Clinical and applied immunology reviews最新文献

Virtually all immunological variables investigated to date in animals and humans display biological periodicity. Circadian rhythmicity is revealed in circulating cells, lymphocyte metabolism and transformability, circulating hormones and other substances that may exert various actions on different targets of the immune system, cytokines, receptors, and adhesion molecules. Immune cells have recently started to be examined for the presence of clock genes (hPer1, hPer2, hPer3, hDecl) that were found to be expressed in a circadian manner in human peripheral blood mononuclear cells. Melatonin acts as an arm of the circadian clock, giving a time-related signal to the immune system. This review discusses the physiological basis of this effect. Melatonin has a general immunoenhancing effect in many species, including humans. This depends on the ability of melatonin to enhance the production of cytokines as well as on its reported anti-oxidant and anti-apoptotic action. Melatonin acts on specific membrane receptors expressed on immunocompetent cells with MT2 receptors playing apparently the major role. Immune cells also possess a reasonably well-characterized nuclear melatonin receptor. Melatonin may favor a T helper (Th) type 1 response. Physiologically, nocturnal melatonin concentration correlates with the rhythmicity of Th-1 / Th-2 ratio. The possible undesirable implications of the immunoenhancing effects of melatonin in patients with autoimmune disorders is discussed.

It has become increasingly appreciated that signals mediated by the lymphotoxin beta receptor (LTßR), a tumor necrosis factor (TNF) family receptor, mediate various outcomes in both the developing and adult immune systems. In the adult animal, the LTαβ pathway is indispensable for the maintenance of stromal cell networks in the secondary lymphoid tissues. Since these networks are key controlling elements for the positioning of immune cells such as lymphocytes, it was hypothesized that blocking LTßR signaling may be a novel approach for inhibiting pathogenic autoimmune responses. To this end, multiple autoimmune models have been tested in mice that are genetically deficient in LTαβ/LTßR molecules or tested in mice that are treated with LTαβ/LIGHT pathway blocking agents. These studies have revealed an impressive array of autoimmune diseases that are sensitive to LTαβ/LIGHT pathway inhibition, signifying that blockade of LTßR-mediated signals has exciting clinical potential. A common element to these disease models is the recruitment, activation and migration of autoimmune T-lymphocytes. The mechanism of how blocking signals mediated by the LTßR influences autoimmune T-cell responses remains elusive, in particular because LTßR signaling appears to be critical at diverse biological levels. This review will describe the consequences of blocking LTßR-mediated signaling on autoimmune disease models, as well as models of infectious disease and will explore how LTßR activation may regulate T-lymphocyte responses.

Gene therapy offers the potential to treat a wide range of inherited and acquired human diseases. In general, this approach involves the treatment of disease by introducing new genetic instructions into the tissues of patients in order to compensate for abnormal or missing genes or to convey a new function. Moreover, this involves the manipulation of gene expression in somatic cells that are corrective to the patient, but not inherited by subsequent generations; in this sense, gene therapy is no different than other more conventional forms of pharmacological intervention. The therapeutic genes are transferred into the cells of the patient either through the use of recombinant virus vectors or plasmid DNA conjugates. There are currently over 600 gene therapy trials completed, ongoing or pending worldwide. The majority of these are phase I safety trials in the United States and Europe directed toward the treatment of cancer, followed by monogenetic, infectious and vascular diseases. This review includes a brief description of the various vector systems used for gene therapy, as well as an overview of several landmark clinical gene therapy trials, which serve to illustrate the recent evolution and current status of the field. Taken together, these examples illustrate that clinical gene therapy has been marked by both well-publicized failures and a growing potential for profound success.

Leptospirosis is a common zoonosis, which is often overlooked in the differential diagnosis of febrile illness. The epidemiology of leptospirosis has undergone major changes, with a shift away from the traditional occupational disease in developed countries, to a disease associated with recreational exposures. There has also been the recognition of an emerging, potentially epidemic disease associated with excess rainfall in tropical settings, representing a significant public health challenge. Changes in the taxonomy of Leptospira have the potential for confusion over nomenclature. Recent advances in diagnostic methods facilitate the investigation of suspected leptospirosis in clinical diagnostic laboratories.

This review summarizes the development and applicability of an assay to detect an immune complex (IC) of a 90kD glycoprotein tumor-associated antigen (TA90). The antigen is immunogenic in the cancer host and expressed by a variety of solid tumors. In circulation, it induces formation of endogenous antigen-antibody complexes. The presence of TA90-IC has been detected in significantly greater proportions of serum samples from cancer patients compared to normal controls. The postoperative presence of TA90-IC in circulation strongly correlated with subsequent development of clinically detectable recurrence within an average interval of 3 to 19 months. The TA90-IC status after surgery but before initiation of adjuvant therapy consistently correlated with disease-free survival and overall survival. Because of its ability to accurately detect subclinical metastasis and predict survival 1 to 3 months after surgical resection of early-stage cancer, TA90-IC represents a novel and feasible prognostic marker to select candidates for adjuvant therapies and to stratify patients in clinical trials. Expression of TA90 by melanoma, colon cancer, lung cancer, breast cancer and other solid neoplasms makes TA90-IC an ideal marker in the management of early-stage cancer. Its specificity can be significantly enhanced if positive samples are subsequently analyzed by a panel of tumor markers characteristic for a particular type of cancer, such as CA15-3 for breast cancer and carcinoembryonic antigen (CEA) for colon cancer. TA90-IC could be used in conjunction with these site-specific markers as part of a cancer screening program to identify high-risk individuals for closer surveillance.

Systemic lupus erythematosus (SLE) is the archetypical immunologic disease. Approximately 20% of patients present in the first two decades of life. This article highlights some of the differences between pediatric and adult onset lupus.

Children are defined as different from adults on the basis of age. Lupus presents with different gender ratios based on hormonal or pubertal status with more significant skewing toward female patients in the childbearing years. Female patients in the childbearing years appear to have a higher relative risk for mortality. Despite this, children have greater disease severity at onset based on the number of patients who present with significant organ inflammation, the amount of corticosteroids required and the abnormalities in lupus serologies including autoantibodies and low complements. Children present frequently with congenital and acquired complement defects. Children have an increased risk of infections that can be confused with lupus. They have a higher risk of serious pneumococcal infection and may have less protection from vaccinations received at the time of disease onset.

The clinical immunology laboratory is critical in the diagnosis and treatment of pediatric SLE. The rapid analysis and transfer of laboratory results can be life saving for the child with suspected new onset lupus. The laboratory is also helpful in determining disease activity through analysis of immunologic trends over time in pediatric lupus patients. This is especially important in the noncompliant adolescent patient who has a correlation between disease activity and lupus serologic tests. Finally, the clinical immunology laboratory is an important tool for better understanding of the immunologic phenomena associated with lupus and of disease pathophysiology.

The timely breakdown of the extracellular matrix (ECM) is essential in many physiological and biological processes. The matrix-degradation process involves tissue remodeling and immune/inflammatory reactions that occur in the stroma. Thus, the proteolytic and destructive potential of the matrix metalloproteinase (MMP) family is a major concern in several pathological conditions involving ECM degradation. This review details the structures and functions of MMPs and presents an overview of the interaction of MMPs with components of the immune system.