Antigenic relationships of Bence Jones proteins, myeloma globulins, and normal human gama-globulin. (73/1041)

By means of immunodiffusion and immunoelectrophoresis study has been made of antigenic relationships of Bence Jones proteins, and the three classes of normal and pathological immunoglobulins, 7S gamma, beta(2A), and beta(2M). All thirty-nine Bence Jones proteins studied could be classified into either one of two distinct antigenic types, A or B. Both types are related to the immunoelectrophoretically slow (S) fragment of a papain digest of normal gamma-globulin; B is related more closely than A, but neither has antigenic determinants in common with the fast (F) fragment. The 7S gamma myeloma globulins were either immunological type I or II. The papain digests of these proteins produced the S and F precipitin lines in immunoelectrophoresis but multiple bands in starch gel electrophoresis, especially in the F region. The S fraction of type I myeloma globulins is antigenically similar to Bence Jones protein of type B, and the S component of type II myeloma globulins has antigenic determinants in common with type A Bence Jones protein. Correspondingly, myeloma patients with type I globulins and proteinuria usually excrete type B Bence Jones proteins, whereas patients with type II excrete type A proteins. The F fragment is the part common to normal 7S gamma-globulin and types I and II myeloma globulins but is absent in beta(2A) and beta(2M) pathological globulins and in both types of Bence Jones proteins. Papain digests of beta(2A) myeloma globulins produced a single precipitin line in immunoelectrophoresis. beta(2A) myeloma globulins appeared to have two antigenic units, one in common with type B Bence Jones protein and normal gamma-globulin, and another specific to beta(2A). The beta(2A) myeloma patients excreted type B Bence Jones protein. The papain digest of a macroglobulin produced two precipitin lines, the faster of which had antigenic determinants in common with type B Bence Jones protein, the slower seemed specific for the macroglobulin. Five serum micromolecular globulins proved to be either type A or B Bence Jones proteins. From the above results, an antigenic map was constructed showing which determinants are shared and which are specific for normal 7S gamma-globulin, types I and II myeloma globulins, beta(2A) myeloma globulins, a macroglobulin, and types A and B Bence Jones proteins.  (+info)

Prophylactic effect of antivaccinia gamma-globulin against post-vaccinal encephalitis. (74/1041)

In the Netherlands, the frequency of encephalitis after smallpox vaccination is estimated to be 1 in 4000 primary vaccinations in adults and 1 in 50 000 revaccinations. Since immunity seems to reduce the frequency of this complication, it was thought that it might be possible to prevent post-vaccinal encephalitis by a combination of passive and active immunization, a basic immunity being obtainable without risk by the injection of antivaccinia gamma-globulin (AGG). This theory was tested in Dutch military recruits in a double-blind experiment. At the time of primary vaccination the recruits were given an injection in the other arm, either of 2 ml of 16% AGG (treated group) or of 2 ml of placebo solution (control group).It appeared that administration of AGG had a prophylactic effect, since only 3 cases of post-vaccinal encephalitis occurred among the 53 630 recruits in the treated group, as compared with 13 among the 53 044 recruits in the control group. The difference of 10 is significant. The best estimate of the reduction in the frequency brought about by injection of 2 ml of 16% AGG is 77%; the lower limit of this reduction is 29%.The administration of 2 ml of 16% AGG did not interfere with the development of active immunity.  (+info)

Tetanus; the use of human hyperimmune globulin in treatment. (75/1041)

Twenty patients with tetanus were treated with human hyperimmune globulin. The mortality rate in the series was 30 per cent. No complications due to the use of this antitoxin were observed.  (+info)

The antigenic structure of the polypeptide chains of human gamma-globulin. (76/1041)

The antigenic properties of the polypeptide chains of human 7S gamma-globulin have been related to two major non-cross-reacting antigenic determinants of the whole molecule. These determinants, called S and F, were obtained by hydrolysis of gamma-globulin with papain. Antisera against whole gamma-globulin and against S and F fragments were used in techniques of immune diffusion. Light (L) chains of gamma-globulin showed reactions of partial identity with S fragments, and thus are antigenically deficient with respect to these fragments. Antisera directed against F determinants did not react with L chains but did react with heavy (H) polypeptide chain preparations. In addition, the major component of H chain fractions did not appear to contain determinants in common with the S fragments. L chains of a gamma-myeloma protein were shown to be antigenically deficient with respect to the whole myeloma molecule, and antigenically identical with the Bence-Jones protein of the same patient. Correlation of these results with those of previous investigations have led to the conclusions that the S fragment which is known to contain the combining region of antibody molecules, consists in part of L chains or portions of L chains, and that the F fragment, which mediates several other functions of the whole molecule, is composed in part of portions of H chains.  (+info)

Properties of guinea pig 7S antibodies. II. Identification of antibodies involved in passive cutaneous and systemic anaphylaxis. (77/1041)

Guinea pig 7Sgamma(1) antibodies were demonstrated to mediate passive systemic or cutaneous anaphylaxis; guinea pig 7Sgamma(2) antibodies were unable to mediate these reactions. Gamma-2 antibodies specifically inhibited passive cutaneous anaphylactic reactions provoked by gamma-1 antibodies by competing for antigen. However, gamma-2 antibodies were unable to inhibit passive cutaneous sensitization of guinea pigs by a heterologous antibody system. Guinea pig 7Sgamma(2) antibodies appear to lack receptors for fixation to guinea pig tissues and do not compete with sensitizing antibody for receptor sites.  (+info)

A case of vaccinia necrosum (or progressive vaccinia), with severe hypogammaglobulinaemia, treated with n-methyl isatin beta-thiosemicarbazone (33T57). (78/1041)

A fatal case of vaccinia necrosum treated with antivaccinial gamma globulin and N-methyl isatin beta-thiosemicarbazone (33T57) is described. Histological abnormalities found at necropsy included intranuclear as well as cytoplasmic inclusion bodies, absence of lymphoid germinal centres, grey hepatization, and bronchiolar epithelial hyperplasia. Virus titres were highest in the original skin lesion; virus was also found in the lymph node draining it and in the kidney and the brain. No toxic effects could be clearly attributed to the drug used in treatment.  (+info)

Genetic characters of human gamma-globulins in myeloma proteins. (79/1041)

The genetic factors Gm(a), Gm(b), Gm(x), and Inv(a), Inv(b) described for normal human gamma-globulin were all found in different myeloma proteins. A single myeloma protein never contained more than one product of alternate alleles even in heterozygous individuals. However, factors determined by the two different loci were often found in the same myeloma protein. The Gm(a) character of the myeloma protein parallelled that of the normal gamma-globulin of the same serum in most cases. In contrast, the Gm(b) character was usually absent in the myeloma protein when it was directly demonstrable in the normal gamma-globulin. The myeloma proteins from six Negroes were Gm(a+b-), whereas the normal gamma-globulin was Gm(a+b+). This indicates that the effect of gene Gm(b) is similar in Negroes and whites, even though its relation to gene Gm(a) is different in the two races. Gm factors were found only in the 7S gamma-globulin type myelomas and not in other products of plasma cell tumors. Inv characters were, however, present in all four types of proteins studied, namely 7S and 19S gamma-globulins, beta(2A)-globulins, and Bence Jones proteins. In two instances, genetic heterogeneity of the protein products was demonstrated suggesting the proliferation of more than one clone of plasma cells in some multiple myeloma patients. The accumulated evidence obtained in this study strongly suggested that the presence and absence of genetic characters was compatible with the concept that myeloma proteins were closely analogous to individual moieties in the spectrum of normal gamma-globulins rather than truly abnormal proteins. Their study offered evidence of a heterogeneity of genetic characters among the normal gamma-globulins in a given individual. It also appears probable that in normal individuals single plasma cells have a restricted capacity to express genetic information in their protein product.  (+info)

Sequences of synthesis of gamma-1 macroglobulin and gamma-2 globulin antibodies during primary and secondary responses to proteins, salmonella antigens, and phage. (80/1041)

The nature of the antibodies produced by the rabbit during the primary and secondary responses to T(2) phage, proteins, and the O and H antigens of Salmonella typhosa has been determined. Immune sera have been fractionated by zone electrophoresis, sucrose density ultracentrifugation, and anion exchange chromatography. The resulting fractions have been assayed by phage neutralization or hemagglutination (antisera to proteins) or bacterial agglutination. In confirmation and extension of earlier work from this laboratory, the primary response to these antigens, with the exception of the O antigen of the Salmonella, included the early synthesis of 19S, gamma-1 globulin antibody, and the later synthesis of 7S, gamma-2 globulin antibody. The primary response to the O antigen consisted of the synthesis of only a macroglobulin agglutinin. The secondary response to the proteins, including the H antigen of the Salmonella, comprised the early synthesis of large amounts of the 7S gamma-2 globulin antibody to the same level attained during the primary response. The secondary response to the phage consisted in the synthesis of 7S, gamma-2 globulin antibody alone. Treatment of the macroglobulin phage-neutralizing antibody with mercaptoethanol resulted in complete loss of its neutralizing activity. A working hypothesis to explain these observations was presented. A salient feature of this hypothesis was the suggestion that different cells synthesized the two distinct molecular forms of antibody. The significance of the sequential synthesis of the two forms of antibody is not known. It was proposed that the system for synthesis of macroglobulin antibody is an auxiliary system for antibody synthesis, perhaps the first to develop phylogenetically and ontogenetically. It is felt that the present observations indicate a clear-cut qualitative distinction between the primary and secondary responses to immunization whereby these responses might be identified in various experimental situations. It is also felt that these findings with the primary and secondary responses to various antigens in the rabbit may be of widespread occurrence in nature among a variety of species.  (+info)