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Natural killer cells in human autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Natural killer (NK) cells are innate immune cells. Although NK cells are best characterized for their ability to control tumors and infections, recent data have indicated that they also are important regulatory cells by virtue of interactions with many types of immune and nonimmune cells. Thereby, they can affect the outcome of adaptive immune responses and maintain immune homeostasis. Thus, NK cells can either exacerbate or limit immune responses, including those to autoantigens. Here, we discuss current insights into the role of NK cells in human autoimmunity. PMID: 19892538 [PubMed - as supplied by publisher] (S...
Source: Current Opinion in Immunology - November 3, 2009 Category: Allergy & Immunology Authors: Flodström-Tullberg M, Bryceson YT, Shi FD, Höglund P, Ljunggren HG Tags: Curr Opin Immunol Source Type: journals

Autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19879742 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 29, 2009 Category: Allergy & Immunology Authors: Bluestone JA, Kuchroo V Tags: Curr Opin Immunol Source Type: journals

Hypersensitivity and allergy: from mice to men.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19879743 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 29, 2009 Category: Allergy & Immunology Authors: Rothenberg ME, Daëron M Tags: Curr Opin Immunol Source Type: journals

Regulatory T cells and inhibitory cytokines in autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Foxp3(+) regulatory T cells (T(regs)) contribute significantly to the maintenance of peripheral tolerance, but they ultimately fail in autoimmune diseases. The events that lead to T(reg) failure in controlling autoreactive effector T cells (T(effs)) during autoimmunity are not completely understood. In this review, we discuss possible mechanisms for this subversion as they relate to type 1 diabetes (T1D) and multiple sclerosis (MS). Recent studies emphasize firstly, the role of inflammatory cytokines, such as IL-6, in inhibiting or subverting T(reg) function; secondly, the issue of T(reg) plasticity; thirdly, the possi...
Source: Current Opinion in Immunology - October 23, 2009 Category: Allergy & Immunology Authors: Bettini M, Vignali DA Tags: Curr Opin Immunol Source Type: journals

AIRE in the thymus and beyond.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The maintenance of immunologic self-tolerance requires the coordination of multiple complementary systems. Studies of the Autoimmune Regulator (Aire) gene have revealed that Aire promotes self-tolerance partly by inducing the transcription of a wide array of tissue-specific antigens (TSAs), particularly in the thymus. The importance of Aire is highlighted by the fact that patients and mice defective in Aire expression develop a multi-organ autoimmune syndrome. In this review we discuss recent progress in our understanding of Aire's control of immune tolerance at the cellular and molecular levels, and also address the p...
Source: Current Opinion in Immunology - October 12, 2009 Category: Allergy & Immunology Authors: Gardner JM, Fletcher AL, Anderson MS, Turley SJ Tags: Curr Opin Immunol Source Type: journals

Mouse models of allergic diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The increasing prevalence of allergic diseases worldwide is posing significant socio-economic challenges. The pathogenesis of these diseases reflects a complex interaction of genetic and environmental factors. The heterogeneity of disease phenotypes challenges the concept of single mechanisms of disease. As human experimentation is limited, animal models have been developed to provide insights into pathogenesis and potential for discovery of novel therapeutics. Mice have served in models of many of the allergic diseases including asthma, allergic rhinitis, food allergy, atopic dermatitis (AD), and allergic conjunctivit...
Source: Current Opinion in Immunology - October 12, 2009 Category: Allergy & Immunology Authors: Takeda K, Gelfand EW Tags: Curr Opin Immunol Source Type: journals

Mast cells in atopic dermatitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mast cells play as the major effector cells in immediate hypersensitivity through activation via the high-affinity IgE receptor, FcvarepsilonRI, although many other functions have recently been discovered for this cell type. Given the broad array of proinflammatory mediators secreted from FcvarepsilonRI-activated mast cells, as well as sensitization to allergens, IgE elevation, and increased mast cells in a majority of atopic dermatitis patients, mast cells are believed to be involved in the pathogenesis of atopic dermatitis. Numerous animal models have been used to study this epidemic disease. Here we review the recen...
Source: Current Opinion in Immunology - October 12, 2009 Category: Allergy & Immunology Authors: Kawakami T, Ando T, Kimura M, Wilson BS, Kawakami Y Tags: Curr Opin Immunol Source Type: journals

Novel targeted therapies for autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The emergence of new targeted therapies is rapidly improving the treatment of autoimmune disease. These drugs have been variably designed to deplete specific T and B cell subsets, interrupt receptor-ligand interactions, and inhibit the activity of inflammatory mediators relevant to immune function. Abatacept, a co-stimulatory blocker, and rituximab, a B cell depleting antibody, are among the approved therapies seeking new indications, while the newer therapies include Fc receptor-non-binding CD3-specific antibodies, IL-12/23 antibodies, an IL-6 receptor antagonist, a sphingosine-1-phosphate agonist, and small molecule ...
Source: Current Opinion in Immunology - October 11, 2009 Category: Allergy & Immunology Authors: St Clair EW Tags: Curr Opin Immunol Source Type: journals

New roles for mast cells in modulating allergic reactions and immunity against pathogens.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mast cells (MCs) have primarily been associated with mediating the pathological secondary responses to allergens in sensitized hosts. In view of the recent evidence for a MC role in modulating primary immune responses to pathogens, the likelihood for a role of MCs in influencing primary immune response to allergens has grown. New evidence suggests that MCs drive the development of Th2 responses to allergens, particularly when allergen exposure occurs concomitantly with exposure to pathogen products present in the environment. These new roles for MCs in allergy and infection suggest additional drug targets to prevent th...
Source: Current Opinion in Immunology - October 11, 2009 Category: Allergy & Immunology Authors: Hofmann AM, Abraham SN Tags: Curr Opin Immunol Source Type: journals

Innate immunity and allergy in the skin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The skin as an organ has many functions of which the protection against environmental threats may be the most important. Recent investigations have broadened our understanding of the cellular mechanisms of host defense responses of the skin. Interestingly, the three key effector cells of cutaneous innate immunity, that is keratinocytes, dendritic cells, and mast cells, are also critically involved in the elicitation of allergic reactions. Keratinocytes keep bacteria and other pathogens from invading the host, but they can also promote the development of allergic asthma by releasing thymic stromal lymphopoietin. Dendrit...
Source: Current Opinion in Immunology - October 11, 2009 Category: Allergy & Immunology Authors: Metz M, Maurer M Tags: Curr Opin Immunol Source Type: journals

Activating systemic autoimmunity: Bs, Ts, and tolls.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A recent advance in the treatment and understanding of autoimmune disease has been the efficacy of B-cell-targeted therapy. Such therapies are effective for several such diseases, with systemic autoimmunity being a prototypical example. The mechanism of action is not fully defined, but blocking B cell Ag presentation to T cells is likely to be important. T-B interactions probably engender a positive feedback loop that amplifies and sustains autoimmunity. But how is self-tolerance first broken to initiate this loop? I propose, based on recent data, a model in which autoreactive B cells are activated first, independent o...
Source: Current Opinion in Immunology - September 29, 2009 Category: Allergy & Immunology Authors: Shlomchik MJ Tags: Curr Opin Immunol Source Type: journals

Pathogen specific T-lymphocytes for the reconstitution of the immunocompromised host.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cellular immune functions are impaired in hemopoietic stem cell and solid organ transplantation or in cancer and autoimmune diseases treated with intensified immunosuppression. Thus, control of opportunistic pathogens is lost and severe infections break out. Defective cellular immunity can be restored upon endogenous immunoreconstitution or, if delayed, exogenous immunoreconstitution with pathogen specific T-lymphocytes selected or expanded from appropriate donors can be applied. Here we describe how recent developments in basic immunology knowledge and techniques have accelerated progresses of clinical trials in this ...
Source: Current Opinion in Immunology - September 29, 2009 Category: Allergy & Immunology Authors: Li Pira G, Kapp M, Manca F, Einsele H Tags: Curr Opin Immunol Source Type: journals

Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of pulmonary surfactant, respiratory insufficiency, and increased infections. It occurs in various clinical settings that disrupt surfactant catabolism in alveolar macrophages, including a relatively more common autoimmune disease caused by GM-CSF autoantibodies and a rare congenital disease caused by CSF2RA mutations. Recent results demonstrate that GM-CSF is crucial for alveolar macrophage terminal differentiation and immune functions, pulmonary surfactant homeostasis, and lung host defense. GM-CSF is also required to determine the ...
Source: Current Opinion in Immunology - September 28, 2009 Category: Allergy & Immunology Authors: Trapnell BC, Carey BC, Uchida K, Suzuki T Tags: Curr Opin Immunol Source Type: journals

Primary immunodeficiencies: increasing market share.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19796926 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 28, 2009 Category: Allergy & Immunology Authors: Notarangelo LD, Casanova JL Tags: Curr Opin Immunol Source Type: journals

Progress in understanding and exploiting the immune response in solid organ and hemopoietic stem cell transplantation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19782548 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Christiansen FT, Velardi A Tags: Curr Opin Immunol Source Type: journals

Novel genetic etiologies of severe congenital neutropenia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Severe congenital neutropenia (SCN) comprises a heterogenous group of primary immunodeficiency disorders collectively characterized by paucity of mature neutrophils. In recent years, progress has been made with respect to the elucidation of genetic causes underlying syndromic and non-syndromic variants of SCN. Most cases of autosomal dominant SCN are associated with mutations in the neutrophil elastase (ELA-2/ELANE) gene, autosomal recessive forms of this disorder can be caused by mutations in the gene encoding the mitochondrial protein HAX-1. Rarely, SCN can be caused by mutations in the gene encoding the transcriptio...
Source: Current Opinion in Immunology - September 23, 2009 Category: Allergy & Immunology Authors: Boztug K, Klein C Tags: Curr Opin Immunol Source Type: journals

Immune reconstitution after haematopoietic stem cell transplantation: obstacles and anticipated progress.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Improvement of immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a key issue determining the clinical outcome of this widely used therapeutic approach. To this end, new strategies have been prompted by recent discoveries in immunology. In the setting of human leukocyte antigen (HLA) geno(pheno)identical HSCT, better prevention and treatment of acute and chronic graft-versus-host disease (GvHD) could significantly attenuate the thymic epithelium damage responsible for delayed and incomplete T-cell reconstitution. In a haploidentical setting, methods that would significantly accelerate neothy...
Source: Current Opinion in Immunology - September 16, 2009 Category: Allergy & Immunology Authors: Cavazzana-Calvo M, André-Schmutz I, Dal Cortivo L, Neven B, Hacein-Bey-Abina S, Fischer A Tags: Curr Opin Immunol Source Type: journals

The influence of NK alloreactivity on matched unrelated donor and HLA identical sibling haematopoietic stem cell transplantation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Numerous retrospective studies have been reported analysing the role of HLA mismatches that confer donor NK alloreactivity towards the recipient on the outcome of haematopoietic stem cell transplantation. A bewildering variety of findings have been observed with different studies showing either beneficial or deleterious effects on outcome. This review organises the reports into those that use similar definitions of NK alloreactivity, suggests possible reasons for such disparate results and assesses whether any recommendations can be made in relation to donor selection. There is growing evidence that the effect of human...
Source: Current Opinion in Immunology - September 15, 2009 Category: Allergy & Immunology Authors: Witt CS Tags: Curr Opin Immunol Source Type: journals

Solid phase assays for HLA antibody detection in clinical transplantation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The complement dependent microlymphocytotoxicity assay has been used for over 40 years for detecting HLA antibodies in transplant patients. This method has been replaced recently by more sensitive solid phase assays such as ELISA and bead based technology including the Luminex method. The introduction of these techniques into clinical practice has revealed previously undetected sensitisation in some patients and allowed the accurate assignment of antibody specificities directed at HLA-DQ and HLA-DP which was not previously possible. However it is emerging that despite the advantage of sensitivity some HLA antibodies de...
Source: Current Opinion in Immunology - September 15, 2009 Category: Allergy & Immunology Authors: Tait BD Tags: Curr Opin Immunol Source Type: journals

Human leukocyte antigen antibodies in chronic transplant vasculopathy-mechanisms and pathways.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transplant recipients exhibiting posttransplant antibodies are at a higher risk for acute and chronic antibody mediated rejection (AMR). The primary alloantigens recognized by antibodies in recipients with AMR are the highly polymorphic HLA class I and class II molecules expressed on the surface of the endothelial cells (ECs) of the graft. Traditionally, anti-HLA antibodies were thought to mediate graft injury through complement-dependent mechanisms. However, recent studies indicate that antibodies can also contribute to alterations in EC function through complement-independent mechanisms by transducing intracellular s...
Source: Current Opinion in Immunology - September 10, 2009 Category: Allergy & Immunology Authors: Li F, Atz ME, Reed EF Tags: Curr Opin Immunol Source Type: journals

Innate receptors and microbes in induction of autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cells of the adaptive immune system (T and B cells) causing autoimmunity require activation signals that are normally provided by the innate immune system. Innate signaling receptors are obvious candidates for participation in the induction of autoimmunity, and the nature of these receptors suggests that microbes could be the triggers. Recent publications describing the development of autoimmunity in sterile conditions and in animals deficient in innate signaling question the requirement of these receptors for initiation of autoimmunity. In addition, the role of the non-pathogenic (commensal) microbiota as a regulator ...
Source: Current Opinion in Immunology - September 8, 2009 Category: Allergy & Immunology Authors: Chervonsky A Tags: Curr Opin Immunol Source Type: journals

When selecting an HLA mismatched stem cell donor consider donor immune status.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Until now, hematopoietic stem cell (HSC) donor selection has been almost exclusively based on selecting a (near) HLA identical donor but many patients fail to find a suitable donor. However all donors have been exposed during fetal life and by breastfeeding to microchimeric maternal cells and molecules, which may induce long lasting T regulator cells. Likewise fetal cells invade the maternal circulation and one-third of the mothers are immunized to the paternal antigens of the child, while part of the mothers become tolerant to them. By taking the alloimmune status of the HSC donor into account, HLA mismatched grafts a...
Source: Current Opinion in Immunology - September 4, 2009 Category: Allergy & Immunology Authors: van Rood JJ, Oudshoorn M Tags: Curr Opin Immunol Source Type: journals

Hyper-IgE syndrome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hyper-IgE syndrome (HIES) is a complex primary immunodeficiency characterized by atopic dermatitis associated with extremely high serum IgE levels and susceptibility to infections with extracellular bacteria. Nonimmunological abnormalities, including a distinctive facial appearance, fracture following minor trauma, scoliosis, hyperextensive joints, and the retention of deciduous teeth are also observed in most patients. Recent studies have demonstrated that dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) gene result in the classical multisystem form of HIES, whereas a null ...
Source: Current Opinion in Immunology - August 27, 2009 Category: Allergy & Immunology Authors: Minegishi Y Tags: Curr Opin Immunol Source Type: journals

Natural killer cell allorecognition of missing self in allogeneic hematopoietic transplantation: a tool for immunotherapy of leukemia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Donor-versus-recipient natural killer (NK) cell alloreactivity has been established as a key therapeutic element in HLA haplotype mismatched hematopoietic transplants in adult AML and pediatric ALL and as a possible beneficial effector in cord blood transplant for AML. It is effected by functional NK cells which express inhibitory killer cell immunoglobulin-like receptor(s) (KIR) for self-class I ligand(s), sense missing expression of donor KIR ligand(s) in the recipient and mediate alloreactions. At present NK cell allotherapy for leukemia is deployed through stem cell transplantation (and ensuing NK cell reconstituti...
Source: Current Opinion in Immunology - August 27, 2009 Category: Allergy & Immunology Authors: Velardi A, Ruggeri L, Mancusi A, Aversa F, Christiansen FT Tags: Curr Opin Immunol Source Type: journals

Post-transplant monitoring of renal allografts: are we there yet?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transplantation has emerged as the therapy of choice for many patients with end organ failure. One of the major goals is to tailor immunosuppressive therapy to the individual needs of every patient to balance the risk for rejection and over-immunosuppression. This will require diagnostic tools that can detect harmful processes in the allograft early, and that can be measured repeatedly. This review will consider recent advances in our understanding of the molecular nature of these processes and how this information is being utilized to design novel diagnostic assays to non-invasively monitor allografts. Highlighted is ...
Source: Current Opinion in Immunology - August 25, 2009 Category: Allergy & Immunology Authors: Nickerson P Tags: Curr Opin Immunol Source Type: journals

Functional extracellular eosinophil granules: novel implications in eosinophil immunobiology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human eosinophils contain within their cytoplasmic granules multiple preformed proteins, including over three dozen cytokines with nominal Th1, Th2 and immunoregulatory capabilities, and four distinctive cationic proteins. The secretion of these granule-derived proteins within eosinophils occurs principally by a mechanism whereby selected proteins are mobilized into vesicles for transport to and release at the cell surface. In contrast, the enigmatic presence of membrane-bound cell-free granules extruded from eosinophils has been long recognized in tissues associated with eosinophilia, including allergic diseases and r...
Source: Current Opinion in Immunology - August 23, 2009 Category: Allergy & Immunology Authors: Neves JS, Weller PF Tags: Curr Opin Immunol Source Type: journals

Immune tolerance in allergy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Research on the mechanisms of immune regulation in allergy and asthma has shown substantial progress in recent years and has led to a variety of allergen-specific therapeutic and preventive approaches. Studies on the area of allergen-specific immunotherapy (allergen-SIT) have provided substantial knowledge on the mechanisms of allergic disease with novel developments for treatment and prevention. Several studies have demonstrated that increased numbers and the activation of allergen-specific T regulatory cells correlate with successful allergen-SIT. Particularly, targeting of the molecular mechanisms of immune toleranc...
Source: Current Opinion in Immunology - August 20, 2009 Category: Allergy & Immunology Authors: Akdis M Tags: Curr Opin Immunol Source Type: journals

Structural alterations in peptide-MHC recognition by self-reactive T cell receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The crystal structures of five autoimmune T cell receptor (TCR)-peptide-MHC complexes reveal substantial structural alterations compared to antimicrobial TCRs. The two human TCRs bind their self-peptide-MHC ligands with an altered topology, while the three mouse receptors recognize a self-peptide that only partially fills the MHC-binding groove. In most cases the peptide is contacted only by a subset of available TCR complementarity-determining loops and there is a paucity of hydrogen bonds from TCR to peptide. These suboptimal binding properties may have enabled escape from negative thymic selection. While only minute...
Source: Current Opinion in Immunology - August 18, 2009 Category: Allergy & Immunology Authors: Wucherpfennig KW, Call MJ, Deng L, Mariuzza R Tags: Curr Opin Immunol Source Type: journals

The role of T helper subsets in autoimmunity and allergy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The classification of T helper (T(H)) cells in subsets has progressively expanded and more effector subsets, besides T(H)1 and T(H)2, have been documented. These include follicular helper T cells (T(FH)), and the more recent T(H)17, 'T(H)9', and 'T(H)22'. In addition, T(H) are no longer thought of as terminally committed effector cells, with plasticity now recognized. Identification of the molecular mechanisms that drive differentiation of T(H) cells has established a link between environmental factors and T(H) subsets, with regard to both the initiation and severity of immune disorders. The role of T(H) in autoimmune-...
Source: Current Opinion in Immunology - August 13, 2009 Category: Allergy & Immunology Authors: Veldhoen M Tags: Curr Opin Immunol Source Type: journals

Management of the highly sensitized patient.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
One of the major challenges in the current era of organ transplantation is to find suitable organs for highly sensitized patients. Different approaches have been successful in a proportion of the patients. Several organ exchange organizations are currently implementing an acceptable mismatch program similar to the one developed by Eurotransplant. The basis of such a program is the accurate definition of those HLA antigens or epitopes toward which the patient did not form antibodies. Donors, who are compatible with the combination of the HLA type of the recipient and these acceptable HLA mismatches, will have a negative...
Source: Current Opinion in Immunology - August 11, 2009 Category: Allergy & Immunology Authors: Claas FH, Doxiadis II Tags: Curr Opin Immunol Source Type: journals

The immunopathogenesis of Crohn's disease: a three-stage model.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pathogenesis of Crohn's disease (CD) has remained an enigma for at least a century. There was considerable optimism that genetic linkage and genome-wide association (GWA) studies had identified genes causally responsible. However, the realisation that these genes make a relatively minor contribution to the development of CD has led to the acceptance of a 'missing heritability'. In contrast to the weak genetic effects, patients with CD almost without exception exhibit a gross phenotype, namely a profound systemic failure of the acute inflammatory response. This results in markedly delayed clearance of bacteria from ...
Source: Current Opinion in Immunology - August 6, 2009 Category: Allergy & Immunology Authors: Sewell GW, Marks DJ, Segal AW Tags: Curr Opin Immunol Source Type: journals

Genetics of hypogammaglobulinemia: what do we really know?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the past, immunodeficiencies were categorized based on clinical and laboratory findings in the affected patient. Now we are more likely to define them based on the specific gene involved. One might expect this shift to increase the precision and clarity of diagnosis but in the last few years it has become increasingly clear that identification of a mutation in a specific gene may not tell the whole story. Some gene defects may reliably result in clinical disease, others may act as susceptibility factors that are more common in patients with immunodeficiency but can also be found in otherwise healthy individuals. Dis...
Source: Current Opinion in Immunology - July 31, 2009 Category: Allergy & Immunology Authors: Conley ME Tags: Curr Opin Immunol Source Type: journals

Genetic etiologies of leukocyte adhesion defects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Up to now three distinct syndromes affecting several steps in the leukocyte adhesion cascade have been described. In LAD I the firm adhesion of leukocyte to the endothelium is defective, because of mutations in the gene encoding the beta(2)-integrin. Recent works both in human and animal models shed light on various mutations and their physiological importance. Furthermore, the beneficial effect of gene therapy is also becoming clear. LAD II which involved the first phase of the cascade, the rolling phase, is caused by mutations in the specific fucose transporter to the Golgi apparatus. Gene targeted mice were able to ...
Source: Current Opinion in Immunology - July 30, 2009 Category: Allergy & Immunology Authors: Etzioni A Tags: Curr Opin Immunol Source Type: journals

Innate-like recognition of microbes by invariant natural killer T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Invariant natural killer T cells (iNKT cells) express a restricted T cell antigen receptor (TCR) repertoire and they respond rapidly to glycolipid antigens presented by CD1d. These glycolipid antigens have hexose sugars in alpha-linkage to two types of lipids that can bind to CD1d. Recent work has shown that the responses of iNKT cells to antigen-bearing microbes can have a profound impact on the development of inflammatory diseases. iNKT cells overcome the limitation of their limited TCR diversity by also responding in a foreign antigen-independent fashion to some infectious agents, similar to NK cells. Recent results...
Source: Current Opinion in Immunology - July 28, 2009 Category: Allergy & Immunology Authors: Kronenberg M, Kinjo Y Tags: Curr Opin Immunol Source Type: journals

T cells in mycobacterial infection and disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There has been an increase in our understanding of the complexity of the T cell response to mycobacterial infection recently. Improved tools have allowed the determination of the location and kinetics of naïve T cell activation in the mouse as well the variety of function of mycobacteria-specific cells in humans. There is also an increased appreciation of the balance required during mycobacterial infection between anti-bacterial activity and control of the immunopathologic response. The integration of the T cell functional data with the consequences of infection should improve rational vaccine design. PMID: 19...
Source: Current Opinion in Immunology - July 28, 2009 Category: Allergy & Immunology Authors: Cooper AM Tags: Curr Opin Immunol Source Type: journals

Fine-tuning of T cell responses during infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Adequate control of infection relies on development of a tailored immune response according to the requirements of a given infection. This is achieved by the continuous crosstalk between innate and adaptive immunity. Pathogen diversity is deciphered via a plethora of receptors converging signals to adaptor molecules; tissue sites and environment generate additional signals that further influence T cell lineage decisions. Within this continuum of interactions, fine-tuning of the ensuing T cell responses together with plasticity of the committed T cells ensure development of balanced immune responses maintaining homeosta...
Source: Current Opinion in Immunology - July 28, 2009 Category: Allergy & Immunology Authors: Dorhoi A, Kaufmann SH Tags: Curr Opin Immunol Source Type: journals

CD8(+) T cells in Trypanosoma cruzi infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD8(+) T cells have emerged as crucial players in the control of a number of protozoan pathogens, including Trypanosoma cruzi, the agent of human Chagas disease. The recent identification of the dominant targets of T. cruzi-specific T cells has allowed investigators to follow the generation of and document the functionality of T cell responses in both mice and humans. Although slow to develop in the early stages of the infection, T. cruzi-specific CD8(+) T cells reach prodigious levels and remain highly functional throughout chronic infections in mice. Following drug-induced cure during either the acute or chronic stag...
Source: Current Opinion in Immunology - July 28, 2009 Category: Allergy & Immunology Authors: Padilla AM, Bustamante JM, Tarleton RL Tags: Curr Opin Immunol Source Type: journals

T cell responses in microbial infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19643590 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - July 27, 2009 Category: Allergy & Immunology Authors: Modlin RL, Brenner MB Tags: Curr Opin Immunol Source Type: journals

Age-associated declines in immune system development and function: causes, consequences, and reversal.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19632102 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - July 22, 2009 Category: Allergy & Immunology Authors: Dorshkind K, Swain S Tags: Curr Opin Immunol Source Type: journals

Effects of aging on B cell function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ability to make an optimal immune response to vaccines and infectious agents declines with age in humans and animal models. Recent advances have shown intrinsic B cell defects in aged mice and humans, including decreases in Ig class switch recombination (CSR), activation-induced cytidine deaminase (AID), and E47 transcription factor. Effects on somatic hypermutation (SHM) have been varied depending on the system studied. Increase of AID in mice has shown improved CSR but not SHM. The reported microarray analysis of human B cell subsets may now be used to delineate B cell defects with aging and all the advances presente...
Source: Current Opinion in Immunology - July 13, 2009 Category: Allergy & Immunology Authors: Frasca D, Blomberg BB Tags: Curr Opin Immunol Source Type: journals

Rejuvenation of the aging T cell compartment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The elderly face significant risk for susceptibility to infection and cancer because of declining immune function. Various agents used in the setting of bone marrow transplantation and aging studies represent promising approaches to combating T cell defects in the aging population. Preclinical and clinical studies on the T cell reconstitution effects of sex steroid ablation, keratinocyte growth factor, the growth hormone pathway, and the cytokines interleukin-7, interleukin-12, and interleukin-15 indicate that these strategies may be used to alleviate the effects of T cell deficiencies in the elderly. PMID: 1960839...
Source: Current Opinion in Immunology - July 13, 2009 Category: Allergy & Immunology Authors: Holland AM, van den Brink MR Tags: Curr Opin Immunol Source Type: journals

Immunosenescence: what does it mean to health outcomes in older adults?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The most profound consequences of immune senescence with respect to human health are the increased susceptibility to infectious diseases and decreased vaccine efficacy. Changes in both innate and adaptive immune function converge in the reduced response to vaccination and protection against infection and related diseases. The decline in thymic output of naïve T cells diminishes responses to novel antigens, such as West Nile Virus, while clonal expansions leading to defects in the T cell repertoire are associated with blunted responses of memory T cells to conserved epitopes of the influenza virus. Recent studies o...
Source: Current Opinion in Immunology - June 28, 2009 Category: Allergy & Immunology Authors: McElhaney JE, Effros RB Tags: Curr Opin Immunol Source Type: journals

Human innate immunity against African trypanosomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Humans are naturally resistant to infection by the African trypanosome prototype Trypanosoma brucei brucei, and only two variant clones of this parasite can avoid this innate immunity and cause sleeping sickness. The resistance to T. brucei is due to serum complexes associating apolipoprotein A-1 (apoA1) with two primate-specific proteins, apolipoprotein L-1 (apoL1) and haptoglobin-related protein (Hpr). We discuss recent advances on the respective functions of apoL1 and Hpr in this system. ApoL1 was found to share structural and functional similarities with proteins of the apoptotic Bcl2 family, and to kill trypanosom...
Source: Current Opinion in Immunology - June 23, 2009 Category: Allergy & Immunology Authors: Pays E, Vanhollebeke B Tags: Curr Opin Immunol Source Type: journals

The evolved functions of CD1 during infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD1 proteins display lipid antigens to T cell receptors. Studies using CD1d tetramers and CD1d-deficient mice provide important insight into the immunological functions of invariant NK T cells (iNKT) during viral and bacterial infections. However, the mouse CD1 locus is atypical because it encodes only CD1d, whereas most mammalian species have retained many CD1 genes. Viewed from the perspective that CD1 is a diverse gene family that activates several of classes of T cells, new insights into lipid loading and infection response are emerging. PMID: 19541469 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 18, 2009 Category: Allergy & Immunology Authors: Kasmar A, Van Rhijn I, Moody DB Tags: Curr Opin Immunol Source Type: journals

Biomarkers of human immunosenescence: impact of Cytomegalovirus infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Age-associated failing systemic immunity, loosely termed 'immunosenescence', is thought to contribute to the increased incidence and severity of infectious disease in old people. It would therefore be of great practical as well as academic interest to accurately identify which of the multitude of alterations to immune parameters thus far reported are causally related to a person's clinically unfavourable health status, in order to identify the mechanisms of immune ageing and intervene to restore appropriate immunity. This is an enormous current challenge, as it requires longitudinal studies in a very long-lived species...
Source: Current Opinion in Immunology - June 14, 2009 Category: Allergy & Immunology Authors: Derhovanessian E, Larbi A, Pawelec G Tags: Curr Opin Immunol Source Type: journals

Tumor suppressor mechanisms in immune aging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cancer-aging hypothesis suggests that the activation of some tumor suppressor mechanisms beneficially prevents cancer but also untowardly promotes mammalian aging. Along these lines, activation of tumor suppressor mechanisms that inhibit the cell cycle (e.g. p16(INK4a) and p53) in response to DNA damage and other age-promoting stimuli has taken center stage in immune-aging research. Immune cells are intrinsically susceptible to transforming events due to V(D)J recombination, a high rate of cellular turnover and requisite long-term self-renewal. Therefore, the DNA damage response and cell cycle regulation play a cle...
Source: Current Opinion in Immunology - June 14, 2009 Category: Allergy & Immunology Authors: Liu Y, Sharpless NE Tags: Curr Opin Immunol Source Type: journals

Effects of aging on hematopoietic stem and progenitor cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although relationships between cellular and organismal aging are not well understood, several studies describe age-related changes in hematopoietic stem cells (HSCs) with functional consequences for the hematopoietic system. Importantly, aged hematopoietic stem and progenitor cells (HSPCs) differ from their younger counterparts in functional capacity, the complement of proteins on the cell surface, transcriptional activity, and genome integrity. These changes, however, are likely the result of a combination of cell-intrinsic and microenvironment-derived influences. Evolving views of the composition of the HSC compartme...
Source: Current Opinion in Immunology - June 2, 2009 Category: Allergy & Immunology Authors: Waterstrat A, Van Zant G Tags: Curr Opin Immunol Source Type: journals

Genetic and epigenetic regulation of aging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Many age-associated conditions, such as the decrease in regenerative capacity of tissues, appear to be determined by a decline in the function of specific somatic stem cells. Although it is obvious that the genotype determines the average lifespan of different species, the variation in lifespan of individuals within a species seems to be more affected by the accumulation over time of molecular errors that compromise adult stem cell function. These molecular alterations can occur at both the genetic and epigenetic levels and depend on hereditary, environmental, and stochastic factors. This complex multifactorial mixture...
Source: Current Opinion in Immunology - June 2, 2009 Category: Allergy & Immunology Authors: Fraga MF Tags: Curr Opin Immunol Source Type: journals

Effects of aging on T cell function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Immunosenescence influences many components of the immune system. Most importantly, profound changes in T cell function are evident in older individuals. The impact of aging on specific T cell subsets has been difficult to examine, but recent advances in murine model systems and new insights into T cell function have allowed for the more precise examination of how T cell responses change with aging. Importantly, recent studies have shown that age-related enhancement of both Th17 generation and regulatory T cell function may contribute to significant changes in immune function. In this review, we summarize the current v...
Source: Current Opinion in Immunology - June 2, 2009 Category: Allergy & Immunology Authors: Haynes L, Maue AC Tags: Curr Opin Immunol Source Type: journals

The microanatomy of B cell activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The logistic problem of B cell antigen encounter in the lymph node has recently been studied by dynamic imaging using two-photon microscopy. These studies combined with the early studies of antigen transport have yielded a more complete picture of the orchestration of B cell activation in vivo. Here we summarize the recent advances and focus on the specialized macrophages that are critical to this process and the role of B cells themselves as antigen transporting cells. PMID: 19481917 [PubMed - in process] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 31, 2009 Category: Allergy & Immunology Authors: Phan TG, Gray EE, Cyster JG Tags: Curr Opin Immunol Source Type: journals