The phagocytic activity of the neutrophilic granulocytes in patients with chronic candidiasis of the skin and mucous membranes]

24 patients with chronic candidiasis of the skin and mucous membranes have been examined. The following parameters have been evaluated: (1) ingestive capacity, (2) fungicidal capacity, (3) the state of the myeloperoxidase mechanism of respiratory explosion. In chronic candidiasis of the skin and mucous membranes the ingestive capacity of neutrophil granulocytes has been found to remain unchanged, constituting 70 +/- 3.5% in healthy persons and 60 +/- 4.2% in patients 60 minutes after interaction. The study has revealed the decrease of fungicidal activity in 50% of the patients which is probably linked with the constant activation of oxygen-dependent killing mechanisms (the index of the spontaneous nitro blue tetrazolium test has proved to be 8.9 +/- 0.8% in healthy persons and 15 +/- 3.4% in patients with candidiasis of the skin and mucous membranes) and the decreased reserve of the functional activity of neutrophil granulocytes. The activity of myeloperoxidase in patients with candidiasis of the skin and mucous membranes has been found to remain unchanged.     

Immune system function in candidiasis patients

To compare the clinical picture and the immunological characteristics, 58 candidiasis patients differing by the severity and dissemination of the disease were examined. Chronic candidiasis of the skin and mucous membranes, the most severe and disseminated form of the disease, is associated with a decrease in the number of T-lymphocytes and changes in their subpopulations, as well as high titers of Candida albicans antigen and antibodies to it in blood sera. The immune system of patients with visceral candidiasis and chronic vulvovaginal candidiasis was similar to that of healthy persons in the characteristics under study. Immediate and mixed hypersensitivity occurred in candidiasis patients more frequently than in healthy persons. In extremely severe forms of Candida infection immediate hypersensitivity prevailed.     

Modifications to the surface of T-lymphocytes in chronic candidiasis of the skin and mucous membranes

27 patients with chronic candidiasis of the skin and mucous membranes have been examined with a view to study the expression of E-receptors and its changes after the incubation of T-lymphocytes with theophylline, levamisole, thymaline and Candida albicans antigen. This study has revealed that, in comparison with healthy persons, most patients show decreased expression of E-receptors, and the character of their changes after incubation with the above-mentioned preparations is essentially different. The deviations revealed in this study have been regarded as the modification of T-cell membranes, which is seemingly one of the reasons of the weak competence of T-cells. In its turn, the expression of E-receptors may be considered as an indicator of the influence of different factors on T-lymphocytes. Substances altering the level of cyclic nucleotides in the cell, the antigenic fractions of the fungal causative agent, the suppression or blocking the action of thymic hormone-like substances may serve as such factors.     

流行性出血热患者皮肤组织内病毒抗原及免疫复合物检测与意义

应用常规病理、免疫病理及超微病理技术,对３３例流行性出血热（ＥＨＦ）患者皮肤活检标本的病理变化及病毒抗原、免疫复合物进行观察,同时与血清病毒抗原、抗体及循环免疫复合物检出情况进行比较。在２３例ＥＨＦ患者皮肤微血管内皮细胞中检出病毒抗原,部分组织中可同时检出免疫球蛋白及Ｃ３,少数组织仅能检出病毒抗原或免疫球蛋白。配对血清小也可检出ＥＨＦ病毒抗原、抗体及循环免疫复合物。组织及血清免疫复合物形成与血清补体Ｃ３水平下降有关,组织内肥大细胞脱颗粒与血清ＩｇＥ水平升高相关,提示多种变态反应参与了流行性出血热的发病机制。     

Development of a non-immunising,paraspecific vaccine from attenuated pox viruses: a new type of vaccine

The various research periods leading to the development of paraspecific vaccines are described. Paraspecific vaccines are new, pyrogen-free, non-toxic preparations that contain non-immunising antigens and can be used to generate endogenic protective, non-antigen specific mechanisms in the sense of paramunization in humans and animals. They consist of highly attenuated and inactivated (0.05% Betapropiolactone) virus strains of various poxvirus genera. They activate the T helper cells and cellular elements of the paraspecific (innate) immune system and initiate the associated production and release of cytokines (cytokine cascade) with the goal of eliminating dysfunctions of the immune systems, rapidly enhancing the individual's non-pathogen- and non-antigen-specific defences and exerting a regulatory effect on the interplay between the immune, hormone, nervous and vascular systems (signal-transduction mediators). They can be used systemically (intramuscularly) and locally (mucous membranes, skin). Immunization with paraspecific vaccines does not lead to postvaccinal complications and can be carried out as often as necessary, even for a number of years. They are compatible with conventional medicines and conventional specific vaccines. Closely linked protein complexes in the envelopes of the virus particles are responsible for their efficacy, some of those envelope protein complexes possess the properties of weak super antigens. Paraspecific vaccines have proved effective in combating viral infections, in particular herpes and hepatitis B and C infections, and chronic inflammatory diseases, and also as adjuvant therapy for tumours, for curing stress-related disturbances and dysfunctions of the immune system.     

Nature of the restructuring of the T- and B-immunity systems in patients with cutaneous and visceral candidiasis

The examination of 90 patients with superficial and visceral candidiasis, as well as Candida carriers, has revealed that the heavy contamination of the body with fungi of the genus Candida is accompanied by the specific transformation of the immune system, manifested by differences in the character of sensitization to Candida antigens: in the patients with superficial and visceral candidiasis the B-system of immunity is sensitized to a greater degree, while in the Candida carriers the sensitization of the T-system is more pronounced. Despite the fact that the immune system of patients with the disseminated form of visceral candidiasis is capable of developing the delayed hypersensitivity (DH) reaction to bacterial allergens, such patients have been shown to develop DH to Candida antigens only in rare cases. This is probably due to disturbances in their immunocompetent systems, caused, seemingly, by the secondary immune insufficiency.     

An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family

We describe a large family in which a combination of chronic mucocutaneous candidiasis (fungal infections of the skin, nails, and mucous membranes) and thyroid disease segregate as an autosomal dominant trait with reduced penetrance. The family includes (a) four members with both candidiasis and thyroid disease, (b) five members, including one pair of phenotype-concordant MZ twins, with candidiasis only, and (c) three members with thyroid disease only. A whole-genome scan using DNA samples from 20 members of the family identified a candidate linkage region on chromosome 2p. By sampling additional individuals and genotyping supplementary markers, we established linkage to a region of approximately 15 cM bounded by D2S367 and D2S2240 and including seven adjacent markers consistent with linkage. With a penetrance estimate of.8, which was based on pedigree and affected status, the peak two-point LOD score was 3.70 with marker D2S2328, and the peak three-point LOD score was 3.82. This is the first linkage assignment of a dominant locus for mucocutaneous candidiasis.     

Mechanisms of antibacterial immunity of mucous membranes

A survey based on both literary data and the authors own results, concerning the mechanisms of sIgA-mediated antibacterial immunity, is presented. Secretory IgA is characterized as a specific component of the immune system of mucous membranes, which can recognize harmful bacterial and distinguish them from indigenous microflora physiologically colonizing the mucous membranes, to fix them to the mucous membrane surface and to direct further factors, such as mucin, lysozyme,etc. (which form the effector component of the mucous membrane immunity system) for thvir final inactivation and neutralization.     

生命信息安全控制体系整体结构性构建与分析

在前期生命信息安全控制原理探讨的基础上,基于整体论的思考,旨在构思能表述生命信息安全控制体系实质内涵的几何图形。所作图呈圆台形,自上而下依次为2大部分(内在部分和外延部分),5个层次(特异性识别系统、泛特异性识别系统、皮肤黏膜、共生微生物及外环境开放接触面)。在圆台形生命信息安全控制体系中,圆台形的中心轴为生命信息安全控制轴;特异性识别系统、泛特异性识别系统、皮肤、黏膜和共生微生物组成内在部分;外延部分即外环境开放接触面;内在部分各部间以及与外延部分之间存在物质、能量、信息交流沟通传递的空间界面。特异性识别系统建立在泛特异性识别系统基础上,置于最顶端,寓意着生物进化高级发展的一种客观结局,泛特异性识别系统与特异性识别系统作为一个整体和共生微生物层次联系,其中安插皮肤、黏膜组织层次,符合宏生物与微生物之间存在的完全不可分割的相关关系客观事实。共生微生物层次举足轻重,所占份额最大,主导整个体系的稳定性,成为整个体系的基座。就上述5个层次及其相互关系的解析归纳,证明构建的圆台形几何图能真实客观反映出生命信息安全控制体系各层次之间完全不可分割、相互依存影响的关系。     

Is there a role for antibody testing in the diagnosis of invasive candidiasis?

During the last decades, the use of antibody tests for the diagnosis of invasive mycoses has declined as a consequence of the general belief that they are insensitive and non-specific. However, there is a clear evidence that antibodies can be detected in highly immunodeficient patients (such as bone marrow transplant recipients), and that those antibodies are useful for the diagnosis. Antibody tests are currently in use as diagnostic tools for some primary mycoses, such as the endemic mycoses, aspergilloma, allergic bronchopulmonary aspergilosis and sporothrichosis. For invasive candidiasis, diagnostic methods must differentiate Candida colonization of mucous membranes or superficial infection from tissue invasion by this microorganism. Substantial progress has been made in diagnosis of invasive candidiasis with the development of a variety of methods for the detection of antibodies and antigens. However, no single test has found widespread clinical use and there is a consensus that diagnosis based on a single specimen lacks sensitivity. It is necessary to test sequential samples taken while the patient is at greatest risk for developing invasive candidiasis to optimize the diagnosis. Results obtained from a panel of diagnostic tests in association with clinical aspects will likely be the most useful strategy for early diagnosis and therapy.     

Inmunologia de las Candidiasis

Resumen Se presenta el estudio realizado en 70 casos de candidiasis con diversas localizaciones mediante pruebas de fijación de complemento, aglutinación, inmunodifusión e inmunoelectroforesis.Las pruebas de fijación de complemento e inmunodifusión presentaron títulos elevados sólo en aquellos enfermos que padecían candidiasis sistémicas, estas reacciones fueron sistemáticamente negativas en los casos de candidiasis superficiales.El anticuerpo específico presentó una movilidad electroforética semejante a la 1 g G. El antígeno más adecuado para las pruebas serológicas fue el sobrenadante de células deCandida albicans rotas en aparato Sorvall Ribi Cell fractionator.La prueba de aglutinación tiene menor valor pues se observaron escasas reacciones positivas en pacientes con candidiasis superficiales.La prueba cutánea fue positiva en la mayoría de los enfermos con candidiasis superficiales y broncopulmonares y, por el contrario, negativas en los casos examinados con septicemias y endocarditis.

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Summary Sera from 70 patients with candidiasis have been studied by means of agglutination, complement fixation, agar gel immunodiffusion tests and immunoelectrophoresis technic. High titers in complement fixation and immunodiffusion tests have been registered in patients with systemic candidiasis, while the serologic study in those patients with superficialCandida infections gave negative results.Electrophoretic motility similar to that of 1 g G was observed in the specific antibody in candidiasis.Disrupted cells ofCandida albicans with Sorwall Ribi Cell fractionator gave the best antigens. Agglutination test seems to be of little diagnostic value.Positive skin test has been obtained in the majority of patients with superficial and bronchopulmonary candidiasis, while in those patients with septicemia and endocarditis negative results have been registered.

     

Fine structural and enzyme histochemical observations on the dorsal tail tubercle of Mertensiella caucasica (Urodela,Amphibia)

Summary Dorsal tubercle and skin of Mertensiella caucasica have been investigated with the electron microscope and enzyme histochemical methods. The epidermis of the tubercle consists of 8–9 cell layers, that of normal dorsal skin of 5–6. The tubercle is filled with large mucous glands which are surrounded by an almost complete layer of smooth muscle cells (myoepithelial cells). Their glandular cells undergo cyclical changes and are characterized by specific secretory granules, which differ from those of the relatively small mucous glands of the normal dorsal skin.In the connective tissue of the tubercle a relatively rich supply of nerve fibres has been found, which in part contain synaptic and dense core vesicles or accumulations of mitochondria. In the normal dorsal skin nerve fibres occur less frequently.The following enzymes have been demonstrated in the mucous glands of the tubercle: SDH, acid phosphatase, unspecific esterases, E 600 resistant esterase.The tubercle seems to stimulate the female cloaca chemically and mechanically.     

IgG, IgM, IgA, secretory IgA and the complement components C3, C4 and C9 in the large intestine in nonspecific ulcerative colitis and Crohn disease

The immunohistological study of the large intestines excised from 20 patients with ulcerous colitis and Crohn's disease was made with the use of the indirect immunofluorescence test. A considerable increase in the number of IgG immunocytes has been noted in the lamina propria of the mucous membrane, especially in infiltrations around ulcers. In cases of a highly active inflammatory process accompanied by the pronounced destruction of the epithelium, IgG and C3, C4, C9 were detected in the epithelium of crypts and in blood vessels of the mucous membrane and the submucosa. One-third of the patients showed a decrease in the number of crypts with secretory and serum IgA. The authors suggest that immune complexes take part in maintaining the chronic inflammatory process.     

Secreted aspartic proteases as virulence factors of Candida species

Candida infections have emerged as a significant medical problem during the last few decades. Among the different virulence traits of C. albicans, secreted proteolytic activity has been intensively investigated. Pathogenesis of the various forms of candidiasis was shown to be associated with the differential and temporal regulation of the expression of genes coding for secreted aspartic proteases (Sap). These enzymes act as cytolysins in macrophages after phagocytosis of Candida, are present in tissue penetration and are also involved in adherence to epithelial cells. Since the introduction of new antiretroviral therapeutics such as HIV protease inhibitors, oropharyngeal candidiasis is less often observed in AIDS patients. Different HIV aspartic protease inhibitors were able to inhibit the C. albicans Saps involved in adherence. The lower rates of oropharyngeal candidiasis observed in individuals receiving antiretroviral combination therapy could reflect not only an improvement in the immune system but also direct inhibition of Candida Saps by HIV protease inhibitors. Therefore, the development of specific aspartic protease inhibitors might be of interest for the inhibition of candidiasis.     

Clonal Strain Persistence of Candida albicans Isolates from Chronic Mucocutaneous Candidiasis Patients

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. albicans individual single colony isolates from 6 unrelated CMC patients to multilocus sequence typing (MLST). Multiple colonies were typed from swabs taken from multiple body sites across multiple time points over a 17-month period. Among isolates from each individual patient, our data show clonal and persistent diploid sequence types (DSTs) that were stable over time, identical between multiple infection sites and exhibit azole resistant phenotypes. No shared origin or common source of infection was identified among isolates from these patients. Additionally, we performed C. albicans MLST SNP genotype frequency analysis to identify signatures of past loss of heterozygosity (LOH) events among persistent and azole resistant isolates retrieved from patients with autoimmune disorders including CMC.     

Protease inhibitors prevent plasminogen-mediated,but not pemphigus vulgaris-induced,acantholysis in human epidermis

Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. It is caused by autoantibodies directed against desmosomes, which are the principal adhesion structures between epidermal keratinocytes. Binding of autoantibodies leads to the destruction of desmosomes resulting in the loss of cell-cell adhesion (acantholysis) and epidermal blisters. The plasminogen activator system has been implicated as a proteolytic effector in pemphigus. We have tested inhibitors of the plasminogen activator system with regard to their potential to prevent pemphigus-induced cutaneous pathology. In a human split skin culture system, IgG preparations of sera from pemphigus vulgaris patients caused histopathologic changes (acantholysis) similar to those observed in the original pemphigus disease. All inhibitors that were tested (active site inhibitors directed against uPA, tPA, and/or plasmin; antibodies neutralizing the enzymatic activity of uPA or tPA; substances interfering with the binding of uPA to its specific cell surface receptor uPAR) failed to prevent pemphigus vulgaris IgG-mediated acantholysis. Plasminogen-mediated acantholysis, however, was effectively antagonized by the synthetic active site serine protease inhibitor WX-UK1 or by p-aminomethylbenzoic acid. Our data argue against applying anti-plasminogen activator/anti-plasmin strategies in the management of pemphigus.     

Animal models in the analysis of Candida host-pathogen interactions

An increasingly diverse array of clinically relevant animal models of candidiasis have been established that mimic both the immune perturbations of the host and tissue-specific features of candidiasis in humans. Cause-and-effect analysis of Candida host-pathogen interactions using these animal models has made a quantum leap forward in the genomic era, with the concurrent construction of C. albicans mutants with targeted mutations of putative virulence factors, the application of microarrays and other emerging technologies to comprehensively assess C. albicans gene expression in vivo, and construction of transgenic and knockout mice to simulate specific host immunodeficiencies. The opportunity to combine these powerful tools will yield an unprecedented wealth of new information on the molecular and cellular pathogenesis of candidiasis.     

Enfermedades invasoras por hongos levaduriformes en el receptor de un trasplante de órgano sólido

Invasive yeast diseases are uncommon nowadays in solid organ transplant recipients. Invasive candidiasis (2%) usually presents during the first month after transplantation in patients with risk factors. Both common and transplant-specific risk factors have been identified, allowing very efficacious targeted prophylaxis strategies. The most common clinical presentations are fungaemia and local infections near the transplantation area. Cryptococcosis is usually a late infection. Its incidence remains stable and the specific risk factors have not been identified. When cryptococcosis is detected very early, transmission with the allograft should be considered. The most common clinical presentations include meningitis, pneumonia, and disseminated infection. Intracranial hypertension and immune reconstitution syndrome have to be considered.No therapeutic clinical trials have been conducted in solid organ transplant recipients, thus treatment recommendations are derived from data obtained from the general population. It is particularly important to consider the possibility of drug-drug interactions, mainly between azoles and calcineurin inhibitors. Both invasive candidiasis and cryptococcosis increase the mortality significantly in solid organ transplant recipients.     

The immunopathological mechanisms of the skin lesion in erysipelas patients

The localization of bound IgG, IgA, IgM and component C3 of the complement in the focus of skin lesion in patients with different forms of erysipelas has been studied by the method of direct immunofluorescence. The presence of fixed immune complexes and component C3 in the affected areas of the skin at the acute period of the disease and their absence in the healthy areas of the skin have been established, which seems to be indicative of the presence of the local immunocomplex process in erysipelas. This process is one of the mechanisms of erysipelatous inflammation.     

A method for determining specific circulating immune complexes in patients with acute Sonne dysentery]

The antigen-specific method for the determination of specific immune complexes in the blood serum of patients with acute Sonne dysentery has been developed on the basis of the enzyme-linked immunosorbent assay with the use of reagents manufactured in the USSR. The possibility of the early prognostication of prolonged carrier state by using the proposed method for the determination of the level of specific circulating immune complexes has been shown.