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Chapter 1: The physiological role of lysyl tRNA synthetase in the immune system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lysyl tRNA synthetase (LysRS) is an aminoacyl-tRNA synthetase (AaRS). This group of ancient proteins, known for their critical role in translation, was found in recent years to function in a variety of other roles. Besides its enzymatic activity in aminoacylation of tRNA, LysRS can produce dinucleotide diadenosine tetraphosphate (Ap(4)A). Intracellularly, it is found mainly in the cytoplasm as a part of a multisynthetase complex where it interacts with several proteins, most notably AIMP2. Besides its role in translation it has been demonstrated that LysRS can act as a cytokine-like molecule, secreted by cells and havi...
Source: Advances in Immunology - September 18, 2009 Category: Allergy & Immunology Authors: Nechushtan H, Kim S, Kay G, Razin E Tags: Adv Immunol Source Type: journals

Chapter 2: Kill the bacteria...and also their messengers?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We consider here a previously neglected aspect of recovery from infectious diseases: how animals dispose of the dead microbes in their tissues. For one of the most important disease-causing microorganisms, Gram-negative bacteria, there is now evidence that the host catabolism of a key microbial molecule is essential for full recovery. As might be expected, it is the same bacterial molecule that animals sense to detect the presence of Gram-negative bacteria in their tissues, the cell wall lipopolysaccharide (LPS). Here, we discuss current knowledge about LPS sensing with emphasis on the host enzyme that inactivates this...
Source: Advances in Immunology - September 18, 2009 Category: Allergy & Immunology Authors: Munford R, Lu M, Varley A Tags: Adv Immunol Source Type: journals

Chapter 3: Role of SOCS in allergic and innate immune responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytokines are powerful mediators of the immune response that, following initial release by components of the innate system, drive effector functions as well as stimulate the additional arms of the response. Their individual functions are diverse, with stimulatory and inhibitory actions, with the resultant systemic immune response a summation of these actions. The frequently opposing effects of cytokines determine that the blockade of one results in the functional augmentation of the other. Thus, the differential regulation of cytokines profoundly influences the character of the immune response. The suppressor of cytoki...
Source: Advances in Immunology - September 18, 2009 Category: Allergy & Immunology Authors: Cassel SL, Rothman PB Tags: Adv Immunol Source Type: journals

Chapter 4: Multitasking by exploitation of intracellular transport functions the many faces of FcRn.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The MHC Class I-related receptor, FcRn, transports antibodies of the immunoglobulin G (IgG) class within and across a diverse array of different cell types. Through this transport, FcRn serves multiple roles throughout adult life that extend well beyond its earlier defined function of transcytosing IgGs from mother to offspring. These roles include the maintenance of IgG levels and the delivery of antigen in the form of immune complexes to degradative compartments within cells. Recent studies have led to significant advances in knowledge of the intracellular trafficking of FcRn and (engineered) IgGs at both the molecul...
Source: Advances in Immunology - September 18, 2009 Category: Allergy & Immunology Authors: Ward ES, Ober RJ Tags: Adv Immunol Source Type: journals

Chapter 1 Antigen Presentation by CD1 Lipids, T Cells, and NKT Cells in Microbial Immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The discovery of molecules capable of presenting lipid antigens, the CD1 family, and of the T cells that recognize them, has opened a new dimensionin our understanding of cell-mediated immunity against infection. Like MHC Class I molecules, CD1 isoforms (CD1a, b, c and d) are assembled in the ER and sent to the cell surface. However, in contrast to MHC molecules, CD1 complexes are then re-internalized into specific endocytic compartments where they can bind lipid antigens. These include a broad scope of both self and foreign molecules that range from simple fatty acids or phospholipids, to more complex glycolipids, iso...
Source: Advances in Immunology - June 27, 2009 Category: Allergy & Immunology Authors: Cohen NR, Garg S, Brenner MB Tags: Adv Immunol Source Type: journals

Chapter 2 how the immune system achieves self-nonself discrimination during adaptive immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We propose an "Avidity Model of Self-Nonself Discrimination" in which self-nonself discrimination is achieved by both central thymic selection and peripheral immune regulation. The conceptual framework that links these two events is the understanding that both in the thymus and in the periphery the survival or the fate of T cells is determined by the avidity of the interactions between T cell receptors (TCRs) on T cells, specific to any antigens and MHC/antigen peptides presented by antigen-presenting cells (APCs). We envision that the immune system achieves self-nonself discrimination, during adaptive immunity, not by...
Source: Advances in Immunology - June 27, 2009 Category: Allergy & Immunology Authors: Jiang H, Chess L Tags: Adv Immunol Source Type: journals

Chapter 3 cellular and molecular mechanisms in atopic dermatitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atopic dermatitis (AD) is a pruritic inflammatory skin disease associated with a personal or family history of allergy. The prevalence of AD is on the rise and estimated at approximately 17% in the USA. The fundamental lesion in AD is a defective skin barrier that results in dry itchy skin, and is aggravated by mechanical injury inflicted by scratching. This allows entry of antigens via the skin and creates a milieu that shapes the immune response to these antigens. This review discusses recent advances in our understanding of the abnormal skin barrier in AD, namely abnormalities in epidermal structural proteins, such ...
Source: Advances in Immunology - June 27, 2009 Category: Allergy & Immunology Authors: Oyoshi MK, He R, Kumar L, Yoon J, Geha RS Tags: Adv Immunol Source Type: journals

Chapter 4 micromanagers of immune cell fate and function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MicroRNAs (miRNAs) regulate cell fate during development and in response to environmental cues. Here, we review the emerging story of how miRNAs regulate immune cell development and function. PMID: 19477322 [PubMed - in process] (Source: Advances in Immunology)
Source: Advances in Immunology - June 27, 2009 Category: Allergy & Immunology Authors: Petrocca F, Lieberman J Tags: Adv Immunol Source Type: journals

Chapter 5 immune pathways for translating viral infection into chronic airway disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
To better understand the immune basis for chronic inflammatory lung disease, we analyzed a mouse model of lung disease that develops after respiratory viral infection. The disease that develops in this model is similar to asthma and chronic obstructive pulmonary disease (COPD) in humans and is manifested after the inciting virus has been cleared to trace levels. The model thereby mimics the relationship of paramyxoviral infection to the development of childhood asthma in humans. When the acute lung disease appears in this model (at 3 weeks after viral inoculation), it depends on an immune axis that is initiated by expr...
Source: Advances in Immunology - June 27, 2009 Category: Allergy & Immunology Authors: Holtzman MJ, Byers DE, Benoit LA, Battaile JT, You Y, Agapov E, Park C, Grayson MH, Kim EY, Patel AC Tags: Adv Immunol Source Type: journals

Chapter 1 TSLP in Epithelial Cell and Dendritic Cell Cross Talk.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dendritic cells (DCs) are professional antigen-presenting cells that have the ability to sense infection and tissue stress, sample and present antigen to T lymphocytes, and instruct the initiation of different forms of immunity and tolerance. The functional versatility of DCs depends on their remarkable ability to translate collectively the information from the invading microbes, as well as their resident tissue microenvironments. Recent progress in understanding Toll-like receptor (TLR) biology has illuminated the mechanisms by which DCs link innate and adaptive antimicrobial immune responses. However, how tissue micr...
Source: Advances in Immunology - February 24, 2009 Category: Allergy & Immunology Authors: Liu YJ Tags: Adv Immunol Source Type: journals

Chapter 2 natural killer cell tolerance licensing and other mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Armed with potent cytotoxic and immunostimulatory effector functions, natural killer (NK) cells have the potential to cause significant damage to normal self cells unless controlled by self-tolerance mechanisms. NK cells identify and attack target cells based on integration of signals from activation and inhibitory receptors, whose ligands exhibit complex expression and/or binding patterns. Preservation of NK cell self-tolerance must therefore go beyond mere engagement of inhibitory receptors during effector functions. Herein, we review recent work that has uncovered a number of mechanisms to ensure self-tolerance of N...
Source: Advances in Immunology - February 24, 2009 Category: Allergy & Immunology Authors: Jonsson AH, Yokoyama WM Tags: Adv Immunol Source Type: journals

Chapter 3 biology of the eosinophil.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this review, we aim to put in perspective the biology of a multifunctional leukocyte, the eosinophil, by placing it in the context of innate and adaptive immune responses. Eosinophils have a unique contribution in initiating inflammatory and adaptive responses, due to their bidirectional interactions with dendritic cells and T cells, as well as their large panel of secreted cytokines and soluble mediators. The mechanisms and consequences of eosinophil responses in experimental inflammatory models and human diseases are discussed. PMID: 19231593 [PubMed - in process] (Source: Advances in Immunology)
Source: Advances in Immunology - February 24, 2009 Category: Allergy & Immunology Authors: Blanchard C, Rothenberg ME Tags: Adv Immunol Source Type: journals

Chapter 4 basophils beyond effector cells of allergic inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite being first described in humans nearly 130 years ago, the basophil granulocyte has received little recognition other than being the least common leukocyte circulating in blood. Even after its identity as the source of histamine released by blood cells in response to reaginic IgE, its role in allergic disease has largely been viewed as redundant to that of the tissue mast cell. This line of thought, however, is changing with evidence that has emerged during the last 15 years. Not only have these rare cells been shown to constitute a significant source of cytokines (IL-4 and IL-13) vital to the pathogenesis of al...
Source: Advances in Immunology - February 24, 2009 Category: Allergy & Immunology Authors: Schroeder JT Tags: Adv Immunol Source Type: journals

Chapter 5 DNA Targets of AID Evolutionary Link Between Antibody Somatic Hypermutation and Class Switch Recombination.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe properties of the S sequences, and discuss species and isotypic differences among S regions. Common properties of SHM and CSR target sequences suggest that evolution of S regions might involve the duplication and selection of SHM hotspots. PMID: 19231595 [PubMed - in process] (Source: Advances in Immunology)
Source: Advances in Immunology - February 24, 2009 Category: Allergy & Immunology Authors: Hackney JA, Misaghi S, Senger K, Garris C, Sun Y, Lorenzo MN, Zarrin AA Tags: Adv Immunol Source Type: journals

Chapter 6 interleukin 5 in the link between the innate and acquired immune response.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interleukin-5 (IL-5) is an interdigitating homodimeric glycoprotein that is initially identified by its ability to support the in vitro growth and differentiation of mouse B cells and eosinophils. IL-5 transgenic mouse shows two predominant features, remarkable increase in B-1 cells resulting in enhanced serum antibody levels, predominantly IgM, IgA, and IgE classes and in expansion of eosinophil numbers in the blood and eosinophil infiltration into various tissues. Conversely, mice lacking a functional gene for IL-5 or IL-5 receptor alpha chain (IL-5Ralpha) display a number of developmental and functional impairments ...
Source: Advances in Immunology - February 24, 2009 Category: Allergy & Immunology Authors: Takatsu K, Kouro T, Nagai Y Tags: Adv Immunol Source Type: journals

Chapter 1 immune regulation by B cells and antibodies a view towards the clinic.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
B lymphocytes contribute to immunity in multiple ways, including production of antibodies, presentation of antigen to T cells, organogenesis of secondary lymphoid organs, and secretion of cytokines. Recent clinical trials have shown that depleting B cells can be highly beneficial for patients with autoimmune diseases, implicating B cells and antibodies as key drivers of pathology. However, it should be kept in mind that B cell responses and antibodies also have important regulatory roles in limiting autoimmune pathology. Here, we analyze clinical examples illustrating the potential of antibodies as treatment for immune...
Source: Advances in Immunology - September 7, 2008 Category: Allergy & Immunology Authors: Hoehlig K, Lampropoulou V, Roch T, Neves P, Calderon-Gomez E, Anderton SM, Steinhoff U, Fillatreau S Tags: Adv Immunol Source Type: journals

Chapter 2 cumulative environmental changes, skewed antigen exposure, and the increase of allergy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The human immune system evolved over many hundreds of million of years in the ancestors of vertebrates and mammals to defend them against infectious and parasitic organisms in their natural habitats. By the time the Primates and Rodentia orders diverged about 88 million years ago, the human immune system was largely configured. From about 125,000 years ago, marked by the use of fire, Homo sapiens began to make substantial changes in their living environment and lifestyle. Here, we examine those changes in two phases, before and after the Industrial Revolution, and analyze their impact on the exposure of our immune syst...
Source: Advances in Immunology - September 7, 2008 Category: Allergy & Immunology Authors: Chang TW, Pan AY Tags: Adv Immunol Source Type: journals

Chapter 3 New Insights on Mast Cell Activation via the High Affinity Receptor for IgE.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mast cells are innate immune cells that function as regulatory or effector cells and serve to amplify adaptive immunity. In adaptive immunity these cells function primarily through cell surface Fc receptors that bind immunoglobulin antibodies. The dysregulation of their adaptive role makes them central players in allergy and asthma. Upon encountering an allergen (antigen), which is recognized by immunoglobulin E (IgE) antibodies bound to the high affinity IgE receptor (FcvarepsilonRI) expressed on their cell surface, mast cells secrete both preformed and newly synthesized mediators of the allergic response. Blocking of...
Source: Advances in Immunology - September 7, 2008 Category: Allergy & Immunology Authors: Rivera J, Fierro NA, Olivera A, Suzuki R Tags: Adv Immunol Source Type: journals

Chapter 4 B cells and autoantibodies in the pathogenesis of multiple sclerosis and related inflammatory demyelinating diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion wi...
Source: Advances in Immunology - September 7, 2008 Category: Allergy & Immunology Authors: McLaughlin KA, Wucherpfennig KW Tags: Adv Immunol Source Type: journals

Chapter 5 human B cell subsets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18772006 [PubMed - in process] (Source: Advances in Immunology)
Source: Advances in Immunology - September 7, 2008 Category: Allergy & Immunology Authors: Jackson SM, Wilson PC, James JA, Capra JD Tags: Adv Immunol Source Type: journals

T Cell Activation and the Cytoskeleton: You Can't Have One Without the Other.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
More than a quarter of a century has passed since the observation that T cells rapidly polarize their actin and microtubule cytoskeletal systems toward antigen-presenting cells during activation. Since this initial discovery, several receptors on T cells (e.g., T cell receptor [TCR], co-receptors, integrins, and chemokine receptors) have been identified to regulate these two cytoskeletal networks through complex signaling pathways, which are still being elucidated. There is now an undeniable body of biochemical, pharmacological, and genetic evidence indicating that regulators of actin and microtubule dynamics are cruci...
Source: Advances in Immunology - May 27, 2008 Category: Allergy & Immunology Authors: Gomez TS, Billadeau DD Tags: Adv Immunol Source Type: journals

HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Population studies have shown that among all the genetic factors linked with autoimmune disease development, MHC class II genes on chromosome 6 accounts for majority of familial clustering in the common autoimmune diseases. Despite the highly polymorphic nature of HLA class II genes, majority of autoimmune diseases are linked to a limited set of class II-DR or -DQ alleles. Thus a more detailed study of these HLA-DR and -DQ alleles were needed to understand their role in genetic predisposition and pathogenesis of autoimmune diseases. Although in vitro studies using class-II restricted CD4 T cells and purified class II m...
Source: Advances in Immunology - May 27, 2008 Category: Allergy & Immunology Authors: Mangalam AK, Rajagopalan G, Taneja V, David CS Tags: Adv Immunol Source Type: journals

Roles of Zinc and Zinc Signaling in Immunity: Zinc as an Intracellular Signaling Molecule.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Zinc (Zn) is an essential nutrient required for cell growth, differentiation, and survival, and its deficiency causes growth retardation, immunodeficiency, and other health problems. Therefore, Zn homeostasis must be tightly controlled in individual cells. Zn is known to be important in the immune system, although its precise roles and mechanisms have not yet been resolved. Zn has been suggested to act as a kind of neurotransmitter. In addition, Zn has been shown to bind and affect the activity of several signaling molecules, such as protein tyrosine phosphatases (PTPs). However, it has not been known whether Zn itself...
Source: Advances in Immunology - May 27, 2008 Category: Allergy & Immunology Authors: Hirano T, Murakami M, Fukada T, Nishida K, Yamasaki S, Suzuki T Tags: Adv Immunol Source Type: journals

The SLAM and SAP Gene Families Control Innate and Adaptive Immune Responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The nine SLAM-family genes, SLAMF1-9, a subfamily of the immunoglobulin superfamily, encode differentially expressed cell-surface receptors of hematopoietic cells. Engagement with their ligands, which are predominantly homotypic, leads to distinct signal transduction events, for instance those that occur in the T or NK cell immune synapse. Upon phosphorylation of one or more copies of a unique tyrosine-based signaling motif in their cytoplasmic tails, six of the SLAM receptors recruit the highly specific single SH2-domain adapters SLAM-associated protein (SAP), EAT-2A, and/or EAT-2B. These adapters in turn bind to the ...
Source: Advances in Immunology - May 27, 2008 Category: Allergy & Immunology Authors: Calpe S, Wang N, Romero X, Berger SB, Lanyi A, Engel P, Terhorst C Tags: Adv Immunol Source Type: journals

Conformational Plasticity and Navigation of Signaling Proteins in Antigen-Activated B Lymphocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Over the past two decades our view of the B cell antigen receptor (BCR) has fundamentally changed. Being initially regarded as a mute antibody orphan of the B cell surface, the BCR turned out to be a complex multimolecular machine monitoring almost all stages of B cell development, selection, and activation through a plethora of ubiquitously and cell-type-specific effector proteins. A comprehensive understanding of the many BCR signaling facets is still out but a few common biochemical principles outlined in this review operate at the level of receptor activation and orchestrate specific wiring of intracellular transdu...
Source: Advances in Immunology - May 27, 2008 Category: Allergy & Immunology Authors: Engels N, Engelke M, Wienands J Tags: Adv Immunol Source Type: journals

New insights into adaptive immunity in chronic neuroinflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Understanding the immune response in the central nervous system (CNS) is crucial for the development of new therapeutic concepts in chronic neuroinflammation, which differs considerably from other autoimmune diseases. Special immunologic properties of inflammatory processes in the CNS, which is often referred to as an immune privileged site, imply distinct features of CNS autoimmune disease in terms of disease initiation, perpetuation, and therapeutic accessibility. Furthermore, the CNS is a stress-sensitive organ with a low capacity for self-renewal and is highly prone to bystander damage caused by CNS inflammation. T...
Source: Advances in Immunology - November 6, 2007 Category: Allergy & Immunology Authors: Siffrin V, Brandt AU, Herz J, Zipp F Tags: Adv Immunol Source Type: journals

Regulation of Interferon-gamma During Innate and Adaptive Immune Responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interferon-gamma (IFN-gamma) is crucial for immunity against intracellular pathogens and for tumor control. However, aberrant IFN-gamma expression has been associated with a number of autoinflammatory and autoimmune diseases. This cytokine is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by Th1 CD4 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops. Herein, we briefly review the functions of IFN-gamma, the cells that produce it, the cell extrinsic signals that induce its production and influence the di...
Source: Advances in Immunology - November 6, 2007 Category: Allergy & Immunology Authors: Schoenborn JR, Wilson CB Tags: Adv Immunol Source Type: journals

The expansion and maintenance of antigen-selected CD8(+) T cell clones.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The biological purpose of the mature, postthymic CD8(+) T cell is to respond to microbial antigens with a developmental program of clonal expansion and concomitant differentiation leading to effector cells (T(EFF)) that provide antimicrobial defense. Because many microbial infections persist into a chronic phase, this antigen-stimulated developmental program must be capable of continually generating T(EFF), perhaps for the lifetime of the individual. This chapter proposes that the ability of a CD8(+) T cell clone to maintain the continual production of T(EFF) during periods of persistent antigenic stimulation is based ...
Source: Advances in Immunology - November 6, 2007 Category: Allergy & Immunology Authors: Fearon DT Tags: Adv Immunol Source Type: journals

Inherited Complement Regulatory Protein Deficiency Predisposes to Human Disease in Acute Injury and Chronic Inflammatory StatesThe Examples of Vascular Damage in Atypical Hemolytic Uremic Syndrome and Debris Accumulation in Age-Related Macular Degeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this chapter, we examine the role of complement regulatory activity in atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). These diseases are representative of two distinct types of complement-mediated injury, one being acute and self-limited, the other reflecting accumulation of chronic damage. Neither condition was previously thought to have a pathologic relationship to the immune system. However, alterations in complement regulatory protein genes have now been identified as major predisposing factors for the development of both diseases. In aHUS, heterozygous mutations leading to...
Source: Advances in Immunology - November 6, 2007 Category: Allergy & Immunology Authors: Richards A, Kavanagh D, Atkinson JP Tags: Adv Immunol Source Type: journals

Fc-Receptors as Regulators of Immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Receptors for immunoglobulins [Fc-receptors (FcRs)] are widely expressed throughout the immune system. By binding to the antibody Fc-portion, they provide a link between the specificity of the adaptive immune system and the powerful effector functions triggered by innate immune effector cells. By virtue of coexpression of activating and inhibitory FcRs on the same cell, they set a threshold for immune cell activation by immune complexes (ICs). Besides their involvement in the efferent phase of an immune response, they are also important for modulating adaptive immune responses by regulating B cell and dendritic cell (D...
Source: Advances in Immunology - November 6, 2007 Category: Allergy & Immunology Authors: Nimmerjahn F, Ravetch JV Tags: Adv Immunol Source Type: journals

Fate decisions regulating bone marrow and peripheral B lymphocyte development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In adult mammals, bone marrow pluripotent hematopoietic stem cells generate B lymphoid-specified progeny that progress through a series of well-characterized stages before generating B-cell receptor expressing B lymphocytes. These functionally immature B lymphocytes then migrate to the spleen wherein they differentiate through transitional stages into follicular or marginal zone B lymphocytes capable of responding to T-dependent and -independent antigens, respectively. During the terminal stages of B lymphocyte development in the bone marrow, as well as immediately following egress into the peripheral compartments, B l...
Source: Advances in Immunology - September 19, 2007 Category: Allergy & Immunology Authors: Monroe JG, Dorshkind K Tags: Adv Immunol Source Type: journals

Tolerance and autoimmunity: lessons at the bedside of primary immunodeficiencies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The recent progress in the genetic characterization of many primary immunodeficiencies (PIDs) allows for a better understanding of immune molecular and cellular mechanisms. The present chapter discusses associations between PIDs and autoimmune diseases (AIDs) in this new light. PIDs are classified according to the frequency of association with AIDs, defining four groups of conditions: systematic (more than 80% of all patients), strong (10-80%), mild (less than 10%), and absent (no available descriptions). Several general conclusions could be drawn: (1) pathological autoimmune (AI) manifestations are very frequently ass...
Source: Advances in Immunology - September 19, 2007 Category: Allergy & Immunology Authors: Carneiro-Sampaio M, Coutinho A Tags: Adv Immunol Source Type: journals

B-cell self-tolerance in humans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Two mechanisms account for generation of the human antibody repertoire; V(D)J recombination during the early stages of B-cell development in the bone marrow and somatic mutation of immunoglobulin genes in mature B cells responding to antigen in the periphery. V(D)J recombination produces diversity by random joining of gene segments and somatic mutation by introducing random point mutations. Both are required to attain the degree of antigen receptor diversification that is necessary for immune protection: defects in either mechanism are associated with increased susceptibility to infection. However, the downside of prod...
Source: Advances in Immunology - September 19, 2007 Category: Allergy & Immunology Authors: Wardemann H, Nussenzweig MC Tags: Adv Immunol Source Type: journals

Manipulation of Regulatory T-Cell Number and Function with CD28-Specific Monoclonal Antibodies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Suppressor or "regulatory" CD4 T cells play a key role in the control of autoimmunity and overshooting immune responses to foreign antigens, but can also obstruct effective anticancer therapies. The homeostasis and activation of these regulatory T cells (Treg cells) is tightly connected to that of effector CD4 T cells via the costimulatory receptor CD28 and the cytokine IL-2: Both subsets require costimulation to be activated by antigen, and Treg cells additionally depend on IL-2 produced by effector CD4 T cells in a costimulation-dependent fashion. Depending on the therapeutic aim, blockade, or stimulation of CD28 wit...
Source: Advances in Immunology - September 19, 2007 Category: Allergy & Immunology Authors: Hünig T Tags: Adv Immunol Source Type: journals

Osteoimmunology: a view from the bone.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Osteoimmunology can be defined in a very broad sense as the field of research focusing on interrelations between bone and the immune system. This is a rather opened field that covers at least three different issues. The first one is developmental, that is, organogenesis of the bones and immune systems. The second is post-developmental, that is, the role of the bone in the regulation of the immune response and role of the immune cells on the regulation of bone homeostasis. The third one is related to pathologies: Can immune cells be involved in the development of bone-related pathology? Can deregulation of the bone be c...
Source: Advances in Immunology - September 19, 2007 Category: Allergy & Immunology Authors: David JP Tags: Adv Immunol Source Type: journals

Mast cell proteases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mast cells (MCs) are traditionally thought of as a nuisance for its host, for example, by causing many of the symptoms associated with allergic reactions. In addition, recent research has put focus on MCs for displaying harmful effects during various autoimmune disorders. On the other hand, MCs can also be beneficial for its host, for example, by contributing to the defense against insults such as bacteria, parasites, and snake venom toxins. When the MC is challenged by an external stimulus, it may respond by degranulation. In this process, a number of powerful preformed inflammatory "mediators" are released, including...
Source: Advances in Immunology - September 19, 2007 Category: Allergy & Immunology Authors: Pejler G, Abrink M, Ringvall M, Wernersson S Tags: Adv Immunol Source Type: journals

Preface.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 17560269 [PubMed - in process] (Source: Advances in Immunology)
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Alt FW, Honjo T Tags: Adv Immunol Source Type: journals

Discovery of activation-induced cytidine deaminase, the engraver of antibody memory.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Discovery of activation-induced cytidine deaminase (AID) paved a new path to unite two genetic alterations induced by antigen stimulation; class switch recombination (CSR) and somatic hypermutation (SHM). AID is now established to cleave specific target DNA and to serve as engraver of these genetic alterations. AID of a 198-residue protein has four important domains: nuclear localization signal and SHM-specific region at the N-terminus; the alpha-helical segment (residue 47-54) responsible for dimerization; catalytic domain (residues 56-94) shared by all the other cytidine deaminase family members; and nuclear export s...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Muramatsu M, Nagaoka H, Shinkura R, Begum NA, Honjo T Tags: Adv Immunol Source Type: journals

DNA Deamination in Immunity: AID in the Context of Its APOBEC Relatives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The activation-induced cytidine deaminase (AID)/apolipoprotein B RNA-editing catalytic component (APOBEC) family is a vertebrate-restricted subgrouping of a superfamily of zinc (Zn)-dependent deaminases that has members distributed throughout the biological world. AID and APOBEC2 are the oldest family members with APOBEC1 and the APOBEC3s being later arrivals restricted to placental mammals. Many AID/APOBEC family members exhibit cytidine deaminase activity on polynucleotides, although in different physiological contexts. Here, we examine the AID/APOBEC proteins in the context of the entire Zn-dependent deaminase super...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Conticello SG, Langlois MA, Yang Z, Neuberger MS Tags: Adv Immunol Source Type: journals

The role of activation-induced deaminase in antibody diversification and chromosome translocations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although B and T lymphocytes are similar in many respects including diversification of their antigen receptor genes by V(D)J recombination, 95% of all lymphomas diagnosed in the western world are of B-cell origin. Many of these are derived from mature B cells [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262] and display hallmark chromosome translocations involving immunoglobulin genes and a proto-oncogene partner whose expression becomes deregulated as a result of the translocation reaction [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 2...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Ramiro A, San-Martin BR, McBride K, Jankovic M, Barreto V, Nussenzweig A, Nussenzweig MC Tags: Adv Immunol Source Type: journals

Targeting of AID-Mediated Sequence Diversification by cis-Acting Determinants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
After their assembly by V(D)J recombination, immunoglobulin (Ig) genes undergo somatic hypermutation, gene conversion, and class switch recombination to generate additional antibody diversity. The three diversification processes depend on activation-induced cytidine deaminase (AID) and are tightly linked to transcription. The reactions occur primarily on Ig genes and the molecular mechanisms that underlie their targeting to Ig loci have been of intense interest. In this chapter, we discuss the evidence linking transcription and transcriptional control elements to the three diversification pathways, and we consider how ...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Yang SY, Schatz DG Tags: Adv Immunol Source Type: journals

AID-Initiated Purposeful Mutations in Immunoglobulin Genes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Exposure brings risk to all living organisms. Using a remarkably effective strategy, higher vertebrates mitigate risk by mounting a complex and sophisticated immune response to counter the potentially toxic invasion by a virtually limitless army of chemical and biological antagonists. Mutations are almost always deleterious, but in the case of antibody diversification there are mutations occurring at hugely elevated rates within the variable (V) and switch regions (SR) of the immunoglobulin (Ig) genes that are responsible for binding to and neutralizing foreign antigens throughout the body. These mutations are truly pu...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Goodman MF, Scharff MD, Romesberg FE Tags: Adv Immunol Source Type: journals

Evolution of the immunoglobulin heavy chain class switch recombination mechanism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a model for CSR in which transcription through S regions provides DNA substrates on which AID can generate DSB-inducing lesions. We also discuss how phosphorylation of AID may mediate interactions with cofactors that facilitate access to transcribed S regions during CSR and transcribed variable regions during the related process of somatic hypermutation (SHM). Finally, in the context of this CSR model, we further discuss current findings that suggest synapsis and joining of S region DSBs during CSR have evolved to exploit general mechanisms that function to join widely separated chromosomal DSBs. PMID: 17560...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Chaudhuri J, Basu U, Zarrin A, Yan C, Franco S, Perlot T, Vuong B, Wang J, Phan RT, Datta A, Manis J, Alt FW Tags: Adv Immunol Source Type: journals

Beyond SHM and CSR: AID and Related Cytidine Deaminases in the Host Response to Viral Infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
As the primary effector of immunoglobulin somatic hypermutation (SHM) and class switch recombination (CSR), activation-induced cytidine deaminase (AID) serves an important function in the adaptive immune response. Recent advances have demonstrated that AID and a group of closely related cytidine deaminases, the APOBEC3 proteins, also act in the innate host response to viral infection. Antiviral activity was first attributed to APOBEC3G as a potent inhibitor of HIV. It is now apparent that the targets of the APOBEC3 proteins extend beyond HIV, with family members acting against a wide variety of viruses as well as host-...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Rosenberg BR, Papavasiliou FN Tags: Adv Immunol Source Type: journals

Role of AID in Tumorigenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A hallmark of mature B-cell lymphomas is reciprocal chromosomal translocations involving the Ig locus and a proto-oncogene, which usually result in the deregulated, constitutive expression of the translocated gene. In addition to such translocations, proto-oncogenes are frequently hypermutated in germinal center (GC)-derived B-cell lymphomas. Although aberrant, mistargeted class switch recombination (CSR) and somatic hypermutation (SHM) events have long been suspected of causing chromosomal translocations and mutations in oncogenes, and thus of playing a critical role in the pathogenesis of most B-cell lymphomas, the m...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Okazaki IM, Kotani A, Honjo T Tags: Adv Immunol Source Type: journals

Pathophysiology of B-Cell Intrinsic Immunoglobulin Class Switch Recombination Deficiencies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR def...
Source: Advances in Immunology - June 17, 2007 Category: Allergy & Immunology Authors: Durandy A, Taubenheim N, Peron S, Fischer A Tags: Adv Immunol Source Type: journals

Class switch recombination: a comparison between mouse and human.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Humans and mice separated more than 60 million years ago. Since then, evolution has led to a multitude of changes in their genomic sequences. The divergence of genes has resulted in differences both in the innate and adaptive immune systems. In this chapter, we focus on species difference with regard to immunoglobulin class switch recombination (CSR). We have compared the immunoglobulin constant region gene loci from human and mouse, with an emphasis on the switch regions, germ line transcription promoters, and 3' enhancers. We have also compared pathways/factors that are involved in CSR. Although there are remarkable ...
Source: Advances in Immunology - March 27, 2007 Category: Allergy & Immunology Authors: Pan-Hammarström Q, Zhao Y, Hammarström L Tags: Adv Immunol Source Type: journals

Anti-IgE Antibodies for the Treatment of IgE-Mediated Allergic Diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pharmacological purposes of the anti-IgE therapy are to neutralize IgE and to inhibit its production to attenuate type I hypersensitivity reactions. The therapy is based on humanized IgG1antibodies that bind to free IgE and to membrane-bound IgE on B cells, but not to IgE bound by the high-affinity IgE.Fc receptors on basophils and mast cells or by the low-affinity IgE.Fc receptors on B cells. After nearly 20 years since inception, therapeutic anti-IgE antibodies (anti-IgE) have been studied in about 30 Phase II and III clinical trials in many allergy indications, and a lead antibody, omalizumab, has been approved ...
Source: Advances in Immunology - March 27, 2007 Category: Allergy & Immunology Authors: Chang TW, Wu PC, Hsu CL, Hung AF Tags: Adv Immunol Source Type: journals

Immune semaphorins: increasing members and their diverse roles.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The semaphorin family consists of soluble and membrane-bound proteins originally identified as axonal guidance cues functioning during neuronal development. However, it is becoming increasingly clear that semaphorins play diverse roles in organogenesis, vascular growth, and tumor progression. In addition, emerging evidence indicates that several semaphorins, called "immune semaphorins," play crucial roles also during immune responses. Extensive studies on the immune semaphorins have revealed not only parallels but also differences in the semaphorin functions between the immune and nervous systems, providing unexpected ...
Source: Advances in Immunology - March 27, 2007 Category: Allergy & Immunology Authors: Kikutani H, Suzuki K, Kumanogoh A Tags: Adv Immunol Source Type: journals

Tec kinases in T cell and mast cell signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Tec family of tyrosine kinases consists of five members (Itk, Rlk, Tec, Btk, and Bmx) that are expressed predominantly in hematopoietic cells. The exceptions, Tec and Bmx, are also found in endothelial cells. Tec kinases constitute the second largest family of cytoplasmic protein tyrosine kinases. While B cells express Btk and Tec, and T cells express Itk, Rlk, and Tec, all four of these kinases (Btk, Itk, Rlk, and Tec) can be detected in mast cells. This chapter will focus on the biochemical and cell biological data that have been accumulated regarding Itk, Rlk, Btk, and Tec. In particular, distinctions between th...
Source: Advances in Immunology - March 27, 2007 Category: Allergy & Immunology Authors: Felices M, Falk M, Kosaka Y, Berg LJ Tags: Adv Immunol Source Type: journals