory.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The maintenance of memory CD4 T cells is crucial for the establishment of immunological memory. The Polycomb (PcG) and Trithorax group (TrxG) genes control key developmental regulators such as the homeobox genes, and these two antagonize each other in the same developmental processes. Recently, PcG gene Bmi1 has been found to control memory Th1/Th2 cell survival and TrxG gene MLL is to control the maintenance of memory Th2 cell function selectively. Therefore, in memory CD4 T cells, PcG and TrxG genes appear to control distinct processes in a distinct manner, which indicates a novel regulatory feature of the PcG/TrxG g...
Source: Seminars in Immunology - March 6, 2009 Category: Allergy & Immunology Authors: Nakayama T, Yamashita M Tags: Semin Immunol Source Type: journals

Stem cell-like plasticity of naïve and distinct memory CD8(+) T cell subsets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Stem cell-like plasticity of naïve and distinct memory CD8(+) T cell subsets. Semin Immunol. 2009 Mar 6; Authors: Stemberger C, Neuenhahn M, Gebhardt FE, Schiemann M, Buchholz VR, Busch DH Most models regarding the 'clonal' origin of CD8(+) T cell effector and memory subset diversification suggest that during the first contact of a naïve T cell with the priming antigen-presenting cell major decisions for subsequent differentiation are made. Data using novel single-cell T cell tracking technologies demonstrate that a single naïve CD8(+) T cell can give rise to virtually all different subtypes of e...
Source: Seminars in Immunology - March 6, 2009 Category: Allergy & Immunology Authors: Stemberger C, Neuenhahn M, Gebhardt FE, Schiemann M, Buchholz VR, Busch DH Tags: Semin Immunol Source Type: journals

Surviving the crash: Transitioning from effector to memory CD8(+) T cell.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
One outcome of infection is the formation of long-lived immunological memory, which provides durable protection from symptomatic re-infection. In response to infection or vaccination, T cells undergo dramatic proliferation and differentiate into effector T cells that mediate removal of the pathogen. Following pathogen clearance, the majority of effector cells die, restoring lymphocyte homeostasis. However, a small number of antigen-specific cells survive and seed the memory T cell population. Here, we focus on recent advances in identifying the key proteins and transcription factors that allow a portion of effector CD8...
Source: Seminars in Immunology - March 5, 2009 Category: Allergy & Immunology Authors: D'Cruz LM, Rubinstein MP, Goldrath AW Tags: Semin Immunol Source Type: journals

Memory T cells need CD28 costimulation to remember.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The activation and expansion of naïve T cells require costimulatory signals provided by CD28 and TNF family members. In contrast, for many years it was believed that memory T cells do not require CD28 costimulation for expansion during secondary responses. This was based on in vitro experiments that suggested the re-activation of memory T cells is somewhat independent of costimulation. Recent in vivo evidence, however, has challenged this and shown that both CD4+ and CD8+ memory T cells require CD28 costimulation for maximal expansion and pathogen clearance. This requirement has important implications for host imm...
Source: Seminars in Immunology - March 4, 2009 Category: Allergy & Immunology Authors: Boesteanu AC, Katsikis PD Tags: Semin Immunol Source Type: journals

Plasmacytoid dendritic cells in the skin: To sense or not to sense nucleic acids.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Plasmacytoid dendritic cells (pDCs) are specialized sensors of viral nucleic acids that initiate protective immunity through the production of type I interferons (IFNs). Normally, pDCs fail to sense host-derived self-nucleic acids but do so when self-nucleic acids form complexes with endogenous antimicrobial peptides produced in damaged skin. Whereas regulated expression of antimicrobial peptides may lead to pDC activation and protective immune responses to skin injury, overexpression of antimicrobial peptides in psoriasis drives excessive sensing of self-nucleic acids by pDCs resulting in IFN-driven autoimmunity. In s...
Source: Seminars in Immunology - February 26, 2009 Category: Allergy & Immunology Authors: Conrad C, Meller S, Gilliet M Tags: Semin Immunol Source Type: journals

Endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The unfolded protein response as a consequence of endoplasmic reticulum (ER) stress has recently been implicated as a novel mechanism that may lead to inflammatory bowel disease (IBD). Impairment of proper ER stress resolution in highly secretory Paneth and, to a lesser extent, goblet cells within the epithelium can primarily lead to intestinal inflammation. An inability to manage ER stress may not only be a primary originator of intestinal inflammation as exemplified by genetic polymorphisms in XBP1 that are associated with IBD but also a perpetuator of inflammation when ER stress is induced secondarily to inflammator...
Source: Seminars in Immunology - February 21, 2009 Category: Allergy & Immunology Authors: Kaser A, Blumberg RS Tags: Semin Immunol Source Type: journals

Generation of Immunoglobulin diversity in human gut-associated lymphoid tissue.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The organised gut associated lymphoid tissue (GALT) exists adjacent to an extensive and diverse luminal flora. The follicle associated epithelium and associated dendritic cells and lymphocytes form a tightly fortified gateway between the flora and the host that permits connectivity between them and chronic activation of the lymphoid compartment. As a consequence, plasma cell precursors are generated continuously, and in abundance, in GALT by clonal proliferation. Clonal proliferation alone on this scale would reduce the spectrum of B cell specificity. To compensate, GALT also houses molecular machinery that diversifies...
Source: Seminars in Immunology - February 20, 2009 Category: Allergy & Immunology Authors: Spencer J, Barone F, Dunn-Walters D Tags: Semin Immunol Source Type: journals

Innate T cell responses in human gut.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
One arm of the gut-associated immune system is represented by a vast collection of T lymphocytes which participate in the subtle interplay between innate and adaptive immune mechanisms and maintain homeostasis at the main body external surface. Mounting data are providing exciting new insight into the innate-like mechanisms which enable intestinal T cells to rapidly sense local conditions and which broaden the spectrum of their functions and regulation at this strategic location. Herein we discuss how innate-like T cell recognition by unconventional T cell subsets and expression of innate NK receptors might modulate im...
Source: Seminars in Immunology - February 19, 2009 Category: Allergy & Immunology Authors: Meresse B, Cerf-Bensussan N Tags: Semin Immunol Source Type: journals

Immune homeostasis in the respiratory tract and its impact on heterologous infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Innate immunity at mucosal surfaces requires additional restraint to prevent inflammation to innocuous antigens or commensal microorganisms. The threshold above which airway macrophages become activated is raised by site-specific factors including the receptors for transforming growth factor beta, interleukin 10 and CD200; the ligands for which are produced by, or expressed on, respiratory epithelium. We discuss such site-specific regulation and how this is continually altered by prior infections. Resetting of innate reactivity represents a strategy for limiting excessive inflammation, but in some may pre-dispose to se...
Source: Seminars in Immunology - February 13, 2009 Category: Allergy & Immunology Authors: Wissinger E, Goulding J, Hussell T Tags: Semin Immunol Source Type: journals

The genetic and evolutionary balances in human NK cell receptor diversity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In primates and cattle two ancient killer-cell immunoglobulin-like receptor (KIR) lineages independently evolved to become diverse NK cell receptors. In mice, KIR genes were sidelined to the X chromosome, a possible consequence of pathogen-mediated selection on the receptor for IgA-Fc. In humans, KIR uniquely form two omnipresent haplotype groups (A and B), postulated here to play complementary and necessary roles in immune defense and reproduction. The basis of KIR3DL1/S1 polymorphism is three ancient lineages maintained by long-term balancing selection and present in all human populations. Conserved and variable NK c...
Source: Seminars in Immunology - November 24, 2008 Category: Allergy & Immunology Authors: Parham P Tags: Semin Immunol Source Type: journals

NK cell receptors in rodents and cattle.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Natural killer (NK) cells discriminate between normal syngeneic cells and infected, neoplastic or MHC-disparate allogeneic cells. The reactivity of NK cells appears to be regulated by a balance between activating receptors that recognize non-self or altered self, and inhibitory receptors recognizing normal, self-encoded MHC class I molecules. Subfamilies of NK receptors undergo rapid evolution, and appear to co-evolve with the MHC. We here review present views on the evolution and function of NK cell receptors, with an emphasis on knowledge gained in cattle and rodents. PMID: 18977671 [PubMed - as supplied by publi...
Source: Seminars in Immunology - October 31, 2008 Category: Allergy & Immunology Authors: Dissen E, Fossum S, Hoelsbrekken SE, Saether PC Tags: Semin Immunol Source Type: journals

Tumor-specific immune responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18977672 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - October 31, 2008 Category: Allergy & Immunology Authors: Schreiber H Tags: Semin Immunol Source Type: journals

Antigens for cancer immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Progress in tumor immunology has not been translated to effective immunotherapies for cancer. Most of the current effort in basic and clinical research concentrates on generating effective immune responses against model or well characterized antigens, yet vaccines targeting defined antigens have been less clinically successful than those based on whole tumor cells or their extracts. This review considers characteristics of proteins that determine how effectively they might serve as targets of immune control, and how different sources of antigens have fared in clinical trials. PMID: 18951039 [PubMed - as supplied by...
Source: Seminars in Immunology - October 22, 2008 Category: Allergy & Immunology Authors: Neller MA, López JA, Schmidt CW Tags: Semin Immunol Source Type: journals

NK cell receptors and their MHC class I ligands in host response to cytomegalovirus: Insights from the mouse genome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The complex interaction between natural killer (NK) cells and cytomegalovirus is a paradigm of the co-evolution between genomes of large DNA viruses and their host immune systems. Both human and mouse cytomegalovirus posses numerous mechanisms to avoid NK cell detection. Linkage studies, positional cloning and functional studies in mice and cells, have led to the identification of key genes governing resistance to cytomegalovirus, including various NK cell activating receptors of major histocompatibility complex (MHC) class I. These receptors, however, seem to require either viral or host MHC class I molecules to opera...
Source: Seminars in Immunology - October 21, 2008 Category: Allergy & Immunology Authors: Pyzik M, Kielczewska A, Vidal SM Tags: Semin Immunol Source Type: journals

Avian NK activities, cells and receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Natural killer (NK) activity has been examined in birds for over 30 years, but evidence that avian NK activity plays crucial roles in disease is only suggestive. In chickens, NK activity is mediated by TCR0 cells in the intestinal epithelium, but elsewhere subsets of alphabeta and gammadelta T cells (NKT cells) may be more important. There are few lectin-like NK receptor genes, located in the genomic region syntenic with the natural killer complex (NKC) as well as the major histocompatibility complex (MHC). In contrast, a huge number of Ig-like receptor genes are located in a region syntenic with the leukocyte receptor...
Source: Seminars in Immunology - October 21, 2008 Category: Allergy & Immunology Authors: Rogers SL, Viertlboeck BC, Göbel TW, Kaufman J Tags: Semin Immunol Source Type: journals

The evolution of NK cell diversity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18938087 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - October 18, 2008 Category: Allergy & Immunology Authors: Makrigiannis AP, Parham P Tags: Semin Immunol Source Type: journals

Retinoic acid production by intestinal dendritic cells and its role in T-cell trafficking.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Vitamin A deficiency causes a marked reduction in the number of T and B cells in the small intestinal tissues. The vitamin A metabolite retinoic acid imprints lymphocytes with gut-homing specificity upon antigenic stimulation. In the small intestinal lamina propria, Peyer's patches, and mesenteric lymph nodes, there are dendritic cells capable of producing retinoic acid. Their capacity depends on the expression of retinal dehydrogenases (RALDH). RALDH2, encoded by Aldh1a2, is a major isoform of RALDH in the intestinal dendritic cells under specific pathogen-free conditions, and can be induced by multiple factors consti...
Source: Seminars in Immunology - October 10, 2008 Category: Allergy & Immunology Authors: Iwata M Tags: Semin Immunol Source Type: journals

The roles of retinoic acid in lymphocyte differentiation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18838279 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - October 4, 2008 Category: Allergy & Immunology Authors: Iwata M Tags: Semin Immunol Source Type: journals

Augmentation of antibody responses by retinoic acid and costimulatory molecules.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Antibody production is crucial for a successful vaccine response. Beyond the ability of vitamin A (VA) and its active metabolite, all-trans-retinoic acid (RA) to restore growth in VA-deficient animals, supplementation with VA and/or treatment with RA can augment antibody responses in both VA-deficient and VA-adequate animals. RA alone, and in combination with stimuli that are ligands for the Toll-like receptor family, can augment the adaptive immune response leading to a heightened primary antibody response, and a stronger recall response upon restimulation. Mechanisms may include regulation of cell populations, type 1...
Source: Seminars in Immunology - September 24, 2008 Category: Allergy & Immunology Authors: Ross AC, Chen Q, Ma Y Tags: Semin Immunol Source Type: journals

From the diet to the nucleus: Vitamin A and TGF-beta join efforts at the mucosal interface of the intestine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The vitamin A metabolites, including retinoic acid (RA), form ligands for retinoic acid-related nuclear receptors and together they play pleiotropic roles in various biological processes. Recently, we described that RA also functions as a key modulator of transforming growth factor-beta (TGF-beta)-driven immune deviation, capable of suppressing the differentiation of interleukin-17 secreting T helper cells (T(H)17) and conversely promoting the generation of Foxp3(+) T regulatory (Treg) cells. This review will focus on the role of RA in the reciprocal TGF-beta-driven differentiation of T(H)17 and Treg and on the importa...
Source: Seminars in Immunology - September 20, 2008 Category: Allergy & Immunology Authors: Mucida D, Park Y, Cheroutre H Tags: Semin Immunol Source Type: journals