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Biomedical subjects

W Haas

Publications and source records attributed to W Haas.

At least 55 records · Page 3Linked to original sources

Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease.

Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4(+) Th1 cells. Because Th2 cells antagonize Th1 cell functions in several ways, it is believed that immune deviation towards Th2 can prevent or cure autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease used as a model for multiple sclerosis. Using an adoptive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-specific TCR transgenic mice were transferred into normal and immunodeficient mice. Th1 cells caused EAE in all recipients after a brief preclinical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mice and in alphabeta T cell-deficient mice, albeit after a longer preclinical phase. Normal or gammadelta T cell-deficient mice were resistant to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadmininstration of Th2 cells in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induced by previously activated Th1 cells cannot be prevented by normal lymphocytes nor by previously activated Th2 cells.

Animals↗

Miracidial host-finding in Fasciola hepatica and Trichobilharzia ocellata is stimulated by species-specific glycoconjugates released from the host snails.

The miracidia of Fasciola hepatica and Trichobilharzia ocellata approach their host snails Lymnaea truncatula and L. stagnalis by increasing their rate of change of direction (RCD) in increasing gradients of snail-conditioned water (SCW), and they perform a turnback swimming in decreasing gradients. Both hostfinding responses in both species were induced by glycoconjugates with a molecular weight of > 30 kDa that were sensitive to hydrolysis with pronase E and oxidation with NaIO4. Alkaline cleavage revealed that they contained carbohydrates linked O-glycosidically via serine and N-acetylgalactosamine. Miracidia clearly preferred SCW from their specific host snail versus other sympatric snail species and did not respond to water conditioned with fish, tadpoles, or leeches. Differences in the chemical characteristics of SCW from the intermediate hosts L. truncatula and L. stagnalis could be shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotting, and subsequent carbohydrate detection. The first step of purification of the effective signaling SCW components from both snail species was achieved by ion-exchange chromatography.

Animals↗

Schistosoma mansoni cercariae: stimulation of acetabular gland secretion is adapted to the chemical composition of mammalian skin.

The chemical signals of mammalian skin that stimulate the secretion of acetabular gland contents of Schistosoma mansoni cercariae were determined by exposing cercariae to fractions of human and pig skin surface obtained by thin-layer chromatography. Postacetabular gland secretion was stimulated by hydrophilic skin extracts but was often combined with a secretion of preacetabular glands. Secretion of preacetabular glands, which contain enzymes for skin lysis, could be selectively stimulated with skin surface lipids. Two different mechanisms of lipid-stimulated preacetabular gland release could be distinguished. First, secretion in combination with penetration behavior and probably tegument transformation was stimulated by the fraction of free fatty acids. Second, secretion independent of penetration behavior and tegument transformation was exclusively stimulated by glucosylceramides and phospholipids, probably phosphatidylcholines. The secretion mechanisms seem to allow a continuous lysis of epidermal macromolecules during the skin passage of the cercariae. Free fatty acids occur in the uppermost skin layers and may stimulate the combination of the first response; phospholipids and glucosylceramides are restricted to deeper epidermal layers and may stimulate the enzyme secretion there. An active preacetabular gland release was also stimulated by toxic chemicals, which could suggest an emergency penetration program for impaired cercariae.

Adaptation, Physiological↗

Schistosoma mansoni miracidial host-finding: species specificity of an Egyptian strain.

The effect of snail-conditioned water (SCW) from Biomphalaria alexandrina, a pigmented and an albino strain of B. glabrata, and Lymnaea stagnalis on the host-finding behavior of miracidia of two Brazilian and one Egyptian strain of Schistosoma mansoni was studied. Miracidia of the Egyptian strain significantly preferred their suitable host B. alexandrina versus the other snail species with their behavior patterns of host location and their responses after contact with the host. However, miracidia of both Brazilian strains did not differentiate between SCW from three of the snail species; only the pigmented B. glabrata elicited weaker responses. The releasing cues of SCW for miracidial host-finding phases are macromolecular glycoconjugates. An analysis of SCW by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), blotting, and subsequent carbohydrate detection showed that the band patterns of glycoconjugates differed significantly among the four snail strains. Therefore, differing chemical characteristics of the signaling glycoconjugates could be the basis for the observed host specificity in miracidial host-finding.

Agar↗

Schistosoma mansoni and S. haematobium: miracidial host-finding behaviour is stimulated by macromolecules.

The miracidia of Schistosoma mansoni and S. haematobium approach their host snails by increasing their rate of change of direction (RCD) in increasing gradients of snail-conditioned water (SCW), and they perform a turnback response in decreasing gradients. After contact with the host "repeated investigation" is the typical host-specific response. Both species show no significant directed chemotactical orientation towards their snail hosts. All three host-finding responses (increased RCD, turnback response, and "repeated investigation") seem to be stimulated in both species by a similar component of SCW, a macromolecular glycoconjugate with a molecular weight > 30,000. The saccharide chains seem to be O-glycosidically linked via serine and N-acetylgalactosamine. The glycoconjugate is sensitive to lysozyme which may suggest that muramic acid as a gastropod-specific component is involved in the recognition process. Small molecular components of SCW, as well as magnesium chloride offered as pure chemical, may cause a moderate increase in the RCD. Therefore a minor contribution of these components to the host-finding response of schistosome miracidia cannot be excluded. That schistosome miracidia respond to complex macromolecules as host cues may indicate an adaptation to avoid interference of the host-finding with ubiquitous small molecular mud components and it might enable the miracidia to achieve a high degree of host-specificity in their host-finding.

Animals↗

Finding and recognition of the snail intermediate hosts by 3 species of echinostome cercariae.

Finding and recognition of snail second intermediate hosts was studied in cercariae of 3 echinostome species. The cercariae of the 3 species accumulated in snail-conditioned water (SCW) with 2 types of orientation mechanisms and responded to different small molecular weight ( < 500 Da) components of SCW. Pseudechinoparyphium echinatum and Echinostoma revolutum cercariae returned by swimming an arc, when swimming in decreasing concentration gradients of SCW (turn-back swimming). The stimulating cues of SCW were identified as hydrophilic organic molecules, probably possessing amino groups. Amino acids contributed to the attractivity of SCW, at least in P. echinatum, but they could not account for the complete attractivity of SCW. Hypoderaeum conoideum were directed chemotactically and swam along increasing concentration gradients of small peptides within SCW, but in decreasing SCW gradients they showed no turn-back swimming. Chemotactic orientation in H. conoideum only started 1 h after emission, which may assist the cercariae to leave the immediate area of their first intermediate host snails and to disperse. Attachments occurred specifically to snail hosts in the 3 species and were stimulated by macromolecular mucus compounds, probably mainly by viscoelastic properties of the mucus. The results of this study show, that host-finding mechanisms and the stimulating host cues of snail invading echinostome cercariae differ considerably from those of schistosome miracidia.

Animals↗

Physiological analyses of host-finding behaviour in trematode cercariae: adaptations for transmission success.

Physiological analyses of the behaviour of several cercarial species which actively find and invade their hosts have revealed very complex sequences of behaviour patterns and responses to very different stimuli from the environment and the host. A result of these physiological studies is that the behaviour patterns of each of the species investigated are surprisingly individual. The behavioural patterns of host-finding of those species analysed in some detail reveal profound adaptations to maximize transmission success. This can be demonstrated for movement patterns during swimming, for responses to environmental conditions such as gravity, light and temperature, for responses to stimuli emanating from the host such as shadows, water turbulence and chemical compounds and especially for the responses after contact with the host. The behaviour patterns can be interpreted as adaptations to: (1) dispersal by leaving the habitat of the snail intermediate host and distribution within the area; (2) long survival by energy saving swimming behaviour, by avoiding responses to inappropriate stimuli, by selecting favourable microhabitats and probably by avoiding predation; (3) finding and invading particular host types by selecting microhabitats frequented by the hosts and responding to sequences of specific stimuli emanating from the hosts.

Adaptation, Physiological↗

The diagnosis of pulmonary tuberculosis by gaschromatographic detection of tuberculostearic acid using flame ionisation detectors.

It has been shown that the detection of tuberculostearic acid (TBSA) with gas chromatography-mass-spectrometry provides a highly specific, sensitive and rapid method for the diagnosis of various forms of tuberculosis. However, the need for complex and expensive equipment prevented the more widespread use of this method. We report on the application of conventional gas chromatography with flame ionization detectors in the detection of TBSA in sputum samples. TBSA was detected in all patients with proven pulmonary tuberculosis before treatment or under treatment for less than 4 weeks (n = 18). Six of these patients (33%) had a negative microscopy result at the time of the study. Sputum samples from patients under therapy for longer than 4 weeks (n = 20) were TBSA-positive in 15 cases (75%). Only in two cases was the diagnosis by microscopy and/or culture not met by TBSA-detection. All sputa of 20 control patients with lung diseases other than tuberculosis were TBSA negative. Additional analysis of patients' data showed a significant relationship (P < 0.005) between the relative amounts of TBSA detectable in the sputum samples and the duration of therapy. It is concluded that conventional capillary gaschromatography may be sensitive and specific enough to be used for the detection of TBSA in sputum of patients with pulmonary tuberculosis.

Chromatography, Gas↗

[Occurrence of swimmer's itch in Tyrol].

Cercariae from trematodes of birds are capable of penetrating human skin causing a dermatitis, called swimmer's itch. In 1992, after a hot dry summer there was a marked increase in the incidence of cercarial dermatitis in Austria. Although the increased incidence of this complaint can be quite worrisome for the population, the occurrence of swimmer's itch can, in fact, generally be seen as harmless. Cercarial dermatitis responds well to treatment with topical antihistamines or cortisone; even without medication the skin rash heals within 2-3 weeks. The effectiveness of various preventive measures (such as protective sun cream or patting the skin dry) is controversial. The use of molluscicides is definitely contraindicated due to the inoffensive nature of this dermatitis. While it is usually easy to recognize swimmer's itch when there is an increased incidence, the diagnosis is often missed when it occurs sporadically, due to its unspecific characteristics.

Adolescent↗

Schistosoma haematobium cercarial host-finding and host-recognition differs from that of S. mansoni.

Schistosoma haematobium cercarial host-finding responses differ from those of Schistosoma mansoni. The attachment response to warm substrata is more sensitive and intense and is inhibited by unphysiologically warm substrata. Attachment is also stimulated by L-arginine as the exclusive chemical cue of the human skin surface (threshold 3 microM); however, the response is drastically lower than that of S. mansoni cercariae. No chemical host stimulus could be identified for an enduring contact with the host after attachment. After attachment, the cercariae creep in a temperature gradient toward heat source; their response is, however, more sensitive than that of S. mansoni (threshold 0.03 vs. 0.15 C/mm). Creeping S. haematobium cercariae orientate in chemical gradients in the same way as S. mansoni cercariae toward L-arginine as the exclusive chemical signal of the human skin surface. The selective benefit of this behavior is not yet understood. The penetration of both species is stimulated by free fatty acids from the human skin surface, not by heat. Thus, S. haematobium responds more to thermal host signals, whereas S. mansoni prefers chemical host signals.

Animals↗

Gamma/delta cells.

Before TCR rearrangements, T cell progenitors are committed not only to the alpha beta and gamma delta T cell lineage but also to various subsets of both lineages. In the mouse, distinct gamma delta T cell subsets can develop in the fetal thymus, the adult thymus, or independently of a thymus, probably in intestinal epithelia. The two subsets that develop in the fetal thymus home to and are maintained throughout adult life in the skin and the mucosa of the uterus, vagina, and tongue. They are monospecific. This unusual restriction in receptor repertoires is the result of severe limitations in the generation of diversity in the fetal progenitors of these subsets and the thymic selection. After birth, one gamma delta T cell subset appears in the blood, spleen, and lymph nodes and one in the intestinal epithelia. The receptor repertoires of these subsets are characterized by the preferential usage of particular V gamma gene segments and extensive junctional diversity. Several murine and human gamma delta T cell clones have been shown to recognize classical MHC class I and class II proteins or MHC class I-like proteins, and in very few cases the presented peptides are known. We suspect that the various murine gamma delta T cell subsets interact with different antigen presenting cells which utilize different antigen presenting proteins and reside in different tissues. The function of gamma delta T cells remains unknown. Preliminary results of experiments with gene knock out mice which lack either alpha beta T cells or gamma delta T cells or both suggest that gamma delta T cells do not function as helper cells in humoral immune responses but may complement alpha beta T cells in the defense against various microorganisms.

Animals↗

Schistosoma mansoni and Trichobilharzia ocellata: comparison of secreted cercarial eicosanoids.

Schistosoma mansoni cercarial transformation and early stages of penetration can be correlated to specific eicosanoid products. Cercarial eicosanoids are suggested to play immunoregulatory roles during penetration. We examined production of cercarial eicosanoids by S. mansoni compared with that of the duck parasite Trichobilharzia ocellata after incubation with linoleate. Secretions were separated by reversed-phase high pressure liquid chromatography and also quantified by radioimmunoassay. The 2 parasites, differing in their immune evasion, synthesized the same types of prostaglandins, leukotrienes, and hydroxy-eicosatetranoic acids in similar quantities. Eicosanoid fractions of both species also showed a similar inhibition of superoxide production by human neutrophils. The coincidence of eicosanoid production suggests a function of eicosanoids in processes that are similar in both species.

Animals↗

Miracidium of Schistosoma mansoni: a macromolecular glycoconjugate as signal for the behaviour after contact with the snail host.

1. The behaviour of the miracidium of Schistosoma mansoni after contact with agar blocks containing Biomphalaria glabrata snail conditioned water (SCW) or its components, was studied. 2. "Repeated investigation" was the most specific response at contact with the snail host. 3. Fractionation and specific chemical treatment of SCW revealed that this response was stimulated by a lysozyme sensitive glycoconjugate with a mol. wt greater than 300,000. 4. Low molecular weight components of SCW had no stimulatory effect on the miracidia, although MgCl2 offered as pure chemical did so.

Animals↗

Development and selection of gamma delta T cells.

The gamma delta T-cell population, a subpopulation of T cells formed through cell lineages that are independent of the alpha beta T-cell lineage, consists of multiple subsets with distinct receptor repertoires and homing properties. While the cell sublineage is a critical factor in the determination of homing specificity, both cell sublineage and receptor-dependent selection are instrumental in the determination of the functional repertoire.

Animals↗

Physiological analysis of cercarial behavior.

The behavior of trematode cercariae was made accessible to physiological analyses by splitting the continuous flow of behavior into separate units of behavior patterns. Such phases include active, passive, and resting phases in the intermittent swimming mode, attachment to the host, remaining on the host, directed creeping to suitable entry sites, and penetration phases including penetration movements, tail shedding, tegument transformation, and secretion of enzymes. Each of these phases may be stimulated by separate environmental and host signals. The pattern of the responses and the chemical, thermal, mechanical, and visual stimuli have been described in some detail but only a few studies have dealt with the question of how these responses are coordinated by receptors and nervous systems. Highly specific and sensitive chemoreceptors for host signals such as carbon dioxide, L-arginine, fatty acids, and glycoproteins have been defined from cercarial behavior, but they have not yet been allocated to morphological structures. Analyses of cercarial behavior of 6 schistosomatid and 4 fish-infecting species revealed that the individual parasite species show different behavioral patterns and respond to very different host signals, even though they infect congeneric hosts. The adaptive benefits of such behavioral diversity and complexity still are to be elucidated.

Animals↗

Migration of Trichobilharzia ocellata schistosomula in the duck and in the abnormal murine host.

The migration of Trichobilharzia ocellata schistosomula in the duck host and the accidental mouse host was studied by the detection of [75Se]-methionine in radiolabelled cercariae using autoradiography of compressed host tissues and by the recovery of schistosomula following the mincing and incubation of host tissues. Exposure via duck feet (30 min) and mouse tails (60 min) resulted in low infection rates: 3.9% in the duck and 3.1% in the mouse. However, when mice were infected via the abdominal skin using the ring method, 25% of the cercariae were recovered in the skin. In the duck, schistosomula left the skin within 3 days post-infection (p.i.) and were detected in the lungs between days 2 and 4 p.i. Thereafter, only few radioactive foci were found in the liver, kidney and intestine. In the mouse, schistosomula were detected in the lungs within 10 h and for up to 6 days p.i., and some foci were detected in the liver and intestine on days 2-5 p.i. On days 3-4 p.i., 36% of the detectable parasites in the mouse (91 foci in 10 mice) had migrated from the skin to other organs. Living schistosomula could be extracted from mouse skin and lungs only until day 4 p.i. The schistosomula of T. ocellata migrate faster within their vertebrate hosts than do those of Schistosoma mansoni, indicating that the former may use other transformation and immune-evasion mechanisms.

Animals↗