Biomedical subjects
G Kronvall
Publications and source records attributed to G Kronvall.
Does nonspecific T-lymphocyte stimulation of B lymphocytes occur during reversal reaction in borderline leprosy?
Serum immunoglobulins G, A, and M were estimated in 14 patients with border-line cases of leprosy at commencement of treatment and subsequently when they developed 'reversal reaction'. There was a significant increase in all immunoglobulin levels during the reaction, with a subsequent fall; the postreaction values for IgG and IgA were below the base-line figures. Additonal investigations in six patients indicated that the rise was a nonspecific one, not brought about by an increase in antimycobacterial antibodies. It seems likely that the rise in immunoglobulins during reaction is due to nonspecific T-lymphocyte stimulation of B lymphocytes.
Interaction of streptococci with the Fc fragment of IgG.
The capacity of human IgG to interact with beta-haemolytic streptococci was studied in order to localize the site of interaction on the IgG molecule. The reactivity of different proteolytic fragments of IgG with streptococci group A, type M 1 and type M 56, group C and group G, was investigated by measuring their inhibitory effect on the uptake of 125I labelled IgG myeloma protein by the streptococci. Equivalent molar amounts of Fc fragment and undigested IgG inhibited the uptake of 125I labelled IgG myeloma protein equally well while only slight inhibition was obtained by F(ab')2 preparations. No reactivity was found with IgM, Fab or chymotrypsin produced fragment Fc', of IgG. The reactivity of IgG with the streptococci was localized to the Fc fragment. Since the Fc' fragment was non-reactive, the CH2 domain was probably carrying the IgG structures involved in the interaction with streptococci.
Studies of mycobacterial antigens, with special reference to Mycobacterium leprae.
Eight individual antigens were detected in soluble antigen preparations from Mycobacterium leprae bacilli by using pools of serum samples from lepromatous leprosy patients as antibody reagents in crossed immunoelectrophoresis. Two of these antigens were analyzed further. Antgent no. 1 gave an elution pattern on Sephadex G-200 corresponding to a molecular weight of 285,000. This antigen was also present in three slow-growing and eight fast-growing mycobacterial species. There was a reaction of complete identity in immunological tests using lepromatous serum pools as well as with rabbit antisera raised against M. leprae and M. smegmatis. Antigen no. 21 of M. leprae showed antigenic heterogeneity when compared with other species. Three types of antigenic determinants were detected; one, called 21A, was shared by all mycobacteria, another, called 21B, was limited to antigen no. 21 of M. leprae; a third, called 21C, was present in all mycobacteria except the leprosy bacillus. This submolecular heterogeneity may indicate a separate taxonomic position of M. leprae among the mycobacteria.
Immune complexes and complement hypercatabolism in patients with leprosy.
The occurrence of immune complexes in the serum and the level of the C3 breakdown product C3d in the plasma from patients with leprosy were studied by quantitative methods and the results were compared in various forms of the disease. These studies were performed on sixty-two samples from twenty-six patients. The serum 125I-C1q binding activity was found to be increased by more than 2 s.d., as compared to the normal values, in most of the sera from patients with erythema nodosum leprosum (ENL) (80%) and uncomplicated lepromatous leprosy (82%), but also in the sera from patients with tuberculoid leprosy (58%). In vitro studies suggested that immune complexes involving mycobacterial antigens were present in leprosy sera. An increased C3d level (greater than 2s.d.) was also found in most of the plasma from patients with ENL (70%), but rarely in the plasma from patients with uncomplicated lepromatous leprosy (18%) and never in tuberculoid leprosy patients' plasma. The absence of a significant correlation between the 125I-C1q binding activity and the C3d level in leprosy patients may suggest that extravascular immune complexes are involved in the complement activation occurring in ENL. The quantitation of C3d in plasma may be of some practical interest in the early diagnosis of ENL complications of leprosy.
Lymphocyte transformation test in leprosy; correlation of the response with inflammation of lesions.
Lymphocyte transformation tests (LTT) using 'whole washed" and 'sonicated" preparations of Mycobacterium leprae (M. leprae) as antigen were studied in eighty-one patients with borderline leprosy. The results were correlated with the histological and the clinical pictures. There was a good correlation with the histological spectrum, LTT responses generally being higher in the borderline tuberculoid leprosy patients and lower in the borderline lepromatous. However, considerable variation was noted in each group of the borderline leprosy spectrum, and it was found that this was due in part to the degree of inflammation in the skin. Thus those with 'inflamed" skin lesions had higher responses than those with 'silent" lesions, and even those with borderline lepromatous leprosy with inflamed lesions had higher responses than those with borderline tuberculoid leprosy whose lesions were silent. Those who had reversal reactions, where inflammation is very marked, had very high LTT responses which fell with treatment of the reaction with steroids. It thus appears that the LTT in leprosy is influenced by the occurrence of hypersensitivity reactions as well as by the patient's ability to resist bacillary multiplication.
Antigenic heterogeneity in patients with reactions in borderline leprosy.
Fifteen patients with borderline leprosy who developed "reversal" reactions were studied from the inception of treatment. Thirteen showed an appreciable increase in lymphocyte transformation (LT) when preparations of Mycobacterium leprae were used as antigen. The LT responses to either "whole" or "sonicated" preparations of the bacillus in these 15 patients and in nine others also in reaction correlated with the clinical presentation. Those with skin disease predominating in the reaction showed an appreciable increase in LT when whole M leprae was used as antigen. Those with nerve disease predominating showed an increase with sonicated M leprae. In those with both skin and nerve disease there was an increase with both antigen preparations. The ratios of the LT test results (whole to sonicated M leprae) showed highly significant differences between the three groups.
Experimental murine leprosy. IX. Antibodies against Mycobacterium lepraemurium in C3H and C57BL mice with murine leprosy and in patients with lepromatous leprosy.
Sera from C3H and C57BL mice infected with Mycobacterium lepraemurium (MLM) and from human leprosy patients were examined for antibodies against MLM by a crossed immunoelectrophoresis (CIE) technique. Altogether antibodies against six or seven MLM antigens were found in the mouse sera. After a small inoculum of MLM, C3H mice produced more antibodies than C57BL mice. After a large inoculum both strains produced about the same amount of antibodies but showed qualitative differences in their response patterns. A serum pool from patients with lepromatous leprosy contained antibodies against six MLM antigens; five of these were identical with the antigens against which antibodies were found in infected mice. C57BL mice that had lost their delayed-type hypersensitivity to MLM during the course of a disseminated infection showed a fairly strong antibody response to three antigens and a weak response to three others. Since almost the same spectrum of antibodies, although in lower titres, could be demonstrated in C57BL mice with intact delayed-type hypersensitivity to the bacilli, these antibodies did not seem to interfere with the expression of cell-mediated immunity.
Amyloid-related serum component (protein ASC) IN LEPROSY PATIENTS.
The presence of amyloid-related serum component, protein ASC, in serum samples from 63 leprosy patients was investigated. Protein ASC was detected in 38% of the patients. A correlation to the disease spectrum of leprosy was apparent: polar lepromatous cases, 64% positive; borderline lepromatous, 50%; borderline tuberculoid, 36%; subpolar tuberculoid, 17%; and polar tuberculoid, negative. Antibody activity against the a antigen of Mycobacterium leprae was also determined, showing a similar correlation to the disease spectrum. Serum samples from 23 apparently healthy Ethiopians serving as controls showed a protein ASC incidence of 22%. This figure is significantly higher than the frequency found by others among healthy Norwegian blood donors. Immunoglobulin M levels among patients were elevated in the borderline lepromatous and poplar lepromatous groups. The three tuberculoid groups did not differ in this respect from the control group but were all elevated as compared to a normal Caucasian serum pool. Although raised immunoglobulin M levels seemed to parallel increased frequencies of protein ASC in the patient groups as well as in controls, this correlation might be only secondary to a primary derangement in T-cell function.
Preliminary taxonomic studies on the leprosy bacillus.
Antigens extracted from leprosy bacilli obtained from infected human and armadillo tissues have been examined by immunodiffusion analysis with serum samples from lepromatous patients and with immune sera raised in rabbits. Using the best combinations of serum and antigen extracts, 12 antigenic constituents were found in the leprosy bacilli. Six of these were antigens common to all mycobacteria and nocardiae, 4 were specific to the leprosy bacillus and the position of 2 could not be determined. Groups ii and iii antigens (i.e. those associated with the slow growing and fast growing subgenera of mycobacteria) were not found in theleprosy bacillus, suggesting some relationship with M. vaccae and similar strains, in which these antigens are also missing. Lymphocyte transformation tests performed on lymph node cells of mice infected or immunized with leprosy bacilli also showed the leprosy bacillus to have a closer relationship with M. vaccae than with other mycobacteria.
The use of protein A-containing Staphylococcus aureus as a solid phase anti-IgG reagent in radioimmunoassays as exemplified in the quantitation of alpha-fetoprotein in normal human adult serum.
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A rountine diagnostic test for IgA and IgM antibodies to rubella virus: absorption of IgG with Staphylococcus aureus.
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Phylogenetic aspects of staphylococcal protein A-reactive serum globulins in birds and mammals.
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Capacity of group A, B, C, D, and G streptococci to agglutinate sensitized sheep red cells.
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Slide agglutination method for the serological identification of Neisseria gonorrhoeae with anti-gonococcal antibodies adsorbed to protein A-containing staphylococci.
A rapid slide agglutination test has been developed for the identification of Neisseria gonorrhoeae that are primarily detected as oxidase-positive colonies in gonococcal cultures. The technique is based on the specific nonimmune reactivity between the Fc portion of immunoglobulin (Ig)G and staphylococcal protein A. IgG molecules adsorbed to stabilized staphylococci will thereby become oriented with their antigen-reactive sites that are directed outwards. Protein A-containing staphylococci with unabsorbed anti-gonococcal antibodies gave positive co-agglutination reactions with gonococci but also with meningococci, some Moraxella, Haemophilus, and Pseudomonas strains. These crossreactions were eliminated by absorption of the anti-gonococcal antiserum with meningococcal and Moraxella organisms prior to the coating of reagent staphylococci. In the routine culture diagnosis of N. gonorrhoeae the use of specific gonococcal reagent staphylococci gave concordant results with fermentation procedures and immunofluorescent techniques.
Reactions between certain strains of pneumococci and Fc of IgG.
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A rapid slide-agglutination method for typing pneumococci by means of specific antibody adsorbed to protein A-containing staphylococci.
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Purification of staphylococcal protein A using immunosorbents.
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