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Colonic patches, the counterparts of Peyer's patches in the small intestine, are dynamically regulated lymphoid tissues in the colon that have an important role in defensing against microbial infections. Berberine is an isoquinoline alkaloid extracted from medicinal herbs including Rhizoma coptidis and has long been used for the treatment of infectious gastroenteritis, but its impact on the colonic lymphoid tissues (such as colonic patches) is unknown. In this study, we aimed to investigate whether berberine had any influences on the colonic patches in mice with bacterial infection. The results showed that oral berberine administration in bacterial infected mice substantially enhanced the hypertrophy of colonic patches, which usually possessed the features of two large B-cell follicles with a separate T-cell area. Moreover, the colonic patches displayed follicular dendritic cell networks within the B-cell follicles, indicative of mature colonic patches containing germinal centers. Concomitant with enlarged colonic patches, the cultured colon of infected mice treated with berberine secreted significantly higher levels of interleukin-1β (IL-1β), IL-6, TNF-α, and CCL-2, while NLRP3 inhibitor MMC950 or knockout of NLRP3 gene abrogated berberine-induced hypertrophy of colonic patches, suggesting the involvement of the NLRP3 signaling pathway in this process. Functionally, oral administration of berberine ameliorated liver inflammation and improved formed feces in the colon. Altogether, these results indicated that berberine was able to augment the hypertrophy of colonic patches in mice with bacterial infection probably through enhancing local inflammatory responses in the colon., (Copyright © 2020. Published by Elsevier B.V.)

Research into marsupial adaptive immunity during ontogeny has been hampered by the lack of antibodies that react to marsupial immunological cell populations. In this study, newly synthesised polyclonal antibodies to the T cell marker, CD8, have been developed and used to investigate the ontogeny and distribution of this T cell population in the tammar wallaby. Immunohistochemical analysis indicated that the distribution of the CD8 lymphocytes in the lymphoid tissues of tammar neonates during the first 144 days of pouch life was similar to that of the eutherian mammals. However, CD8α(+) lymphocytes were observed in the intestines of tammar neonates prior to their first appearance in the cervical thymus, an observation that has not been found in eutherians. A dual labelling immunohistochemical approach was used for the indirect demonstration of CD4 and enabled the simultaneous detection in the tammar wallaby tissues of the two major T-lymphocyte populations, CD4 and CD8 that are associated with adaptive immunity. As in eutherian mammals, CD4(+) cells were the predominant T cell lymphocyte subset observed in the spleen while in the nodal tissues, an age-related decrease in the CD4(+)/CD8(+) ratio was noted. These antibodies provide a new immunological tool to study the role of T cell subsets in marsupial immunity and disease pathogenesis studies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The development, structural diversification, and functional maturation of mammalian immunologic repertoire at mucosal surfaces and the systemic lymphoid tissue is a remarkably dynamic and continuous process, which begins in early fetal life and eventually culminates in variable degree of senescence or cellular death with advancing age. This brief overview will highlight the status of our current understanding of the ontogeny of mucosal immunologic response. The role of mucosal microflora and other environmental macromolecules in the regulation of mucosal immunity relative to the process of ageing will also be reviewed., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

The CD1 molecules are cell-surface proteins that bind and present foreign lipids and glycolipids to T cells in a manner similar to the MHC system. While the mammalian CD1 antigen presentation pathway is well characterized, little is known about CD1 in non-mammalian vertebrates. Previous studies have identified two CD1 homologues in the chicken. We developed a monoclonal antibody designated NL1-1.A1 specific for the chCD1-1 isoform and have used this to characterize CD1 expression in tissues and cells of normal adult and embryonic chickens. The chCD1-1 isoform is expressed on a high proportion of cells in the spleen and bursa. Cells in the spleen that stain for CD1 are also positive for IgM and consistent with identification of these as B cells. In the skin, chCD1-1 is expressed on cells with dendritic morphology along the dermal-epidermal boundary and in epidermal sheets consistent with chicken Langerhans cells. Staining of cells in the medullary region of the chicken thymus was also observed. The CD1 proteins in mammals traffic to intracellular compartments to acquire lipid antigens for subsequent presentation to T cells on the surface. Consistent with data from mammal CD1 proteins, chCD1-1 partially co-localized with a lysosomal marker in the myeloid cell line BM2. Taken together, these data support broad distribution of chCD1-1 in both lymphoid and non-lymphoid tissues of the chicken that is remarkably similar to the distribution of CD1 isoforms in mammals.

Although rabbits represent an important animal model, little is known about the lymphoid organ development in this species. In the present study, lymphocyte subsets in peripheral blood, spleen, mesenteric and popliteal lymph nodes in newborn and 2-, 4-, 6- and 8-week old and adult were characterized. Lymphocyte subsets were detected using flow cytometry and monoclonal antibodies against rabbit CD4, CD8, T-cell-specific antigen and cross-reactive antibody against B-cell antigen CD79alpha. In neonates, lower numbers of T cells were detected in both peripheral blood and spleen than in mesenteric lymph nodes. In comparison with other compartments, CD79alpha(+) cells prevailed in the spleen. Post-natal development was characterized by a decreased CD4(+)/CD8(+) ratio due to increasing frequency of CD8(+) lymphocytes in all organs but mesenteric lymph nodes, where it was due to decreased numbers of CD4(+) lymphocytes. Another significant feature was the increase of B cells in peripheral blood and mesenteric lymph nodes.

Secondary lymphoid organs provide the necessary microenvironment for the cooperation of antigen-specific T- and B-lymphocytes and antigen-presenting cells in order to initiate an efficient immune response. Remarkable progress in understanding of the mechanisms of lymphoid organogenesis was achieved due to the analysis of various gene-targeted mice. This review primarily focuses on the role of lymphotoxin (LT) in development, maturation and maintenance of secondary lymphoid organs.

Diversification of the primary antibody repertoire occurs in young rabbit appendix. As a prelude to molecular investigation of whether human appendix has a similar role, we compared the lymphoid morphology and distribution of common B- and T-cell subsets in frozen and/or paraffin-embedded normal appendix specimens at various ages. IgA, IgM and IgG staining patterns were similar in frozen human and rabbit appendices. The elongated follicles of the young human and rabbit appendices regressed with age to resemble Peyer's patches. Although similar in morphology to the bursa, human and rabbit appendix follicles differ in that they do not involute completely with age and contain significant numbers of germinal center (GC) T cells although the number is low early in life. If the human appendix functions as a primary lymphoid organ, it may occur during the first few months of age when the GC T-cell density is low.

The aim of the present report was to study in growing Wistar rats the development of immunocompetent cells in the bronchus-associated lymphoid tissue (BALT). We found at day 4 postpartum, a high number of TCRgamma/delta+ T cells and very few CD8alpha+, CD8beta+, CD5+, TCRalpha/beta+ T cells in BALT. The latter cells and CD4+ T cells increase with age. Even though T cells expressing TCRgamma/delta outnumber those expressing TCRalpha/beta early in development, until 45 days of age, alpha/beta+ predominate over gamma/delta+ T cells only in adult rats (60 days of age). Moreover, a predominance of suppressor/cytotoxic T cells over T-helper cells was found in 60 days old rats. Surprisingly, more CD8alpha+ than CD8beta+ T cells in BALT are observed. The number of IgA+ B and CD4+ T cells found in the BALT increases with age. The early appearance - 4 days of age - of all T-cell phenotypes in BALT especially of gamma/delta+ T cells may imply a benefit to respond to inhaled antigen soon after birth.

At birth the tissues of marsupial immune system are underdeveloped. The young animal is not immunocompetent. Histological and immunohistochemical studies of pouch young epithelial tissues provide a clear picture of tissue development but the timing of onset of immunocompetence awaits definition. The survival of the neonatal marsupial in a microbially rich environment is dependent on maternal strategies, including immunoglobulin transfer via milk and, in some species, prenatally via the yolk sac placenta. It is also likely that pouch secretions play a role. This review summarizes our current knowledge of the pathway of immunological development in marsupials and the protection and threats afforded by the pouch environment.

B cell and immunoglobulin (Ig) heterogeneity was demonstrated in carp, Cyprinus carpio L., using two monoclonal antibodies (MAbs; WC14, WCI12) produced against carp serum Ig. Immunochemical results showed that both WCI4 and WCI12 react with a protein determinant on the heavy chain of Ig (relative molecular mass approximately 70,000). Immunofluorescence microscopic and flow cytometric analyses of lymphoid cells suggest three distinct subpopulations of B cells and plasma cells: WCI4+12- cells, WCI4-12+ cells, and WCI4+12+ cells. WCI4-12+ and WCI4+12+ anti-DNP antibody-secreting cells were also demonstrated with the ELISPOT assay in pronephros and spleen cell suspensions from primary immunised carp. Affinity chromatography of carp serum and sequential immunoprecipitation of 125I-labelled peripheral blood leucocyte (PBL) membrane proteins only indicated the presence of two antigenically different Ig molecules, i.e., WCI4-12+ and WCI4+12+ molecules. WCI4+12- molecules could not be detected by affinity chromatography or immunoprecipitation. During ontogeny, a shift in percentages of WCI4+12- and WCI4-12+ cells was found in the spleen and the pronephros. In these organs, WCI4+12- cells formed the majority of B cells at 2 weeks of age, but the percentages of this cell type decreased during ontogeny. On the other hand, the percentages of WCI4-12+ cells increased during development, and these cells became the major population of B cells from 13 weeks onward. The proportion of WCI4+12+ cells remained almost constant during ontogeny. The distribution of B cell subpopulations in blood was more or less stable at all ages. The functional significance of Ig heterogeneity in fish and in particular carp is discussed.

Previous studies on the morphology of the lymphomyeloid tissues in the dogfish, Scyliorhinus canicula, have been confined to adults. This study was restricted to the structure and functioning of the developing immune system in embryonic and post-hatch dogfish. A major feature of the developing immune system in S. canicula, is the succession of haemopoietic/lymphoid tissues. The liver is the first tissue to contain immunoglobulin positive cells at 2 months, followed by the interstitial kidney at 3 months. The thymus, spleen, and Leydig organ appears at 4 months while the epigonal and gut-associated lymphomyeloid tissues are the last tissues to differentiate. The haemopoietic/lymphoid nature of the kidney and thymus disappear at post-hatch and the other lymphomyeloid tissues persist through adult life. By the time of egg case splitting (ca. 6 months), when embryos receive massive exposure to water-borne antigens, the structural development of most of the lymphomyeloid tissues is well advanced.

We have studied the ontogenic development of immunoglobulin M (IgM) and of IgM-bearing cells in the rainbow trout, Oncorhynchus mykiss. Lymphocytes showing cytoplasmic IgM were first observed in embryos at 12 days before hatch (14 degrees C). At this stage, no cells positive for surface IgM were present. Lymphocytes bearing surface IgM were observed at 8 days before hatch (14 degrees C). Unfertilized trout eggs contained detectable amounts of IgM (11.2 +/- 2.6 micrograms/g of egg weight), indicating that transfer of IgM from mother to embryo can occur in salmonids. The levels of IgM from whole fish increase slowly after the appearance of intraembryonic cells that express surface IgM. The amount of IgM/g of tissue peaks around hatch, but this parameter shows lower values up to 2 months after hatch.

Aggregates of lymphocytes were demonstrated from 70 days gestation (term 150 days in sheep) in the proximal colon and rectum. Immunoperoxidase staining for 5'-bromo-2'-deoxyuridine incorporation and IgM, indicated that the lymphocyte population of lymphoid follicles in fetal sheep colon was actively dividing and surface IgM positive. Enzyme histochemistry for 5'-nucleotidase showed that the lymphocytes developed in a meshwork of positive reticular cells, suggestive of developing follicles. Follicle aggregates were distributed in a characteristic pattern in lambs, with major accumulations in the ascending colon and in the rectum. In adult sheep a partial atrophy of follicle aggregates was observed. The microscopic structure of large intestinal aggregates showed similarities to the jejunal Peyer's patch (PP), with broad follicles containing a prominent corona and wide interfollicular areas in older lambs. The apparent deep penetration of crypts into the lymphoid tissue proper, which is a frequently reported phenomenon for colon follicles, was dependent on the contractile state of the mucosa, as judged from its absence in specimens where the intestinal wall had been stretched before fixation.

Marijuana components modulate a variety of immune response parameters. The cannabinoids delta 9-tetrahydrocannabinol (THC) and 11-hydroxy-tetrahydrocannabinol (11 OH-THC) are known to depress the in vitro proliferative response of murine lymphoid cells to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). In the present report the effects of THC and 11 OH-THC on adult thymus and spleen cells were compared to effects on lymphoid cells of those organs from juvenile mice at various ages. The results demonstrate differences in susceptibility to cannabinoid-induced suppression by lymphoid cells from different organs and different age mice. In adults, thymus cells were suppressed more readily than spleen cells. Splenocytes from mice under 2 weeks old were suppressed much more readily than those from older mice. Cell populations from organs with higher proportions of L3T4+/Lyt2- cells were more difficult to suppress. The possible mechanisms involved and directions for future work are discussed.

The development of bronchus associated lymphoid tissue was studied in normal rats, in serial sections, using both routine histological techniques and the two-step immuno-peroxidase method on cryostat sections for demonstration of T lymphocytes, IgM-, IgG- and IgA-bearing B lymphocytes and plasma cells, respectively. BALT first appears 4 days postpartum (p.p.) as a condensation of reticulum cells near a lymph vessel, between the main bronchus and the accompanying artery. Only a few lymphocytes are present at first. Vascularisation is considerable 8 days p.p. and includes high endothelial venules. Leucocytes are seen in transit in both blood- and lymph vessel walls. Lymphocytes populate the area under the epithelium from about 2 weeks p.p. A few IgM, IgG- and IgA-bearing B cells are already present at 4 days, and rapidly increase in numbers; T cells usually appear at day 8. Discrete T- and B-cell areas do not appear until 4 weeks and are only observed regularly after 12 weeks, when secondary follicles appear. BALT starts development at a similar time to other peripheral lymphoid organs but apparently achieves immunological activity later. It is concluded that antigens probably play an important part in organising BALT.

The ontogenic development of the bursa-dependent lymphoid tissue in the chicken has been studied using rabbit antisera specific for B lymphocyte sub-populations and two elements of the bursal microenvironment. The antigens investigated were: the chicken B lymphocyte antigen ( CBLA ); mature B lymphocyte antigen ( CMBLA ); a foetal-associated antigen ( CFAA ) present on embryonic haemopoietic cells and adult bone marrow and bursa cells; immunoglobulin (Ig) and IgG; a bursa-specific cortical reticulin fibre antigen ( CBRFA ); a gut-associated mucin antigen ( CGAMA ) present on bursal medullary reticular epithelial (REp) cells. The development of suspected precursor cells was examined using a rabbit antiserum specific for foetal spleen cells. The major finding was the interrelationship between developing B cells and the bursal microenvironment. The first CBLA - and CFAA -positive cells were detected in the bursa at day 8 of incubation but their precise localization was difficult to assess. In 12-15 day embryos, both these cells were found predominantly in the tunica-propria in close proximity to cells bearing the reticulin fibre antigen CBRFA . This close association between CBLA -, CFAA - and CBRFA determinants represents the earliest stages of B cell differentiation and mimics that found in the adult bursa cortex. By day 18, the majority of bursa cells expressed CBLA and Ig and were localized in the developing medullary follicles, the REp cells of which were CGAMA -positive, demonstrating a very early interaction between intestinal tract contents, bursal REp cells and B cell maturation. Around hatching some bursa cells showed a marked increase in the membrane expression of CBLA and Ig, and the simultaneous expression of CMBLA and IgG. These cells were present in medullary follicles; CBRFA was present on cortical reticulin fibres which provided a supporting framework for the more immature CFAA -positive cells.

The effect of an evolutionary adaptation to low environmental temperature on the development of lymphoid organs was examined in Harpagifer antarcticus from Signy Island (South Orkney Islands; 60 degrees 43'S, 45 degrees 38'W). Thymus, pronephric kidney and spleen were typical, both in position and structural development, of those observed in warmer-water teleosts. The pronephric kidney was the first organ to be infiltrated by leucocytes, at 1 h post-hatch, though the infiltration of the thymic epithelia and the development of the splenic anlage were not observed until 4 weeks post-hatch. Full development of the lymphoid organs was not achieved until the juvenile stage. Although an increased infiltration of the thymus, by subepithelial connective tissues and epithelial mucous cells, occurred in the juvenile and adult stages, there was no evidence of an advanced stage of thymic regression or involution in the adult Harpagifer. Thus, a suppressive influence of the low temperature environment, on the onset and degree of lymphoid organ development and thymic involution, was indicated in this species.

In lymphoid tissues of mice, there exist LPS-reactive B cells which can differentiate to IgM-secreting plaque-forming cells (IgM-PFC) and PFC secreting antibodies against bromelain-treated mouse erythrocytes (BrMRBC) by LPS activation. In this study, four groups of LPS-reactive B cells in spleen, peritoneal cavity and mesenteric lymph nodes from 2- and 10-week-old mice were compared and enumerated as precursors of IgM-PFC and anti-BrMRBC PFC on days 1 and 2 after LPS activation in quantitative culture conditions. The induction of each of four PFC responses in peritoneal cells was sensitive to LPS and anti-mouse IgM antibodies as much as the induction of the respective PFC response in spleen cells. The ratios of four groups of PFC to each other were different among three tissues and between two ages. These findings support the view that the four groups of LPS-reactive B cells in each tissue are mostly in distinct subpopulations of B cells from each other, and the respective groups of different lymphoid tissues at different ages belong to the same subpopulation.

The ultrastructure of the lympho-hemopoietic tissue of the typhlosole and opisthonephros of larval Petromyzon marinus was studied throughout the life cycle. In both locations, lympho-hemopoietic tissue houses a connective tissue stroma and is irrigated by a system of enlarged blood sinuses lined by a continuous endothelium. The typhlosolar and opisthonephric lympho-hemopoietic tissue consists of mature and developing blood cells belonging to erythroid, lymphoid, monocytic and granulocytic lineages. During metamorphosis there is a total degeneration of the larval opisthonephros and a full transformation of the digestive apparatus. As a consequence of these modifications the typhlosole and the opisthonephros lose their hemopoietic capacity. These changes are discussed in view of the role played in them by the so-called "hemopoietic inductive microenvironments", principally the stroma supporting apparatus and vascularization pattern.

Monospecific antiserum against chick duodenal vitamin D-dependent calcium-binding protein (D-CaBP) was used to localize this protein by the peroxidase-antiperoxidase method (PAP) in the thymus, spleen and bursa of Fabricius of normal growing chicks in 20 day old embryos; in normal growing chicks at 1, 2, 3, 4 and 6 weeks of age in chicks fed a rachitogenic diet for 4 weeks. In the normal chick thymus, D-CaBP was localized throughout the cytoplasm and in the nucleus of cortical epithelial reticular cells (ERC) and in Hassal's corpuscles of the medulla. In the normal spleen reticular cells of the marginal zones showed dense deposition of reaction product in the nucleus and throughout the cytoplasm. In the bursa of Fabricius, only a few scattered cells in the medulla showed some staining. Wide variation was encountered in D-CaBP staining in the thymus and spleen of 4 week old chicks from different broods. In 4 week old rachitic chicks, staining in the thymus and in the spleen was generally reduced in intensity and occasionally was entirely absent. The presence of D-CaBP in some reticular cells of the thymus, spleen and bursa of Fabricius, identifies these lymphoid organs as vitamin D3 targets. Thus, 1,25(OH)2D3 may have an important role in some aspects of the immune defence mechanism.