Hemagglutinin-specific complement-dependent cytolytic antibody response to influenza infection.

The host defense response to influenza infection is complex. Specific humoral antibodies develop to the strain-specific surface antigens, the hemagglutinin and the neuraminidase, and to the internal antigens (matrix and nucleoprotein) which are common to all influenza A viruses (1). Antibodies to the hemagglutinin, which is the major surface antigen, neutralize viral infectivity (2). In addition to antibodies which have been detected against virion antigens, a cytotoxic T-cell response with specificity against the viral hemagglutinin on influenza-infected target cells (3-5) has been recently described. A more cross-reactive cytotoxic T-cell response has also been observed when a nonpermissively infected target cell is used in cytotoxicity assays (6,7). The present report describes the development during influenza infection and after vaccination of a cytolytic humoral antibody response which is directed against the hemagglutinin on infected target cells. This antibody-mediated lysis of infected cells in complement dependent, as has been reported with other virus infections (8-11).

Intra-blood-brain barrier measles virus antibody synthesis in multiple sclerosis patients.

Antibodies to nine viruses were measured in serum and CSF of MS patients, patients with other neurologic diseases (OND), and healthy controls. The extent of antibody production inside the blood-brain barrier (BBB) was determined by making a new correction for BBB permeability. Compared with OND and healthy controls, MS patients as a group had significantly higher corrected CSF:serum antibody ratios for measles virus but not to the other eight viruses studied. The incidence of significantly high CSF:serum ratios for measles antibody in MS patients was 50%, and in the other two control groups it was 0 to 12%. The incidence of corrected antibody ratios to the other eight viruses was not significantly different among the three groups.

Cytolytic, complement-dependent antibodies to measles virus in rhesus monkeys after administration of live or killed virus.

Infection of rhesus monkeys with measles virus induced specific complement-dependent cytolytic antibodies during the early phase of acute infection. The development of maximal levels of the complement-dependent cytolytic antibodies appears to be dependent on the respiratory rather than the parenteral route of infection and on the use of live rather than killed measles virus. These levels of cytolytic antibodies seem to be independent of levels of simultaneously developing neutralizing and hemagglutinating antibodies. It is proposed that complement-dependent cytolytic antibodies play an important role in the elimination of acute measles virus in vivo by lysing the foci of infected cells and by blocking the spread of virus by cell fusion.

Immune responses during measles infection in immunosuppressed Rhesus monkeys.

Rhesus monkeys immunosuppressed with horse anti-human thymocyte gamma-globulin (ATG) were infected with measles and simultaneously inoculated with sheep erythrocytes (SRBC), a thymus-dependent antigen, and with pneumococcal polysaccaride type III (SSS-III), a thymus-independent antigen. ATG treatment alone suppressed SRBC antibody production, had no effect on SSS-III antibody production, and effectively eliminated circulating T cells compared to nonsuppressed monkeys. ATG treatment of measles-infected monkeys resulted in delayed virus clearance and delayed antibody production compared to nonsuppressed infected monkeys. After cessation of ATG treatment, measles antibodies and T cells reached normal levels, and measles virus was eliminated. Thus, immune clearance of measles virus is T cell-dependent, but the relative roles of cellular- and humoral-mediated immunity in vivo could not be clearly separated. Also, measles infection was associated with a decreased T cell mitogen responsiveness of circulating lymphocytes but not of lymph node lymphocytes, suggesting an altered circulating pattern of the cells responsible for delayed hypersensitivity. Also, measles infection had no effect on T-dependent antibody production to SRBC.

Analysis of complement-dependent antibody-mediated lysis of target cells acutely infected with measles.

A sensitive assay for the detection of complement-dependent cytolytic measles-antibodies in monkey and human sera is described. The high sensitivity of the technique is dependent upon the use of Vero or MA-104 cells acutely infected with a high-titered, non-syncitiogenic strain of attenuated measles virus. Cytolytic antibody titers of serum can be determined either by endpoint dilution in the presence of a standard dilution of heterologous (guinea pig) complement or by percentage of lysis of a specific number of target cells at a standard dilution of immune serum (1:32). The latter technique proved expedient in the comparison of cytolytic activities of large numbers of serum samples. Clearly, the alternative complement pathway is effective in lysis of these cells, but neither the classical nor the alternative pathway alone appears to be as effective as both pathways combined. No prozone effect occurred with homologous complement, and inhibition of lysis was eliminated by washing sensitized cells before addition of heterologous complement. Lysis of measles-infected cells untreated with measles antibody occurred in the presence of both normal and C4-deficient guinea pig serum at high concentrations, but no such activity occurred with non-immune human or rhesus serum. Antibody-mediated complement-dependent lysis of measles-infected cells may be an important immune defense against acute measles infection.

Search for type-C oncornavirus-related genetic information in tissues from patients with systemic lupus erythematosus.

Single-stranded 3H-DNA probes complementary to the RNA of Rauscher murine leukemia virus and of simian sarcoma virus were prepared using techniques that permitted complete transcription of the viral genome of each virus. These probes were used in DNA-DNA hybridization studies with the cellular DNA from uncultured specimens of spleens and placentas of patients with systemic lupus erythematosus (SLE). No proviral DNA sequences related to these viruses were detected in these tissues. The results presented here do not support previously reported antigenic data implicating type-C oncornavirus infection of these organs in SLE.

Sensitive neutralization test for virus antibody. 1. Mumps antibody.

A sensitive mumps virus plaque neutralization test has been developed based on the potentiation of virus-antibody complexes by heterologous anti-immunoglobulins (AIG). The enhanced neutralization test was approximately 100 times more sensitive than the conventional neutralization test or the hemagglutination-inhibition test. Using AIG against human immunoglobulin G (IgG) or human IgM permitted determination of the relative titers of the two classes of mumps antibody. The test does not require special equipment or expertise and can be readily introduced in virological laboratories.

Raised cytomegalovirus-antibody level in cerebrospinal fluid of schizophrenic patients.

The serum and cerebrospinal fluid (CSF) of 60 schizophrenic patients and 26 controls were analysed for viral antibody against cytomegalovirus (CMV), vaccinia virus, herpes simplex virus type 1 (HSV), and type A influenza virus. A CSF/serum antibody ratio more than 2 standard deviations above the mean of the controls suggested local antibody production in the central nervous system. 68% of the patients had an increased CSF/serum antibody ratio for CMV antibody, 14% for vaccinia antibody, 4% for HSV antibody, and 15% for influenza virus antibody.

Search for Epstein-Barr and type C oncornaviruses in systemic lupus erythematosus.

Lymphoblastoid cell lines were derived from patients with active systemic lupus erythematosus by allowing spontaneous transformation of peripheral B lymphocytes (B cells) harboring endogenous Epstein-Barr virus or by superinfecting peripheral lymphocytes with exogeneous Epstein-Barr virus. Results of extensive studies aimed at identifying type C oncornaviruses in these lymphoblastoid cells were entirely negative by electron microscopy, DNA-DNA hybridization, reverse transcriptase assays, and cocultivation experiments. These results do not support the postulated association of oncornavirus infection in human systemic erythematosus.

Neuromuscular and immunochemical abnormalities in an adult man with Kawasaki disease.

A 40-year-old black man developed the primary features of Kawasaki disease, along with a pronounced distal motor and sensory neuropathy, abnormal electromyograms, and elevated creatine kinase levels. Results of the biopsy of a distal muscle showed myonecrosis, some type II grouping, immunoglobulin deposition in the sarcolemma, and disordered sarcomeric alignment with dilated T-tubules and terminal cisternae. Immunologic evaluation showed high concentrations of cryoglobulins and circulating immune complexes. It is possible that several manifestations of Kawasaki disease are mediated by immune complex deposition in vessels and tissues.

The Quadriplegia Index of Function (QIF): sensitivity and reliability demonstrated in a study of thirty quadriplegic patients.

The Quadriplegia Index of Function (QIF) was originally developed by the authors in 1980 because the popular Barthel Index was deemed too insensitive to document the small but significant functional gains made by quadriplegics (tetraplegics) during medical rehabilitation. The QIF has now been tested on a group of 30 complete quadriplegic patients at admission to and discharge from inpatient medical rehabilitation. Resultant scores were compared to those simultaneously obtained by the Barthel Index and the Kenny Self-Care Evaluation. The QIF was found to be more sensitive (46 per cent improvement as opposed to 30 per cent by the Kenny Self Care Evaluation and 20 per cent by the Barthel Index). The QIF was also tested for reliability. Ratings by three different nurses, working independently, were found to be significantly positively correlated for all sub-scores (p less than .001). We conclude that the QIF provides a useful option in choosing a functional assessment instrument for use with quadriplegic patients.