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Circulating tissue antigens (CTA) were investigated in 143 patients with disorders involving injury of the liver and of other organs and in forty-eight normal subjects by immunodiffusion techniques using rabbit anti-human liver serum containing antibodies to a liver-specific antigen and to tissue antigens of wide organ distribution. Analysis of serum samples by double immunodiffusion showed up to three CTA in the following cases: fifteen out of eighteen, viral hepatitis (VH), two out of thirteen, other infectious diseases, two out of ten, alcoholic cirrhosis, seven out of twenty-one, congestive heart failure (CHF), four out of fourteen, myocardial infarction, ten out of twenty-one, trauma, two out of thirteen, carcinoma and three out of thirty-three, miscellaneous diseases. Forty-eight normal subjects showed no CTA. Immunoelectrophoresis of most of the positive eases showed two to three CTA, while a few cases showed four to six. Absorption tests with organ extracts demonstrated that in most patients, CTA were substances shared by several organs. However, in two cases of VH, in two cases of CHF with liver necrosis and in two cases of trauma to the liver, one of the CTA was shown to be liver specific. The CTA were susceptible to digestion by pronase and were found to be relatively thermolabile. Positive sera showed higher glutamic oxaloacetic transaminase and lactic dehydrogenase activities than the negative sera. These preliminary data suggest that further investigation on CTA in disease involving tissue injury and necrosis may be rewarding. [ABSTRACT FROM AUTHOR]

Sera from patients with squamous carcinoma of the cervix uteri and from control patients were examined, by means of indirect immunoflourescence, for antibodies to cell constituents in frozen sections of cervical and other tissues. Cervical carcinoma cells were found to possess cytoplasmie antigens, which reacted with antibodies in autologous and homologous sera. More than half the patients with carcinoma of the cervix had detectable antibodies to cytoplasmic antigens. Comparison of reactions of individual sera and tissues, together with absorption experiments, indicated that either or both of two common cytoplasmic antigens were present in all carcinomas of the cervix and that the same antigens were present in some non-malignant cervices. A high incidence of antinuclear antibodies was found in patients with squamous carcinoma of the cervix, adenocarcinoma of the cervix or body or the uterus, or pre-malignant cervical lesions. [ABSTRACT FROM AUTHOR]

Acute sialoadenitis, ascribed to local formation of immune complexes, develops in sensitized rats after a single intraductal challenge with the sensitizing antigen. Multiple intraductal challenges induce a state of non-reactivity of the organ characterized by a lack of inflammatory reaction to the sensitizing antigen. This non-reactivity is antigen-specific, since introduction of ovalbumin, after multiple intraductal instillations of bovine serum albumin (BSA), elicits an inflammatory response in animals immunized with the two antigens. At the same time, instillation of BSA into the contralateral gland, which has not been challenged, causes acute adenitis. Anti-BSA antibodies are detected in the serum and parotid saliva at the time of refractoriness of the gland. The phenomenon is a transient one since the faculty of the salivary gland to respond by an inflammatory reaction recovers after a challenge-free period. These experiments bring to light a new phenomenon, the possible mechanisms of which are discussed. [ABSTRACT FROM AUTHOR]

A distinctive fragment of the HL-A antigen molecule which retains characteristic structural features of the intact molecule has been obtained from soluble HL-A antigens by mild degradation procedures. When molecular fragments of 48,000 Daltons which are derived from cultured human lymphoid cells and carry HL-A alloantigenic activity are exposed to a pH of 2.4 in glycine buffer for 15 minutes at 0-4°, they split and a fragment of 11,000 Daltons can be isolated by gel filtration. This fragment does not carry HL-A alloantigenic activity but does carry HL-A common activity. This common activity had previously been found on papain-solubilized HL-A antigens as well as on intact lymphoid cells. It is immunogenic in rabbits and reacts with antiserum raised in rabbits against lymphoid cell membrane fractions. These small fragments appear to be characteristic, common structural components of HL-A antigen molecules of 48,000 Daltons and hence are designated 'HL-A common-portion fragments'. Similar molecular fragments are found in solutions of the HL-A molecular fragments of 48,000 Daltons that have been stored in buffer at pH 7.8 at 4° for some time. [ABSTRACT FROM AUTHOR]

Lymph node cells from preimmunized rabbits were cultured with varying concentrations of antigen in autologous serum which had been collected before immunization. [3H]Thymidine was added after 18 hours of culture and the cells were harvested at 24 or 66 hours for the determination of the radioactive labelling of acid-precipitable material. Preheating serum (56°, 20 minutes) enhanced labelling in both control and antigen-treated cultures. This 'heat effect' had an early (24 hour) non-specific component, independent of antigen concentration, and a late (66 hour) specific component which was most evident at high antigen concentrations. The conditions of preheating serum (temperature and time) required to produce the heat effect were similar to those required to remove haemolytic activity against rat erythrocytes. However, at certain temperatures and times there were discrepancies. These discrepancies, and data from experiments in which preheated and unheated sera were mixed in varying proportions, or interchanged in different sequences, were explicable on the basis of (i) a requirement for complement in stoichiometric quantities dependent on the number of cells being inhibited, (ii) the involvement of the majority of the cultured cells in the early non-specific component of the heat effect, but only cells capable of proliferating in response to added antigen in the late specific component, (iii) the secretion of complement by cultured cells. Preheating serum (66&deg:, 20 minutes) depressed labelling in control and antigentreated cultures and reduced agglutinating activity against both autologous and heterologous erythrocytes. The results are discussed in relationship to models which require that the size of a specific lymphocyte clone be positively or negatively regulated by the concentration of antigen specific for that clone. With increasing antigen concentration three effects on cells bearing specific receptor sites are distinguished. (i) Cell stimulation under conditions of antigen concentration and cell receptor specificity such that only a few antigen molecules can bind to cells. (ii) Complement-dependent inhibition under conditions such that more antigen molecules can bind to cells. (iii) Complement-independent inhibition under conditions, possibly unphysiological, such that very large quantities of antigen molecules can bind to cells. [ABSTRACT FROM AUTHOR]

To obtain further evidence that complement is involved in both the early, non-specific and the late, specific, components of the heat effect (Forsdyke, 1973b), lymph node cells from preimmunized rabbits were cultured with varying concentrations of antigen in autologous preimmunization serum treated with one of three specific complement inhibitors, inulin, Zymosan or cobra venom factor. The Zymosan particles were removed before use of the serum in cultures, but the other inhibitors were not removed. Inulin only slowly removed haemolytic activity from serum and enhanced the late response to high concentrations of specific antigen. The inulin concentrations required to remove haemolytic activity were similar to those required to enhance the response to antigen. Zymosan-pretreated serum enhanced labelling with 3H]thymidine in both control and antigen-treated cultures to a proportionate extent. No late specific enhancement of labelling was detected, probably because of the secretion of complement by cultured cells. The interpretation of data obtained when Zymosan was left in cultures was complicated by Zymosan acting as an antigen and inducing a primary response to itself. Cobra venom factor reduced the labelling of both control and antigen-treated cultures so that the non-specific component of the heat effect was not detectable. However, the response to high concentrations of specific antigen was enhanced. It is concluded that although each complement inhibitor shows unique individual characteristics in the system, on balance the results support the view that the activity responsible for both components of the heat effect is complement. [ABSTRACT FROM AUTHOR]

Lymph node cells from immunized rabbits were cultured with varying concentrations of antigen in preheated (56°, 30 minutes) autologous serum which had been collected before immunization. [3H]Thymidine was present for the last 6 hours of the 24-hour culture period and the radioactive labelling of acid-precipitable material was then determined. Changes in labelling due to variations of culture conditions were interpreted according to whether they were specific for control or antigen-treated cultures or non-specific. Cell concentration and serum concentration were predominantly non-specific variables influencing the labelling in control and antigen-treated cultures to a proportionate extent. However, at serum concentrations below 5 per cent labelling was disproportionately inhibited in antigen-treated cultures; there were further minor disproportionate inhibitions at higher serum concentrations. Labelling was inhibited by increasing the concentration of serum from 25 to 50 per cent, mainly due to a non-diffusible competitive inhibitory activity. Isotope-dilution analysis of the effects of serum on labelling over a wide range of serum concentrations indicated that the relationship was a complex one with at least three step-wise stimulations of the maximum labelling rate being produced by increasing the serum concentrations from 0 to 25 per cent. Labelling in antigentreated cultures containing post-immunization serum was less than labelling in cultures containing an equal volume of preimmunization serum, but labelling in control cultures was enhanced by post-immunization serum. These results are shown to be compatible with the proposals (i) that labelling in control cultures reflects the response of cells to low concentrations of endogenous antigens, and (ii) that preimmunization serum and post-immunization serum contain ‘natural’ and ‘acquired’ antibodies respectively, which normally buffer cell-borne receptor sites against reaction with endogenous and exogenous antigens. [ABSTRACT FROM AUTHOR]

The level of the third component of complement was measured in serial specimens of serum taken from thirty-one patients with acute viral hepatitis. Fourteen of the thirty-one patients were positive for the hepatitis-associated antigen. A characteristic fluctuation was observed in twenty-nine of the thirty-one patients. This consisted of an initial fall of the level of C3, followed by an increase to a higher than normal level and then a gradual return to normal. No difference was observed between the patients who were positive and those who were negative for the hepatitis-associated antigen. These results support the view that immune complexes play a significant role in the pathogenesis of acute viral hepatitis. [ABSTRACT FROM AUTHOR]

The variation in the serum level of specific IgG, IgM and IgA antibodies during different stages of hydatid disease has been demonstrated by a technique of fluorescent microscopy that uses monospecific anti-human immunoglobulin conjugates and freeze-dried antigens. The technique is easy to perform and our results suggest that the test is sensitive and specific. Specific IgG antibodies are present in patients with either current or past infections. IgM antibodies, detected during periods of antigenic activity, disappear soon after removal of the cyst. In many cases IgA antibodies also disappear soon after removal of the cyst. Cross-reactions between the antigens and antibodies of hydatid disease and schistosomiasis are shown to be present mainly in the IgG immunoglobulin and only to a much smaller extent in the IgA. [ABSTRACT FROM AUTHOR]

Specific interchange takes place between 131I-marked antibody combined with cellular antigens and the free unmarked antiserum antibody in three systems studied: (A) bovine cells with (i) human infectious mononucleosis serum and (ii) rabbit anti-bovine serum and (B) human Rh D-positive cells with Rh incomplete anti-D serum. The rate of interchange is much lower than the initial combination of an unmarked antibody with an unoccupied antigenic site, and also is slower in the Rh incomplete system than in the other systems studied. Rabbit anti-bovine red cell antiserum partly interchanges with 131I-marked infectious anti-body on bovine cells, but the reverse interaction does not apparently take place at all. Possible reasons are put forward to explain this. The infectious mononucleosis interchange reaction has a large temperature coefficient (about 4·9) which corresponds to a heat of reaction of 29,000 cal. [ABSTRACT FROM AUTHOR]

Dissociation rate measurements were determined on antisera following single and multiple intravenous injections of antigen and after injection of antigen incorporated into adjuvant. It was found that regardless of the amount, route, or number of injections the dissociation characteristics of all sera were similar, reaching the same maximum binding strength within the same time period following immunization. The relative production of 19S and 7S antibody was studied and it was found: (a) insufficient 19S antibody is formed to account for the change in dissociation characteristics that occur following immunization; (b) at the same stage of immunization, 19S and 7S antibody have similar rates of dissociation from antigen, but 19S antibody combines more slowly with antigen than 7S antibody; (c) the haemagglutination technique show's no correlation with binding or precipitin methods when estimates as to the relative amounts of 19S and 7S antibody present in sera are made. [ABSTRACT FROM AUTHOR]

Reverse passive cutaneous anaphylaxis experiments were performed in guinea pigs with rabbit gamma globulin and human gamma globulin as antigens and horse, sheep or hen sera containing antibodies against these antigens. These antibodies were unable to directly sensitize the guinea-pig skin but when the reverse technique was used, namely, the antigen (gamma globulin) was injected before the antibody, characteristic anaphylactic reactions were obtained. It is concluded that, if a suitable antigen is used, which can be fixed to the host by the reverse technique, sera from species which cannot directly sensitize the guinea pig can nevertheless give typical anaphylactic reactions. [ABSTRACT FROM AUTHOR]

Rabbit antisera to human tracheal mucosa, liver and gastric mucosa, after complete absorption with human serum, reacted with extracts of all human tissues tested. Monkey tissue extracts also reacted, but tissues of other species did not. The reactions were attributed to `species-specific tissue antigens'. Two of the most prominent antigens were partially isolated and characterized by chromatography, gel filtration, and electrophoresis. Antigen I migrated as β2-globulin, Antigen E as a β1-globulin. The antigens persisted in malignant and in long-term cultured cells. [ABSTRACT FROM AUTHOR]

Studies the relations between the electrophoretic properties of antibodies formed by different individuals to the same antigen or group of antigens. Characteristics of the antithyroglobulin antibodies; Features of the sera obtained from patients with thyroid gland diseases; Implications of the serum characteristics on previously acquired immunological facts.