It is known that there is a genetic basis for the spectrum of disease severity in cutaneous leishmaniasis. Here, Emanuela Handman and coworkers show that this association is polygenic, and they have identified 3 loci associated with susceptibility. The nature of the response required for successful vaccination is also discussed.
This paper reviews the Seventh Human Leucocyte Differentiation Antigen (HLDA7) workshop. Due to the limitations of “blind” antibody screening, which had been evident at the previous meeting in 1996, participants at HLDA7 adopted a more selective approach to the choice of antibodies by identifying new CD specificities. This resulted in the addition of more than 80 new CD specificities. Plans for the eighth and subsequent workshops are also previewed.
Professional antigen-presenting cells (APCs) can capture and present exogenous antigen on major histocompatibility class (MHC) I molecules to cytotoxic T cells (CTLs), by the poorly understood process of cross-presentation. Here, William R. Heath and colleagues show that APCs scan the periphery and present class I-restricted tissue derived antigens to naive CTLs in the lymph nodes. They outline a working model of the process and outline outstanding questions.
Introduction: Since the seminal description of asthma as a disease of reversible airway obstruction by Salter in 1859, therapy has been targeted to relax smooth muscle including β2 agonists and xanthines. The discovery that oral and then inhaled corticosteroids could prevent episodic bronchoconstriction and reduce bronchial hyperresponsiveness in parallel with resolution of mucosal inflammation provided the basis for considering asthma as a chronic inflammatory disease. Analysis of mucosal biopsies and cells recovered by lavage has revealed polarisation of the CD4 T cell repertoire to Th-2 like T cells that exhibit co-ordinate secretion of cytokines encoded in a cluster on chromosome 5q31-33, IL-3, IL-4, IL-5, IL-9, IL-13 and GM-CSF [1]. These cytokines have the capacity to support the mast cell, basophil and eosinophil and isotype switching of B cells to IgE. In the respiratory mucosa, mast cells, basophils and eosinophils are themselves sources of Th-2 cytokines and, under certain circumstances, can induce local B cell IgE production. The demonstration that corticosteroids can inhibit production of these cytokines and induces eosinophil and mast cell apoptosis provides an explanation for the therapeutic efficacy of this drug class.
Jacques Miller represents one of the most important contributors to modern immunology. In this short paper, he briefly touches on the various areas to which he has contributed, with the attending publications from 1961 to 1999 attesting to the magnitude of this contribution.
The differentiation of a bone-marrow multipotent hemopoietic stem cell into lymphoid-committed precursors is poorly understood. Here, L. Wu and colleagues discuss the identification of a common lymphoid precursor in mouse bone marrow and lymphoid-restricted precursors in the thymus, and interestingly, the ability of both of these cells to give rise to dendritic cells.
Mucosal administration of antigen is known to have tolerogenic potential; however, it may also prime systemic cytotoxic T lymphocytes (CTL) and even exacerbate autoimmune disease. Here, Leonard C. Harrison and colleagues use the nonobese diabetic (NOD) mouse model of diabetes to develop strategies to minimize immunity and maximize tolerance, that have broad implications for other diseases.
The mechanisms of pancreatic beta-cell destruction by the immune system in type 1 diabetes remain to be elucidated. Here, Thomas W.H. Kay and coworkers dissect out the roles of perforin, interferon gamma (IFN-gamma), interleukin 1 (IL-1),and Fas, and attempt to link up what can be demonstrated in vitro with in vivo findings.
As we move into the 21st century, it is a privilege for The Walter and Eliza Hall Institute to be able to showcase its current immunology portfolio. This brief historical perspective will set the scene.
Clustering of major histocompatibility complex (MHC)-peptide complexes on antigen-presenting cells (APCs) was shown to be induced by supramolecular assemblies of T-cell receptors (TcRs) in order to trigger T-cell Activation, Here, Anne Vogt and Harald Kropshofer discuss novel findings whereafter B cells and dendritic cells (DCs) ore skilled to build up various types of protein clusters composed of MHC class ii-peptide, tetraspan, and costimulatory molecules without the involvement of T cells.
T-cell receptor (TcR) engagement with its ligand can elicit a variety of responses in the T cell. Here,Yuri Sykulev tries to unravel some of the factors that influence the nature of the T-cell response, including the development of productive TcR-peptide major histocompatibility complex (MHC) bonds, and how variations in patterns of secondary TcR-mediated events may trigger different responses.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease whose etiopathogenesis is poorly understood. Here, Martin Herrmann and coworkers analyze changes in various immunological parameters, including autoantibodies, complement, phagocytosis, T-cell responses and apoptosis,and suggest a model that links these together to explain the development of the disease.
One of the cornerstones of immunology research in The Walter and Eliza Hall Institute, Gus Nossal, has contributed immensely to our understanding of B cells. Here, he briefly outlines the long and distinguished tradition of B-cell research at the Institute, spanning four decades.
In chronic inflammatory disease lesions, lymphocytes ore resistant to activation-induced cell death,through CD95. This protection may be mediated by CD44, and here Ursula Gunthert and Britt Johansson examine and discuss CD44 isoform expression in a range of diseases, and their therapeutic implications.
A novel family of proteins that suppress cytokine signaling (SCOS) have recently been described. Here, Christopher L. Greenhalgh and Douglas J. Hilton provide an update on these, including the effects of gene knockouts or of overexpression,which indicate a role for them in a wide range of systems.
The polarization of CD4 T cells into Th1 and Th2 cells is well known, and here Emmanuel Scotet examines the specific regulation of Th2 specific molecules such os cytokines (IL-4, IL-5) and the chemokine receptor CCR3. Chromatin remodeling, a relatively poorly understood process, appears to have a role in their regulation.
