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Using peroxidase-labelled antibodies, the ultrastructural localization of IgA and secretory component (SC) was investigated in duodeno-jejunal biopsies from six children with coeliac disease and compared with that observed in non-coeliac mucosa. In normal intestinal mucosa this study confirmed the presence of IgA in the rough endoplasmic reticulum and the perinuclear space of numerous subepithelial plasma cells and on the lateral cell membranes of villous and especially crypt epithelial cells. SC was only detected in the epithelium and principally in crypt epithelium where in was identified in endoplasmic reticulum, Golgi saccules, perinuclear spaces and on lateral cell membranes. These findings support the suggestion that SC is synthesized mainly in crypt epithelium and acts as a receptor on epithelial cell membranes for dimeric IgA. In untreated coeliac patients. SC was observed at the same sites, but SC staining was reduced in damaged surface epithelial cells. The number of IgA immunocytes was increased and heavy deposits of IgA were found on basement membranes. In post-treatment biopsies, no abnormality was apparent. After re-exposure to gluten, depositions of IgA on basement membranes were the only early change. The unaltered distribution of SC and IgA in crypt epithelium strongly suggests that the epithelial transport mechanism of secretory IgA is normal in coeliac disease. [ABSTRACT FROM AUTHOR]

Peripheral blood lymphocytes from 16 patients with juvenile rheumatoid arthritis and 27 age-matched healthy controls have been studied, using several lymphocyte markers: electrophoretic mobility (EM), E-rosettes, immunofluorescence, and refringency. Eight patients (mean age, 6 years) were selected with a typical EM pattern—that is, a decrease in the mean EM of T cells and increase in B versus T-cell ratio. The other group of patients (mean age, 11 years) showed no significant difference when compared with their age-matched controls, with the exception of the positive refringence test. These findings suggest an impairment in the maturation of the immune system in childhood, which in turn may be responsible for the increased susceptibility to disease. [ABSTRACT FROM AUTHOR]

A method using a mechanical procedure for isolation of lymphocytes from the epithelium of human intestinal mucosa allows the study of some of their characteristics and functions. Most of the isolated cells are of the T lineage (E+ and T3+) and express the phenotype associated with cytotoxic-suppressor T cells (T8). A large number contain intracytoplasmic granules. Granules are stained with alcian blue (pH 2.2), are metachromatic with Toluidine blue (pH 4) and some are shown to incorporate 35sulphate, suggesting that they contain sulphated mucopolysaccharides. As these cells are similar in many respects to the large granular lymphocytes that mediate natural killer activity in the peripheral blood, their natural cytotoxicity was tested against K 562 target cells. No activity was detected among the human intraepithelial lymphocytes and treatments with known potentiators of natural killer activity, ie, interferon or PHA-depleted conditioned medium containing Il-2, failed to reveal any cytotoxic activity. [ABSTRACT FROM PUBLISHER]

T-cell subsets have been analysed in 23 cases of primary immunodeficiency with monoclonal antibodies. Functional assays investigating T-cell function-proliferative response to mitogens, antigens, and allogeneic cells, cytotoxicity generated against allogeneic target cells and helper function to pokeweed mitogen-induced immunoglobulin synthesis-were performed in parallel in the same patients. The results enabled us to delineate four groups of patients. The first group consisted of patients in whom marker and function studies show concordant data, with either normal or strongly decreased T-cell number and function. The second group consisted of patients in whom various degrees of functional abnormality coexist with subnormal T-cell number and increased suppressor T-cell proportion. In the third group, we collected all patients who showed functional deficiencies without marker abnormalities. Finally, there was a small group composed of patients whose T-cell pattern was strongly suggestive of abnormal differentiation. [ABSTRACT FROM AUTHOR]

An 18-year-old man with tendency to respiratory infections had a serum IgA level of only 2% of normal whereas his salivary lira amounted to 50% of the lower normal concentration range. Moreover, both the rectal and jejunal IgA-producing cell populations were of normal size. Nevertheless, a relative increase of salivary IgM and a distinctly raised number of IgM-producing cells in jejunal mucosa indicated an imbalance in his secretory immune system. This possibility was supported by the presence of an excess of J chain in most of his intestinal leA immunocytes, probably reflecting a reduced synthetic rate of IgA. The number of tonsillar IgA-producing cells was only slightly below the normal range: most of them lacked J chain, as normal, and could thus be a source of his serum IgA, which was mainly monomeric. A marked deficiency of IgA-producing cells in his bone marrow supported the notion that this tissue site normally is the major source of monomeric IgA. This study suggests that a generally defective IRA system may be topically activated owing to the persistent antigenic and mitogenic load on mucosa-associated lymphoid tissues. Our findings are not consistent with a general regulative compartmentalization of monomer- and dimer-producing IgA immunocyte populations. [ABSTRACT FROM AUTHOR]

HLA class II antigens and the LFA-l (lymphocyte function-associated type 1) glycoprotein family are cell surface structures of central importance in many lymphocyte reactions. Specific antibodies are normally restricted to particular IgG subclasses. In order to study the mechanism of isotype restriction we have analysed specific IgG1, IgG2, IgG3 and IgG4 antibodies directed against a number of different protein and polysaccharide antigens in individuals with HLA class II or LFA-I deficiency. HLA class II deficiency resulted in decreased total IgG2, IgG4 and IgA in 4/4 patients, whereas total IgM and IgG were low in 2/4. In HLA class II deficiency the levels of specific antibodies directed against protein as well as polysaccharide antigens were frequently low. Virtually normal total as well as specific antibody levels were found in individuals with both severe and moderate forms of LFA-1 deficiency. There was no clear evidence for an abnormal subclass pattern of specific antibodies with a shift from one subclass to an isotype which is normally not used, in any of the patient groups investigated. [ABSTRACT FROM AUTHOR]

Serum IgG subclass levels were determined using a competitive indirect immunoenzymatic assay with monoclonal antibodies in 16 patients with ataxia-telangiectasia. Eight children had igA deficiency, two had lgG and IgA deficiency and six patients showed no immunoglobulin class abnormality. However, IgG4 and IgG2 levels were undetectable or low in almost every patient. An IgG3 deficiency was associated with the IgG2-1gG4 defect in three patients with undetectable IgA. IgGl was very low in one patient with a total IgG deficiency. There was no clear correlation between subclass levels and the occurrence of infections. [ABSTRACT FROM AUTHOR]

Epstein-Barr (EB) virus serology was correlated with the results of immunological investigations of three inherited immunodeficiency diseases, in an attempt to understand the immune mechanisms controlling EB virus infection. In nine patients with Wiskott-Aldrich syndrome (WAS), the constant lack of anti-EB virus associated nuclear antigen (EBNA) was accompanied by a consistent Impairment of allogeneic cytotoxicity. We confirmed a frequent absence of anti-EBNA antibody in ataxia telangiectasia (AT), and we showed a correlation between the level of anti-EBNA response and the mixed leucocyte response (MLR), i.e.. an absence of anti-EBNA antibody correlated with a decreased MLR. In two of three untreated patients with Chediak-Higashi syndrome (CHS), high persistent titres of anti-EA antibodies were observed, which were possibly related to a defective natural killer (NK) cell activity. In spite of previous infection with EB virus, none of the 41 patients exhibited clinical signs attributable to the virus, suggesting that residual or compensatory mechanisms must have limited activation of the virus. In patients with AT and WAS these mechanisms may include NK cell activity, which is not depressed in these syndromes, whereas in patients with CHS, they may involve T cell cytotoxicity. [ABSTRACT FROM AUTHOR]