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Biomedical subjects

H K Muller

Publications and source records attributed to H K Muller.

At least 91 records · Page 5Linked to original sources

Cell-mediated immunity in healthy adults in Antarctica and the sub-Antarctic.

Cell-mediated immune responses were studied in 2 Antarctic and sub-Antarctic groups at quarterly intervals over a wintering year, using the cutaneous CMI Multitest. The sub-Antarctic population at Macquarie Island (M.I.) had levels of responsiveness and hypoergy comparable to other healthy populations in temperate regions. The Antarctic group at Mawson showed decreased scores and total number of positive responses to antigens, and a significantly elevated incidence of anergy and hypoergy. Quarterly skin testing showed considerable variability in subject responsiveness to specific antigens at different times over the year. However, only 2 antigens at M.I., trichophyton and proteus, showed a significant seasonal variation in score. There was no statistically significant seasonal variation in antigen scores at Mawson. It is concluded that environment and stress factors in Antarctic expeditions are responsible for the decreased immunological responsiveness.

Acclimatization↗

Carcinogen-induced depletion of cutaneous Langerhans cells.

The chemical carcinogen 7,12-dimethylbenz (a) anthracene (DMBA) is a potent carcinogen which, when applied to the skin of BALB/c mice weekly for 7-8 weeks, causes the induction of macroscopically visible skin tumours. We report that DMBA also depletes Langerhans cells (LC) from treated skin; the number of cutaneous LC is reduced by nearly 50% 3 days after the first application of DMBA, and continues to decrease upon further treatment. After 7-8 weeks of DMBA application, while tumours are becoming macroscopically visible, there is a considerably lower LC density in treated skin. Upon cessation of the DMBA treatment, the LC repopulate the skin, returning to control values within 55-64 days. During this repopulation of the skin by LC, the tumours begin to decrease in size. Since LC function as local cutaneous antigen-presenting cells, and are responsible for initiation of an immune response against antigens in the skin, their depletion during tumour induction may allow DMBA-transformed cells to circumvent the immune system and form tumours. Their reappearance associated with tumour regression suggests that the LC are involved in an immune response against the tumours.

9,10-Dimethyl-1,2-benzanthracene↗

The migration of lymphocytes into rat popliteal lymph nodes during antigenic promotion or competition between heterologous erythrocytes.

The injection of chicken and sheep red blood cells (CRBC and SRBC) into rat popliteal lymph nodes either together or sequentially 2, 4, 6, or 8 days apart resulted in an enhanced immune response when the second antigen was injected 2 or 4 days after the injection of the first antigen (antigenic promotion) or a suppressed immune response when the second antigen was injected 6 days after the injection of the first antigen (antigenic competition). The immune response to either antigen was dependent upon the time of administration of the second antigen with respect to the first antigen. Lymphocyte migration into antigenically stimulated lymph nodes was greater when the two antigens were injected sequentially rather than together. Further, the migration of lymphocytes into the lymph node was enhanced when the second antigen was injected during the inductive or suppressive phase of the immune response to the first antigen (CRBC) regardless of whether the same (CRBC) or an antigenically unrelated antigen (SRBC) was used as the second antigen. While antigenic promotion may in part be explained by the increased rate at which lymphocytes migrate into lymph nodes, lymphocyte migration is also enhanced during antigenic competition. This suggests that while suppressor cells/factors may regulate the effector phase of an immune response they do not directly modulate the migration of blood-borne lymphocytes into the lymph node.

Animals↗

A novel structure in the stomach and intestine of two species of Australian marsupial mice.

A tubular or sac-like structure with a well defined lumen which occasionally contained parasites was found in the outer muscle wall of the small and large intestine in 32 out of 40 male and 35 of 40 female marsupial mice of the two species, Antechinus swainsonii and Antechinus stuartii (Macleay). A similar structure was also found in the muscle layers of the stomach in 5 marsupial mice of both species. The cellular matrix of the structure appeared to be composed of randomly organized macrophage-like cells and in one case there was evidence of an inflammatory reaction to parasites within the lumen. The origin of this tube is either vestigial or the result of reactive changes.

Animals↗

Stress related involution of lymphoid tissues in Australian marsupial mice.

Involution of the thoracic thymus in two species of marsupial mouse, Antechinus swainsonii (Waterhouse) and Antechinus stuartii (Macleay) was shown to be unrelated to corticosteroid action and to be complete before puberty. A stress response in male marsupial mice is caused by an androgen related drop in the plasma corticosteroid binding globulin concentration which gives rise to an increase in the plasma free glucocorticoid concentration. The high concentrations of free glucocorticoids in the plasma just prior to the breeding season causes a rapid involution of the spleen and lymph nodes while the gut associated lymphoid tissues remain unaffected. The concentration of free glucocorticoids also rises in females, but it never attains the high concentrations observed in males. Nevertheless, the spleen and lymph nodes do involute to some extent in some females and the degree of involution appears to be related to the relative concentration of plasma free glucocorticoids. At the conclusion of the breeding season, there is a complete mortality in males of the population, due to a stress response in which the compromised immune system clearly plays a role.

Animals↗

The gut-associated lymphoid system of two species of Australian marsupial mice, Antechinus swainsonii and Antechinus stuartii. Distribution, frequency and structure of Peyer's patches and lymphoid follicles in the small and large intestine.

The distribution and number of Peyer's patches (5) in two species of marsupial mice, Antechinus swainsonii and Antechinus stuartii was found to be the same even though the length of the intestine in the latter species was half that of the former. Both species lack a caecum and appendix. The position of the Peyer's patches is unusual in that the first three Peyer's patches are on the right side of the small intestine whereas the penultimate and ultimate Peyer's patches are large, contain many lymphoid follicles and are in an anti-mesenteric position in the small intestine and sometimes in the large intestine (ultimate Peyer's patch). The number of Peyer's patches in eutherian mice of similar size, and intestinal length is greater (13) although the number of Peyer's patch lymphoid follicles per centimeter intestine is less (1.8) than in A. swainsonii (4) and A. stuartii (4.4). Marsupial mice have most of their lymphoid follicles confined to a few large Peyer's patches, whereas eutherian mice have fewer lymphoid follicles per unit intestinal length, more Peyer's patches (with fewer lymphoid follicles) evenly distributed along the intestine and more single lymphoid follicles interspersed between them.

Animals↗

Characterization of retraction spaces in basal cell carcinoma using an antibody to type IV collagen.

'Retraction spaces' observed in 18 of 30 basal cell carcinomas were readily classified into two distinct types using the PAP immunoperoxidase technique and an antibody to human type IV collagen, raised in rabbits. In processing artefacts, true retraction spaces were observed between the epithelial cells and the basal lamina, while in areas of stromal mucinous change, accumulation of mucinous material resulted in clear spaces separating the normal stroma from the overlying basal lamina.

Antibodies↗

Flow cytometric detection of histamine binding to lymphocytes.

Using flow cytofluorimetry histamine binding was demonstrated by 90-100% of human peripheral blood lymphocytes. Cells were labelled with fluorescein isothiocyanate-human albumin-histamine (FITC-HA-His) and analysed using a Fluorescence Activated Cell Sorter (FACS-II). A parallel control FITC-HA conjugate and blocking with both free histamine and histamine bound to albumin were used to establish specificity. The binding of histamine could be blocked with both H1 and H2 type histamine antagonists. Nylon wool separated T and B lymphocyte subpopulations showed the same high proportions of histamine binding cells.

Animals↗

Migration of blood-borne lymphocytes into antigen-stimulated lymph nodes. A study of the kinetics of lymphocyte recruitment throughout an immune response.

The kinetics of lymphocyte recruitment into rat popliteal lymph nodes stimulated with varying doses of allogeneic lymphocytes or purified protein derivative of tuberculin differed markedly. The number of blood-borne lymphocytes entering lymph nodes stimulated with allogeneic lymphocytes was greater and the duration of their entry more prolonged than in lymph nodes stimulated with the soluble antigen purified protein derivative of tuberculin. When individual antigenic doses were compared, lymphocyte recruitment into popliteal lymph nodes was shown to be dependent upon antigenic dose; higher doses of antigen resulting in increased levels of lymphocyte recruitment. In addition it was found that there is no linear relationship between lymph node weight changes and the extent of lymphocyte recruitment.

Animals↗

The basal lamina in basal cell carcinoma, Bowen's disease, squamous cell carcinoma and keratoacanthoma: an immunoperoxidase study using an antibody to type IV collagen.

The basal lamina in a variety of skin tumours was assessed with an antibody to type IV collagen and the peroxidase-antiperoxidase (PAP) technique. The antibody was raised in rabbits against type IV collagen isolated from human placental tissue. The basal lamina in Bowen's disease was essentially intact while squamous cell and basal cell carcinomas showed focal loss in areas of tumour cell invasion. However, both tumours showed preservation of basal lamina around the majority of projections and nests of tumour within the dermis. Many keratoacanthomas showed extensive loss of the basal lamina. This loss appears associated with advanced keratinization at the base of the lesion and may represent an involutional change possibly secondary to inflammation. It is concluded that epidermal tumour cells following local invasion may cease migration and produce a distinct continuous basal lamina similar to that of the normal dermo-epidermal junction. Loss of basal lamina appears restricted to foci of ongoing tumour invasion.

Basement Membrane↗

The entry of T and B lymphocytes into rat popliteal lymph nodes undergoing a graft-versus-host reaction.

The entry of radiolabeled blood-borne T and B lymphocytes into resting popliteal lymph nodes and popliteal lymph nodes stimulated with semiallogeneic lymphocytes was investigated in rats. Thoracic duct lymphocytes separated into T- and B-lymphocyte populations on nylon-wool columns were radiolabeled with 51chromium and equal numbers of T or B lymphocytes were injected intravenously. While the ratio of T and B lymphocytes in the blood is approximately 3:1 it was found that the ratio of T to B lymphocytes migrating into lymph nodes was approximately 9 T to 1 B lymphocyte in both resting and antigenically stimulated lymph nodes. Since the ratio of T to B lymphocytes in thoracic duct lymph is similar to that of blood, there is a disparity between the number of T cells entering and leaving lymph nodes. These results suggest that some T lymphocytes may return to the blood directly and/or there is increased T lymphocyte death in lymph nodes.

Animals↗

Lymphocyte migration during the development of regional lymph node anergy in experimental tumor growth.

The development of lymph node anergy in Wistar rats to growing Walker carcinoma 256 was studied in vitro using the 51Cr-release cytotoxicity assay. Cell-mediated cytotoxicity to the tumor peaked in draining lymph nodes 11 days after tumor transplantation. By 14 days, the regional lymph node had become anergic to the tumor at a time when cell-mediated cytotoxicity was still increasing in the more distal contralateral lymph node. Lymphocyte migration into resting, cytotoxic, and anergic lymph nodes was analyzed to determine if altered cell migration into the regional lymph node was associated with the development of anergy. Lymphocyte migration was found to be enhanced in both cytotoxic and anergic regional lymph nodes of tumor-bearing animals. It is concluded that lymph node anergy in this experimental tumor system is not related to changes in lymphocyte migration patterns; rather, it is the result of alterations in the microenvironment of the lymph node which prevents the expression of cytotoxic effector cells.

Animals↗

Tuberculin anergy in clinically normal individuals. I. Lymphokine and lymphocyte transformation studies.

Tuberculin anergy was demonstrated in a number of clinically normal individuals who, on being immunized with Bacillus Calmette-Guérin (BCG), failed to demonstrate a positive Mantoux skin test. Lymphoid cells from these anergic subjects when stimulated with purified protein derivative (PPD) in vitro did not produce macrophage migration inhibition factor (MIF). Lymphocyte transformation studies demonstrated that while Mantoux-positive, non-BCG immunized Mantoux-negative and anergic individuals could all undergo blast cell transformation in the presence of PHA, only lymphoid cells from Mantoux-positive and a proportion of anergic people were capable of blast cell transformation when cultured with PPD. These results suggest that more than one mechanism may account for tuberculin anergy in clinically normal people operating at the level of lymphokine production and in some cases lymphocyte transformation.

Adult↗

Bursal and thymic reticular epithelial cells in the chicken: induction of B- and T-lymphocyte differentiation by in vitro monolayer cultures.

The role of chicken bursal and thymic reticular epithelial cells (REp cells) in the induction of B- and T-lymphocyte differentiation has been investigated using in vitro culture of these cells. Splenic adherent cells were used as controls. Precursor populations were obtained predominantly from embryonic bone marrow or spleen and incubated with REp cell monolayers for 72 hr. Differentiation was assessed by the expression of specific membrane antigens: chicken B lymphocyte-specific antigen (CBLA) and chicken T lymphocyte-specific antigen (CTLA). Bursal REp cells specifically induced approximately 20-30% of the embryonic cells to express CBLA but had no influence on CTLA expression. Conversely, CTLA, but not CBLA, was induced in approximately 20% of the embryonic cells by the thymic REp cell cultures. No effect on the expression of either antigen was observed with the splenic adherent cells. The induced cells correspond to the first stage of B- and T-lymphocyte differentiation found in vivo. The assay system also facilitated the study of shifts in precursor content of various organs with development. Whereas embryonic bone marrow of all ages studied contained both B- and T-lymphocyte precursors, these were not demonstrable in donors after hatching. Use of 12-day embryonic bursa and thymus suspensions as sources of stem cells indicated that precommitment to the B- or T-lymphocyte lineage is irreversible.

Aging↗

Bursal and thymic reticular epithelial cells in the chicken: preparation of in vitro monolayer cultures.

To study the nature of reticular epithelial (REp) cells and their role in the specific microenvironments of the chicken bursa and thymus, a method was developed for the in vitro culture of purified preparations of these cells. For comparison, similar cultures of splenic adherent cells were also performed. REp cell-rich bursa medullary follicles and mildly trypsinized thymic fragments were X-irradiated (850 rad) to eliminate remaining lymphocytes and transferred to culture flasks. In bursal cultures, after 2-4 days incubation the basement membrane (BM) encapsulating the follicles disrupted and the immediately underlying epithelial cells grew out as a monolayer. By 10 days, REp cells at the periphery developed cytoplasmic processes; occasionally these cells appeared to "bud-off" and grow as isolated dendritic cells. Thymic REp cells were generally slower to proliferate but formed a monolayer by 10-14 days. Splenic adherent cells developed extensive growth within 4 days. REp cells were distinguished from fibroblasts, when present, morphologically and by their limited phagocytic ability. The former were also periodic acid-Sciffs reagent (PAS)-positive and produced reticulin granules. Bursal REp cells were also positive for a gut-associated mucin, but this may have been bound in vivo prior to culture. Neither T nor B lymphocyte-specific antigens were detectable on the cultured REp cells or splenic adherent cells, but they were all rich in cytoplasmic actin. A major feature of REp cells to emerge in this study was the obvious presence of subpopulations of these cells, which raises important questions as to their exact nature and lineage. The accompanying paper details the ability of the bursal and thymic REp cell cultures to induce B-or T-lymphocyte differentiation, respectively, in vitro.

Animals↗

The migration of blood-borne lymphocytes into rat popliteal lymph nodes stimulated with xenogeneic red blood cells.

The recruitment of radiolabelled blood-borne lymphocytes into rat popliteal lymph nodes (PLN) was investigated following the injection of varying doses of chicken (CRBC) or sheep red blood cells (SRBC) into the hind foot pad. Within the dose range tested (10(5)-10(8) RBC) an increase in the dose of injected antigen resulted in elevated levels of lymphocyte recruitment into the draining popliteal lymph node. The kinetics of lymphocyte recruitment with the same dose of CRBC or SRBC was similar even though these red cells differ in size and are antigenically non-cross-reactive. While little is known of the mechanisms which control the rate of entry of blood-borne lymphocytes into antigen-stimulated lymph nodes, the extent of lymphocyte recruitment was shown to be directly related to the quantity of antigen injected.

Animals↗