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R Pabst

Publications and source records attributed to R Pabst.

At least 91 records · Page 5Linked to original sources
PubMed1998

Bronchus-associated lymphoid tissue (BALT) and larynx-associated lymphoid tissue (LALT) are found at different frequencies in children, adolescents and adults.

The lung in 98 and the larynx in 51 consecutive autopsies (age: 17th gestational week to 99 years) were studied for the presence of organized lymphoid tissue in the epiglottis and in the wall of larger bronchi. Bronchus-associated lymphoid tissue (BALT) was seen in about 40% of patients younger than 20 years of age but in older patients only in exceptional cases. In the wall of the epiglottis, however, larynx-associated lymphoid tissue (LALT) was found at a frequency of approximately 80% in patients younger than 20 years and in 56% of the patients older than 20 years. The clinical relevance of LALT as a physiological entry site for antigens or for vaccination protocols using aerosols needs to be studied in further experiments.

Adolescent↗
PubMed1998

Interpreting data on lymphocyte subsets in the blood of HIV patients - organ distribution, proliferation and migration kinetics are critical factors.

Lymphocytes stay in the blood only a short time before migrating to lymphoid and nonlymphoid organs. They represent only about 2% of all lymphocytes in the body. The ratio of CD4+/CD8+ lymphocytes in the blood depends on age and genetic influences. In HIV infection not only relative but also absolute numbers of lymphocyte subsets should be determined. The different effects of proliferation and apoptosis on lymphocytes in HIV infection have to be considered. Lymphocyte levels in the blood of HIV patients do not mirror alterations in the lamina propria of the gut or lymph nodes. The dynamic aspects of lymphocyte life span and migration during HIV infection and the progression to AIDS as well as the effects of treatment have to be taken into consideration to enable a meaningful interpretation of experimental data. More data from animal models of HIV infection are needed to study these kinetic aspects.

Age Factors↗
PubMed1998

Three-dimensional distribution of intercellular adhesion molecule-1 on lymphocytes in the high endothelial venule analyzed by backscatter electron imaging.

The intercellular adhesion molecule-1 (ICAM-1) is a ligand for the beta2 integrin. It is present on the vascular endothelium and plays an important role in cell to cell interaction in lymphocyte recirculation. ICAM-1 is expressed not only on the endothelium but also on other cells, especially lymphocytes adhering to the endothelium, B cells and mitogen-stimulated T cells. To define the functional role of ICAM-1 in lymphocytes, the three-dimensional distribution of ICAM-1 on the surface of lymphocytes in the rat mesenteric lymph node HEV was investigated by immunoscanning electron microscopy. ICAM-1 expression was closely associated with variations in surface structures of lymphocytes, which showed a cap-like structure, membrane ruffles and slender microvilli. ICAM-1 was preferentially localized on the cell surface including membrane ruffles (about 90% of all counted gold particles), but rarely on the microvilli (10%). The results suggest that activated lymphocytes with variations in surface structures demonstrate moderate expression and preferential localization of ICAM-1. This seems to enable a three-dimensional interaction of the microvilli of one lymphocyte with the surface membrane of another cell and might be a prerequisite for cluster formation between them, as seen in antigen presentation.

Animals↗
PubMed1997

Contribution of serum IgA to intestinal lymph IgA, and vice versa, in minipigs.

Immune cells in pig gut lymph are rather well studied, but data on gut lymph immunoglobulins and their origin are nonexistent. Such data are important to understand the interplay between pig systemic and intestinal immunity as a basis for vaccination studies. In some species, gut lymph contributes much to plasma IgA, but apparently not in humans. To estimate the contributions of pig serum IgA to intestinal lymph IgA and vice versa, concentrations of IgA, IgG, IgM, albumin, haptoglobin, C3 and alpha 2-macroglobulin were measured by radial immunodiffusion in paired porcine intestinal lymph and serum samples. All proteins, except IgA, had lymph/serum ratios (< 1.0) inversely related to their size, depending on passive diffusion from serum. The mean lymph/serum ratio of IgA was 2.2 instead of an expected 0.50 or 0.65 (dimer or monomer, respectively), indicating that of the IgA in gut lymph, 22.7 or 29.5% came from serum, vs 77.3 or 70.5% from the intestine. Percentage of polymeric IgA, measured by gelfiltration and corrected radial immunodiffusion, was 64.3% in porcine mesenteric lymph and 47.3% in serum. As the pig plasma volume and daily gut lymph flow into circulation were known, it could be calculated that roughly 31% of the total plasma IgA originated daily from local intestinal synthesis, reaching blood via mesenteric lymph.

Animals↗
PubMed1997

Larynx-associated lymphoid tissue (LALT) in young children.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) plays a central role in mucosal immunity. Whereas the characteristics and function of MALT in the intestine are well established, almost nothing is known about MALT in the larynx. METHODS: In this study we examined the morphology and the lymphocyte subset composition of MALT in the larynges of children who had died of sudden infant death or various defined traumatic or nontraumatic causes. RESULTS: Organized lymphoid tissue was found in the supraglottic parts of the larynx in nearly 80% of the children in both groups. This lymphoid tissue showed all morphological signs of MALT, such as typical lymphoid follicles with germinal centers, infiltration of the overlying epithelium by lymphocytes, and high endothelial venules (HEV). Thus we will use the term LALT (larynx-associated lymphoid tissue) to refer to this tissue. The lymphoid follicles of LALT contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably, T lymphocytes of both subset types and B lymphocytes were observed in comparable numbers in the parafollicular area. CONCLUSIONS: We assume that LALT is a physiological structure of the larynx in young children. The morphology and the distribution of lymphocyte subsets are similar to those of MALT in the human gut. LALT may be a regular part of the mucosal immune system in young children with the role of respiratory inductive site for mucosal immunity.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1997

Retrospective evaluation of undergraduate medical education by doctors at the end of their residency time in hospitals: consequences for the anatomical curriculum.

Reform of the undergraduate medical curriculum, including the debate on which of its parts or subjects are superfluous, is a topic of interest in many countries. On being examined at the end of their specialization period, doctors were asked to grade the relevance of all subjects in the undergraduate curriculum for training to become a medical doctor. The subjects that gained the highest grades were internal medicine, gross anatomy, physical examination course, physiology, and pharmacology. The five subjects graded least relevant were biomathematics, terminology, social medicine, medical physics, and medical chemistry. More than 80% of the doctors expressed interest in special lectures and courses, e.g., in topographic anatomy at the beginning of their postgraduate training. Retrospective evaluations at the end of residency time are helpful "evidence" to be considered in reforming the medical curriculum, and in particular in defining "core" and "optional" parts of the curriculum. The data show that anatomy is graded as highly relevant in the undergraduate medical curriculum by doctors at the end of their postgraduate training.

Adult↗
PubMed1997

The fate of activated T cells migrating through the body: rescue from apoptosis in the tissue of origin.

After activation within a lymphoid tissue, T lymphocytes enter the blood, where they circulate and then re-enter many organs. However, they predominantly end up in the tissue of origin, a phenomenon so far thought to be caused by organ-specific homing. We analyzed the fate of T cells from different sources stimulated via the T cell receptor and CD28 and then injected intravenously into rats. Our results showed that preferential proliferation and reduced apoptosis, rather than preferential immigration, were responsible for the accumulation of activated T cells in the tissue of origin, explaining how immune responses can spread from site to site but still be restricted to certain regions. Manipulating the life span of such cells might be a promising approach to influencing immune responses.

Animals↗
PubMed1997

Comparison of the immunohistology of mucosa-associated lymphoid tissue in the larynx and lungs in cases of sudden infant death and controls.

The respiratory tract of children in the first two years of life, unlike that of adults, contains bronchus-associated lymphoid tissue (BALT) and larynx-associated lymphoid tissue (LALT) with no differences in frequency between SID and control children. Using immunohistochemical methods we examined the distribution of B, T, CD4+ and CD8+ lymphocytes, HLA-D+ cells, CD68+ macrophages and proliferating cells, comparing bronchus-associated and larynx-associated lymphoid tissue of sudden infant death cases and controls. In all groups the lymphoid tissue was organized in lymphoid follicles and parafollicular areas. With no differences in the cellular composition of BALT and LALT the lymphoid follicles contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably T lymphocytes of both subset types and B lymphocytes were observed in equal numbers in the parafollicular areas in contrast to gut-associated lymphoid tissue. However, the respiratory tract of young children with no differences between SID and controls might play a similar role in mucosal immunity and might function as an inductive site.

Bronchi↗
PubMed1997

Jejunal and ileal Peyer's patches in pigs differ in their postnatal development.

The postnatal development of the jejunal and ileal Peyer's patches was studied before and after weaning in 1-, 1.5- and 2-month-old pigs. The follicles of the jejunal Peyer's patches grew with age and were two times longer and wider in specified pathogen-free and conventional pigs than in germ-free animals, thus indicating an influence of the living microbial antigens from the gut lumen. In germ-free pigs the size of the ileal Peyer's patch follicles increased between the 1st and 2nd month, whereas in the specified pathogen-free and conventional animals these follicles were comparable in size in all three age groups. In 1- to 1.5-month-old pigs the interfollicular area of jejunal Peyer's patches was wider (0.1 +/- 0.04 mm) than that of the ileal Peyer's patch (0.04 +/- 0.03 mm). Immunohistological studies showed that in germ-free pigs preferentially surface IgM+ but few IgA+ B cells were present in the follicles, domes and dome epithelia. In specified pathogen-free and conventional pigs the B cells expressed different levels of surface or cytoplasmic IgM or IgA. In all groups studied, more T cells were observed in the jejunal than in the ileal Peyer's patch. Here, few T lymphocytes were found because of the small interfollicular areas. Small numbers of Null cells were distributed in the interfollicular regions of all animals. The results show that living microbial antigens have a major influence on the jejunal and ileal Peyer's patches in pigs. The morphological differences between the two types of Peyer's patches are an indication that they develop differently during postnatal life. So far it remains unclear whether these morphological differences reflect a specific function of the pig's ileal Peyer's patch, such as the expansion of the genetically determined B cell repertoire as has been reported for sheep.

Animals↗
PubMed1997

Autotransplantation of the spleen in the rat: donor leukocytes of the splenic fragment survive implantation to migrate and proliferate in the host.

Loss of the spleen may lead to fatal bacterial infections. As a preventive procedure splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the protective function of this procedure, partly because the process of regeneration after implantation of splenic tissue is not fully understood. In the present study the question was addressed of whether, in contrast to the current view, leukocytes survive the phase of necrosis after implantation of splenic fragments. Rats (LEW.7A; host) received splenic fragments of a congenic rat strain (LEW.7B; donor). These fragments first underwent almost complete necrosis, then regenerated, finally developing the typical splenic compartments. Twenty weeks after implantation, leukocytes which had survived the implantation procedure (7B positive; donor) and those which had migrated from the host into the splenic implant (7B negative; host) were differentiated using a specific monoclonal antibody (anti-7B) and immunohistology. In addition, the rats received 5-bromo-2-deoxyuridine (BrdU) 1 day before the splenic autotransplant and several lymphoid and non-lymphoid organs were removed. This thymidine analogue is incorporated in proliferating cells during the S-phase of the cell cycle and can be revealed by immunohistology. The present study demonstrates that macrophages and B and T lymphocytes survive the implantation procedure and are found in the organ compartments of the splenic autotransplant. The lymphocytes proliferate and migrate into lymphoid and non-lymphoid organs. Both the number of surviving leukocytes in the splenic autotransplants and the number of donor lymphocytes found in various host organs varied considerably between single animals. Thus, not only fibroblasts but also macrophages and lymphocytes survive the avascular implantation of splenic fragments. The surviving leukocyte subsets may be involved in the regulation of the regeneration of the different splenic compartments, so increasing their numbers may finally lead to an improvement in the function of splenic autotransplants in the clinical situation.

Animals↗
PubMed1997

Lymphocyte dynamics: caution in interpreting BAL numbers.

In various allergic and inflammatory lung diseases the number and subset composition of lymphocytes in the bronchoalveolar lavage (BAL) fluid are taken as indicators of the state of the disease. The number of lymphocytes in the BAL fluid depends on three main parameters: (1) entry into the bronchoalveolar space from the different compartments of the lung, (2) persistence in the bronchoalveolar space which is modified by the rate of local proliferation and apoptosis, and (3) exit into the draining bronchial lymph node via the lymphatic system. In healthy individuals lymphocytes in the BAL fluid seem to be a stable pool: each day there is hardly any entry, local cell division or cell death and few lymphocytes emigrate from this compartment. In contrast, during inflammatory, toxic and allergic reactions all parameters can increase rapidly with more lymphocytes entering, proliferating and/or undergoing apoptosis locally. Very little is known about factors such as cytokines and chemokines which may regulate these parameters. When interpreting data on lymphocyte numbers in patients, lymphocyte dynamics in the bronchoalveolar space have to be considered, and in the future it may be possible to manipulate these lymphocyte fluxes for therapeutic purposes.

Apoptosis↗
PubMed1997

The lung as a source and a target organ for T- and B-lymphocytes.

In lung transplantation, a substantial number of donor leukocytes are transferred from the donor to the recipient by the graft. Using a rat model, it was analyzed in this study to what extent leukocytes leave the lung, to which phenotype they belong, and to which organs they migrate. The model used was the orthotopic transplantation of the left lung of LEW.7B(RT7b) rats into LEW(RT7a) recipients. Lung allografts are not rejected in this strain combination, which differs only in the RT7 system, a genetic polymorphism of CD45. Using the RT7b marker (monoclonal antibody His41), the distribution of donor leukocytes passively transferred with the graft was studied by immunohistology 2 wk after transplantation. At this time, 2.9 +/- 0.1% (n = 6) of the peripheral blood leukocytes in the recipients were derived from the donor lung. The donor cell population detected in the blood consisted of T cells (59 +/- 4%), B cells (5.1 +/- 0.2%) and a surprisingly high fraction of natural killer (NK) cells (36 +/- 3%). No monocytes or granulocytes were found. In lymph nodes, spleen and thymus donor-derived T- and B-cells could be shown in typical T- and B-areas, respectively. Donor-derived leukocytes were found in the liver and the skin. In the tissue and the bronchoalveolar lavage (BAL) of the host lung, predominantly T cells were found. Furthermore, in the donor tissue and BAL more than 70% of T- and B-cells were host type, demonstrating that the donor lung had been repopulated to a great extent by host lymphocytes. This supports the relevance of BAL as a diagnostic tool in lung diseases. Thus, the lung is an immunologically important site, releasing lymphocytes which migrate to other organs and also attracting many lymphocytes from the circulation.

Animals↗
PubMed1997

Long-term oral application of 5-bromo-2-deoxyuridine does not reliably label proliferating immune cells in the LEW rat.

To study the lifespan of immune cell populations in the LEW rat, 5-bromo-2-deoxyuridine (BrdU) was administered in the drinking water. After 12 weeks, the epithelium of gut and skin was completely BrdU+. In contrast, thymus, bone marrow, and germinal centers of Peyer's patches contained only a few BrdU+ cells, although most should have been labeled during this time. The lack of labeling was due neither to obvious toxic effects of BrdU on these organs nor to insufficient detection of incorporated BrdU. Analysis of the kinetic pattern of the appearance of BrdU+ cells in bone marrow, blood, spleen, and lymph nodes over 12 weeks revealed that the dosage of BrdU initially was high enough to label the proliferating cells in the bone marrow, but then became too low, although the BrdU uptake of the rats was similar over the entire time. This indicates that in the LEW rat the metabolism of orally applied BrdU changes over time, leading to a reduction in the amount of BrdU available for incorporation into the DNA below a level necessary for labeling all proliferating cells. This effect appears to be species- and strain-dependent, and should be considered when the BrdU technique is used.

Administration, Oral↗
PubMed1997

Lymphocyte migration: an essential step in understanding the effects of vaccination.

When an antigen has passed the epithelial barrier of the skin or mucosal surfaces it has to be processed and presented by accessory cells to lymphocytes. These reactions take place in lymphoid organs, such as the regional lymph nodes, Peyer's patches and tonsils, but also in the spleen if the antigen entered the blood directly. The respective lymphocyte clone expands by proliferating, and primed lymphocytes of the B and T cell series emigrate from the lymphoid organs. The traffic of lymphocytes is regulated by the interaction of a series of adhesion molecules with endothelial cells and lymphocytes. Several earlier ideas, for instance one specific "homing receptor" for each organ and different receptors for B and T lymphocytes, or exclusive migratory routes for "memory" and "naive" lymphocytes, have had to be replaced by the concept of a much more complex, multistep, cascade-type reaction. Most migration routes show "preference" rather than "selectivity". The regulation of the entry of activated T and B lymphocytes into the parenchyma of non-lymphoid organs, e.g. the lamina propria of the gut, is not as well as understood as the entry into a lymph node. A further important aspect in lymphocyte traffic is the regulation of lymphocyte migration within the organs, including the interaction between lymphoid cells and the extracellular matrix. the basic mechanisms of lymphocyte migration have to be considered when the effects of vaccination procedures are interpreted.

Animals↗
PubMed1996

Induction of protective immunity by aerosol or oral application of candidate vaccines in a dose-controlled pig aerosol infection model.

In order to outline basic concepts for the design of a bacterial aerosol infection model, the development of a pig model with Actinobacillus pleuropneumoniae is described. First, reproducibility of aerosol parameters should be maintained by optimizing generating and sampling conditions. Survival rates of the chosen strain must be predictable. Secondly, inhalation conditions for the recipients have to be standardized to enable the determination of deposition sites and the dose administered. Subsequently, dose-response relationship should be evaluated to find a suitable challenge dose. Furthermore, it seems necessary to establish methods to obtain local specimens for determination of the local immune responses. The present study demonstrates that after aerosol challenge pigs were completely protected after inhalation and partially protected after oral application of A. pleuropneumoniae vaccines and describes techniques to administer bacteria in a dose-dependent, viable way. Using the infection model several stages of the disease from acute pleuropneumonia to chronic infection can be induced for research purposes.

Actinobacillus Infections↗
PubMed1996

Ultrastructural localization of the intercellular adhesion molecule (ICAM-1) on the cell surface of high endothelial venules in lymph nodes.

BACKGROUND: The high endothelial venules (HEV) in the lymph nodes are essential for lymphocyte recirculation. As a first step, the HEV surface interacts with lymphocytes through adhesion molecules. It is important to know where adhesion molecules are expressed on the surface ultrastructure and how these structures interact with lymphocytes. METHODS: To demonstrate the ultrastructural mechanism of interaction between the HEV surface and lymphocytes through the intercellular adhesion molecule (ICAM-1), rat mesenteric lymph nodes were perfused through the superior mesenteric artery with the primary antibody (antirat ICAM-1 antibody) and secondary antibody (antimouse IgG coupled to 15 nm gold particles), which were diluted with hypothermic University of Wisconsin (UW) solution. After the immunoreaction, we analyzed the HEV three-dimensionally and quantitatively using immunoscanning electron microscopy (ISEM) combined with transmission electron microscopy (TEM). RESULTS: HEV expressed ICAM-1 in a 5-30-fold higher concentration than other vessels. Its distribution was extensive over the luminal surface of the cell down to the junctional area. The endothelial surface of HEV undulated to form branched microfolds, along which ICAM-1 was expressed. Cytoplasmic processes of lymphocytes were seen in microfurrows between microfolds and adhered to the sides of the folds. CONCLUSIONS: These observations imply that the microfolds expressing ICAM-1 and microfurrows are specific ultrastructural features for trapping lymphocytes, thus initiating lymphocyte emigration into the lymph node parenchyma.

Animals↗