Fetal and early postnatal development of the porcine tonsils of the soft palate.

Tonsils are mucosa-associated lymphoid tissues located at the openings of the gastrointestinal and respiratory tracts, which play a key role in the surveillance of inhaled or ingested pathogens and can concurrently be reservoirs of infectious agents. Therefore, tonsils are important for the immunology and hygiene management of domestic animals, including pigs. However, the process of their fetal developmental has been poorly described, at least in part, because rodents lack tonsils. Therefore, we performed a histological analysis of porcine tonsils of the soft palate from 60 to 100 days of gestation (DG) and from 2 to 14 days post partum (DP). This analysis showed that lymphoid aggregations first appear at DG65, gradually develop during the fetal stage, and expand after birth. In addition, the mRNA expression of chemokine genes involved in lymphoid aggregation and localization was analyzed. CCL19 expression showed the most marked increase and a sharp peak after birth. CCL21 expression changed moderately but showed an interesting bimodal pattern. CXCL13 expression steadily increased throughout the study period. Thus, we demonstrated the mRNA expression of chemokine characteristically changed accompanying tonsillar development.

Developmental anatomy of the tonsil and its implications for intracapsular tonsillectomy.

OBJECTIVE: To describe the developmental anatomy of the human tonsil from the embryonic period through adulthood and to use this information to define the applicability of intracapsular tonsillectomy in the management of disease. DESIGN: Descriptive-anatomic. SUBJECTS: (1) Normal embryos and fetuses from two archival collections, (2) children with adenotonsillar hypertrophy and (3) adult autopsy material. RESULTS: The second branchial pouch is visible in the 4th post-conceptional week and demonstrates canalization and branching in the 8th week. Lymphoid infiltration of the lamina propria occurs in the seventh month of intrauterine life. Primary follicles form late in gestation, but germinal center stimulation does not occur until shortly after birth. During the first year of life, there is rapid proliferation of lymphoid elements and formation of active germinal centers. During the phase of maximum tonsillar hyperplasia, the lymphoid elements proliferate rapidly, increasing tonsillar bulk. In senescence, there is involution of the lymphoid elements and proliferation of fibrous tissue in the capsule and trabeculae. The overall bulk of the tonsil is much decreased. CONCLUSIONS: There is an intimate relationship between the epithelial and lymphoid components of the tonsil which continues through life. To adequately control upper airway obstruction of tonsillar origin and recurrent tonsillar infection in childhood, total or near total intracapsular tonsillectomy likely will prove the minimum acceptable surgical intervention. Changes in tonsillar anatomy after the first decade may alter operative choice in older patients.

Histological studies on the ontogeny of bovine palatine and pharyngeal tonsil: germinal center formation, IgG, and IgA mRNA expression.

The development and distribution of lymphocyte subsets in calf palatine and pharyngeal tonsil were examined. During prenatal development, B cells were distributed in the subepithelial area, and T cells and MHC class II(+) cells were found in the deep layer of B-cell area, respectively, in both tonsils. At neonatal stage, lymphoid follicle containing a few CD4(+) cells have been formed in both tonsils. IgG(+) and IgA(+) cells were found in the parafollicular and epithelial area. At 3 months old, many germinal centers were recognized in both tonsils. CD4(+) cells and IgG mRNA expression were detected in light zone of germinal centers. Many IgG, and IgA mRNA expressions also could be detected in the parafollicular and subepithelial area of both tonsils. The data suggest that both tonsils have an important role of local immune defense against invading antigen after birth. The comparison of the histological characteristics of tonsil and Peyer's patch during ontogeny is also discussed.

Developmental relation between palatine tonsils and kidney.

The evolutionary changes of the immune process in the whole line of representatives of the organisms were followed. The immune organs responsible for processing the antigens evolved from the derivatives of coelomic lining over the gut folds to the immune organs developed in the gill region of the digestive tract. Among them the tonsils have to be considered as a very modern evolutionary immune organ. They develop also as the latest in ontogeny even though their primordium contributes very early to the IgA production. The results of the host-antigen reactions have to be eliminated by the excretory organs, which are in invertebrates represented by body poruses and various types of simple segmentally arranged nephridia which are in contact with the gills. These nephridia have evolved in lower vertebrates in pronephros, further in mesonephros and finally in kidneys with filtrating nephrons. In case of defective elimination, the more voluminous immunocomplexes can form the subendothelial or mesangial deposits.

Morphological study of development and functional activity of palatine tonsils in embryonic age.

Palatine tonsils play an important role in the development of the immune system, being the first organ in the lymph system which analyses and reacts to antigenic stimulation. In this study, the peritonsillar area of Waldeyer's ring was investigated in 88 normal human embryos which were examined histologically and immunohistochemically. The progressive development of palatine tonsils during embryonic life is discussed. The first appearance of tonsils is in about the 14th-15th week followed by a parallel development of B- and T-cell regions which accounts for the high incidence of non mucosa-associated lymphoid tissue lymphomas among all tonsillar lymphomas and the higher incidence of T-cell-lymphomas, in comparison to the mucosa-associated lymphoid tissue of the digestive system. The way in which the human body develops the palatine tonsils quickly and prepares them to react to the first antigenic stimulation, are discussed.

The sequence of reticularisation of epithelium of human palatine tonsil: scanning electron microscopic study.

The changes appearing during the development of the human palatine tonsil, both in the surface and in the tonsillar crypt epithelium, were studied from samples of the 16th to 40th prenatal weeks. From the 18th week, we observed areas of mesh-like epithelium in an originally homogeneous stratified squamous epithelium, i.e. the reticularisation began in the tonsillar crypt epithelium. The important role of the epithelial basal membrane in this process is discussed. The diffuse spongy-form type of reticularisation as well as the formation of the intraepithelial passages between the epithelial columns are described. The lymphoid cells and macrophages migrated through these microcrypts and they were frequently seen near the crypt epithelial micropores on the surface of the reticularised epithelium.

Langerhans cells in the epithelium of the human palatine tonsil during the prenatal development.

In the 18th week of the prenatal life large light cells of mesenchymal origin enter the crypt epithelium of the palatine tonsil to start its reticularisation. They are considered precursors of Langerhans cells.

Prenatal and postnatal changes of the human tonsillar crypt epithelium.

The tonsillar crypt shows infiltration of lymphoid cells in the epithelium and the highly porous or discontinuous basement membrane. However, the relationship between developmental period and the significance of the disrupted epithelial basement membrane and infiltration of lymphoid cells within the human tonsillar crypt epithelium is still obscure. The present study was designed to determine the prenatal and postnatal changes of the human tonsillar crypt epithelium in 4 fetuses, 4 neonates, 1 infant, 5 children and 4 adults using immunohistochemical stains with polyclonal anti-laminin and monoclonal anti-type IV collagen antibody, and transmission electron microscope. The tonsillar crypt epithelium from all fetuses and neonates showed infiltration of many lymphoid cells and an intact basement membrane by immunohistochemistry. Transmission electron microscope revealed pores in the basement membrane through which lymphocytes passed. Tonsils from a 4-month-old infant showed focal disruption of the basement membrane by immunohistochemical staining. The tonsils from children and adults showed that there was massive disruption of the basement membrane with lymphoid cell infiltration in the tonsillar crypt epithelium by immunohistochemical staining and transmission electron microscopy. In conclusion, lymphoid cell infiltration and holes of the basement membrane of the tonsillar crypt epithelium are normal developmental findings, whereas disruption of the basement membrane of the tonsillar crypt epithelium is pathological.

Development and immunophenotyping of the pharyngeal tonsil (adenoid) in cattle.

Immunoperoxidase staining and electron and light microscopy were used to characterize the development of the pharyngeal tonsil in 98 cattle aged between 30 days of gestation and 12 years. The rugae of the pharyngeal tonsil were poorly formed before 95 days of gestation. Microvillous (M) cells associated with intra-epithelial leucocytes (lympho-epithelium) were scattered among ciliated and goblet cells covering most of the surface in post-natal animals. Intra-epithelial leucocytes were rare in fetuses, but ciliated and M cells could be distinguished. Leucocytes of the lamina propria started to accumulate at approximately 120 days of gestation. A loose accumulation of mononuclear cells progressed into a B-cell rich upper and T-cell rich lower layer, with typical lymphoid tissue organization in post-natal animals and lymphoid involution in aged cattle. Primary lymphoid follicles formed at 5 months of gestation, but germinal centres did not form until 2 to 4 weeks after birth. Except for null cells, the relative number of cells staining for each leucocyte phenotype or MHC class II antigen increased with age, especially during the neonatal period. The early development, strategic location and specialized structure of the pharyngeal tonsil suggest an important role in modulating inhaled antigens in cattle. Fetal and neonatal calves had minimal lymphoid tissue priming, as indicated by lack of secondary follicles, low MHC class II expression and few intra-epithelial leucocytes. The phenotypic differences may be relevant to the increased susceptibility of calves to infectious diseases shortly after birth.

Immunohistochemical studies on ontogeny of bovine lymphoid tissues.

Developing lymphoid tissues of bovine fetuses ranging from 70 to 270 days of fetal age were examined by histological and immunohistochemical procedures. In the peripheral blood, surface membrane immunoglobulin bearing cells (B-lymphocytes) and sheep red blood cell rosette forming cells (T-lymphocytes) had already appeared by 70 days of fetal age. In the lymph nodes intracytoplasmic IgM positive cells appeared at 90 days of fetal age. The cells positive for IgG appeared at 150 days of fetal age and IgA positive cells appeared at 180 days of fetal age. The spleen contained intracytoplasmic immunoglobulin positive cells at almost the same time as those in the lymph nodes. In the ileocecal region, IgM positive cells and IgG positive cells were present at 180 days of fetal age and IgA positive cells were present at 210 days of fetal age. The tonsils contained IgM positive cells and IgG positive cells at 240 days of fetal age. In the thymus, terminal deoxynucleotidyl transferase positive cells appeared at 90 days of fetal age.

[Embryogenesis of the human tongue]. / Embriogenez iazyka cheloveka.

Developmental peculiarities of the tongue as a whole and its main structural elements (muscles, membranes, glands, lingual tonsil) have been studied in 120 human embryos and fetuses 5-week-old--9-month-old. Transmissive electron microscopy, electron histochemistry (for estimation of 5'-nucleotidase activity), staining of semithin slices with toluidine blue and aniline++ pink have been applied. Problems on migration of myogenic elements in the developing tongue have been discussed. Ultrastructure of gustatory bulbs of the human fetus tongues has been investigated. A complete formation of the tongue takes place by the 8th-9th months of the prenatal development.

High-endothelial postcapillary venules in the fetal palatine tonsil.

Postcapillary high-endothelial venules were studied in the palatine tonsils of 48 fetuses and 19 children aged from the 10th gestational week to the end of the first year of life. Light microscopy was used to study their localization and distribution in extrafollicular lymphatic tissue in histological sections. The anlage of the venules was detected as early as in the 14th gestational week. Transmission electron microscopy was used to study the ultrastructure of high-endothelial cells and adjacent connective tissue structures of the venular wall.

Lymphocyte migration through the wall of postcapillary venules in the fetal development of human palatine tonsil.

Migration of lymphoid cells through the wall of postcapillary venules was studied in the palatine tonsils of five human fetuses. The direction of the migration of lymphoid cells as observed in the early fetal period seems to be mostly from the lumen of the venule into the tonsillar parenchyma. Migration starts with the adherence of the lymphocyte by means of a cytoplasmic projection to the cellular surface of a high-endothelial cell. The projection slips between two neighbouring endothelial cells and extends to settle on the basal membrane of the endothelium. After the disruption of the basal lamina the lymphocyte migrates into the subendothelial connective tissue and further into the extrafollicular tissue of the tonsil. The possibility of transendothelial migration of lymphoid cell through the wall of the postcapillary venule is discussed. Even in case, when the lymphocyte appears to be completely enveloped by the cytoplasm of the endothelial cell it may be in reality the intercellular migration--the lymphoid cell is pressed into the cytoplasm of an endothelial cell.

The ontogeny of human lymphocyte recirculation: high endothelial cell antigen (HECA-452) and CD44 homing receptor expression in the development of the immune system.

In the present report we have studied the expression of a lymphocyte homing receptor, the CD44 antigen, and of HECA-452, a high endothelial-specific antigen, during the development of the human immune system. We found that prothymocyte immigrants of the thymus already expressed the CD44 antigen. Similarly, the first peripheral T lymphocytes in fetal lymph nodes, tonsils and gut-associated lymphoid tissue were also CD44+. Cortical thymocytes and germinal center cells were CD44-. CD44 antigen expression was, thus, not limited to mature recirculating lymphocytes. This suggests that CD44 may not only be involved in recirculation of mature lymphocytes but also in the migration of prothymocytes to their site of maturation, i.e. the thymus. High endothelial venules (HEV) were not demonstrable at the early onset of lymphocyte immigration into the developing lymphoid organs. However, when large-scale influx of lymphocytes occurred, it paralleled HEV development. HECA-452 antigen expression preceded the morphological transformation of endothelium into a HEV phenotype. Expression of this antigen therefore, independently reflected the specialized nature of high endothelium. In a patient with complete DiGeorge's syndrome normal HEV developed, indicating that the presence of T lymphocytes is not a requirement for HEV development. Interestingly, a subpopulation of venules located in the thymic medulla near the cortico-medullary junction expressed the HECA-452 antigen. These vessels, which had flat or intermediately high endothelium, are probably involved in lymphocyte migration to the thymus.

Development and functional anatomy of the human tonsilla palatina.

The tonsilla palatina, belonging to the gut-associated lymphoepithelial organs (GALT), shows close morphological and functional correlation between the lymphatic tissue of mesenchymal origin and the endodermal epithelium of the second pharyngeal pouch. During the 4th fetal month epithelial crypts grow down into the connective tissue and are infiltrated by non-epithelial cells. In the underlying lymphoid tissue the first primary follicles with precursors of follicular dendritic reticulum cells can be localized already in the 14th fetal week post conceptionem (p.c.). The parafollicular areas develop into T-cell regions. Interdigitating cells in these regions as well as within the crypt epithelium express the HLA-DR antigen. They were frequently found in close contact with T-helper cells. This fact is discussed as an indication of the tonsillar crypt epithelium partly serving as T-cell region. But also B-cells and macrophages invade the crypt epithelium in great numbers with a distinctly different distribution. Natural killer (NK) cells (Leu-7-positive) are localized within the crypt epithelium. Small Leu-7-positive lymphocytes (probably precursors) have been found to be numerous in the germinal centers. The interaction of specific stationary cells in the T-cell and B-cell regions is obviously an important factor for the maturation of different subpopulations of immunocompetent lymphoid cells.