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Production of antibody against major trasplantation antigens has been studied in sheep receiving osteoarticular allografts at the knee joint. These investigations have shown that this type of allograft leads to the rapid production of serum antibodies in the recipient animal. It was found that a high proportion of the sheep used in these studies possessed antibodies before operation. A large number of the animals which possessed antibody against major transplantation antigens prior to operation developed a wide spectrum of antibodies after operation more rapidly than did those recipients who had no pre-existing antibody. A smaller number showed an increase in antibody spectrum which was comparable with non-sensitized recipients. An analysis of the patters of antibody production was carried out in order to assess the possible benefits of reducing the bony component of the graft in lowering its immunogenicity. It was found that the thickness of bone carried by the graft was largely irrelevant and the immune response was initiated with only small amounts of bone. There is some evidence in this data that the surface area of bone is important in determining the pattern of the immune response. [ABSTRACT FROM AUTHOR]

Outbred Swiss mice show a stable level of circulating thymic factor (TF) (measured by its action on theta-positive rosette-forming cells (RFC)) until the 6th month of life. Afterwards, this level progressively declines. Swiss mice genetically selected as 'high' and 'low' responders for anti-sheep red blood cell haemagglutinin production show no difference with ordinary Swiss mice with regard to serum TF level. This observation is compatible with previous results showing that the selection mainly induces changes in B-cell reactivity without T-cell modification. Conversely, genetic selection of Swiss mice based on spontaneous antinuclear autoantibody production (tested by immunofluorescence) induces a decrease in TF level, which has already become significant by 2 months of life. The mice thus selected (Swan mice) which present autoimmune manifestations and immune complex disease, like NZB and B/W mice, show the same premature cessation of TF as these other autoimmune mice. Such abnormality is compatible with the T-cell deficiency of NZB, B/W and Swan mice. [ABSTRACT FROM AUTHOR]

Serial sera from nine volunteers, injected 10 years ago with sheep erythrocytes and showing heterophile antibody responses comparable to those seen in infectious mononucleosis, were retrieved from storage and examined for antibodies to Epstein-Barr virus (EBV) related antigens. Eight of the nine volunteers had preexisting antibodies to EBV, as determined by neutralization tests and by indirect immunofluorescence reactions with fluorescein-conjugated antibodies to human IgG, but not with anti-human IgM conjugates. The EBV-specific reactivities remained unchanged after immunization. The results indicate that: (a) EBV- or EBV antigen-containing lymphoblasts from carrier or freshly infected cultures contain no detectable heterophile antigen; (b) immunization with sheep erythrocytes does not evoke antibodies which interact with EBV or EBV-infected cells. These points are supported especially by the results obtained with the heterophile antibody-positive, anti-EBV-negative serum of one of the volunteers who subsequently sustained a primary EBV infection. It is unlikely, therefore, that immunization with heterophile antigen will induce immunity to infectious mononucleosis, apart from the fact that heterophile antibody responses are largely restricted to the IgM class. [ABSTRACT FROM AUTHOR]

The results suggest that the anaemia in mice associated with the injection of C. parvum is mediated by an immune mechanism. Survival studies of 51Cr-labelled red blood cells (RBC) in splenectomized and unsplenectomized mice show that mice immunized with C. parvum three times, clear RBC faster than unimmunized mice. However, hyperimmunized mice stabilized their haemoglobin concentrations above their minimum level and did not clear 51Cr-labelled RBC faster than unimmunized mice. All mice produced antibody against C. parvum but remained direct Coombs'-negative. Serum from immunized animals did not contain opsonins for -51Cr-labelled RBC. The reticulocytosis, normal osmotic fragility tests and normal survival times of 51Cr-labelled RBC from C. parvum-immunized mice all suggest that the main direct influence of the micro-organism is extrinsic of the RBC. Antigens from the micro-organism were adsorbed by erythrocytes in vitro. It is hypothesized that the anaemia is caused by destruction of RBC brought about by antibody reacting with bacteria that have been adsorbed by RBC. [ABSTRACT FROM AUTHOR]

A red cell autoantibody in low titer was demonstrated in one-third of Ugandan sera tested by performing the Combs test. on enzyme (bromelain) treated erythrocytes, The authoantibody was found Keith increased frequency in subjects over 40 years of age and in those with the haemocyte anaemia in pregnancy syndrome. But was not detected in medical students. Two subjects with autoantibody\ie's and normal haemoglobin values has na normal re dell survival The authoantibody was not associated with acute attacks of malaria. The possible relationships of the autoantibody to the he\haemolytic anaemia in pregnancy and the tropical spend meagerly syndromes are discussed. [ABSTRACT FROM AUTHOR]

We have described a new autoantibody present in the serum of diseased NZB mice reactive with autochthonous and syngeneic fibroblasts. allogeneic cells are not affected. This antibody can be specifically absorbed both by fibroblasts and lymphocytes from NZB but not from control mice. The antibody cannot act as a block from diseased NZB mice. This suggests that the precise antigenic specificities of the cell-mediated and antibody responses are different [ABSTRACT FROM AUTHOR]

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]

Patients with breast carcinoma, fibrocystic disease, and fibroadenoma have antibody to an antigen prepared from homologous breast carcinoma. In 50% of patients with breast carcinoma, this antibody, detected by immunodiffusion and complement fixation, appears within 2 weeks of radical mastectomy. This antibody also appears in a lower percentage of the sera of patients with fibrocystic disease and fibroadenoma. Gel permeation chromatography indicates the antigen to be a high molecular weight compound. [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]

A cytomegalovirus (CMV) induced early antigen (EA) was demonstrated in fibroblasts infected in the presence of the DNA inhibitor cytosine arabinoside (Ara C). In the dose used (20 /(g/ml) Ara C blocked DNA synthesis completely, as judged by thymidine incorporation and autoradiography. The percentage of EA positive cells was 0.6 8 hr post-infection, increasing to 50 and 65% on the two following days. EA differed from late antigens (LA), present in CMV-infected but otherwise untreated fibroblasts, with regard to distribution and antigenic specificity. Sera differed in their reactivity to EA at comparably high anti-LA titres. Direct immunofluorescence staining of EA-positive cells was only blocked with high titred anti-EA sera, but not with high titred anti-LA sera with a low or negative anti-EA-titre. Anti-CMV-EA did not cross react with antibodies against EBV, Herpes simplex or varicella/zoster. A collection of 115 serial sera from forty-five acutely CMV-infected patients was tested for anti-EA and anti-LA antibodies. The diagnosis was confirmed by the occurrence of a significant rise in CF antibodies and/or virus isolation. Sera taken before illness (five patients) had neither anti-LA nor anti-EA antibodies when tested al a 1 :40 dilution. All patients in the acute phase of this disease had anti-LA titres between 1:640 and ≧ 1 : 10240. 43/45 of these patients developed anti-EA at titres between 1:40 and ≧ 1:2560. As a rule EA-antibodies were detected 10-19 days after the onset of symptoms. Anti-EA tended to peak later than anti-LA and declined again within a few months. Anti-LA was maintained at nearly constant levels. This applied also for antibodies detected in the CMV complement fixation (CF) test. Sera from healthy seropositive donors or from patients with unrelated bacterial or viral infections contained anti-LA-antibodies in titres ranging from 1:40 to 1 : 1280 as a rule, but had no anti-EA-antibodies. Diagnostically significant increments or declines in the anti-HA titres were observed more frequently than corresponding changes in the levels of anti-LA and CF antibodies. In view of the transitory nature of the anti-EA response, the presence of this antibody in an acute phase serum at a titre of ≧ 1: 80 can be taken as suggestive of a current primary infection. [ABSTRACT FROM AUTHOR]

Successive injections of HgA-positive red cells were given at intervals of 2-3 months to HgA-negative rabbits. In forty-four out of fifty-one animals, red cell survival became progressively shorter and, in the majority of instances, anti- HgA was found in the serum. Characteristically, the first survival curve was initially normal but showed 'collapse' after a mean interval of 17 days; following subsequent injections, cells were cleared at an accelerated rate. In the remaining seven HgA-negative rabbits the survival of HgA-positive red cells was either repeatedly normal or was subnormal after the first one or two injections and became almost normal following further injections. In four out of six of these animals, following additional injections of HgA-positive cells given in with FCA, anti-HgA became detectable in the serum, Thus, some animals which appeared to he non-responders to HgA as judged by normal survival of HgA-positive red cells after i. v. injection alone showed some response when antigen was also given in, with adjuvant. [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]

An increase in the level of acid phosphatase, β-glucuronidase and cathepsin D in macrophages was obtained by cultivating the cells in medium containing high serum concentration and by injecting macrophage donors with thioglycollate. A high level of the three hydrolytic enzymes in the stimulated macrophages does not correlate with a high uptake or degradation of the polypeptide antigen (TG)-PRO--L. Moreover, macrophages with a low level of enzymes (unstimulated cells) pinocytose and degrade (TG)-PRO--L more efficiently than macrophages with a high content of hydrolases. Unstimulated macrophages from responder (SJL) mice pinocytose and degrade (TG)-PRO--L more efficiently than macrophages from the non-responder (DBA/1) animals although the two cell populations had similar levels of hydrolases. [ABSTRACT FROM AUTHOR]

The regulation of the immune responses by antibody administered passively on peritoneal exudate cells (PEG) was studied in guinea-pigs. The immunogenicity of sheep red blood cells (SRBC) associated with PEC for the induction of delayed hypersensitivity (DH) to soluble erythrocyte antigen was enhanced when PEG were incubated with anti-SRBG antibody. In contrast, the antibody response to SRBC was depressed. This phenomenon was only observed with specific antibody and was partially blocked when PEG covered with anti- SRBC antibody were incubated with rabbit anti-guinea-pig globulin serum. Comparable amounts of anti-SRBC antibody injected separately had no enhancing effect. Anti-SRBC sera from which the cytophilic antibody activity had been removed were inactive. PEG-associated SRBC were usually more immunogenic than the same amount of `free' SRBC for the induction of delayed hypersensitivity and always more immunogenic for antibody production. These observations suggested that macrophage cytophilic antibody might be involved in the regulation of the immune response and play a role in the preferential induction of delayed hypersensitivity in the studied system. [ABSTRACT FROM AUTHOR]

Polyanion-immunoglobulin complexes, considered important factors in the pathogenesis of glomerulonephritis common in systemic lupus erythematosus, were found and isolated from sera of NZB mice by selectively binding them to an anion-exchange cellulose (DE52). Accurate quantification of such complexes was possible, in terms of immunoglobulin content, by means of an antiglobulin complement-fixation assay. In sera of NZB mice the concentration of immune complexes increased up to about 11 months of age and then it declined, whereas in the sera of the C57B1 and HaICR strains of mice, which do not develop spontaneous glomerulonephritis, the concentration was lower initially but increased steadily with increasing age and reached an equivalent level at about 27 months. The complexes were composed primarily of immunoglobulins of the IgG class bound to native DNA. The finding of significant levels of circulating immune complexes in mouse strains without renal disease suggests that such complexes, although necessary, might not be sufficient and solely responsible for overt glomerulonephritis. [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]

Antigens reactive with autologous and homologous sera have been demonstrated in human sweat, but not in serum, amniotic fluid, urine, or secretions of other glands investigated. The antisweat precipitins (IgG) were demonstrated in 33% of adult hospital staff and 40% of adult blood donors. While the incidence of positive antisweat precipitin tests (ASP) was elevated in many skin disorders, it was depressed in diabetes and patients receiving methotrexate therapy for psoriasis. [ABSTRACT FROM AUTHOR]

The kinetics of the antibody response in cattle have been analyzed and the following results were obtained: A single administration of proteins to cattle given intravenously or as alum-precipitated antigen evoked a concurrent synthesis of γM- and γG-antibodies as reflected in the serum 7 days following immunization. Employing the antigen binding capacity method for assaying antibody activity, the γG-antibody collected 7 days after immunization exceeded by several times that of the γM-class. The γG-antibody response as reflected in serum and colostrum three weeks after primary stimulation showed a marked increase when compared with their respective antibody levels formed earlier. The colostral 19 S antibody, composed of 19 S γG-globulin and the easily discernible γM-component was also increased and surpassed by several times the γM-antibody level in a 3-weeks serum. When colostrum was fed to the newborn calf, the γG-antibody appeared to be absorbed quantitatively by the intestinal tract, whereas the high molecular weight globulins (19 S) were transmitted much less efficiently. This might indicate that some sort of selective absorption occurred between different classes of immunoglobulins. Kinetic studies of the secondary response demonstrated that in cattle serum an anamnestic reaction exists for γM-antibody as well as for γG-antibody. The dissociation of the 19 S molecules from serum and colostrum by reduction and alkylation produces little effect on the antigen binding capacity of the monomer subunits obtained. The kinetic characteristics of serum and colostral 19 S- and γG-antibodies were studied by measurement of the association rates, γM-Antibodies present in serum 7 days following antigenic challenge had a higher affinity for protein antigens than γG-antibody molecules. There is considerable evidence, however, that the affinity of the γG-antibody for the antigenic determinants increased progressively with time after immunization. [ABSTRACT FROM AUTHOR]

The bovine J blood-group substance is dissolved in the serum. The total lipids extracted from serum containing the J antigen (termed J+ serum) show haptenic activity in the homologous bovine J system. The total lipids from J- serum, however, show no haptenic activity. The J+ total lipids are, therefore, thought to contain the determinant group of the J antigen. In fractionation experiments the lipids to be tested were mixed with crude glycerophospholipids extracted from J- serum, since it has been known that auxiliary lipids are required for maximum haptenic effects. The haptenic activity is completely destroyed by periodate oxidation, it does not decrease, however, by deacylation of ester lipids. Various fractionation procedures in addition to deacylation led to a purified glycosphingolipid that proved to be highly active as a J hapten. The low-density lipoproteins prepared from J+ serum as well as the total lipids extracted from these lipoproteins inhibit the hemolysis of J+ erythrocytes in the J system. These results suggest that the J blood-group substance dissolved in bovine J+ serum is a lipoprotein and that its determinant group is a glycosphingolipid. [ABSTRACT FROM AUTHOR]

The article presents subject index for the journal "Clinical and Experimental Immunology." Some of the subjects included are: Allergen antibodies, a modified radioallergosorbent test for the in vitro detection of, 617; Anaemia, autoimmune haemolytic; Chromium survival studies in patients with different kinds of warm autoantibodies, 559; Antibodies and anti-kidney antibodies in kidney transplanted patients and patients with renal disease, occurrence and cross-reactivity of heterophile, 191; Antibodies to tubercle bacilli in sera from non-tuberculous and tuberculous individuals. Universal occurrence of, 65; Antilymphocyte globulin by human peripheral lymphocytes, uptake of, 423.

A liver-specific, water-soluble autoantigen (F-antigen) was detected by double diffuion using specifically prepared antiserum in thirty of 285 adult serum samples tested. F-antigen was found most frequently in disorders associated with hepatocellular destruction such as metastatic cancers (four of eleven patients) and viral hepatitis (eight of twenty-five). It was also found in serum from patients with cirrhosis (three of twenty-eight), steatonecrosis (two of thirteen) and hepatocellular carcinoma (two of eleven). These preliminary results suggest that further study of F-antigen in human disease states is warranted. [ABSTRACT FROM AUTHOR]

Presence of hepatitis-associated antigen (HAA) was investigated in 504 sera from 116 patients with SLE and was found in 41% of them. HAA was present in at least one serum in 75% of the patients but there were variations in presence and titres in the same patient at different times. Except for a tendency of HAA to appear or rise in titre with lupusi nactivation following corticosteroid or immunosuppresive therapy, there was no correlation between its presence and disease activity, specific organ involvement, antinuclear antibodies or immunoglobulin levels. All but one of twelve lupus patients with recurrent bacterial infections had HAA at high titres. HAA appeared in the serum of a patient upon development of IgA deficiency. HAA antigenaemia in systemic lupus erythematosus seems a consequence rather than a cause of the immunological derangement in this disease. [ABSTRACT FROM AUTHOR]

A sensitive gel filtration radioimmunoassay was used to test for antibodies to the basic protein of myelin, the antigen of experimental autoimmune encephalomyelitis, in serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and other diseases. Sera and CSF from patients with MS gave results similar to those for controls including subjects with various neurological diseases Binding of 125I-basic protein by seven-fold concentrated CSF was shown to be due to α-globulin. Free basic protein, as a possible auto-immunogen, was sought in the serum and seven-fold concentrated CSF of patients with MS and controls by competitive inhibition in the radioimmunoassay, but none was demonstrable. if an immunological mechanism is to be invoked in the initiation of destruction of the basic protein of myelin in MS, then either pathogenic 'antibody' must be absorbed in vivo to the target antigen in the central nervous system or the initiating events must be mediated entirely by sensitized lymphocytes. [ABSTRACT FROM AUTHOR]

A sensitive gel filtration radioimmunoassay was used to test for antibodies to the basic protein of myelin, the antigen of experimental autoimmune encephalomyelitis, in serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and other diseases. Sera and CSF from patients with MS gave results similar to those for controls including subjects with various neurological diseases Binding of 125I-basic protein by seven-fold concentrated CSF was shown to be due to α-globulin. Free basic protein, as a possible auto-immunogen, was sought in the serum and seven-fold concentrated CSF of patients with MS and controls by competitive inhibition in the radioimmunoassay, but none was demonstrable. If an immunological mechanism is to be invoked in the initiation of destruction of the basic protein of myclinin MS, then either pathogenic `antibody' must be absorbed in vitro to the target antigen in the central nervous system or the initiating events must be mediated entirely by sensitized lymphocytes. [ABSTRACT FROM AUTHOR]

The appearance of a new virus specific antigen was demonstrated by an indirect immunofluorescence technique on cell surfaces of CMV infected human fibroblasts, 48-72 hr after inoculation. The development of antibodies to these membrane antigens was followed in thirty-nine serial sera from twelve patients with a virologically and/or serologically confirmed CMV infection. In all patients except one, membrane antibodies could be detected, Sera from four patients collected before infection were negative, as were sera taken 1-13 days after onset of symptoms. From the end of the second week of illness CMV-membrane antibodies as well as CMV macroglobulin antibodies to intracellular antigens were detectable. The membrane antibodies persisted until 335 days after onset of illness. They were mainly of the IgM class. Most positive sera also reacted with non-infected fibroblasts but to a lesser degree. This reaction became negative after prior absorption of the sera with non-infected fibroblasts, whereas the reaction with CMV-infected cells remained positive. Controls consisted of forty-five sera from healthy persons and nine sera from patients suffering from other herpes virus infections with antibodies to herpes simplex, zoster/varicella and Epstein-Barr virus. All but two sera were negative in the membrane immunofluorescence test. [ABSTRACT FROM AUTHOR]

A second polymorphic trait of rabbit serum high density lipoprotein (HDL) has been revealed by a new antiserum. The antigen detected by this antiserum appears to be inherited as an autosomal dominant trait. No obvious association was found between the new polymorphic trait (provisionally referred to as the R 67 antigen) and the already established MDL antigen, Hl 1. [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]

Antibodies in human sera against four different antigens of human spermatozoa discovered by means of an indirect two-layer immunofluorescence technique (IFT) were characterized by determination of the class of immunoglobulins to which they belonged. A three-layer IFT using monospecific antisera against human IgG, IgA or IgM as the second layer was employed together with fractionation of sera on Sephadex G-200 or DEAE-cellulose followed by testing of the concentrated pools in a two-layer IFT. The study revealed that antibodies against the antigen in the front part of the acrosome were primarily IgM and those against the antigen in the tail primarily IgG. Antibodies against antigens in the equatorial segment and the postnuclear cap showed a varying predominance of these two immunoglobulins. Spermatozoal antibody as IgA was found only in small amounts. [ABSTRACT FROM AUTHOR]

By means of the antigen-antibody crossed electrophoresis of Laurel! twenty-two different candida albicans precipitins were demonstrated in a serum from a 56-year-old woman suffering from idiopathic hypoparathyroidism and chronic candidiasis. This precipitin response is remarkably strong, but a detailed evaluation of the finding must await further investigations. lt is mentioned how the human precipitins may be quantitated and the titres expressed in arbitrary rabbit precipitin units. The antigen-antibody crossed electrophoresis may be useful in other infections, and possibly in certain autoimmune diseases, in order quantitatively to screen patient sera for a multitude of precipitins without purification of the individual antigens. [ABSTRACT FROM AUTHOR]

134 liver biopsies obtained from 124 patients with various diseases of the liver were examined by the direct immunofluorescent technique for the Australia antigen. FITC-labelled IgG fractions prepared from three different sera containing anti- body to the Australia antigen were used. Controls included FITC-labelled IgG fractions of sent containing antibodies against human immunoglobulins, complement factors and herpes simplex virus. The three antibodies to the Australia antigen employed showed identical fluorescent patterns and reacted with the same biopsies. In 68 biopsies prepared and examined within 12 hr, speckled or granular fluorescence was noted in the nuclei of the hepatocytes in all cases irrespective of the clinical or histological diagnosis or the serological reaction for the Australia antigen. The antigen in the nuclei of the hepatocytes proved to be very labile. It is concluded that IgG prepared from sera containing antibodies to the Australia antigen may have two antigenic specificities, one precipitating with the Australia antigen in serum and another reacting by immunofluorescence with a labile antigen which appears to be a constituent of normal liver cell nuclei. [ABSTRACT FROM AUTHOR]

Immunoconglutinin is an auto-antibody against hidden antigenic determinants or C3 and C4 components revealed following complement involvement in an antigen antibody interaction. Sequential determinations of immunoconglutinin. β1C globulin and various parameters of renal function have been undertaken in eight patients following cadaveric renal transplantation. In the four patients who underwent an acute rejection episode during the period of study, the immunoconglutinin titre rose to high and significant levels suggesting that antibody production and utilization of complement `may play a role in renal allograft rejections. There were fluctuations in the serum β1(C3) globulin concentrations with time in each patient but no correlation could be found with rejection episodes. [ABSTRACT FROM AUTHOR]

Analysis of the sera of seventeen patients with a selective deficiency of IgA revealed that 24% gave a precipitin reaction on gel diffusion with normal bovine serum and milk. None of 100 normal adults and only one of approximately 500 patients with various diseases without an IgA deficiency had precipitins when studied by this same technique. Analysis of the nature of this reaction revealed that an IgG type antibody present in the human sera was reacting with the Fc fragment of the IgM present in bovine milk and serum. An immunologically identical reaction occurred with goat and sheep, and reactions of partial identity with horse and pig sera. No reactions were found with sera from other species including man. In two of the IgA deficient sera additional but much weaker precipitin lines were noted with cow milk. These data are consistent with the hypothesis that oral immunization with the highly antigenic macroglobulin present in cow milk was facilitated by the mucosal antibody defect accompanying the IgA deficiency. [ABSTRACT FROM AUTHOR]

The influence of antigen dosage on reagin formation to haemocyanin in rabbits was studied. Using large doses of antigen, reagin formation was more readily elicited, the induction period was shorter and the persistence of reagins in serum was longer than when low antigen doses were employed. Reagin synthesis was readily induced after intravenous administration of antigen. Immunization with antigen mixed with varying doses of IgG antibody resulted in a suppressed formation of antibodies reactive in passive haemagglutination and in a total inhibition of reagin formation. The inhibition of reagin synthesis was long-lasting and booster injections of antigen did not result in the appearance of reagins. 'Hyposensitization' with series of injections of antigen or antigen-antibody mixtures resulted in an initial decrease of the reagin litres, but restoration of reagin levels was observed already about 2 weeks following cessation of the treatment. The possible implications of the results for the specific immunologic therapy of allergic disorders are discussed. [ABSTRACT FROM AUTHOR]

Sera from patients with idiopathic autoimniune haemolytic anaemia (Al HA) were studied, by the immunofluorescent technique, for the presence of circulating organ-specific and non-organ-specific autoantibodies. in patients with warm AIHA there was an increased incidence in the non-organ-specific autoantibodies, compared to normal controls: In. 15% of sera studied there were antinuclear antibodies detectable, and in 5 % antimitochondrial antibodies were present. In cold ATHA, however, the frequency of these autoantibodies was not increased. The incidence of organ-specific autoantibodies was normal in both cold and warm AIHA. No correlation was found between the occurrence of these autoantibodies and pattern of serum immunoglobulin concentration, specific serological feature, or clinical manifestation. The significance of the increased incidence of tissue autoantibodies and their relation to autoimmune haemolytic anaemia remains to be elucidated, but in some way may be due to increased immunological reactivity. [ABSTRACT FROM AUTHOR]

Certain foetal calf sera (FCS), upon initial injection, elicit delayed dermal reactions in some but not all guinea-pigs. The FCS that evoke significant dermal responses also initiate in vitro blastogenesis of lymphocytes taken from animals exhibiting the dermal reactions. A correlation exists between the severity of the in vivo reactions and the degree of blastogenesis observed. An explanation for these observations has been suggested, i.e. that some guineapigs possess spontaneously developed delayed hypersensitivity for antigen(s) contained in FCS. [ABSTRACT FROM AUTHOR]

Immunologic changes iii patients and experimental animals with skin burns include impairment of delayed hypersensitivity and the presence of autoantibodies. We have studied thirty-one patients with burns (2-46% area. 1 2-82 years old) to determine the incidence of autoantibodies, to evaluate their clinical significance and to explore the burn syndrome as a model of autoimmunity. By indirect immunofluorescence, sixteen sera (52%) showed antiepithelial ('pemphigus-like') antibody and seven gave basement layer staining. The antibody did not fix complement in vitro. Eleven (35%) had antinuclear antibodies reactive with rat liver nuclei. Tests for anti DNA and deoxyribonucleoprotein were negative. Twenty patients had positive latex fixation tests (LFT) (67%) with titres above 1:80 in eight. Eight of twenty-eight (32%) had a positive sheep cell agglutination test (SCAT). Patients over 59 years tended to be more reactive in tests for rheumatoid factor (RF) than the younger group. The incidence of positive LFT and SCAT was significantly higher than controls. There was no clear relationship of the presence of one antibody to the other nor to the severity and final outcome of the injury. [ABSTRACT FROM AUTHOR]

Precipitating serum antibodies to Escherichia coli O antigens from some infants and children with acute pyelonephritis were studied. These precipitins were largely resistant to reduction with 2-mercaptoethanol and were localized in the 7S fraction after gel filtration of the patient sera through Sephadex G-200. The precipitins were inhibited by anti-IgG serum, but not by anti-IgA or -IgM sera using a combined single and double diffusion method. The IgG nature of the precipitins investigated was also substantiated by immunofluorescence studies of precipitates formed by E. coli O antigens and the corresponding antibodies in double diffusion plates. Possible reasons for the occurrence of IgG precipitins predominantly in patients with recurrent attacks of pyelonephritis are discussed. [ABSTRACT FROM AUTHOR]

Intact IgG antibody can terminate established immune responses, whereas F(ab')2 antibody cannot do so. The difference between the two antibodies appears to be qualitative. F(ab')2 antibody, but not pepsin-digested normal serum, can interfere with the suppression and termination of immune responses induced by intact IgG antibody. These results are discussed in terms of the tripartite inactivation model. [ABSTRACT FROM AUTHOR]

Thermal regulation of the immune response was studied in toads following single injections of bacteriophage f2. The immune response was markedly inhibited in animals kept at 15° as compared to the controls (25°). The appearance of serum antibodies was delayed in animals kept at 15° for the first post-immunization week but their peak antibody levels were similar to those in toads maintained at 25° throughout. Transfer of animals from 25° to 15° 2 weeks after immunization only temporarily depressed the serum antibody levels but caused a marked delay in conversion from heavy to light antibodies. Our results are in keeping with the hypothesis that lowered environmental temperatures inhibit a variety of metabolic processes which may be concerned with the utilization of antigen and/or the synthesis of antibodies. [ABSTRACT FROM AUTHOR]

Immunochemical identification of a distinct immunoglobulin class associated with mouse reaginic antibody and designated IgE has been performed. An antiserum against mouse reaginic antibody was prepared in rats by immunization with homologous peritoneal mast cells sensitized with mouse reaginic antibody. This antiserum, after adequate absorption, recognized only one component existing in mouse serum or fractions of serum containing reaginic antibody. This component was not any of the already known γ1, γ2, IgA or IgM immunoglobulins; its immunoglobulin nature was indicated by its antigen-binding capacity in radioimmunodiffusion analysis. Fractionation experiments (zone electrophoresis, gel filtration on Sephadex G-200) showed that there was a strict association between reaginic anaphylactic activity and IgE immunoglobulin. Molecular weight of IgE was found to be about 200,000. In biological tests, anti IgE neutralized anaphylactic activity attributed to reaginic antibody, but not that attributed to γ1-antibody. Anti-IgE degranulates normal and sensitized mouse peritoneal mast cells, and rat peritoneal mast cells after they have been sensitized by mouse reaginic antibody. [ABSTRACT FROM AUTHOR]

The localization of HL-A histocompatibility antigens at the surface of human lymphocytes in electron microscopy has been studied using hybrid antibodies to bind electron-dense particles (ferritin and plant viruses) to anti-HL-A antibody. A discontinuous distribution of the markers is observed at the cell surface, which is identical with that described for H-2 antigens on mouse lymphocytes with the same technique. Double labelling experiments suggest that the areas of the cell surface where HL-A antigens are detected contain also the heterologous lymphocyte antigens detected by an anti-thymocyte serum and that HL-A antigens are not renewed at a detectable level during the period of the labelling procedure in the areas of the cell surface which are not labelled primarily with ferritin-anti-IgG-anti-HL-A complexes. The interpretation of the discontinuous labelling of HL-A antigens with direct immunoferritin techniques is discussed. [ABSTRACT FROM AUTHOR]

Human lymphocytes were fractionated on gradients of bovine serum albumin (BSA). Cells obtained from the more dense layers bound antigen specifically. Cells capable of interacting with antigen contained antibody which was separable with the nuclear components of the cell. Immune cells contained antibody which was specific for the immunizing antigen. Cell-bound antibody mediated and, in the presence of isologous antibody, slightly enhanced the uptake of antigen. Specific antibody passively bound to cell membranes did not promote uptake of antigen. Antigen which bound to lymphocytes in vitro was not enzymatically digested within the cell but became bound to acid-insoluble nuclear DNA. [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]

The inert matrix of polymerized normal rabbit serum was given defined antigenicity by allowing selected human proteins to diffuse into small pieces of the gel. After fixation and paraffin embedding, serial sections with uniform distribution of reactive antigen were obtained. Such sections are recommended for determination of specificity and optimal working titre of fluorescent antibodies; as substrate for titration of serum antibodies; and as standards for quantification of tissue antigens. [ABSTRACT FROM AUTHOR]

Chicken anti-bovine serum albumin antibody was isolated by precipitation with albumin at pH 8.6 in 13 per cent NaCl, solution of the precipitate at pH 11.3-11.5 in 0.9 per cent NaCl, and separation of the antibody from the antigen by gel filtration at the same pH. The purified antibody precipitated its antigen and was precipitated by rabbit antiserum to chicken serum. [ABSTRACT FROM AUTHOR]

Serum samples from twenty dogs infected with Echinococcus granulosus were tested for the presence of homocytotropic skin-sensitizing antibodies. Five of the twenty sera were positive in this test, while none of the sera from twenty normal dogs was positive. The antibody was thermolabile and susceptible to 2 mercaptoethanol reduction. Reaginic antibodies to cestode antigens have not been described previously in dogs, though they are frequently associated with helminth infection in other animals and may play a role in acquired resistance. [ABSTRACT FROM AUTHOR]

The delayed-type iso-hypersensitivity that guinea-pigs acquire spontaneously towards a β-globulin antigen of other guinea-pigs has been measured in vitro. Serum containing the antigen specifically triggers lymphocytes from naturally iso-hypersensitive animals to undergo blastogenic response. This reaction is similar to that of lymphocytes cultured in the presence of antigen to which cell donors have been intentionally immunized. Thus, the in vitro technique of DNA synthesis may be used to detect both artificially induced and naturally occurring delayed-type hypersensitivities. In addition, naturally existing delayed hypersensitivity offers a plausible explanation for reports of spontaneous transformation of lymphocytes by homologous or heterologous serum and of certain other in vitro phenomena involving interaction of lymphoid cells from non-immunized donors. [ABSTRACT FROM AUTHOR]