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Three infants developed severe hemolytic anemia following the second or third diphtheria-pertussistetanus vaccination. Direct antiglobulin tests were positive, and the infant most severely affected also had reduced serum complement levels, indicating an immunological mechanism for the hemolysis. The presence of IgM on the erythrocytes from 2 of the infants could be demonstrated by antiglobulin tests or immunization experiments. Heat eluates of the erythrocytes from one of the infants contained antibodies to tetanus and diphtheria toxoids, as well as to Bordetella pertussis, suggesting that these antibodies were antigenically bound to the erythrocytes. Virus antibodies or isoagglutinins, present in the serum, were not found in the eluate. No antibodies against the vaccine components could be demonstrated in eluates of erythrocytes from control subjects. In vivo experiments showed that tetanus and diphtheria toxoids were easily bound to human erythrocytes. This finding could help explain the pathogenesis of the autohemolysis.

Rabbit antiserum to a citric acid extract of human skeletal muscle (CA) stained epithelial thymoma cells as well as skeletal muscle. Thymomas from two myasthenia gravis (MG) patients showing no circulating anti-CA antibodies prior to thymectomy were also stained by the antiserum. Thus, in these patients as well, the thymoma and skeletal muscle possess common antigens. The rabbit and the human antibodies most probably reacted with different antigens, apparently located close to each other in the cell membrane. The reason why anti-CA antibodies cannot be detected in serum from a few MG patients with a thymoma may be that the thymoma-associated antigen is not present in vivo in these cases, or that an inhibiting factor blocks the antibody synthesis. Both patients developed anti-CA antibodies post-operatively, which favours the latter explanation.

Receptors for the Fc part of IgG (Fc gamma R) and HLA-DR antigens were detected in thymus tissue from patients with myasthenia gravis (MG) using monoclonal antibodies (B1D6 and OKIa1) in indirect immunofluorescence. The amount of Fc gamma R and HLA-DR antigens was increased on epithelial reticular cells and on interdigitating reticular cells in hyperplastic thymus as compared to normal thymus. In thymomas from MG patients the neoplastic epithelial cells expressed Fc gamma R, whereas only a few cells had HLA-DR antigens. Neither thymocytes nor B lymphocytes in the hyperplastic thymuses and in the thymomas were stained by B1D6.

The inflammatory mononuclear cell infiltrates observed in lesional skin from patients with discoid lupus erythematosus (DLE), sarcoidosis, and secondary syphilis have been characterized in situ. Immunological markers (human T lymphocyte antigens and receptors for sheep erythrocytes, C3b, C3d and Fc gamma) were studied by using immunofluorescence tests with IgG F (ab')2 preparation of anti-T lymphocyte serum, hemadsorption with tissue sections, and tests with soluble immune complexes of peroxidase. In DLE, T lymphocytes were the dominant cell type. In sarcoidosis, the epithelioid cells, including giant cells, had markers similar to macrophages. The lymphohistiocytic cells consisted mainly of macrophages, some T lymphocytes and a few B lymphocytes. In secondary syphilis (condylomata lata), macrophages and T lymphocytes were the dominant cell types, and relatively few B lymphocytes were detected.

A combined indirect immunofluorescence technique with a murine monoclonal antibody against human Ia-like antigens (OKIal) and an IgG F(ab')2 preparation of a rabbit anti-T lymphocyte serum was used to study Ia-like antigens on T lymphocytes in skin lesions of psoriasis, lichen planus and discoid lupus erythematosus. The majority of the T lymphocytes in the various skin lesions expressed Ia-like antigens. T lymphocytes expressing Ia-like antigens were also demonstrated in the dermis and the epidermis in sections of unaffected skin, although of a markedly lower proportion than in affected skin. The results may indicate that the T lymphocytes in these skin lesions are activated cells involved in cell-mediated immune reactions.

Patients clinically free from disease after potentially curative resection of gastric carcinoma, stages I, II and III (pTNM) were studied. The concentrations of immunoglobulins and complement components were quantified at 3-month intervals during the first year after surgery. The values in the individual patients showed no systematic variation with time while there was no clinical evidence of disease. The mean concentrations of C4 and C1-INH, however, were higher in 22 patients with later recurrence (0.43 +/- 0.10 and 0.43 +/- 0.07 g/l, respectively) than in 34 patients who were alive and disease-free at follow-up (0.36 +/- 0.07 and 0.36 +/- 0.04 g/l). The mean serum concentrations of IgG, IgA, IgM and C3 showed no intergroup difference. High levels of C4 and C1-INH postoperatively apparently indicate that the patient still harbours malignant disease with poor prognosis.

Antibodies against skeletal muscle antigens and against thymic myoid cells were examined in sera from 40 patients with myasthenia gravis (MG). Using an indirect immunofluorescence technique, antibodies against the surface of muscle cells were found in 23 sera, and antibodies against muscle cell cross-striations in 28 sera. Antibodies against thymic myoid cells were found in 27 sera, stained cells also occurring in fetal thymus from 14 weeks of gestation and in hyperplastic thymus from MG patients. Sera which stained myoid cells also stained muscle cell cross-striations. Sera from all the 20 patients with thymoma contained antibodies to a citric acid extract of skeletal muscle (CAE) as detected by indirect haemagglutination, whereas sera from 20 comparable patients without thymoma did not contain CAE antibodies. The myoid cell antibodies could be absorbed by homogenized muscle, but not by CAE-coated sheep erythrocytes. Different antibody patterns are seen among different MG patients; close associations were found between cross-striational and myoid cell antibodies, and between CAE-antibodies and a thymoma.

Hyperbaric oxygen (HBO) treatment has been reported to cause amelioration of clinical symptoms in patients with multiple sclerosis (MS). We have treated 10 MS patients with hyperbaric oxygen (100% O2 at 2 atmospheres absolute for 90 min daily for a total of 20 exposures), and performed immunological studies on peripheral blood and cerebrospinal fluid (CSF). After treatment there was a significant increase in total and helper T lymphocyte counts in peripheral blood, as well as an increase in both E, Fc gamma and C3b receptor-bearing lymphocytes. The responses to the mitogens PHA, con A and PWM were unchanged. Granulocytes showed an increased proportion of Fc gamma receptor and C3b receptor positive cells after treatment. The O2 consumption of granulocytes also increased, but phagocytosis, as measured by chemiluminescence, was unchanged. Serum IgA levels were slightly increased, while IgG and IgM concentrations remained unchanged after treatment. Cerebrospinal fluid cell counts, protein and IgG concentrations, as well as IgG indexes remained unchanged.

Extracts from myelinated and unmyelinated nerves, prepared using Tris-HCl buffer with EDTA and ME, contained functionally active receptors for the Fc region of IgG (FcR). This was evident from the results obtained in indirect haemagglutination and rosette inhibition assays. Using a monoclonal antibody, a functional active 40-kDa FcR was purified from the nerve extracts. The receptor was a single-chained glycoprotein with low affinity for native IgG, apparently belonging to the FcRII family. In addition, peripheral nerve extracts contain FcR not recognised by the monoclonal antibody.

An infectivity inhibition micro-method was used to detect interferon (IFN) in sera from 20 healthy individuals before and after UVA irradiation, and in sera from 22 healthy individuals before and after UVB irradiation. The serum levels of IFN, immunoglobulins (Ig) and complement components (C) were examined before irradiation, after 10 and 20 exposures, and 4 weeks after irradiation. The median serum IFN level in both the UVA and the UVB group increased significantly during irradiation, most markedly during the 10 first exposures. Four weeks after irradiation the median IFN level was reduced in both groups, but had not reached the pre-irradiation levels. The IFN level was unchanged or reduced in 2 individuals in the UVA group and in 5 individuals in the UVB group. Characterization experiments indicated the presence of both acid-stable and acid-labile IFN-alpha and IFN-gamma. The mean serum IgG concentration was significantly reduced 4 weeks after UVA irradiation, whereas IgA, IgM, C3 and C4 were not affected. The mean serum concentrations of IgG and C4 were significantly reduced 4 weeks after UVB irradiation, whereas the mean concentrations of IgM and C3 were significantly increased. The concentration of IgA was not affected.

The aims of the present study were to demonstrate FcR activity of dental periapical granulomas and to correlate the activity with the degree of lymphoreticular cell infiltration. Cryostat sections of 46 out of 51 granulomas adsorbed sheep erythrocytes(E) sensitized with rabbit IgG antibodies (A) (EA). No adsorption occurred using erythrocytes sensitized with F(ab')2 fragments of IgG. IgG and Fc fragments of human of rabbit IgG inhibited the binding of EA, whereas F(ab')2 fragments, human IgA, IgM or albumin did not, indicating the presence of receptors for the Fc region of IgG. Periodate, neutral formaldehyde and phospholipase C abolished the FcR activity whereas neuraminidase had no effect. Comparison of sections binding EA and adjacent sections stained with haematoxylin and eosin showed that EA adhered to areas infiltrated with mononuclear cells. The degree of binding of EA coincided with the density of mononuclear cell infiltration. Point attachments between the tissue sections and the adsorbed EA could be demonstrated by scanning electron microscopy. Sections with no infiltrates did not bind EA.

Serum from 20 of 137 patients (15%) with myasthenia gravis (MG) contained antibodies to a citric acid extract (CAE) of skeletal muscle. A thymoma was found in all 19 of these patients who were thymectomized. There was no evidence of thymoma in patients who did not have CAE antibodies. Serum from 40 of the same 137 patients (30%) contained antibodies that gave a cross-striational immunofluorescent pattern in skeletal muscle. This pattern was seen with serum from 16 of the 20 thymoma patients, but also with serum from 24 patients without thymoma. The cross-striation antibodies were not absorbed by CAE coated on to tanned sheep erythrocytes. Accordingly, antibodies detected in the two tests have different specificities.

The alpha-fetoprotein serum concentration was determined by radioimmunoassay in 22 epileptic patients treated with phenytoin. The concentration was normal in all of the patients. The IgA concentration in serum was below 0.20 g/l in 15 of the patients and normal in 7 (0.60-3.30 g/l). IgG and IgM concentrations were normal. The total number of lymphocytes was significantly reduced in the epileptic patients compared to healthy controls, while the relative percentage of various mononuclear blood cell sub-populations did not differ between the patients and the controls. The response to PHA stimulation was lower in the patients than in the controls for all PHA concentrations tested, the differences, however, were not significant at a 5% level. The results indicate that alpha-fetoprotein does not participate in the pathogenesis of the immune disturbances observed in patients with epilepsy.

A patient with Sézary syndrome is presented. By phase contrast and scanning electron microscopy Sézary cells were demonstrated in peripheral blood and in skin tissue. Investigation of atypical mononuclear cells seen in the peripheral blood showed that these cells lack receptors for sheep erythrocytes. C3 and Fcgamma. Similarly, an examination of dermal mononuclear cell infiltrates showed that most of the cells lack receptors for sheep erythrocytes, C3 and Fcgamma.

Glomerular complement receptors (GCR) were demonstrated by the adsorption of C3 coated sheep erythrocytes to cryostat sections of human kidneys. An epithelial localization of the GCR is implied by the binding pattern of the indicator cells. The GCR activity was reduced in all glomeruli where in vivo deposition of immunoglobulin and C3 along the capillary wall was observed. In fourteen out of nineteen biopsies where deposits in the mesangium were seen, reduced GCR activity was also observed, whereas GCR activity was normal in the other five. Immunofluorescence and haemadsorption tests performed on the same section showed that C3 deposits corresponded to areas showing reduced complement receptor activity. Areas outside the C3 deposits adsorbed indicator cells coated with various amounts of C3 similarly to the adsorption to glomeruli seen in normal adult and fetal kidneys. Sclerotic glomeruli showed no GCR activity. The results indicate that the complement receptors play a role for the binding of complement-containing complexes in glomeruli.

The Fc receptor activity in placental extracts prepared using EDTA and 2-mercaptoethanol was assayed using an indirect hemagglutination technique with sheep erythrocytes sensitized with rabbit IgG. The agglutinating activity of the extract was not affected by storage at -70 degrees C, by rapid freezing and thawing, by treatment with periodic acid, formaldehyde, neuraminidase, trypsin, pronase, or phospholipase C. Papain abolished the activity, indicating that the receptor is a protein. Reduction and alkylation had no effect on the agglutinating activity, indicating that -S-S-bonds are not important for binding. In the presence of 0.6 M NaCl the agglutinating activity was abolished, indicating that electrostatic interactions are of significance. The solubilized Fc receptor shows so many similarities to the previously studied in situ Fc receptor that they are probably identical.

Fc gamma receptor (FcR) from human placenta was solubilized using EDTA and 2-mercaptoethanol and purified by affinity chromatography on human IgG-coated Sepharose 4B. BALB/C mice were immunized with FcR and monoclonal antibodies were obtained by growing hybridoma cells following fusion of spleen cells with P3 X 63Ag8 myeloma cells. Using an immunofluorescence technique, the IgG1 monoclonal antibody secreted by clone B1D6 stained the FcR-positive areas in sections of placental tissue. The endothelium of the foetal stem vessels stained more strongly than did the trophoblasts. The antibody also inhibited the haemadsorption to placental tissue of erythrocytes (E) sensitized with IgG antibodies (A), (EA), and inhibited the agglutination of EA by FcR. The data indicate that the monoclonal antibody reacts with the placental FcR at the binding site for IgG, or with an epitope close to the binding site. Apparently, the FcR in different anatomical areas in the placenta have a common antigenic determinant.

Sheep erythrocytes (E), sensitized with unheated rabbit antiserum containing IgG antibodies (EA), bound human C4 when heat-inactivated serum was used as the source of complement (EAC). The EA were not agglutinated by antiserum to rabbit C3 and were not lysed in the presence of C4-deficient guinea pig serum. The EAC were agglutinated by antiserum to human C4, lysed by the addition of C4-deficient serum and were reactive in immune adherence. They were not agglutinated by antiserum to human C3. Accordingly, the cells could be designated as EAC14. They were stable and could be stored at 4 degrees C for at least 1 week without haemolysis occurring, and with no loss of reactivity in immune adherence test. E sensitized in the presence of EDTA or with heat-inactivated rabbit serum did not bind C4.

HLA-DR antigens and receptors for the Fc part of IgG (Fc gamma R) were examined in cryostat sections and imprints of 12 thymuses from fetuses, infants and children. A double-marker technique, with an anti-T cell serum produced in rabbit and the monoclonal antibody OKIal, was used to study the localization of the thymocytes and the HLA-DR antigens. Membrane-bound HLA-DR antigens were found on about 5% of the thymocytes. A larger proportion of the thymocytes were surrounded by HLA-DR-positive material, probably associated with the thymic epithelial cells. Fc gamma R detected by human aggregated IgG were found on most epithelial cells, but only on a few thymocytes. However, in some areas Fc gamma R were demonstrated on most of the cells stained by the anti-T cell serum. A similar pattern for staining of Fc gamma R was obtained using an anti-Fc gamma R serum produced in rabbit. Fc gamma R were detected on one-third to one-half of the OKT3+ or OKT8+ thymocytes, but only on a few OKT4+ cells. Fc gamma R were present on nearly all the OKT6+ thymocytes at 11 weeks of gestation, whereas in thymuses from older individuals only a few OKT6+ cells had Fc gamma R. The proportions of double-stained cells did not vary much in fetuses older than 14 weeks of gestation, in infants or in children. The results indicate that HLA-DR antigens and Fc gamma R are not correlated to any specific stage of cell maturation.

The inflammatory cell infiltrates in human dental periapical granulomas were studied through the demonstration of receptors (R) for fragments C3b and C3d of the complement component C3, C3bR and C3dR were detected in cryostat sections by the closed chamber hemadsorption technique. Sheep erythrocytes sensitized with rabbit IgM antibody and coated with human C3B or C3d were used as indicator cells. Of the 62 granulomas studied, 23 showed strong or moderate C3bR activity, and weak C3dR activity was detected in 5 out of 25 specimens. The C3bR activity was abolished by treatment with 0.25 mM periodic acid, indicating that carbohydrate is a part of the C3bR. Using an antiserum to C3R as first layer in indirect immunofluorescence experiments, the C3R was localized to cell membranes. The low C3dR activity indicates that a minor part of the mononuclear cells in the human periapical granulomas were B lymphocytes.

Rabbit antiserum to a citric acid extract of human skeletal muscle (CA) stained both the cell membrane and the cross-striational bands of skeletal muscle cells. The rabbit antiserum also stained the cell membrane of epithelial thymoma cells from myasthenia gravis (MG) patients. Normal and hyperplastic thymus tissue were not stained, apart from scattered myoid thymic cells. Absorption of the antiserum with CA abolished staining of the thymoma, indicating that human skeletal muscle and epithelial thymoma cells possess common antigens.

Cryostat sections of human kidney were incubated with C3b containing immune complexes. The complexes were horseradish peroxidase (HRP) and F(ab')2 fragments of rabbit IgG anti-HRP incubated in C4-deficient guinea pig serum. The peroxidase activity was revealed histochemically. The sections were studied using light and electron microscopy. The bound complexes were localized to the foot processes of the visceral epithelial cells and to the surface of the parietal epithelial cells facing Bowman's space. No receptors could be demonstrated on the endothelial or mesangial cells.

Epithelioid cells, giant cells and mononuclear cells in cryostat sections of lesional skin from 5 patients with chronic cutaneous sarcoidosis were characterized using an indirect immunofluorescence test with monoclonal antibodies. OKM1 (monocyte) antibody stained both epithelioid cells and giant cells as well as some cells in the periphery of the granulomas. OKM1 which reacts with most monocytes in peripheral blood, did not react with tissue macrophages in sections of normal skin, liver, spleen and kidney. The results indicate that the epithelioid and giant cells in the sarcoid granulomas are derived from blood monocytes. OKT3 (pan T cell) antibody stained the majority of cells surrounding the epithelioid cell islands. Examination of adjacent sections showed that more OKT4+ (helper/inducer) than OKT8+ (suppressor/cytotoxic) cells were present in the sarcoid lesions examined.

Acute passive Heymann glomerulonephritis in rats induced heavy proteinuria and highly increased urinary activity of N-acetyl-beta-D-glucosaminidase, acid beta-galactosidase and acid phosphatase. The cortical activity of these acid hydrolases was increased essentially in the large lysosomes as demonstrated by subfractionation of the lysosome-rich mitochondrial-lysosomal fraction, by rate zonal centrifugation. Banding density of small lysosomes shifted or reduced to slightly lower value (1.225 g/ml), which is between the banding densities of small 'light' (1.20 g/ml) and small 'dense' lysosomes (1.235 g/ml) in normal rat kidney cortex. Labelled protein reabsorbed in the proximal tubule is recovered in these populations of small lysosomes as well as in the large lysosomes or 'protein droplets'. Glomerulonephritis also induced a new population of small 'light' lysosomes (density 1.185-1.195 g/ml) enriched in cathepsin D. The previously demonstrated morphological, biochemical, and physiological heterogeneity of renal lysosomes was confirmed and emphasized in the kidney cortex of glomerulonephritic rats. The main changes in the lysosomal populations appear to reflect the increased protein reabsorption as confirmed by the proteinuria.

Immunoglobulins A, G and M and complement components C3, C4 and C1-INH were quantitated in sera taken preoperatively from 168 patients with gastric carcinoma. The values were grouped according to stages (pTNM). The concentrations of C4 and C1-INH increased with advancing stage of disease and were above normal mean values in all stages. The concentration of IgG was below the normal mean value among all the patients and with the lowest concentration in stage III. Concentrations of IgA and C3 were above normal means but without significant relation to stages. There was a positive correlation between the concentrations of IgG and C1-INH in sera from patients with stage IV carcinoma, while the same correlation was negative in stages I-III. Although the results varied among the patients within each stage, the profiles of immunoglobulin and complement concentrations are of value in the preoperative staging of the disease.

Cryostat sections of 66 snap-frozen dental periapical granulomas were examined for T lymphocytes by the closed chamber hemadsorption technique using sheep erythrocytes (E) treated with 2-aminoethylisothiouronium bromide hydrobromide (AET) as indicator cells (AET-E). T lymphocytes were also demonstrated by immunofluorescent staining using a rabbit anti-T lymphocyte antiserum. Eighty-six % of the granulomas showed adherence of AET-E, and often a focal AET-E adherence pattern was seen, indicating a localized infiltration of T lymphocytes. Diffuse, moderate binding of AET-E to sections of some granulomas may be due to recirculating T lymphocytes traversing the tissue. The results of the immunofluorescence test parallelled the results obtained in the hemadsorption test. The results show that mononuclear cell infiltrates of periapical dental granulomas usually contain T lymphocytes. Although their pathogenetic function in dental periapical granulomas is still not known, infiltrates of T lymphocytes indicate that cellular immune reactions are involved.

An indirect haemagglutination (IHA) test using tanned sheep erythrocytes was developed to detect antibodies in sera from rabbits immunized with renal tubular epithelium (RTE) or with glomerular basement membrane (GBM) from rats. The RTE antigen preparation, called Fx1A, sensitized the erythrocytes directly, whereas the GBM preparation had to be treated with collagenase. THe antisera to Fx1A gave titres up to 64,000, and the antisera to GBM up to several million. The sera were monospecific, since they gave no cross-reactions in IHA, precipitation, or absorption tests. Using the IHA test, the quantitative aspects of experimental glomerulonephritis in rats can be studied. Preliminary results obtained in transfer experiments indicate a dose-response relationship between the titres in IHA and the degree of proteinuria.

Fetal rat brain cells, undergoing neoplastic transformation in long-term culture after a single transplacental pulse of N-ethyl-N-nitrosourea on the 18th day of gestation, were investigated for Fc gamma receptors. Rosette assay with cells in suspension and the hemadsorption to cells on coverglasses were used for their detection. The receptors were found on cells after about 2 months in culture. A maximum of 20% of the cells were Fc gamma receptor-positive after 3 months. About 3 weeks later no Fc gamma receptors could be detected. Malignant rat neurogenic cell lines were also negative.

Mononuclear cells in cryostat sections of human dental periapical inflammatory lesions were studied with the aid of murine monoclonal antibodies and with indirect immunofluorescence microscopy. T lymphocytes (OKT3-positive cells) made up a major part of the cells in the infiltrates. They were found mainly in clusters, although single cells were also seen. T helper cells (OKT4) were more numerous than suppressor/cytotoxic T cells (OKT8-positive cells), with a ratio of approximately 2:1. Langerhans cells (OKT6-positive cells) were not demonstrated: only a few scattered HNK 1-positive cells, probably natural killer cells, were detected. A large number of OKM1- and OKIa 1-positive cells were detected in the infiltrates. Their size and number varied considerably in the different areas of the sections. These cells are probably macrophages. Sheets of small OKIa 1-positive cells were also demonstrated, indicating the presence of B lymphocytes or activated T lymphocytes. The results indicate that immune reactions may be of importance in the pathogenesis of periapical inflammatory lesions.

Immune complexes of horseradish peroxidase oxidase (HRP) and rabbit IgG antibodies to HRP were used to study the Fc gamma-receptors in granulomas of cutaneous sarcoidosis. Cryostat sections of skin biopsies were incubated with HRP-anti-HRP, and the peroxidase activity was demonstrated with 3,3-diaminobenzidine tetrahydrochloride and H2O2. Most cells in the granulomas, both epithelioid and giant cells, were stained. By electron microscopy, the reaction products were localized to the plasma membranes of the cells as well-defined granular deposits. No reaction product was demonstrated intra- or extracellularly.

Sera from patients with gonorrhoea were used to study the specificity of human antibodies against determinant a of endotoxin from gonococcal strains 8551, V, and VII. The sera were tested by an indirect haemagglutination technique before and after absorption with endotoxin from the same strains. The sera were used untreated and treated with mercaptoethanol (ME). The untreated and ME-treated sera showed antibody activity against all the a determinants when examined unabsorbed. After absorption with any of the endotoxin preparations the sera usually demonstrated antibody activity against one or both of the other preparations. The pattern of reactivity thus observed differed from one serum to another. Treatment of sera with ME resulted in an altered pattern of reactivity of four of the five sera. The results indicate multispecificity of human antibodies against the a determinants.

Fc gamma-receptors (FcR) in cryostat sections of normal human skin were detected with soluble immune complexes of horseradish peroxidase (HRP) and rabbit IgG anti-HRP (HRP-anti-HRP). The binding of HRP-anti-HRP to Langerhans' cells (LC) was demonstrated using a double immunofluorescence staining in which LC were identified with a CD1a specific monoclonal antibody (Leu 6). The immune complexes gave granular staining of CD1a+ epidermal cells in sections of all specimens from normal skin. The mean percentage of CD1a+ cells that were FcR+ was 49 +/- 11 (n = 8). The FcR+/CD1a+ cells had a clearly defined dendritic pattern. The staining intensity of LC with HRP-anti-HRP was weaker than the intense staining of CD1a-macrophages in the dermis. Results of inhibition experiments indicate that human epidermal LC express low affinity FcR, but the presence of high affinity FcR as well cannot be excluded. The demonstration of FcR expression on normal LC clarifies previous uncertainty on LC membrane receptors, though the functional significance of these receptors is still not well understood.

Receptors for the Fc-part of IgG (FcR) and HLA-DR antigens on endothelial cells in normal and lesional skin from patients with psoriasis were studied in cryostat sections, using soluble immune complexes and monoclonal antibodies. FcR and HLA-DR antigens were detected on endothelial cells of dermal vessels both in sections of normal and lesional skin. The expression of FcR varied from one vessel to another and on endothelial cells within one and the same vessel. The expression of FcR and HLA-DR antigens was enhanced in sections of lesional skin compared with normal skin and most pronounced in lesional skin from active psoriasis. The enhanced expression may be mediated by interferon produced in psoriatic lesions. The presence of FcR and HLA-DR antigens on endothelial cells adds further evidence of he involvement of these cells in immune processes in the skin.

Cryostat sections of placental tissue strongly adsorbed erythrocytes sensitized with IgG antibodies of human, rabbit, and guinea pig origin. No adsorption occurred using erythrocytes sensitized with F(ab')2 fragments. The reaction was strongly inhibited by intact IgG and by Fc fragments, weakly inhibited by pFc' fragments, and not inhibited by Facb and F(ab')2 or albumin. These properties are similar to those of corresponding receptors in normal lymphoid tissues. Results obtained with sections of hydatidiform mole showed that the reaction occurred with the trophoblastic tissue. Porcine placenta had no Fc receptor activity. The presence of an Fc receptor in human placental tissue may therefore be of significance for the selective transfer of IgG from mother to foetus.

The occurrence of C3b and C3d complement receptors and of Fc and E receptors in normal splenic tissue was studied in cryostat sections incubated with specific marker cells. Thereby the topographic distribution of T and B lymphocytes in the splenic tissue was mapped: Te lymphocytes are found especially in the periateriolar sheaths, B lymphocytes in eccentric zones around the arterioles. The cells in the splenic pulp carry especially Fc, but also C3b receptors, whereas C3d receptors appear to be specific of lymphocytes. The basic lymphocyte traffic behind the mapped distribution of the lymphocyte subpopulations in the spleen was elucidated by lymphocyte kinetic studies using autologous 51Cr-labelled reinfused lymphocytes. These studies were performed partly on normal persons and partly on splenectomized persons without immune defects. The results indicate the presence of an exchangeable pool of T as well as of B lymphocytes in the spleen, the T cell pool being larger and making up in normals about 30% of the total exchangeable T lymphocyte mass. The matrix for the T lymphocyte pool in the spleen is the periateriolar sheaths. The difference in structure between the lymph nodes and the lymphoid tissue of the spleen, including differences in the distribution of lymphocyte subpopulations, are explained by the special vascular arrangement in the spleen.

The number of leukocytes and the percentage of cells in various mononuclear subpopulations were determined in 22 patients with epilepsy. The lymphocyte response to PHA were examined in the patients and in selected controls. The patients were grouped according to phenytoin treatment at present or previously, and according to the presence or absence of serum IgA depression. Patients taking phenytoin demonstrated reduced leukocyte counts. The lowest counts were found in phenytoin-treated patients with markedly reduced IgA concentrations. The number of lymphocytes were reduced more than the total leukocyte count in the patients. No significant differences were observed between patients and controls regarding percentage of cells with membrane-bound immunoglobulins, active E-rosetting cells, AET-rosetting cells, EA-rosetting cells, EAC-rosetting cells, and cells with a capacity of phagocytosis. The mean response to PHA stimulation (PHA concentration 0.6 micrograms/ml) was 4634 counts per minute in the patients and 6132 counts per minute in the controls. However, the response to this stimulation varied considerably between individuals in both groups, and the difference between the 2 groups was not statistically significant.

F(ab')2-fragments of a mouse monoclonal antibody (B1D6) reacting with placental receptors for the Fc part of IgG (FcR) were used as affinity reagents for the purification of an antigen from placental extract (PE). The antigen agglutinated ovine erythrocytes (E) sensitized with rabbit antibodies (A) (EA), but not E or E sensitized with F(ab')2-fragments. It reduced the EA rosette-formation with mononuclear cells and the binding of soluble immune complexes to placental tissue. The antigen bound to aggregated IgG and Fc-fragments of IgG, but not to native IgG or F(ab')2-fragments of IgG. The data indicate that the purified antigen possesses FcR activity with low affinity for IgG. SDS-PAGE and Western blot showed one distinct band of approximately 40 kD. The electrophoretic mobility did not change after reduction and the band reacted with concanavalin A indicating that the FcR are single-chained glycoproteins.

Placental extract was prepared with Tris-HCl buffer pH 7.4 containing EDTA and 2-mercaptoethanol. It agglutinated erythrocytes (E) sensitized with subagglutinating amounts of IgG antibodies from rabbits, guinea pigs and mice, but not E sensitized with IgG from chickens. E or E sensitized with F(ab)2 or IgM antibodies were not agglutinated. The agglutination of EA by the extract was inhibited by human, rabbit and guinea pig IgG, but not by bovine and porcine IgG. Aggregated IgG was more inhibitory than monomeric IgG. IgG3 was the most effective subclass. The extract inhibited the formation of EA rosettes with human mononuclear cells, but did not influence the formation of E or EAC rosettes. The significance of the disulfide bonds and the C gamma 3 and C gamma 2 regions was implied by the finding that the extract neither agglutinated E sensitized with preparations of mildly reduced and alkylated IgG, nor with Facb fragments. These preparations did not inhibit the agglutination. The results strongly indicated that the active component was solubilized placental Fc receptor (FcR). Functionally active FcR was purified by affinity chromatography using aggregated human IgG coupled to Sepharose 4B. SDS-PAGE if the purified FcR under reducing conditions showed one distance band corresponding to approx. 47,000 daltons. The band neither consisted o Ig fragments nor Clq. A rabbit antiserum against the FcR inhibited the agglutination of EA by the extract and stained th FcR-positive areas in placenta.

The distribution of receptors for the Fc portion of IgG (Fc gamma R) in chronic marginal and apical periodontitis were studied by using a monoclonal antibody against placental Fc gamma R and soluble immune complexes as indicators. Cryostat sections were used in indirect immunofluorescence technique. Fc gamma R were detected on varying numbers of cells in the inflammatory cell infiltrates, on endothelial cells of certain vessels and in fibrous tissue. In chronic marginal periodontitis Fc gamma R were also observed on cells within the oral gingival epithelium (OGE) and the pocket epithelium (PE). There was a distinct fluorescence in stratum spinosum and occasionally in stratum basale of OGE and in the coronal portion of the PE. Fc gamma R on Langerhans cells could not be demonstrated. In apical periodontitis Fc gamma R were also detected on cells within the epithelium. In some cases epithelium in periapical cysts was positive. Soluble immune complexes bound to morphologically similar, but fewer cells compared to the monoclonal antibody against Fc gamma R. The results indicate that Fc gamma R are generally expressed on cells in inflamed tissue. Thus, this presence of Fc gamma R on certain specialized cells such as endothelial cells and keratinocytes, may endow these cells with functions previously thought to be restricted to cells of the lymphoreticular system.

Mononuclear cells from 10 healthy blood donors were incubated with ethanol at 37 degrees C for 30 min. An ethanol concentration of 10.0 g/l reduced the percentage of active E rosette-forming cells (E RFC) from 25.0 +/- 12.1 to 16.2 +/- 8.7, and the percentage of total E RFC from 70.3 +/- 8.5 to 59.7 +/- 13.5 (p less than 0.01 for both). The percentage of cells with phagocytizing capacity was reduced from 11.7 +/- 5.4 to 7.0 +/- 5.0 by the ethanol treatment (p less than 0.01). Incubation with ethanol at a concentration of 1.0 g/l also significantly reduced the number of active and total E RFC and of phagocytizing cells. Ethanol at a concentration of 0.1 g/l did not influence these cell subpopulations. The number of EA RFC and EAC RFC were not influenced by ethanol.

Glomeruli in Cryostat sections of foetal and adult renal tissues adsorbed sheep erythrocytes sensitized with IgM antibody and human or mouse complement (EAC). Activated complement was essential for the reaction to occur. The receptor had specificity for the C3b fragment of C3 and is probably of protein or glycoprotein nature. Complement receptors in glomeruli may explain the deposition of complement components or complement-containing complexes in immune-complex glomerulonephritis.

Crysotat sections of human choroid plexus adsorbed erythrocytes sensitized with IgG antibodies of human and rabbit origin. No adsorption occurred when the erythrocytes were sensitized with F(ab')2 or Facb fragments. The reaction was strongly inhibited by intact IgG and by Fc fragments and not inhibited by Facb and F(ab')2 or albumin. These properties are similar to those of corresponding receptors in human placenta. The presence of an Fcgamma receptor in choroid plexus may be of significance for the transfer of IgG from blood to cerebrospinal fluid.

The mixed hemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange (PE) were examined in 24 patients, 16 patients with acute form and 8 patients with the chronic form of the disease. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after the PE. Before PE antibodies were detected in sera from 15 of the patients. These patients showed clinical improvement during the treatment, however in one of the patients only after a time interval of 2 weeks. After PE, antibodies were detected in sera from only 3 of the patients. The 9 patients without detectable antibodies showed no clinical improvement.

An infectivity inhibition micromethod was used to detect interferon (IFN) in sera and suction blister fluids from 35 patients with untreated psoriasis vulgaris. IFN (greater than or equal to 16 units/ml) was detected in 56% of the sera (median 25 units/ml), in 77% of the suction blister fluids from lesional skin (median 35 units/ml) and 33% of the blister fluids from unaffected skin (median 10 units/ml). IFN levels were significantly higher in blister fluids from lesional skin than from unaffected skin (P less than 0.05) indicating local IFN production. Results of characterization experiments indicated the presence of both acid stable and acid labile IFN-alpha as well as IFN-gamma in sera and blister fluids. After Goeckerman therapy, IFN was detected in 91% of the sera (median 89 units/ml), in 90% of the blister fluids from lesional skin (median 50.5 units/ml) and in 72% of the blister fluids from unaffected skin (median 26.5 units/ml). The IFN levels in sera were significantly higher than in blister fluids from both lesional skin (P = 0.05), and unaffected skin (P = 0.001). Furthermore, after Goeckerman therapy the IFN levels in blister fluids from unaffected skin and in sera were significantly higher than those in untreated patients (P = 0.01 and P = 0.0001) respectively. The results indicate that UVB radiation induces systemic IFN production.

Skin biopsies from a patient with epidermolysis bullosa acquisita (EBA) were studied ultrastructurally and by immuno-electron microscopy. The specimens were taken from non-predilection areas as well as of the skin predilection areas of the patient. In vivo deposits of IgG were found below the lamina densa associated with the anchoring fibrils in all areas of the skin. The bullae and the artificial friction blisters appeared in the same position on the dermal side of lamina densa. The results suggest that epidermolysis bullosa acquisita is a distinct nosologic entity. The close resemblance of epidermolysis bullosa acquisita to cicatricial pemphigoid in immunofluorescence studies makes the use of immuno-electron microscopy important in the classification of the diseases.

Properties of the IgG receptors were studied by treating tissue sections or suspensions of peripheral mononuclear cells with various chemical reagents and determining changes in their ability to react with IgG-sensitized erythrocytes (EA). A heterogeneity of the Fc receptors was revealed. Iodoacetamide, 2-mercaptoethanol, sodium azide, EDTA, and a pH varying from 6.0 to 8.2 had no effect on Fc receptors in sections of normal lymphoreticular tissue and malignant tissue. Formaldehyde, low pH, and high salt concentrations affected receptor activity to various degrees. Receptors in liver sections and on monocytes were generally more resistant than receptors in spleen sections and on B lymphocytes. Receptors in malignant tissue behaved either like receptors in spleen or like receptors in liver. Although all tissues were sensitive to periodic acid, the Fc receptors in malignant tissue were always more resistant.

Among eight sural nerve biopsies from patients with the Guillain-Barré syndrome (GBS), demyelination was observed in five and endoneural mononuclear cell infiltrates in three. Receptors for the activated third component of complement (C3b) were detected within the nerve fascicles. The receptor activity was reduced in five biopsies, and in vivo deposition of C3 within the endoneurium occurred in four. Immunoglobulins were found in four biopsies and appeared to be localized along the myelin sheaths. Both T and B lymphocytes could be detected in the mononuclear cell infiltrates, but the relative proportions of these cells could not be determined. Macrophages present in two biopsies were found to possess IgG Fc receptors. The results indicate that the complement receptors may play a role in the binding of complement-containing complexes in the nerve during the GBS disease process.

HLA-DR antigens and receptors for the Fc part of IgG (Fc gamma R) were studied in cryostat sections of thymus tissue from 24 fetuses, infants and children, using indirect immunofluorescence and indirect immunoperoxidase technique. HLA-DR antigens, detected by a monoclonal antibody (OKIa 1), occurred on the thymic epithelial cells at 11 weeks of gestation, while Fc gamma R, detected by immune complexes and by human heat-aggregated IgG, were present at 10 weeks of gestation. The intensity of the staining for HLA-DR antigens was maximal at about 18 weeks of gestation, while the Fc gamma R activity was maximal at 10-11 weeks. HLA-DR antigens also occurred along the membrane of a few thymocytes, especially in the cortex, while Fc gamma R-activity occurred along the membrane of most of the immature thymocytes. Thymocytes in suspension were examined from children only. Such thymocytes were not stained by OKIa 1, and only 2-6% had detectable Fc gamma R.