http://www.medimmunol.com The most accessed research articles published by Medical Immunology 2006-09-21T00:00:00Z It has been 50 years since chronic granulomatous disease was first reported as a disease which fatally affected the ability of children to survive infections. Various milestone discoveries from the insufficient ability of patients' leucocytes to destroy microbial particles to the underlying genetic predispositions through which the disease is inherited have had important consequences. Longterm antibiotic prophylaxis has helped to fight infections associated with chronic granulomatous disease while the steady progress in bone marrow transplantation and the prospect of gene therapy are hailed as long awaited permanent treatment options. This review unearths the important findings by scientists that have led to our current understanding of the disease. http://www.medimmunol.com/content/5/1/4 Tracy Assari Medical Immunology 2006, null:4 2006-09-21T00:00:00Z doi:10.1186/1476-9433-5-4 /content/figures/1476-9433-5-4-toc.gif Medical Immunology 1476-9433 ${item.volume} 4 2006-09-21T00:00:00Z XML Members of the NF-kB transcription factor family are differentially expressed in the B cell lineage. Disruption of individual or two NF-kB subunits exhibits distinct defects in B lymphocyte development, activation, and survival. However, the role each NF-kB plays during B cell development has been obscured by molecular compensation. To address this issue, a trans-dominant form of IkBα was transduced into bone marrow cells to act as a pan-inhibitor of NF-kB using a retroviral system. While the development of T-lymphocytes and myeloid cell lineages was not grossly affected by the transduced IkBα gene, a significant reduction in the number and percentage of B lineage cells was apparent in IkBα transduced chimeric mice. IkBα expression decreased the percentage of pre-B and immature B cell subsets in the bone marrow and further impaired the development of follicular mature B cells and marginal zone B cells in the periphery. Introduction of the Bcl-X transgene completely restored the pre-B and immature B cell pool in the bone marrow. However, despite a significant improvement of overall viability of the B cell lineage, Bcl-X expression was insufficient to overcome the maturation block resulting from NF-kB inhibition. Together, our study suggests that NF-kB activity is required for two distinct checkpoints during B cell development: one is for pre-B/immature B cell viability, the other is to provide both survival and maturation signals to ensure the proper development of follicular mature B cells. http://www.medimmunol.com/content/3/1/1 Biao Feng Shuhua Cheng Warren Pear Hsiou-Chi Liou Medical Immunology 2004, null:1 2004-03-29T00:00:00Z doi:10.1186/1476-9433-3-1 /content/figures/1476-9433-3-1-toc.gif Medical Immunology 1476-9433 ${item.volume} 1 2004-03-29T00:00:00Z XML Eradication of the smallpox virus through extensive global vaccination efforts has resulted in one of the most important breakthroughs in medical history, saving countless lives from the severe morbidity and mortality that is associated with this disease. Although smallpox is now extinct in nature, laboratory stocks of this virus still remain and the subject of smallpox vaccination has gained renewed attention due to the potential risk that smallpox may be used as a biological weapon by terrorists or rogue states. Despite having the longest history of any modern vaccine, there is still much to be learned about smallpox vaccination and the correlates of protection remain to be formally defined. This Commentary will discuss the strengths and weaknesses of traditional smallpox vaccination in comparison with immunization using modified vaccinia virus Ankura (MVA), a non-replicating virus with a strong safety record but weakened immunogenicity. http://www.medimmunol.com/content/4/1/2 Mark Slifka Medical Immunology 2005, null:2 2005-03-01T00:00:00Z doi:10.1186/1476-9433-4-2 /content/figures/1476-9433-4-2-toc.gif Medical Immunology 1476-9433 ${item.volume} 2 2005-03-01T00:00:00Z XML The successful use of Bacillus anthracis as a lethal biological weapon has prompted renewed research interest in the development of more effective vaccines against anthrax. The disease consists of three critical components: spore, bacillus, and toxin, elimination of any of which confers at least partial protection against anthrax. Current remedies rely on postexposure antibiotics to eliminate bacilli and pre- and postexposure vaccination to target primarily toxins. Vaccines effective against toxin have been licensed for human use, but need improvement. Vaccines against bacilli have recently been developed by us and others. Whether effective vaccines will be developed against spores is still an open question. An ideal vaccine would confer simultaneous protection against spores, bacilli, and toxins. One step towards this goal is our dually active vaccine, designed to destroy both bacilli and toxin. Existing and potential strategies towards potent and effective anthrax vaccines are discussed in this review. http://www.medimmunol.com/content/4/1/4 Julia Wang Michael Roehrl Medical Immunology 2005, null:4 2005-03-24T00:00:00Z doi:10.1186/1476-9433-4-4 /content/figures/1476-9433-4-4-toc.gif Medical Immunology 1476-9433 ${item.volume} 4 2005-03-24T00:00:00Z XML No description available http://www.medimmunol.com/content/1/1/1 Kendall Smith Medical Immunology 2002, null:1 2002-09-30T00:00:00Z doi:10.1186/1476-9433-1-1 /content/figures/1476-9433-1-1-toc.gif Medical Immunology 1476-9433 ${item.volume} 1 2002-09-30T00:00:00Z XML It has been more than 100 years since the realization that microbes are capable of causing disease. In that time, we have learned a great deal as to how each organism has adapted to the immune system so as to avoid elimination. As well, we have also learned an immense amount since Louis Pasteur first proposed that the solution to infectious diseases was to culture the microbes and attenuate their virulence, so as to use them as vaccines. From the optimism and promise of the 19th century and immunization as the ultimate answer to the invasion by the microbial world, to the scientific realities of the 21st century, it is of interest to retrace the steps of the earliest microbiologists cum immunologists, to realize how far we've come, as well as how far we yet have to go. This editorial focuses on the history of anthrax as a microbial disease, and the earliest efforts at producing a vaccine for its prevention. http://www.medimmunol.com/content/4/1/5 Kendall Smith Medical Immunology 2005, null:5 2005-04-18T00:00:00Z doi:10.1186/1476-9433-4-5 /content/figures/1476-9433-4-5-toc.gif Medical Immunology 1476-9433 ${item.volume} 5 2005-04-18T00:00:00Z XML The interleukin-2 molecule and receptor were the first of the interleukins to be discovered and characterized at the molecular level. Now after 20 years of effort, two groups have succeeded in determining the structure of IL2 bound to the external domains of the three receptor chains in a quaternary complex. What do we know now that we did not know before this structural information was available, and how do these new data help us to develop new therapies? http://www.medimmunol.com/content/5/1/3 Kendall Smith Medical Immunology 2006, null:3 2006-08-14T00:00:00Z doi:10.1186/1476-9433-5-3 /content/figures/1476-9433-5-3-toc.gif Medical Immunology 1476-9433 ${item.volume} 3 2006-08-14T00:00:00Z XML Background: While the ability of bacteriophages to kill bacteria is well known and has been used in some centers to combat antibiotics – resistant infections, our knowledge about phage interactions with mammalian cells is very limited and phages have been believed to have no intrinsic tropism for those cells.Presentation of the hypothesisAt least some phages (e.g., T4 coliphage) express Lys-Arg-Gly (KGD) sequence which binds β3 integrins (primarily αIIbβ3). Therefore, phages could bind β3+ cells (platelets, monocytes, some lymphocytes and some neoplastic cells) and downregulate activities of those cells by inhibiting integrin functions.Testing the hypothesisBinding of KGD+ phages to β3 integrin+ cells may be detected using standard techniques involving phage – mediated bacterial lysis and plaque formation. Furthermore, the binding may be visualized by electron microscopy and fluorescence using labelled phages. Binding specificity can be confirmed with the aid of specific blocking peptides and monoclonal antibodies. In vivo effects of phage – cell interactions may be assessed by examining the possible biological effects of β3 blockade (e.g., anti-metastatic activity).Implication of the hypothesisIf, indeed, phages can modify functions of β3+ cells (platelets, monocytes, lymphocytes, cancer cells) they could be important biological response modifiers regulating migration and activities of those cells. Such novel understanding of their role could open novel perspectives in their potential use in treatment of cardiovascular and autoimmune disease, graft rejection and cancer. http://www.medimmunol.com/content/2/1/2 Andrzej Gorski Krystyna Dabrowska Kinga Switala-Jelen Maria Nowaczyk Beata Weber-Dabrowska Janusz Boratynski Joanna Wietrzyk Adam Opolski Medical Immunology 2003, null:2 2003-02-14T00:00:00Z doi:10.1186/1476-9433-2-2 /content/figures/1476-9433-2-2-toc.gif Medical Immunology 1476-9433 ${item.volume} 2 2003-02-14T00:00:00Z XML There is now effective therapy for infection by the Human Immunodeficiency Virus (HIV), but there is no cure. Consequently, antiviral drugs must be administered continuously to suppress viral replication. Recently, a large phase III international immune-based therapy trial was discontinued because it is difficult to measure clinical endpoints while antivirals are administered. Since the immune system has evolved under the selective force of microbial infections, the immune reaction is antiviral. This commentary explores the rationale of using "Diagnostic Treatment Interruptions" of antiviral therapies to determine efficacies of immune-based therapies. http://www.medimmunol.com/content/1/1/4 Kendall Smith Medical Immunology 2002, null:4 2002-11-21T00:00:00Z doi:10.1186/1476-9433-1-4 /content/figures/1476-9433-1-4-toc.gif Medical Immunology 1476-9433 ${item.volume} 4 2002-11-21T00:00:00Z XML Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding predictions with knowledge concerning HLA allele frequencies, a metric estimating population protection coverage (PPC) was computed and epitope pools assembled. Strikingly, only a minority of immunocompetent HIV-1 infected individuals responds to pools with PPC >95%. In contrast, virus-naive individuals uniformly expand IFNγ producing cells and mount anti-HIV-1 cytolytic activity. This disparity suggests a vaccine design paradigm shift from infected to normal subjects. http://www.medimmunol.com/content/5/1/1 Pedro Reche Derin Keskin Rebecca Hussey Petronela Ancuta Dana Gabuzda Ellis Reinherz Medical Immunology 2006, null:1 2006-05-18T00:00:00Z doi:10.1186/1476-9433-5-1 Healthy cytotoxic T lymphocytes respond to HIV-1 HIV-1 epitopes elicit a better response from cultured cytotoxic T cells of healthy individuals than from cells of infected individuals, offering new hope for vaccinating against AIDS prior to viral infection using HIV-1 epitopes. /content/figures/1476-9433-5-1-toc.gif Medical Immunology 1476-9433 ${item.volume} 1 2006-05-18T00:00:00Z XML