The diagnostic and therapeutic characteristics of inflammatory urogenital diseases in women associated with Ureaplasma urealyticum]

Complex examination of 40 female in- and outpatients at the age 20 to 42 years with inflammatory urogenital diseases was performed. To verify the diagnosis, current clinical, microbiological, endoscopic and ultrasonic procedure were used. It was shown that the inflammatory processes in the urogenital tracts were mainly due to association of opportunistic and/or pathogenic organisms. Optimization of antibacterial therapy of urogenital infections was found possible with using homeopathic agents in the complex therapy. The significance of cooperation of the allied specialists in the choice of the examination and therapy policy for female patients with inflammatory urogenital diseases is indicated.     

Humoral immune responses to microbial infections in the genital tract

Human reproductive tracts represent components of the mucosal immune system with unique features. Although secretory IgA is present, IgG is more abundant, and typical mucosa-associated lymphoid tissue for generating common mucosal immune responses is absent. Antibody responses to genital infections or to locally applied vaccines are usually modest, but alternative strategies for eliciting genital tract antibodies are being developed.     

Immunopathological responses in women with chronic inflammatory diseases of the uterus and appendages and their therapeutic correction

A total of 145 women with chronic inflammatory diseases of uterus and appendages (IDUA) were examined. Bacterioscopy of smears and culture of vaginal, cervical canal and uterine cavity contents were performed in all patients. Direct immunofluorescence and PCR were used for detection of chlamydiae in scrapes and smears and in biopsy specimens taken from endometrium. The number of T lymphocytes and their subpopulations, B lymphocytes as well as the level of plasmatic cells synthesizing IgA, IgM and IgG and secretory IgA (sIgA), immune complexes and C3 component of the complement were determined in biopsy specimens of the endometrium. Pathomorphological examination revealed structural changes characteristic of the immunocomplex disease (secondary deficiency of sIgA, pronounced suppression of IgA production by plasmocytes along with an essential increase in the number of IgG synthesizing cells and immune complexes fixed to the venule endothelium) were detected. Lectin-histochemical study revealed considerable changes in secretory activity of endometrial epitheliocytes manifested by severe suppression of bactericidal activity of the uterine mucus. The detected disturbances of local protective reactions in the endometrium of women IDUA gave grounds for including immunomodulators into the traditional treatment scheme. The latter made it possible to increase essentially the therapeutic effect.     

Hormonal correction of the resident microflora of the vagina and uterus cervix in women with chronic cervicitis

Clinical, microbiological and hormonal examination of women with chronic cervicitis revealed lesions in the upper section of the reproductive tract in a high proportion of those examined, hormonal disturbances being registered in 96.7% of women. Dysbiotic manifestations (suppression of lacto- and bifidoflora and the excessive growth of opportunistic microorganisms) in the uterus cervix and vagina observed in patients with chronic cervititis were not associated with the etiology of the inflammatory process. The degree of dysmicrobiocenosis in the lower section of the genital tract in women with chronic cervicitis depends on the character of hormonal disturbances. The most significant inhibition of the resident flora was observed when ovarian dysfunction occurred and less significant--in cases of hyperprolactinemia and changes in the level of hypophysial hormones. Hormonal disturbances led to contamination of vagina and cervical canal with opportunistic microorganisms that was inversely proportional to the presence of lactic acid bacteria and bifidobacteria in these organs. Complex therapy of women with chronic cervicitis with the use of preparations for the correction of hormonal disturbances made it possible to restore the normal microflora of the genital tract and to improve the results of treatment.     

Disturbance of immune characteristics of the mucous membranes of the respiratory tract in bronchopulmonary diseases in children

A total of 100 children with bronchopulmonary diseases were examined. Of these, in 80 bronchial asthma and in 20 children acute pneumonia were diagnosed. The deficiency of local cell mediated and humoral factors on the mucous membranes of the upper respiratory tracts was established. In the squamous and columnar epithelium cells an increased destruction and cytolysis was noted leading to disturbances in the integrity of the protective barrier of the epithelial cover. In addition, this study revealed the deficiency of neutrophilic leukocytes, pronounced local eosinophilia and the low level of humoral protective factors. In acute pneumonia an increase in the amount of neutrophilic leukocytes in the secretion of the nasal cavity together with the appearance of destructive processes in epithelial cells took place. Pronounced deficiency in serum IgA and IgG was accompanied by compensatory increase in secretory IgA.     

Immunohistochemical observations of immunoglobulin A in the Paneth cells of germ-free and formerly-germ-free rats

Summary The localization of secretory immunoglobulin A (IgA) in Paneth cells was immunohistochemically studied in germ-free (Gf) and ex-Gf rats that had been injected with feces obtained from specific-pathogen-free (SPF) rats. In Gf as well as SPF rats, the secretory granules of Paneth cells and the brush borders of crypt cells exhibited IgA immunoreactivity. At 12 and 24 h after inoculation, it was found that, concomitant with the occurrence of considerable degranulation, the IgA immunoreactivity in Paneth cells disappeared, except of the margin of supranuclear vacuoles. In contrast, the IgA immunoreactivity of the crypt-cell brush borders was unchanged. Four days after inoculation, secretory granules exhibiting IgA immunoreactivity reaccumulated in Paneth cells. The present study suggests that Paneth cells regulate the bacterial milieu in the intestine by releasing secretory granules containing IgA into the crypt lumen.     

Immunohistochemical observations of immunoglobulin A in the Paneth cells of germ-free and formerly-germ-free rats

The localization of secretory immunoglobulin A (IgA) in Paneth cells was immunohistochemically studied in germ-free (Gf) and ex-Gf rats that had been injected with feces obtained from specific-pathogen-free (SPF) rats. In Gf as well as SPF rats, the secretory granules of Paneth cells and the brush borders of crypt cells exhibited IgA immunoreactivity. At 12 and 24 h after inoculation, it was found that, concomitant with the occurrence of considerable degranulation, the IgA immunoreactivity in Paneth cells disappeared, except of the margin of supranuclear vacuoles. In contrast, the IgA immunoreactivity of the crypt-cell brush borders was unchanged. Four days after inoculation, secretory granules exhibiting IgA immunoreactivity reaccumulated in Paneth cells. The present study suggests that Paneth cells regulate the bacterial milieu in the intestine by releasing secretory granules containing IgA into the crypt lumen.     

Microbiocenosis of the mucous membranes of the upper respiratory tract and its correction with acipol in the treatment of patients with acute respiratory virus infections

Clinical and laboratory evaluation of the preparation Acipol in 45 children greatly susceptible to acute respiratory virus infections (ARVI) was carried out. Simultaneously with the clinical analysis, the study of the microflora of the mucous membranes of the upper respiratory tracts and intestine, as well as the levels of secretory IgA in saliva and coprofiltrates before and after treatment, was made. The inclusion of Acipol into the therapy of ARVI patients facilitated their clinical convalescence, uncomplicated course of the disease, correction of disturbances in the biocenosis of the upper respiratory tracts and increased infectious resistance.     

Opportunistic microorganisms in respiratory tract diseases in patients of the Moscow Province region

The respiratory tract microflora in patients with inflammatory processes of the upper and lower respiratory tracts in the Moscow Province region has been studied. Changes in the microflora were found to occur in patients with pyoinflammatory diseases (PID) of the upper and lower respiratory tracts have been found to occur. Gram-positive cocci, mainly staphylococci and streptococci, were shown to play the leading etiological role in the development of PID. As revealed in this study, the microorganisms detected in the inflammations of the upper and lower respiratory tracts are coagulase-negative staphylococci, mainly S. epidermidis, as well as enterococci and streptococci belonging to the group viridans.     

Flow of blood to the ovaries of ewes throughout the estrous cycle: Niswender,G.D., R.T. Moore,A.M. Akbar,T.M. Nett and M.A. Diekman: Biol. Repr., 13: 381, 1975. Department of Physiology and Biophysics,Colorado State University,Fort Collins,Colorado 80523

This study was undertaken to determine whether a specific antimycoplasmal immune response could be detected in the male bovine genital tract and to better define mechanisms of immunity at that site. Specific $\text{Mycoplasma agalactiae}$ subsp. $\text{bovis}$ agglutinins were titrated in the serum, semen and preputial mucus extracts of two bulls with $\text{M. agalactiae}$ induced chronic seminal vesiculitis and of one normal control bull. Titers from infected bulls averaged 64 for serum, 1024 for semen and <8 for preputial mucus extracts whereas the control bull titers were 16 for serum, <8 for semen, and <8 for preputial mucus extracts. Because of the high semen agglutinin titers from infected bulls it was proposed that semen titers may be more useful diagnostically than serum titers.Studies of immunoglobulin levels in semen revealed that IgA, IgG₁ and IgG₂ levels were all much higher in infected bulls than in the control bull. These high semen IgA levels together with the high semen agglutinin titers indicated a local secretory immune response in genital tracts of infected bulls.     

Dynamics of some characteristics of humoral immunity,vaginal interferon status in pregnant women with the relapse of chronic pyelonephritis

65 pregnant women with the exacerbation of chronic pyelonephritis in the III trimester of gestation and 34 healthy pregnant women were examined. The quantitative content of immunoglobulins, the activity of interferon in cervico = vaginal washings and the composition of the vaginal microflora were determined. All patients with the relapse of chronic pyelonephritis exhibited disturbances in the normal microbiocenosis of the genitals and the dysfunction of the local immunity of the genital system, accompanied with a decrease in serum and secretory IgA, an increase in the amount of IgG and IgM, increased interferon activity. Pregnant women with the relapse of chronic pyelonephritis received, in addition to traditional therapy, local treatment with Kipferon suppositories, an immunomodulating preparation. The study revealed that the use of this preparation normalized the characteristics of local immunity, the composition of the microflora' of the genitals and led to the disappearance of the clinical symptoms of the disease.     

Oral and parenteral immunization with HIV immunosome induce the secretion of IgA specific of HIV-1 in the salivary and the production of circulatory IgA in mice and rabbits]

Given the sexual transmission of HIV, the establishment of a genital mucosal immunity through secretory IgA may be necessary to achieve protection. We have investigated if repeated stimulations of oral mucosa with HIV-Immunosomes would lead to the production of secretory IgA in saliva and also, if such an oral immunization could prime the immune system to an early systemic immune response following a parenteral immunisation with a low dose of the antigen. HIV-1 gp 160-specific secretory IgA were detected in the saliva of all rabbits orally immunized with HIV-Immunosomes. As early as one week after the parenteral immunization, high titers of serum IgA, IgM and IgG were detected both in mice and rabbits that had been orally stimulated with the antigen. These antibodies could neutralize HIV infectivity in vitro. Animals that were immunized only parenterally showed a very weak humoral immune response.     

Human male genital tract secretions: both mucosal and systemic immune compartments contribute to the humoral immunity

In contrast to numerous studies of female genital tract secretions, the molecular properties of Abs and the magnitude of humoral responses in human male genital tract secretions to naturally occurring Ags and to mucosal and systemic immunizations have not been extensively investigated. Therefore, seminal plasma (SP) collected from healthy individuals was analyzed with respect to Ig levels, their isotypes, molecular forms of IgA, and for the presence of Abs to naturally occurring Ags, or induced by systemic or mucosal immunizations with viral and bacterial vaccines. The results indicated that in SP, IgG and not IgA, is the dominant Ig isotype, and that IgM is present at low levels. IgA is represented by secretory IgA, polymeric IgA, and monomeric IgA. In contrast to the female genital tract secretions in which IgA2 occurs in slight excess, the distribution of IgA subclasses in SP resembles that in plasma with a pronounced preponderance of IgA1. The IgG subclass profiles in SP are also similar to those in serum. Thus, SP is an external secretion that shares common features with both typical external secretions and plasma. Specifically, SP contains naturally occurring secretory IgA Abs to environmental Ags of microbial origin and to an orally administered bacterial vaccine, and plasma-derived IgG Abs to systemically injected vaccines. Therefore, both mucosal and systemic immunization with various types of Ags can induce humoral responses in SP. These findings should be considered in immunization strategies to induce humoral responses against sexually transmitted infections, including HIV-1.     

Ultrastructural organization of the genital tracts in amphigonic females of Euceraphis betulae Koch (Aphididae: Calaphidinae)

The ultrastructure of the genital tracts in amphigonic females of Aphidoidea is described for the first time, using Euceraphis betulae Koch (Aphididae: Calaphidinae) as a representative. The female reproductive apparatus consists of two ovaries, each one with three/four meroistic telotrophic ovarioles; two sac‐like accessory glands lie laterally to a sac‐like seminal receptacle, opening into the dorso‐medial part of the common oviduct by means of a spermathecal duct. A marked secretory activity takes place in the epithelial cells of all the investigated tracts as shown by ultrastructural observation of many organelles involved in this process. No evident golgian area was observed in the cytoplasm of these cells. Extensive smooth endoplasmic reticulum, whose probable role is here discussed, was observed in epithelial cells of the wall of the accessory gland. Spermathecal duct and seminal receptacle had peculiar features that could be related to different secretory activities carried out by these two parts of the spermatheca.     

Humoral immune response in patients with bronchopulmanory infections to immunotherapy

The content of IgA, IgM, IgG and the level of specific antibodies in the blood serum of patients with bronchopulmonary diseases after a course of immunotherapy with polycomponent vaccine B[symbol: see text]-4 was studied. A rise in the concentration of IgM due to the synthesis of specific antibodies to Proteus vulgaris, Escherichia coli and Klebsiella pneumoniae was found to occur. The examination of sick children revealed that a high proportion of them (54%) showed a pronounced decrease in the level of IgA. The use of the preparation made it possible to enhance the level of IgA.     

Immunohistochemical studies on various aspects of glandular immunoglobulin transport in man

Summary Gland-associated immunocyte populations have been characterized in human tissue specimens from which extracellular immunoglobulins have been removed by saline extraction. There is a striking preponderance of IgA-producing immunocytes adjacent to glands of the gastro-intestinal and respiratory tracts, in minor and major salivary glands, and in lactating mammary glands. Immunohistochemically, these cells have been found to contain dimeric IgA with incorporated J chain. Despite this local IgA production, immunohistochemical tests on alcohol-fixed specimens demonstrate that the glandular stroma is normally permeated predominantly by IgG, most of which is obviously serum-derived. However, the serous glandular cells selectively transmit dimeric IgA, which appears along their lateral borders and apically in the cytoplasm, whereas the epithelial occurrence of IgG is less conspicuous and is restricted to the interstices.The same epithelial cells produce a glycoprotein called the secretory component (SC) which exhibits specific affinity for J chain-containing dimeric IgA and pentameric IgM. In saline-extracted tissue, IgA, but IgG, is retained regularly along the borders of SC-producing cells; this probably reflects complexing between locally formed IgA and SC in the epithelial cell membranes. SC apparently functions as a glandular receptor for dimeric IgA which thus most likely enters the epithelial cells by adsorptive pinocytosis. After covalent stabilization, the IgA-SC complexes are extruded to the gland lumen. Immunohistochemically the Golgi zone has been found to contain free SC but no IgA, whereas SC occurring more apically in the epithelial cell exhibits characteristics of being IgA-associated. Pentameric IgM is handled by the glands in a way similar to dimeric IgA, but local synthesis of IgM is normally negligible, except in the gut.     

Intestinal microecology in some systemic connective tissue diseases

In patients with systemic connective tissue diseases were studied. The species structure intestinal microflora was characterized by decrease of dominating status of anaerobic bacteria and increase of role of opportunistic bacteria. The number of Lactobacillus decreased significantly. Bifidobacterium and Bacteroides was also decreased in number while their detection rate did not change. Opportunistic bacteria with hemolytic activity acquired greater significance in the forming of patients' intestinal microbiocenosis. Significant increase of Staphylococcus and opportunistic Enterobacteriaceae detection rate and density of intestine colonization was detected. Colonization of the intestine by S. aureus was revealed. Comparative analysis of the qualitative and quantitative structure of the intestinal microflora in patients with systemic lupus erythematosus and systemic scleriasis revealed similar patterns. However, colonization of the gut by opportunistic intestinal bacteria, Candida and microorganisms with hemolytic activity was more frequently observed in patients with systemic scleriasis.     

In situ measurement of pH in the secreting canaliculus of the gastric parietal cell and adjacent structures

The gastric H⁺/K⁺-ATPase is located within an infolding (secretory canaliculus) of the apical plasma membrane of gastric parietal cells. Our aim was to measure the pH values in the cytosol and canaliculus of the acid-secreting parietal cell and the adjacent gland lumen in situ. We used ultrafine double-barreled tip-sealed microelectrodes at high acceleration rates for intracellular and canalicular measurements. Immunohistochemical staining of the parietal cells was used to identify the track of the electrode and to estimate the position of the electrode tip at the time of the last intracellular measurement. En route to the deepest regions of the mucosa, where the average gland lumen pH was approximately 3, and on advancing in steps of 2 μm, the electrode entered the cytosol of the parietal cells, where the pH value was 7.4. Advancing the electrode further resulted, in several instances, in a sharp decrease in pH to an average value of 1.7 ± 0.2, which we interpreted as the measurement within the canaliculus. When the electrode was advanced even further, the pH reading returned to the cytosolic value. From the difference in pH between the secreting canaliculus and the adjacent gland lumen, we concluded that the released acid was immediately buffered. Thus, the only cellular structure directly exposed to the highly acidic canalicular content is the apical membrane forming the canaliculus in the parietal cell.     

An important role for polymeric Ig receptor-mediated transport of IgA in protection against Streptococcus pneumoniae nasopharyngeal carriage

The importance of IgA for protection at mucosal surfaces remains unclear, and in fact, it has been reported that IgA-deficient mice have fully functional vaccine-induced immunity against several bacterial and viral pathogens. The role of respiratory Ab in preventing colonization by Streptococcus pneumoniae has now been examined using polymeric IgR knockout (pIgR(-/-)) mice, which lack the ability to actively secrete IgA into the mucosal lumen. Intranasal vaccination with a protein conjugate vaccine elicited serotype-specific anti-capsular polysaccharide Ab locally and systemically, and pIgR(-/-) mice produced levels of total serum Ab after vaccination that were similar to wild-type mice. However, pIgR(-/-) mice had approximately 5-fold more systemic IgA and 6-fold less nasal IgA Ab than wild-type mice due to defective transport into mucosal tissues. Wild-type, but not pIgR(-/-) mice were protected against infection with serotype 14 S. pneumoniae, which causes mucosal colonization but does not induce systemic inflammatory responses in mice. The relative importance of secretory IgA in host defense was further shown by the finding that intranasally vaccinated IgA gene-deficient mice were not protected from colonization. Although secretory IgA was found to be important for protection against nasal carriage, it does not appear to have a crucial role in immunity to systemic pneumococcus infection, because both vaccinated wild-type and pIgR(-/-) mice were fully protected from lethal systemic infection by serotype 3 pneumococci. The results demonstrate the critical role of secretory IgA in protection against pneumococcal nasal colonization and suggest that directed targeting to mucosal tissues will be needed for effective vaccination in humans.     

Medium-chain triglycerides enhance secretory IgA expression in rat intestine after administration of endotoxin

The purpose of this study was to determine whether medium-chain triglycerides (MCTs) modulate the inflammatory immune response to LPS and enhance the expression of secretory IgA in the rat intestine. Rats were given either corn oil or MCTs by gavage daily for 1 wk, and LPS or saline vehicle was administered via the tail vein. They were then killed, and serum and sections from the gut were collected for further analysis. Western blot analysis for secretory IgA revealed that MCTs significantly enhanced its expression in the ileum compared with corn oil in rats administered saline. After LPS challenge, expression of secretory IgA was decreased in the corn oil group but not in the MCTs group. The mRNA expression of IL-6 was assessed by real-time RT-PCR, because IL-6 regulates secretory IgA in the intestine. The expression was significantly greater in the MCTs group than in the corn oil group after LPS injection. Increases in expression of proinflammatory cytokines or chemokines such as TNF-alpha, IL-18, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 in the ileum were significantly blunted by MCTs. In addition, the mRNA expression of the Th2 IgA-stimulating cytokine IL-10 in the ileum and Peyer's patches was significantly greater in the MCTs than the corn oil group. In contrast, the mRNA expression of the Th1 IgA-inhibiting cytokine interferon-gamma was blunted by MCTs. As a result, intestinal injury was significantly reduced. Therefore, MCTs protect the gut by modulating the immune response to LPS and enhancing secretory IgA expression.