Epstein-Barr virus-specific serum immunoglobulin A as an acute-phase antibody in infectious mononucleosis.

Immunoglobulin A (IgA) antibodies to Epstein-Barr virus viral capsid antigen were assayed serially in 19 patients with infectious mononucleosis and in 38 controls. Seventy-four percent of infectious mononucleosis patients demonstrated IgA antibody, whereas this was found in 13% of controls. This antibody appeared early in infectious mononucleosis and was virtually gone 10 weeks after onset. Comparison of IgA antibody kinetics was made with IgG and IgM antibodies to viral capsid antigen, heterophile antibody, and antibody to Epstein-Barr virus early antigen and nuclear antigen. Failure to demonstrate IgA antibody was associated with severe illness, prolonged illness, delay in IgG and anti-Epstein-Barr virus nuclear antigen antibody, and low or absent heterophile and anti-early antigen antibody. Assay of IgA antibody to viral capsid antigen is a potentially useful adjunct in the serodiagnosis of infectious mononucleosis or recent Epstein-Barr virus infection, as are the other antibodies tested, but in this study IgM viral capsid antigen antibody was the only acute-phase antibody present in all patients.     

Liver-specific and shared cell membrane antigens. Studies by light- and electron microscopy.

Liver-specific and shared saline-insoluble cell surface antigens were localized by immunofluorescence as well as by light- and electron microscopic immunoenzyme techniques. Antisera against purified mouse liver cell membranes were surface membrane but not organ-specific. Variable quantities of shared antigens were present in endoderm- and mesoderm-derived organs but not in ectodermal nerve tissue. Species crossreactivity was observed for the rat. Repeated absorption produced liver-specific antisera that reacted with antigenic sites distributed along the entire hepatocyte and sinusoidal cell surfaces. For the precise localization as well as the detection of low concentrations of both liver-specific and nonspecific antigens, the ultrastructural visualization of reactive sites proved essential.     

Insoluble polyanions as activators of both pathways of complement

Soluble polyanions, e.g. dextran sulphate, are known to interact with components of the classical pathway of complement and also to activate the alternative pathway (APC).† Insoluble polyanions offer the opportunity to isolate and to characterize intermediates of the reaction sequence. Sephadex, an insoluble, crosslinked dextran, was substituted with sulphate groups using chlorosulphonic acid. The sulphated Sephadex (SS) activated the APC in normal and in C4-deficient-guinea-pig serum as shown by haemolytic and immunochemical methods. After incubation of SS with normal guinea-pig serum, a C3-cleaving enzyme bound to the SS particles was present. This enzyme was inhibited by antisera against the components C2 and C4. Anti-serum against factor B or anti-C3-Fab had no inhibitory effect. Incubation at 37° inactivated the enzyme; activity was restored by incubation with C2, but not with factors B and D of the APC. These results suggest the presence of the C[unk]42-enzyme bound to the SS particles after incubation with normal serum. However, preincubation of SS with C4 deficient serum did not yield an enzyme which could act on purified C3, but enzymatic activity cleaving C4 and C2 was present, indicating that binding and activation of C1 had occurred. Utilizing purified C[unk]1, it was shown that SS binds purified C[unk]1 in a functionally active state. These data indicate that the polyanion SS has a dual function: SS activates both the APC and the classical sequence. Thus, the chemically simple, ester-linked, anionic sulphate groups, distributed along crosslinked polysaccharide chains, are sufficient to be recognized as initiating signal for both pathways of complement.     

Hydatidiform mole: parental chromosome aberrations in partial and complete moles.

The relationship between parental constitutional chromosome abnormalities and the development of hydatidiform mole was evaluated in series from four institutions. Karyotype analysis was performed on blood samples from 237 patients with a pathological diagnosis of complete mole and 217 of their spouses. One patient was found to have a constitutional balanced translocation, t(11;18), while one spouse was found to have a balanced translocation, t(4;20). Among 125 patients with partial mole and 106 of their spouses, one male was found to be a translocation carrier, t(13;14). No significant increase in the frequency of translocations in the parents of complete moles was found in any of the series considered separately or together. Data from the combined series show no evidence of constitutional parental chromosome aberrations as an aetiological factor in the development of molar pregnancies.     

Cyclosporin A Inhibits a Discrete Step in T-Lymphocyte Stimulation

Cyclosporin A (CyA) interferes with immune responses and prevents growth factor release by stimulated T cells. However, it is not known whether this is due to an effect on the accessory cells, required for T-cell responses, whether antigen recognition cannot occur, or whether later steps, leading to lymphokine production, are blocked. For this reason, the effect of CyA on homogeneous populations of T tumour cells was investigated. The immunosuppressive compound efficiently prevented T-cell growth factor (TCGF) (interleukin 2) release by stimulated tumour cells. Still, the cells retained the surface antigen T3, known to be involved in T-cell stimulation, after treatment with CyA. Furthermore, CyA failed to affect the inhibition of proliferation, observed in a T-cell tumour in response to stimulation, indicating that the cells had received the stimulatory impetus, TCGF release, induced by treatment with a phorbol ester, was only partly sensitive to inhibition by CyA, demonstrating that CyA will interfere with discrete aspects of the stimulation of a T-cell.     

Effect of spleen exposure to ultrasound on cellular and antibody-mediated immune reactions in man

Spleen exposure to ultrasound has been reported to influence antibody response to sheep red blood cell injection in mice (decreased hemagglutination and hemolytic titers and IgM, IgG2a and IgG2b levels and elevated IgG1 levels). In a controlled clinical trial, we investigated the possible immunosuppressive side-effect of splenic exposure (2.0 mW/m², 3.5 MHz, 5 minutes) to ultrasound on the immune response to Rubella vaccination in 41 anti-Rubella antibody-negative volunteers. The measured parameters (blood cell count, IgA, IgM, IgG including subclasses IgG1-IgG4, isoagglutinins, anti-Rubella hemagglutinin and hemolysin titers, complement C3, skin tests to mumps and tuberculin, T, B and O lymphocytes, esterase-positive and negative T-cell subsets) suggest changes dependent on the time of vaccination, but provide no evidence of an immunosuppressive effect of ultrasound in man.     

Two kinds of resting discharge in cat muscle spindles.

1. The behavior of primary endings of cat soleus muscle spindles was studied during shortening steps carried out at different muscle lengths. 2. Spindles were of two kinds: one, silent spindles, whose afferents fell silent after the shortening, at least over part of the range of lengths tested. The second, spontaneous spindles, resumed firing at all lengths. 3. For silent spindles, the duration of the silent period, measured at lengths where they did recover a resting rate, depended directly on muscle length and became shorter at longer lengths. This is what would be expected if the slack introduced in the spindle by the shortening step was removed more rapidly at longer lengths by the higher passive tension. For spontaneous spindles, on the other hand, the duration of the silent period after the shortening was largely independent of muscle length and depended on the spindle's rate of firing immediately before the shortening. 4. At intermediate lengths the discharge of slack spontaneous spindles remained unaffected by an isometric muscle contraction. It was therefore not possible to produce a pause in the discharge, behavior normally taken as typical of spindles. The discharge could be interrupted by the contraction if this was combined with a large shortening movement. 5. It is proposed that when intrafusal fibers are slackened by a shortening step, the resting discharge in spontaneous spindles is generated by a maintained depolarization of the annulospiral ending resulting from extension of the terminal coils by forces from within the receptor. A shortening contraction compresses the spirals to interrupt the discharge. The sensory endings of silent spindles remain below threshold until the spirals have been opened out sufficiently by external stretch.     

Recombinant 25-kDa CD23 and interleukin 1 alpha promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis.

Germinal centers contain a proliferating pool of centroblasts which give rise to non-dividing centrocyte. Centrocytes are programmed to die by apoptosis unless they receive a positive signal for rescue. Rescue, in vivo, is likely to be dependent, initially, on interaction with antigen held on follicular dendritic cells (FDC). A subset of FDC located in that part of the germinal center furthest from centroblasts is particularly rich in CD23. Supernatants containing high levels of soluble CD23 were found not only to encourage the survival of germinal center B cells but also to promote their differentiation toward a plasmacytoid morphology; these activities were diminished following removal of CD23 from the supernatants. Recombinant 25-kDa CD23 was initially found to be incapable of providing the signal for germinal center cell development but on the addition of interleukin 1 alpha which, by itself, was inactive, rescue and differentiation of germinal center B cells were now achieved. Apoptosis in germinal center cells could also be prevented by the ligation of surface CD40 with monoclonal antibody: however, rescue via this pathway was not accompanied by plasmacytoid differentiation. These findings provide a functional rationale to the high level expression of CD23 found within a discrete subset of FDC and indicate a bifurcation in the development of germinal center B cells following their rescue from apoptosis.