Multiple sclerosis: basic immunology

A 24-year-old male presented with a 4 year history of a crusted erythematous papular eruption of the scalp and external auditory meati and a 12 month history of painful perianal ulceration. A diagnosis of Langerhans cell histiocytosis was made and confirmed by skin histology. Extensive investigation revealed no systemic involvement. Rapid improvement occurred after intravenous 2-chlorodeoxyadenosine but relapse of perianal lesions occurred within 5 months. Local radiotherapy to the perianal region resulted in a complete remission sustained over 12 months.     

Tumor immunology

Malignant tumors express antigens that may stimulate and serve as targets for antitumor immunity. Virally induced tumors usually contain integrated proviral genomes in theircellulargenomes and often express viral genome-encoded proteins that may stimulate specific host immune responses. Antigens unique to individual tumors that stimulate specific rejection of transplanted tumors have been demonstrated only in experimental animals. Other tumor antigens that potentially can stimulate immune responses are shared by different tumors. These include products of mutated or rearranged oncogenes or tumor-suppressor genes. Tumors may also overexpress tissue differentiation antigens or embryonic antigens, which also have the potential to be recognized by the immune system. The recent identification of tumor antigens recognized by cytotoxic T cells opens up new possibilities for constructing chemically defined antigens for specific immunotherapy. Treatment of malignant tumors in humans by immunologic approaches, although theoretically attractive, has not yet succeeded on a large scale. Important progress in immunotherapy of cancer is emerging with several different treatment modalities.     

What's new in transplant immunology: problems and prospects

In the past 40 years, transplantation has moved from an experimental form of therapy used almost exclusively for renal failure to an accepted treatment for end-stage kidney disease, heart disease, liver disease, lung disease, and diabetes mellitus. Tissue transplantation for conditions from thermal injury to Parkinson disease is being investigated. The primary barrier in transplantation medicine is the immunologic reaction of the recipient to donor organs and tissues. Currently available drugs permit excellent short-term graft survival but have not led to reliable long-term survival. Recent advances in the understanding of this immune response have suggested new approaches to induction of immunologic tolerance and reduction of late graft losses. Because of the excellent short-term success of current agents, integration of these new approaches into clinical trials is challenging and raises important questions about the design of such trials.     

Field workers'' forum: immunology of leprosy

1. When noradrenaline distributes exclusively into the: extraneuronal o-methylation of about one third of the extracellular space (i.e., when both, neuronal and extraneuronal uptake mechanisms are blocked by the presence of cocaine and corticosterone), the response of rabbit aortic strips to noradrenaline is concentration-dependent and relaxation curves (obtained during wash out and starting from different heights) are parallel. Under these conditions the "time required for relaxation to 50 or 20% of the initial contraction" (t50 and t20, respectively) is positively correlated with the initial height of contraction. 2. Measurements of the rate of relaxation that are independent of the height of the initial contraction are obtained either by appropriate correction of the t50 (or t20) or by determination of the "average rate of relaxation down to the 25% level of maximum contraction". 3. Relaxation experiments should a) be carried out with initial contractions of less than 75% of maximum and b) use a measure of the rate of relaxation that is independent of the initial height of contraction. 4. When the experimental conditions favour the extraneuronal accumulation of noradrenaline, corticosterone affects the relaxation of the strips in a way which is consistent with the view that efflux of unchanged amine from extraneuronal stores influences the rate of relaxation. 5. When extraneuonal uptake is operative and accumulation of noradrenaline is poor (i.e., when extraneuronal catechol-O-methyl transferase is intact), corticosterone affects relaxation in a way which is consistent with the view that normally the extraneuronal system serves as a site of loss. Under these conditions corticosterone prevented, during the first 5 min of wash out, the extracellularly distributed amine. 6. It is concluded that the experimental conditions of relaxation experiments determine whether the noradrenaline stores serve as a source of efflux of unchanged amine or as a site of loss.     

Update in allergy and immunology

Internal medicine has witnessed astounding developments in our understanding of the immune system's role in the pathophysiology of many diseases. The present challenge is to harness this knowledge to develop more effective therapies for immune-related illness. Guidelines for the care of common illnesses such as asthma may encourage appropriate clinical application of advances in our armamentarium against immune disease.     

Parasite immunology: pathways for expelling intestinal helminths

Helminth parasites induce strong immune responses that are initiated by cytokines, in the first instance interleukin-4 and interleukin-13. Recent studies of knockout mice deficient in these mediators or their shared receptor have revealed discrete pathways required for expulsion of different gut parasites.     

Kaposi's sarcoma pathogenesis: a link between immunology and tumor biology

Kaposi's sarcoma (KS) was a rare disease in Europe and North America until a decade ago, when it became the most common neoplasm complicating the acquired immunodeficiency syndrome (AIDS), where it acquires an aggressive course. Clinical and experimental data suggest that, at least in early stage, KS may not be a true sarcoma, but an hyperplastic-proliferative lesion that may regress. At least three components characterize KS lesions: (1) neoangiogenesis and proliferation of spindle-shaped cells of endothelial and macrophage cell origin, some of which may originate from a circulating precursor; (2) a cellular infiltrate represented by macrophages, lymphoid cells, mast cells, and neutrophils; and (3) the infection of spindle cells and mononuclear cells with a new virus of the Herpesvirinae family defined KS-associated herpesvirus or human herpesvirus-8 (HHV-8). KS lesions are highly responsive, in terms of growth, to inflammatory cytokines (IC) and many lesional cell components are able to secrete cytokines and chemokines, which induce paracrine-autocrine mechanisms of growth, angiogenesis, and promote further cellular recruitment. The association between HHV-8 and KS is close; however, the role of the virus in KS development is yet unknown. Nevertheless, the virus has the potential to encode for homologs of cellular cytokines and some chemokines and its reactivation is sensitive to stimuli provided by IC. This review focuses on these aspects of KS pathogenesis, trying to reconcile many of the clinical and experimental observations. Finally, the role of the HIV-1 Tat protein as a factor of progression in AIDS-KS as well as the role of cellular and HHV-8 encoded proto-oncogenes as factors and markers of progression of KS to a true malignancy is reviewed.     

Platelet transfusion: a dose-response study

Early recommendations on prophylactic transfusion of thrombocytopenic patients involved a standard platelet dose of about 0.5 x 10(11)/10 kg body weight. Given the lack of data supporting this dose, we prospectively studied the dose response to platelet transfusions in adults and children with hematologic malignancies. Each patient received, in similar clinical conditions, a medium, high, and very high dose of fresh (< 24 hours old) ABO-compatible platelets, in the form of apheresis platelet concentrates (APC). For the adults, the medium dose was defined as APC containing between 4 and 6 x 10(11) platelets, the high dose between 6 and 8 x 10(11), and the very high dose > 8 x 10(11); for the children, the three doses corresponded to 2 to 4, 4 to 6, and > 6 x 10(11) platelets. The end points were the platelet increment, platelet recovery, and the transfusion interval, and the results were compared with a paired t-test. Sixty-nine adults and 13 children could be assessed. Recoveries in the adults were similar with the three doses (from 28% to 30%), but the high and very high doses led to a significantly better platelet increment (52 and 61 x 10(9)/L, respectively) than the medium dose (33 x 10(9)/L, P < .01). The main difference was in the transfusion interval, which increased with the dose of platelets transfused, from 2.6 days with the medium dose to 3.3 and 4.1 days with the high and very high doses, respectively (P < .01). The positive effect of the high dose was observed regardless of pretransfusional clinical status, but was more marked in patients with no clinical factors known to impair platelet recovery. In these patients, a platelet dose of 0.07 x 10(11) per kg of body weight led to a transfusion interval of more than 2 days in 95% of cases. In patients with clinical factors favoring platelet consumption, the proportion of transfusions yielding an optimal platelet increment and transfusion interval increased with the dose of platelets. The platelet dose-effect was also significant in the children, in whom the high and very high doses led to 1.5-fold to twofold higher posttransfusion platelet counts and transfusion intervals. We conclude that transfusion of high platelet doses can reduce the number of platelet concentrates required by thrombocytopenic patients and significantly reduce donor exposure.     

Clinical immunology in rheumatology

When the Institute of Rheumatology, USSR Ministry of Health, was founded, its first director Academician A. I. Nesterov set up an immunological laboratory to attack the problems of immunodiagnosis and pathogenesis of rheumatism. Since 1958 studies of systemic diseases of connective tissue and autoimmunity under the supervision of Prof. V. A. Nasonova have been under way. Radioisotopic, enzyme immunofluorescence diagnostic assays for antinuclear antibodies (ANA) have been developed. Jointly with Czechoslovakia and the USA, the Institute of Rheumatology standardized the definitions of ANA. The laboratory have proposed the guidelines of the USSR Ministry of Health for immunodiagnosis of rheumatic diseases (RD). For immunodiagnosis, immunofluorescence, enzyme immunoassays, gel precipitation, back electrophoresis, radial immunodiffusion are widely used to measure the concentrations of anticardiolipin antibodies, mitochondrial antibodies, neutrophilic antibodies. The clinical and immunological subtypes of diffuse connective tissue diseases have been identified and characterized. Mixed connective tissue disease, poststreptococcal arthritis are described. The laboratory equipment for polymerase chain reaction permits DNA diagnosis.     

Microbial immunology: a new mechanism for immune subversion

The number of mechanisms that have evolved in microbes to subvert the immune response seems limitless. Tubercle bacilli have found a novel way to coat themselves with the C3 complement protein and invade macrophages by interactions with complement receptors.     

Platelet density and size: the interpretation of heterogeneity

Platelets have been separated according to buoyant density using a colloidal silica-polyvinylpyrrolidone system and subjected to electronic sizing. All density populations were found to be heterogeneous in size, the most dense platelets ranging from less than 3 fl to greater than 21 fl in both man and rat. Light platelet fractions contained no platelets greater than 13 fl in either species. Cohort labeling with [75Se]selenomethionine showed no indication of significant change in platelet buoyant density with ageing; greater specific activity found in young, dense platelets appears to be related to increased protein synthetic activity shown in vitro and likely to occur also in their precursor megakaryocytes. It is postulated that dense, intermediate and light platelets are released synchronously by the three different ploidy classes of megakaryocyte, that varying density indicates differing structural characteristics and presumably differences in function. The present findings do not deny the possibility that platelets decrease in size with ageing but if such occurs, it is not associated with a significant change in platelet buoyant density.     

Understanding immunology in disease development and control

Two functional aspects of the avian immune system, the humoral and the cell-mediated arms, provide the basis for the preventive and protective response against disease-causing microorganisms. On the other hand, certain avian diseases may induce a transient or permanent immunosuppressive state in one or both of these arms, leading to increased disease susceptibility. In addition to the classical immune response, manifested as antibody production or effector cell activation several cytokines and metabolites are also produced. The consequence of cytokine- and metabolite-mediated microenvironments may be either beneficial or result in a noninfectious immunopathology. Nevertheless, the integrity of the immune system and its functional modulation by factors such as genetics, nutrition, and prophylactic approaches continue to be an important focus of attention in current poultry research and production efforts.