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PubMed2000

Conjunctiva-associated lymphoid tissue in the human eye.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) represents a part of the immune system located at mucosal surfaces. Its presence in the human eye is the point in question in the current study. Its occurrence, components, topography, and probable functional significance in the human conjunctiva and lacrimal drainage system were investigated. METHODS: Fifty-three complete conjunctival sacs were obtained from cadaveric eyes, prepared as flat wholemounts, stained, optically cleared, observed in total thickness, and sectioned for light microscopic histology, immunohistochemistry, and electron microscopy. Eight lacrimal sacs and adhering canaliculi were prepared accordingly. RESULTS: Lymphoid tissue was mainly observed in the palpebral conjunctiva, more pronounced in the upper than in the lower lid. It occurred in different forms: 1) In all specimens, diffuse lymphoid tissue of lymphocytes and plasma cells, most of which were IgA positive, formed a thin layer in the lamina propria. The overlying epithelium produced secretory component. 2) In approximately three fifths of the conjunctival sacs, organized follicular accumulations were embedded in this layer. They had a lenticular shape, were composed of B lymphocytes, and were apically covered by lymphoepithelium. 3) Both types could be associated with the conjunctival crypts. Lymphoid tissue with similar characteristics, including secondary follicles, was also observed inside the lacrimal drainage system. High endothelial venules were present in all types of lymphoid tissue. CONCLUSIONS: Human conjunctiva and lacrimal drainage system show an associated lymphoid tissue (suggesting the term conjunctiva-associated lymphoid tissue [CALT]) that contains all components necessary for a complete immune response. Expression of immunoglobulins and secretory component indicates that the conjunctiva belongs to the secretory immune system.

Aged↗
PubMed1975

In vitro synthesis of some complement components (C1q, C3 and C4) by lymphoid tissues and circulating leucocytes in man.

Human lymphoid tissues and peripheral blood leucocytes and monocytes were studies with respect to the synthesis of complement components (C1q, C3 and C4) using an in vitro culture technique. All of the lymphoid tissues investigated (bone marrow, thymus, lymph node, spleen, tonsil, adenoid) synthesize complement components in different patterns. C3 was produced by all lymphoid tissues except the spleen, which was the only lymphoid tissue in which C4 production was regularly found. C1q synthesis was demonstrated in the spleen and adenoid cultures, and occasionally also in those of lymph node tissue. Lymphocytes in peripheral blood from normal individuals and in thoracic duct lymph, and also from patients suffering from chronic lymphatic leukaemia, do not synthesize any of these complement components. Peripheral blood leucocyte samples from normal individuals, containing 60 per cent lymphocytes and 40 per cent monocytes, do synthesize C3, however. Separation of the monocytes from these samples showed that it was in these cells that the synthesis of C3 occurred. Production of C3 by mononuclear phagocytes is also supported by the finding that peripheral blood leucocytes from patients suffering from acute monocytic leukaemia synthesize C3. C1q and C4 synthesis could not be demonstrated in any of the cultures of circulating leucocytes.

Adenoids↗
PubMed1976

Distribution of T and B lymphocytes in lymphoid tissue of infants and children.

Normal lymphoid tissue from children undergoing elective surgery was examined for T and B lymphocyte distribution. Although established for peripheral blood and bone marrow, T and B lymphocyte distributions have not been previously reported for lymph nodes, appendix, thymus, and spleen tissues in children. Thymus-dependent T cells were determined by the sheep erythrocyte rosette technique, and thymus-independent B cells were determined by the fluorescent labeling of surface immunoglobulins A (IgA), G (IgG), and M (IgM). Fifty percent of lymph node cells were either T or B cells; 65% of these cells were T lymphocytes, whereas 58% of B cells were of the IgM subclass. Less than half of the appendix cells were either T or B cells; 47% of these were T lymphocytes, and the remainder B lymphocytes had subclass distribution similar to that of lymph nodes but different from peripheral blood and bone marrow where B cells bearing IgG predominate. Thymus tissue contained 43% T cells and less than 1% B cells, but the spleen was composed largely of B cells, predominantly of the IgM type. Lymphoid tissue from nine children with either inflammatory or neoplastic diseases were studied and included for contrast. This paper establishes relative distribution values for T and B lymphocytes in normal lymphoid tissue and points out the potential use of this technique to quantitate deviations from normal in certain inflammatory and neoplastic diseases.

Adolescent↗
PubMed2006

Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid tissue.

The M cells of nasopharyngeal lymphoid tissue (NALT) have been considered to play an important role for vaccine delivery systems in humans. A number of investigations have reported particle uptake data in NALT of rodents. However, there have been no reports indicating any involvement of the nasopharyngeal lymphoid tissue in human vaccination. In the present study, we investigated whether the epithelium of human adenoid tissues might incorporate fluorescent microparticles using electron and fluorescent microscopy. The dissected adenoid tissues were incubated with various sizes and concentrations of fluorescent microparticles for 120 min at 37 degrees C. Furthermore, the effect of surface coatings of microparticles with cations on the uptake into the epithelium of adenoid tissues was investigated. Transmission electron microscopy revealed that microparticles were taken up by the M cells of human nasopharyngeal lymphoid tissues. The NALT-M cells showed greater uptake of the smallest particles, 0.2 microm in diameter, than those of 0.5, 1.0, or 2.0 microm diameter. It was also revealed that surface coatings with poly-L: -lysin or chitosan resulted in efficient uptake into the NALT. These results indicate that nasal administration of antigenic microparticles, which were coated with cationic materials, probably leads to a useful method of transnasal vaccination against respiratory and intestinal infections in humans.

Adenoids↗
PubMed1989

Lymphatics and lymphoid tissue of the fallopian tube: immunoelectronmicroscopic study.

Lymphoid tissue of the human fallopian tube consists of follicles, lymphoepithelium, and lymphatic and blood capillaries and is located consistently in the interstitial part of the human fallopian tube. Using an immunoelectronmicroscopic technique, we have elucidated the ultrastructure of the lymphoid tissue of the human fallopian tube and the fine distribution and ultrastructure of the lymphatics associated with the rabbit fallopian tube. Lymphatic capillaries arise in the lamina propria mucosa and the periphery of follicles, where they are sparsely distributed, run through the muscular layer, and form a dense network in the subserosa. Characteristic features of the ultrastructure are aggregations of smooth muscle cells, alternating areas of densely and sparsely distributed collagen fibers, and unmyelinated nerve fibers beneath the lymphatic endothelium. Immunoelectronmicroscopic analysis has demonstrated an obvious difference in the distribution of T- and B-lymphocytes in the lymphoid tissue of the human fallopian tube. Many T-lymphocytes are present in the follicles and epithelium, but B-lymphocytes are either absent or rarely found. T-lymphocytes sometimes infiltrate into the basal lamina of the epithelium lying in close contact with the follicles. We conclude that the lymphoid tissue is constantly located in the interstitial part of the human fallopian tube and that intraepithelial lymphocytes, mainly T-lymphocytes, migrate via the basal lamina of the epithelium from follicles. Lymphatic capillaries in the fallopian tube may be the main migratory route of intraepithelial lymphocytes. The intraepithelial lymphocytes and epithelial cells of the fallopian tube have attracted considerable interest as a result of immunological studies of the recognition of spermatozoal antigens and the fertilized ovum.(ABSTRACT TRUNCATED AT 250 WORDS)

Fallopian Tubes↗
PubMed1996

Suppression of HIV replication by lymphoid tissue CD8+ cells correlates with the clinical state of HIV-infected individuals.

Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results add further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Lymphoid tissue in the kidney of the musk shrew, Suncus murinus.

We describe a lymphoid tissue in the kidney of the musk shrew, Suncus murinus. An anatomically well organised lymphoid tissue, resembling the mucosa-associated lymphoid tissue, is associated with the epithelium of the renal pelvis and the ureter, respectively. Lymphoid tissue distributed along the arcuate artery and arcuate vein is not structurally organised in centre and periphery. This tissue type is most prominently developed between blood vessels. Immunocytochemistry revealed S-100-immunoreactive dendritic cells in both, structurally organised and structurally non-organised lymphoid tissues. The lymphoid tissue is innervated by neurofilament-immunoreactive nerve fibres. Some of these nerve fibres are associated with glial fibrillary acidic protein-immunoreactive structures, indicating that they are myelinated.

Animals↗
PubMed1999

Sinonasal mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) is a specialized form of lymphoid tissue that may be acquired at sites in response to chronic inflammation. Most low-grade, B-cell, non-Hodgkin lymphomas that occur at extranodal sites derive from acquired MALT. Confusing and overlapping terms have been used to describe these lymphomas, but immunohistochemical advances now allow more precise subtyping. Our review of the literature yielded only 2 previous reports of sinonasal MALT-derived lymphoma, and we report an additional case in a patient with a history of chronic sinusitis. Current developmental theories of MALT-derived lymphomas are discussed. In addition, we review the clinical, histologic, and immunophenotypic features of MALT-derived lymphomas.

Chronic Disease↗
PubMed1993

Immune events in lymphoid tissues during experimental glomerulonephritis.

To investigate immune events within lymphoid tissues and their role in relation to glomerular disease, systemic lymphoid tissues from rats with accelerated experimental anti-GBM glomerulonephritis or with primed serum sickness glomerulopathy were studied. Following disease induction, changes in leukocytic populations within lymphoid tissues were analysed over a 28 day time course by immunoperoxidase labelling with monoclonal antibodies. In anti-GBM glomerulonephritis there was rapid and severe renal injury and pulmonary hemorrhage (Good-pasture's syndrome). In these rats, antigen (rabbit IgG) was deposited on the GBM and within germinal centres of lymphoid tissues. From day 3 onwards, there was a significant increase in the number of T cells, presumably CD4+ T helper cells, present within enlarged germinal centres of kidney draining lymph nodes, axillary lymph nodes and spleen (p < 0.05) which peaked at day 14 (up to 28% of total cells) when there was intense deposition of rat IgG and C3 on the GBM. Similarly, increased numbers of ED1+ macrophages were evident in both germinal centres and T cell areas (paracortex and periarteriolar lymphoid sheath). Notably, the appearance of IL-2R expression in germinal centres and T cell areas was apparent from day 7 onwards. This was the time when widespread renal interstitial infiltration, cellular immune activation and severe renal functional and histological injury developed. In addition, antigen deposited in germinal centres was found to be associated with CD4+, CD5-, ED1- cells, most probably antigen presenting dendritic cells. In contrast, in acute serum sickness there was no antigen deposited in germinal centres and only mild renal injury and minor changes within lymphoid tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2005

Role of CXC chemokine ligand 13, CC chemokine ligand (CCL) 19, and CCL21 in the organization and function of nasal-associated lymphoid tissue.

Nasal-associated lymphoid tissue (NALT) orchestrates immune responses to Ags in the upper respiratory tract. Unlike other lymphoid organs, NALT develops independently of lymphotoxin-alpha (LTalpha). However, the structure and function of NALT are impaired in Ltalpha(-/-) mice, suggesting a link between LTalpha and chemokine expression. In this study we show that the expression of CXCL13, CCL19, CCL21, and CCL20 is impaired in the NALT of Ltalpha(-/-) mice. We also show that the NALT of Cxcl13(-/-) and plt/plt mice exhibits some, but not all, of the structural and functional defects observed in the NALT of Ltalpha(-/-) mice. Like the NALT of Ltalpha(-/-) mice, the NALT in Cxcl13(-/-) mice lacks follicular dendritic cells, BP3(+) stromal cells, and ERTR7(+) lymphoreticular cells. However, unlike the NALT of Ltalpha(-/-) mice, the NALT of Cxcl13(-/-) mice has peripheral node addressin(+) high endothelial venules (HEVs). In contrast, the NALT of plt/plt mice is nearly normal, with follicular dendritic cells, BP3(+) stromal cells, ERTR7(+) lymphoreticular cells, and peripheral node addressin(+) HEVs. Functionally, germinal center formation and switching to IgA are defective in the NALT of Ltalpha(-/-) and Cxcl13(-/-) mice. In contrast, CD8 T cell responses to influenza are impaired in Ltalpha(-/-) mice and plt/plt mice. Finally, the B and T cell defects in the NALT of Ltalpha(-/-) mice lead to delayed clearance of influenza from the nasal mucosa. Thus, the B and T cell defects in the NALT of Ltalpha(-/-) mice can be attributed to the impaired expression of CXCL13 and CCL19/CCL21, respectively, whereas impaired HEV development is directly due to the loss of LTalpha.

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↗
PubMed1995

Mucosa-associated lymphoid tissue lymphomas.

Mucosa-associated lymphoid tissue (MALT) lymphomas are a distinct subgroup of non-Hodgkin's lymphoma with a particular clinicopathologic behavior. The gastrointestinal tract is involved in two thirds of the cases, but it may be observed in lung, breast, bladder, conjunctiva, kidney, liver, skin, salivary glands, thyroid, and thymus. This type of lymphoma tends to appear in patients with a history of autoimmune disease or chronic inflammatory disorders. In the stomach, this lesion is induced by Helicobacter pylori and is characterized by an accumulation of lymphoid tissue leading to chronic gastritis. The preceding lymphoid disorder is represented by Sjögren's syndrome, Hashimoto thyroiditis, and interstitial lymphoid pneumonia in the thyroid, salivary glands, or lung, respectively. Lymphoma cells initially arise from the marginal zone localized around reactive follicles and secondarily invade epithelial tissue to form the characteristic lymphoepithelial lesion. Patients with gastrointestinal MALT lymphoma generally present with localized disease without any adverse prognostic factors. These patients have long survival rates. Recurrences may appear in the same organ or in other extranodal sites. Nongastrointestinal MALT lymphoma patients seem to have a similar outcome. Patients may be treated with surgery or radiotherapy if the disease is localized, or with single-agent chemotherapy if it is disseminated. Reversion of the chronic inflammatory disorder with antibiotics, such as for gastric involvement, is a new observation that may change therapeutic options in the future.

Breast Neoplasms↗
PubMed1994

Variable endoscopic appearance of colonic lymphoid tissue.

The variable appearance of gut-associated lymphoid tissue at videocolonoscopy has not been well documented. Over a 3-year period all patients undergoing high resolution videcolonoscopy underwent biopsy of any identified abnormalities for correlating histopathologic findings with endoscopic appearance. We identified several distinct patterns for lymphoid tissue: small well-circumscribed nodules, red rings, large coalescing vesicles with or without central pits, or white plaques. A mass-like appearance of the ileocecal valve was present in one patient. Although individually each of these patterns appeared characteristic, overall, variability appeared dependent on the colonic location and underlying disease. Prominent lymphoid tissue was most frequently seen in patients with underlying disorders resulting in stimulation of the immune system. We take this to mean that there is a broader spectrum of colonic lymphoid tissue as assessed by videocolonoscopy than previously appreciated. The variability of these normal structures has potential diagnostic implications.

Adult↗
PubMedDate not supplied

Lesions in subclinical paratuberculosis of goats are associated with persistent gut-associated lymphoid tissue.

The organized gut-associated lymphoid tissue (the Peyer's patches [PPs] of domestic ruminants) is an important site of lesions caused by Mycobacterium avium subsp. paratuberculosis. To investigate the association between PP morphology and the lesions of paratuberculosis in goats, two experiments were performed. Five healthy kids aged 4-5 weeks were examined and the morphology of organized lymphoid tissue in the small intestine was described. Morphological similarities were observed between the ileocaecal-valve PP (ICVPP) and the jejunal PPs (JPPs), with pear-shaped follicles, large submucosal interfollicular T-cell areas, and many intraepithelial leucocytes in the follicle-associated epithelium. The ileal PP (IPP) consisted of elongated follicles, small T-cell areas and few intraepithelial leucocytes. The association between these three locations of PPs and lesions of paratuberculosis was then studied in seven goats inoculated with M. a. paratuberculosis at 5-8 weeks of age and killed 2 years later, while in the subclinical phase of infection. Gross lesions were recorded in five animals and microscopic lesions were observed in the intestine and mesenteric lymph nodes of six animals. The lesions in the small intestine were mainly located in the PPs of the mid-jejunum (JPPs) and ICVPP. Lesions were not present in the intestinal segments that had contained IPP, which had undergone involution during the first 12-18 months of life. These observations indicate that the persistent organized lymphoid tissue in the JPPs and ICVPP, but not the involuted IPP, sustains the development of granulomatous inflammation due to paratuberculosis during the subclinical phase of infection.

Animals↗
PubMed1994

Mucosal-associated lymphoid tissue lymphoma of the conjunctiva.

The recognition of mucosal-associated lymphoid tissue as a distinct entity has lead to the separate classification of tumors arising in this tissue, ie, the mucosal-associated lymphoid tissue lymphoma. Five patients with mucosal-associated lymphoid tissue lymphoma of the conjunctiva are described herein; four of the five patients had bilateral tumors. Laboratory analysis was done using microscopy, immunophenotyping, gene rearrangement analysis using both Southern blot and polymerase chain reaction techniques, and oncogene (bcl-1, bcl-2, and c-myc) rearrangement studies. Typical mucosal-associated lymphoid tissue lymphoma features were seen in all patients; three of four patients who underwent testing with immunphenotyping had light-chain restriction, four of five patients had a clone detected using Southern blot analysis, and all five patients showed clones on polymerase chain reaction analysis. No patient demonstrated oncogene rearrangement. In all patients, complete physical examinations and laboratory tests did not detect any evidence of systemic spread. After treatment, no evidence of local recurrence or dissemination was found during follow-up ranging from 2 to 3 years.

Adult↗
PubMed1993

[Low-grade mucosa-associated lymphoid tissue (MALT) lymphomas].

Lymphomas of mucosa-associated lymphoid tissues (MALT) are localized in organs containing lymphoid tissue in normal subjects (lung) or in organs frequently involved by inflammatory lesions (stomach, salivary glands, thyroid...). In the MALT, lymphoid tissue comprises B and T lymphocytes. Lymphomas of the MALT have been well defined in the gut. Isaacson has proposed a classification of these primary gut lymphomas, distinguishing between B, the most frequent, and T lymphomas, and between low and high grade of malignancy. MALT lymphomas have common morphological characteristics and a particular behaviour: they are localized in their initial site for a long time. Prognostic factors include low histological grade of malignancy and the possibility of a complete surgical resection.

Animals↗
PubMed1989

Skin-associated lymphoid tissue.

Skin-associated lymphoid tissues represents a conceptual framework on which an understanding of cutaneous immunity can be built. It is clear that regional specialization of the immune system exist, and one such specialization is represented by SALT. The skin contains, especially within the epidermis, several important types of lymphoreticular cells whose interactions with antigens and with neighboring keratinocytes lead to elaboration of antigenic signals that can be acted on by immunocompetent lymphocytes. The recirculating properties of a subset of skin-seeking T lymphocytes equips them to migrate preferentially through dermal vessels and the lymph nodes that drain the skin, creating a network of surveillance and communication that ensures that appropriate immune effectors and regulators are produced, and that threatening cutaneous pathogens are eliminated without compromise of skin function. As new experimental information is gathered concerning SALT, new insights are likely to emerge that will illuminate the immunopathogenesis of cutaneous disorders with a strong inflammatory and/or malignant component. It can be anticipated that these new insights will lead to novel therapies for the treatment and prevention of these diseases.

Animals↗
PubMed2004

Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues.

Gut-associated lymphoid tissues (GALTs) interact with intestinal microflora to drive GALT development and diversify the primary antibody repertoire; however, the molecular mechanisms that link these events remain elusive. Alicia rabbits provide an excellent model to investigate the relationship between GALT, intestinal microflora, and modulation of the antibody repertoire. Most B cells in neonatal Alicia rabbits express V(H)n allotype immunoglobulin (Ig)M. Within weeks, the number of V(H)n B cells decreases, whereas V(H)a allotype B cells increase in number and become predominant. We hypothesized that the repertoire shift from V(H)n to V(H)a B cells results from interactions between GALT and intestinal microflora. To test this hypothesis, we surgically removed organized GALT from newborn Alicia pups and ligated the appendix to sequester it from intestinal microflora. Flow cytometry and nucleotide sequence analyses revealed that the V(H)n to V(H)a repertoire shift did not occur, demonstrating the requirement for interactions between GALT and intestinal microflora in the selective expansion of V(H)a B cells. By comparing amino acid sequences of V(H)n and V(H)a Ig, we identified a putative V(H) ligand binding site for a bacterial or endogenous B cell superantigen. We propose that interaction of such a superantigen with V(H)a B cells results in their selective expansion.

Amino Acid Sequence↗