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The previous observations of cross idiotypic specificity of IgM cold agglutinins were further investigated in quantitative precipitin assays and attempts were made to relate shared idiotypic specificity to combining specificity for I, i and Pr antigens of red cells. Shared idiotypic determinants were observed among antJ-I and anti-i antibodies which are now known to have combining specificity for determinants present on precursors of the ABH and Lewis blood group substances. There was evidence that one cold agglutinin. Ma, which had previously been shown to have an unusual kind of I specificity was deficient in the idiotypic determinants associated with the other anti-I proteins. Anti-Pr cold agglutinins, which have specificities unrelated to I-i antigens, were found to have distinct cross idiotypic determinants which were not detected on anti-I and anti-i antibodies. IgA and IgM antibodies with Pr specificity isolated from different individuals were found to share idiotypic determinants. Cross specificity antigens were detected at low concentrations in preparations of normal IgG and IgM, but not in any isolated monoclonal macroglobulins lacking cold agglutinin activity. [ABSTRACT FROM AUTHOR]

Quantitative measurements of immunoglobulins E, A and G were made in tracheobronchial secretion and serum of thirty-four patients in association with bronchoscopy. Measurable quantities of all three immunoglobulins were found in both secretion and serum in all patients, except in one person, in whom IgA was found neither in the secretion nor the serum, and in another person in whom no measurable IgG was found in the secretion. Calculations indicated that all immunoglobulins were produced locally in the tracheo-bronchial mucosa. This applied especially to IgA and IgE, of which 84 and 73% respectively, were calculated to have been produced locally. Quantitative differences between the three immunoglobulins were also apparent between different groups of patients. The number of patients studied is too small, however, for definite conclusions to be drawn in this respect. [ABSTRACT FROM AUTHOR]

Radioiodine-labelled globulins from antisera directed against mouse immunoglobulin, are fixed by cells of various mouse ascites tumours, thus indicating that the cells are coated in vivo with immunoglobulins. The amounts of tumour-bound immunoglobulin in the tumour-bearing animal increase as the time interval between tumour inoculation and the harvest of tumour cells increases. Tumour cells from mice which had been irradiated prior to the tumour inoculation are associated, in general, with lower amounts of immunoglobulin than tumour cells from unirradiated mice. [ABSTRACT FROM AUTHOR]

The serum immunoglobulins IgG, IgA, IgM and IgE were determined together with indirect haemagglutination test in normal subjects and in patients with intestinal and extra-intestinal amoebiasis. The IgG level in intestinal amoebiasis was found to be significantly higher than that of extra-intestinal. Although in intestinal amoebiasis, the concentrations of IgE were comparatively higher than extra-intestinal group, the IgE levels in both groups of amoebiasis were seen to be much higher than that of the normal group. No significant difference was found in the IgA and IgM levels between the three groups of cases. Indirect haemagglutination test was positive in both intestinal and extra-intestinal amoebiasis, but negative in normal subjects. [ABSTRACT FROM AUTHOR]

The frequency of cryoglobulinaemia was statistically significant in acute proliferative endocapillary glomerulonephritis, in membrana-proliferative glomerulonephritis and in lupus glomerulonephritis. They all have in common glomerular cellular proliferation and glomerular deposits of C3. The cryoglobulin's in most of these cases contain IgG and IgM. Except for acute proliferative endocapillary glomerulonephritis, a rather good correlation was observed between the cryoglobulin constituents and the immunoglobulins present in the glomerular tuft. Rheumatoid factor was very rarely found in the serum of these patients. A cryoglobulin characterized by the presence of the three immunoglobulins was also found in cirrhosis of the liver with or without proven glomerulonephritis. [ABSTRACT FROM AUTHOR]

Membrane-associated immunoglobulins of peripheral blood lymphocytes were studied by indirect immunofluorescence for γ, α, μ, κ, and λ chains in healthy subjects and patients with immunologic disease. In healthy subjects, heavy chains were found on 30.7% of lymphocytes (γ 15.3%, α 7.2% and μ 8.2%) and light chains on 32.8% of cells (κ 20.4% and λ 12.4%). Patients with humoral immune deficiencies had fewer immunoglobulin-bearing cells; sarcoidosis or thymectomy patients had normal or decreased immunoglobulin-bearing lymphocytes; cells with light chains were fewer than those with heavy chains on their lymphocytes. In some cases, normal levels of serum immunoglobulins were found in the absence of the corresponding immunoglobulin-bearing cells, and in others normal immunoglobulin-bearing lymphocytes were present in the absence of the corresponding serum immunoglobulins. These data suggest that (1) immunoglobulin-bearing lymphocytes in blood do not reflect the condition of immunoglobulin-synthesizing cells in peripheral lymphoid tissues, and (2) in certain immunologic disorders, either some B-lymphocytes do not synthesize immunoglobulins, or immunoglobulins are in such a situation that the whole molecule or part of the molecule is not visualized by current methods. [ABSTRACT FROM AUTHOR]

Peripheral blood lymphocytes of twenty normal controls and twelve patients with primary immunodeficiencies were examined for surface membrane Ig and receptors for C3 complement (B cell markers) and for spontaneous rosette formation with sheep erythrocytes (T cell markers). In patients with defects in T cell function no lymphocytes forming spontaneous rosettes were seen. In patients with B cell deficiency they were normal or increased. Lymphocytes with membrane immunoglobulins were normal in patients with T cell defect and absent in patients with severe agammaglobulinaemia. Lymphocytes with receptors for C3 complement were increased in patients with T defect and normal in patients with most other forms of immunodeficiency studied. [ABSTRACT FROM AUTHOR]

A study on the synthesis of immunoglobulins (IgG, IgA, IgM, IgD, and IgE), secretory component and complement in normal and pathological skin and in the adjacent mucous membranes (I.e. conjunctiva, nasal, oral and vaginal mucosa) is reported. The results are based on the culture of tissue samples in a medium with two radioactive amino acids and the detection of synthesized proteins by autoradiography of the immunoelectrophoretic pattern of the culture fluid, except in the case of IgE for which the Ouchlerlony technique was used. The results indicate that the normal skin does not synthesize immunoglobulins, whereas normal mucous membranes produce IgG and IgA. In the lesions of various skin diseases immunoglobulins are synthesized, mainly IgG but sometimes also IgA and IgE. The cells responsible for the production of immunoglobulins are plasma cells and lymphoid cells present in the skin lesions and mucous membranes. Synthesis of the free secretory component could be demonstrated only in certain mucous membranes (i.e. conjunctiva, nasal mucosa. and oral mucosa). Complement (C3) synthesis was found in normal skin, mucous membranes (i.e. conjunctiva, nasal and oral mucosa), and in the lesions of such skin diseases as discoid lupus erythematosus. (bullous) pemphigoid, dermatitis herpetiformis, malignant rcticulosis, eczema and lichen planus. Complement production was also demonstrated in allergic skin reactions (i.e. tissue from allergic-positive patch tests, positive Mantoux tests and drug eruptions), but no immunoglobulin synthesis was detected in these lesions. [ABSTRACT FROM AUTHOR]

Scrum immunoglobulins, complement component levels and autoantibodies were measured in patients presenting with acute and chronic liver disease. One-hundred and seventeen patients were studied and the results of the immunological estimations were found to be of value in the differential diagnosis of liver disease when considered in conjunction with clinical and other laboratory findings. The results of the study are of interest in discussing the possible pathogenesis of liver disease. [ABSTRACT FROM AUTHOR]

The catabolism of 131I and 125I paired labelled Fc fragments of myeloma proteins and of H chain disease proteins of different heavy chain subclasses was studied in men and monkeys. In contrast to the previously demonstrated catabolic heterogeneity of intact -γG immunoglobulins, the Fc fragments and H chain disease proteins of all subclasses tested were catabolized at a similar rale. These data suggest that structures not present of the Fc fragments are responsible for the faster turnover rate of 7G3 immunoglobulins and for the differences in half-lives of myeloma proteins within a given subclass. The catabolic features of the H chain disease proteins differed from those of intact γG. Although the whole body half-lives of the two proteins were similar, the fractional turnover rate of the H chain disease proteins was higher than that of γG, on the average 8% of the intravascular pool/day as compared to 4% for γG. One-half to 1% of the intravascular pool of the H chain disease protein and less than 0-1% of the γG was excreted into the urine. An average of 24% of the H chain disease proteins and 44% of the γG equilibrated into the intravascular compartment. [ABSTRACT FROM AUTHOR]

A report is given of the immunologic and haematologic changes in a 24-year-old man with juvenile Gaucher's disease who received a splenic homograft from an unrelated living donor. To judge from the spleen scans, the graft functioned for 6 weeks. During the latter part of this time erythrocytes with donor markers were detected in the recipient's blood, and at the same time antibodies to one of the donor erythrocyte antigens appeared. No lymphocytes of donors type or cytotoxic antibodies to such lymphocytes were found. Three weeks after the transplantation the immunologic reactivity of the recipient lymphocytes, as measured in vitro, was decreased. There were no significant changes in the plasma level of immunoglobulins or coagulation factors. [ABSTRACT FROM AUTHOR]

Antibodies in human sera against four different antigens of human spermatozoa discovered by means of an indirect two-layer immunofluorescence technique (IFT) were characterized by determination of the class of immunoglobulins to which they belonged. A three-layer IFT using monospecific antisera against human IgG, IgA or IgM as the second layer was employed together with fractionation of sera on Sephadex G-200 or DEAE-cellulose followed by testing of the concentrated pools in a two-layer IFT. The study revealed that antibodies against the antigen in the front part of the acrosome were primarily IgM and those against the antigen in the tail primarily IgG. Antibodies against antigens in the equatorial segment and the postnuclear cap showed a varying predominance of these two immunoglobulins. Spermatozoal antibody as IgA was found only in small amounts. [ABSTRACT FROM AUTHOR]

Partial purification of soluble products of guinea-pig lymphocyte activation (LAP) was undertaken by fractional precipitation with ammonium sulphate, ion-exchange and Sephadex chromatography, and by immune precipitation of inducing antigen and of contaminating serum protein. During these purification steps the activity of macrophage migration-inhibition factor (MIF) was concentrated up to 1300-fold and separated from inducing antigen and serum protein. An endpoint assay was devised for expressing antigen-induced MIF activity of LAP fractions as weights of material giving 30% inhibition of migration (MI30 doses). MIF activity precipitated between 50% and 80% saturated ammonium sulphate and eluted from DEAE-cellulose at pH 7-9 at intermediate salt concentrations (0-03-0-2 M phosphate). On Sephadex gel filtration MIF activity was concentrated in fractions of molecular weight range 56,000-82,000 with a smaller amount of activity eluting from 20,000-56,000. After immune precipitation of extraneous protein and elution from DEAE-cellulose, LAP material was found to have an MI30 dose of 0-4 /μg. Materials representative of antigen and serum protein-depleted MIF were selected for intralymphatic injection in order to determine whether MIF-rich LAP fractions were able to induce paracortical distension in guinea-pig lymph nodes (see following paper). [ABSTRACT FROM AUTHOR]

A method for determining the antigen-binding activities of specific immunoglobulins in serum is described. Samples of sera were applied to commercial immunodiffusion plates and unprecipitated proteins eluted. The precipitate circles were challenged with specific radio-labelled antigen and exposed to X-ray film. Blackened circles on the radioautograph were found to be good indices of the antigen-binding activity of each immunoglobulin and could be monitored using a Beckman Model R Analytrol. The height of each analytrol peak provided an objective estimate of the intensity of darkening. Variation in the amount of added radio-antigen had a direct effect upon the intensity of the darkened circle at low concentrations. At a given concentration of antigen, however, all antigen-binding sites became saturated and additional increases in antigen concentration did not further increase the density of blackening. The quantity of antigen required to just saturate the combining sites of a particular immunoglobulin is a measure of the antigen-binding activity of that immunoglobulin. The employment and some of the applications of this relatively simple radio-isotopic technique are discussed. [ABSTRACT FROM AUTHOR]

Improvements have been made in a localized haemolysis in gel replica assay developed previously. The technique is designed to show if an individual antibody producing cell releases antibody of one or more classes. The techniques can also be used to indicate the specificity of antibodies produced by individual cells by using two different antigens in the test system. In experiments where both slides of a slide-pair are untreated or treated identically, and 100% coincidence of plaques is expected, the technique has been shown to detect about 95% coincidence, Pairs of slides treated differently to reveal plaques due to antibodies of different classes show a mean of about 3.5% coincident plaques. This `background' of coincidence which it is thought is not due to `double-producers', is one of the limiting factors of the technique. [ABSTRACT FROM AUTHOR]