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Small amounts of dinitrochlorohenzene (DNCB) in capsule from were fed to 63 adult male volunteers, following which these subjects and 60 control subjects were simultaneously subjected to a sensitizing series of topical applications of the same compound. After sensitization had been achieved, the level of sensitivity was inferred from a quantitative test series. Small amounts of DNCB appeared to have no effect on subsequent sensitization. When more than 20 mgm DNCB were given by mouth, however, a significant decrease in the ultimate level of sensitivity was seen. [ABSTRACT FROM AUTHOR]

A three-step mild procedure is described, that permits isolation of an adenovirus type-2 soluble hexon, penton and fiber antigens in an extensively purified form. This procedure comprises ammonium sulfate precipitation. Sephadex ion-exchange chromatography and adsorption chromatography on an hydroxyapatite column. The final antigen preparations were homogeneous with regard to immunological, electrophoretic and electron microscopic criteria. [ABSTRACT FROM AUTHOR]

The previous observations of cross idiotypic specificity of IgM cold agglutinins were further investigated in quantitative precipitin assays and attempts were made to relate shared idiotypic specificity to combining specificity for I, i and Pr antigens of red cells. Shared idiotypic determinants were observed among antJ-I and anti-i antibodies which are now known to have combining specificity for determinants present on precursors of the ABH and Lewis blood group substances. There was evidence that one cold agglutinin. Ma, which had previously been shown to have an unusual kind of I specificity was deficient in the idiotypic determinants associated with the other anti-I proteins. Anti-Pr cold agglutinins, which have specificities unrelated to I-i antigens, were found to have distinct cross idiotypic determinants which were not detected on anti-I and anti-i antibodies. IgA and IgM antibodies with Pr specificity isolated from different individuals were found to share idiotypic determinants. Cross specificity antigens were detected at low concentrations in preparations of normal IgG and IgM, but not in any isolated monoclonal macroglobulins lacking cold agglutinin activity. [ABSTRACT FROM AUTHOR]

The recognized trend towards the standardization of the leucocyte migration assay prompted the comparison of efficacy of BCG with soluble purified protein derivative (PPD) antigens in this test. Even low BCG concentrations permit high correlations between in vivo and in vitro responses, whilst PPD doses needed to elicit comparable reactions fall within toxic concentrations. BCG-induced inhibition of leucocyte migration is abolished by the protein synthesis inhibitor, cycloheximide. [ABSTRACT FROM AUTHOR]

The macrophage migration inhibition techique was emplyed to study the debvelopment of human maternal cell-met\dilated immune reactions to plecental antigens during the firs pregnancy. Cell-mediated immune reaction to pooled antigens from five placentas could not be demonstrated during the first trimester, In the th month. peripheral blood leucocyte's from seven out of eight primigravidous women tested were ravtive t placental antigens, The one nonreactor became reactive by the th month. All of the primigravidous women tested during subsequent months were immune reactivity in the course of the first pregancy. [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]

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]

Two groups of lepromatous patients (L type of leprosy) were injected intramuscularly and respectively with the Lawrence's transfer factor (LTF) or a ribonucleic acid (RNA) extracted from viable blood lymphocytes of healthy donors hypersensitive to lepromin (48-72 hr and 20-30 days), tuberculin (PPD), toxoplasmin and histoplasmin. Each patient received a single dose of LTF or RNA obtained from 109 lymphocytes and was carefully observed for a period of 4 months. Histopathology of skin lesions and of lymph nodes were repeatedly performed. The results of intradermal tests with antigens were read at different times up to 120 days after the injection of LTF and RNA. Delayed cutaneous reaction to some antigens was induced in three patients injected with LTF and in two others injected with RNA. The lepromin reaction read at the end of 48-72 hr and after 20-30 days remained negative in all patients during 120 days of observation. Clinical and histopathologic signs of transformation into tuberculoid leprosy could not be observed in the eight patients tested. [ABSTRACT FROM AUTHOR]

The reactions of two monoclonal IgM lambda cold agglutinins, Sch and Sher, have been studied in detail with human and animal erythrocyte antigens. Although they were unusual in having lambda and not kappa polypeptide chains, they could be assigned to the anti I and anti-Pr1 groups of cold agglutinins. The findings with serum Sher indicated that the Pr1 antigen may be more complex than previously thought. The occurrence of unexpectedly large numbers of specificities among monoclonal anti-I, anti-i and anti-Pr antibodies is discussed and it is suggested that each monoclonal antibody may recognize only a limited portion of a complex red cell antigen. [ABSTRACT FROM AUTHOR]

Antigenic determinants of Australia antigen (AuAg) may be determined by haemagglutination inhibition with ease and high sensitivity. The reaction depends on the inhibitory effect of the test antigen-positive sample on the agglutination by specific antibody of glutaraldehyde-fixed sheep erythrocytes which have been tanned and coated with AuAg of different specificities. The standard monospecific antibody reactants are directed against one or other of the common antigens, a and Re, or against the subtypic determinants, d,y,w and r. Because it is more sensitive than conventional immunodiffusion or electrosyneresis, and more convenient than radioimmunoassay, haemagglutination inhibition is most suited to large-scale determinations of AuAg subtypes in samples of relatively low antigenic activity. [ABSTRACT FROM AUTHOR]

The experiments described here form part of a series carried out to determine the conditions of antigen presentation which dispose to the production of IgE antibody in the rat. We have found that Hooded Lister rats in comparison with rats of some other strains have an exceptional ability to produce reaginic antibodies responses can be consistently induced with very small doses of antigen and are boosted to high levels with a second dose of antigen. The effect of the dose of antigen on these responses is as follows. [ABSTRACT FROM AUTHOR]

Sheep erythrocyte (SRBC) antigen was delivered directly into the lymphoid component of the appendix or via the appendicular artery, followed by ligation or clamping of appendicular vessels. Antigen was also injected intravenously, into the spleen, or into the thymus. Counts of anti-SRBC plaque-forming cells (PFC) in the appendix were compared with counts in the spleen and thymus. None of the injection routes employed resulted in an elevation of PFC activity above background in the appendix. However, delivery of antigen via the appendicular artery caused a marked increase of PFC activity in the spleen. These results and other available evidence point towards a helper-cell function of lymphocytes in the appendix, and therefore suggest a central role of this organ in humoral immunity. [ABSTRACT FROM AUTHOR]

The time course of the relative distribution of small lymphocytes binding 125I-labelled human thyroglobulin (HTg) in cell suspensions from the peripheral blood and various lymphoid organs was studied in guinea-pigs at progressive intervals up to 28 days after immunization with an emulsion of HTg and BCG in Freund's incomplete adjuvant (FIA). Small lymphocytes binding 125I-labelled HTg were first detected in peripheral blood, popliteal (draining) lymph node, spleen and bone marrow preparations on the 10th day, and in mesenteric (distant) lymph node and thymus preparations on the 14th day after primary immunization. In general, the percentage of these cells increased progressively thereafter until the end of the period of study. Blocking experiments with unlabelled antigens indicated that the binding of 125I-labelled HTg by small lymphocytes was specific. An anti-HTg antibody cytophilic for guinea-pig small lymphocytes was demonstrated by the passive transfer of antigen-binding capacity to lymphocytes of unimmunized animals with hyperimmune guinea-pig serum. It is proposed that, in these experiments, anti-HTg cytophilic antibody was bound first to small lymphocytes in tile tissues participating actively in the immune response (popliteal node, spleen and bone marrow) before spilling over into the general circulation to coat lymphocytes at other sites (mesenteric node and thymus). [ABSTRACT FROM AUTHOR]

A mean of 6.9 per cent of small lymphocytes in peripheral blood preparations and between 1.8 and 2.4 per cent of small lymphocytes in lymph node, spleen, bone marrow and thymus preparations from unimmunized guinea-pigs bound 125I-labelled purified protein derivative of mammalian tuberculin (mammalian PPD). The percentage of these cells fluctuated but did not alter substantially after immunization with BCG or with BCG emulsified with human thyroglobulin (HTg) in Freund's incomplete adjuvant (FIA). Blocking experiments indicated that the binding of 125I-labelled mammalian PPD was specific and there was tentative evidence that the lymphocyte receptors may be IgG. A comparison is drawn between the observed time course of 125I-labelled mammalian PPD- binding small lymphocytes and the response of lymphocytes sensitive to strong histocompatibility antigens, and it is proposed that the propensity of certain anti- gens to induce a delayed hypersensitivity-type response is related to the presence of substantial numbers of antigen-binding cells in unimmunized animals. A noteworthy incidental finding was an unexplained depression in the cellular and humoral responses to mammalian PPD in guinea-pigs that had been immunized with HTg-BCG-FIA emulsion. [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]

Anaphylatoxin generation and histamine release by anaphylatoxin were characterized with a view to determining whether this material is an intermediate for histamine release by antigen and antibody administered to the guinea-pig lung. The histamine-releasing activity of the anaphylatoxin generated by a given amount of antigen-antibody precipitate was comparable to that produced by the same amount of antibody either administered to the lung as a soluble immune complex or used to passively sensitize guinea-pig lung for subsequent challenge with antigen. Anaphylatoxin generation was relatively slow and its histamine-releasing activity more rapid, compared with histamine release by antigen and antibody. Also, the anaphylatoxin-activated process was not inhibited in the presence of phenol, was less markedly inhibited at 20° and was not appreciably enhanced in the presence of maleate or succinate. The same conditions produced moderate to no interference of anaphylatoxin generation. It was concluded that the differing characteristics of anaphylatoxin were not consistent with the possibility that this material functioned as an intermediate for histamine release by antigen and antibody in the guinea-pig lung. [ABSTRACT FROM AUTHOR]

The in vitro 19S-PFC response to SRBC reaches a peak at 4 days. After this time, the number of 19S-PFC gradually decreases with a hall-life in vitro of approximately 20 hours. The factors which influence this rate of decline of 19S-PFC after 4 days in vitro have been investigated. The decline is not the result of non-specific inhibitors in the tissue medium: medium harvested from cultures at the time of the peak PFC response can support another PFC response by fresh spleen cells. The survival of 19S-PFC in culture is a sensitive function of the number of specific T cells in the culture, since removal of T cells enhances the decline of PFC. Evidence is presented that a θ-negative cell with surface receptors for SRBC can specifically enhance the rate of decay of SRBC-specific 19S-PFC in vitro. This decay is mediated by an antigen-specific soluble mediator which cannot be absorbed by specific antigens. This factor is unlikely to be specific hyperimmune mouse IgG since addition of anti-SRBC IgG at 4 days has no affect on the rate of decay of PFC. Although the properties of the supernatant activity have not been characterized, it might be either an anti-receptor antibody or an antigen-antibody complex. [ABSTRACT FROM AUTHOR]

Monkeys and mice were immunized with Rauscher murine leukaemia virus. Two types of leukaemia virus preparations were used as immunogens. One preparation was derived from viraemic plasma and was highly purified by density gradient ultracentrifugation. The other preparation of Rauscher virus was derived from spleen cells and was contaminated with cell membranes. Following immunization with each of these preparations sensitive techniques were utilized to measure antiviral and antileukaemia cell ('cytotoxic') antibody levels on aliquots of the same antiserums. Multiple serums from each animal were tested during the weeks of immunization in order to establish a parallelism or lack of parallelism in the changes in cytotoxic and antiviral antibody levels. In each antiserum the cytotoxic and antiviral titres were virtually the same. This was true whether the animal had been immunized with a purified or a non-purified virus preparation. The presence or absence of contaminating cell membrane material in the immunizing material did not result in an antiserum with increased or decreased cytotoxic to antiviral antibody ratio. This indicated that cytotoxic antibody is probably not the result of immunization against cell membrane antigens ('neoantigens') as distinguished from virus or virion subunit antigens. Conversely, we found that leukaemia cells containing relatively little virus did not lyse in the presence of cytotoxic antibody prepared against either membrane-rich or membrane-poor virus preparations. This finding suggests that virus and not independent neoantigen renders the leukaemia cell lysable by cytotoxic antibody. Our studies therefore minimize the significance and even question the presence of neoantigens in Rauscher leukaemia cells, since the cytotoxic capability of anti-Rauscher antiserum is dependent on the presence of virus and not neoantigen in the immunizing preparations, and since virus and not neoantigen renders the infected cell lysable by anti-Rauscher antibody. [ABSTRACT FROM AUTHOR]

ALG has been isolated from the sera of four horses immunized with mouse thymocytes and its ability to suppress the immune response to SSS-III investigated. All four preparations suppressed the response to this antigen in BALB/c mice but only one was effective in CBA mice. Other ALGs were isolated from sequential bleeds obtained from a single horse. Preparations obtained after only two injections of the donor with mouse thymocytes, were able to suppress the immune response to SSS-III in CBA and BALB/c mice. Studies with selected ALG preparations indicated that they were less effective or ineffective if their administration was delayed until just before challenge with SSS-III. These results indicate that the ability of ALG to suppress thymus-independent immune processes is a variable one, but it is not necessarily a consequence of hyperimmunization of the donor animal. It is however influenced by the ALG protocol used and the strain of animal under test. [ABSTRACT FROM AUTHOR]

The electrophoretic mobility of antibodies to malarial S-antigens was usually γ1. The same antigen-stimulated antibodies with different mobilities in different individuals. IgG antibodies and others probably belonging to the IgM class were detected. IgG dissociated from immune complexes contained light chains of λ type only in two cases and predominantly κ type in a third. This antibody cross-reacted with an antiserum to IgG2. Antibodies to other malarial antigens had restricted mobilities in the γ2 region. [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 antigenicity in guinea-pigs of a series of sequential polymers has been studied. Almost ail the polymers had a repeating sequence of three amino acids and with few exceptions glycine was one of the three residues and proline or a proline homologue one of the others. As a result the majority of the peptides used probably possessed at least in part, the collagen type of triple helix, although with the exception of (Gly-Pro-Gly)n all these polymers were antigenic inducing both a humoral and cell-mediated response. With (D-Ala-Gly-D-Pro)n no humoral response was obtained but there were excellent cell-mediated reactions. The mutual cross-reactivity, both humoral and cell-mediated, between (Gly-Pro-Ala)n and (Pro-Ala-Gly)n emphasized the importance of the sequence in the body of the polymers rather than the sequence at the free ends in determining specificity. This is confirmed by the absence of crossreactivity of both of these polymers with (Ala-Pro-Gly)n . With a series of samples of (Ala-Gly-Pro)n of increasing single chain weight average molecular weight ranging from ca 2,000 to ca 15,000 the most immunogenic for cell-mediated reactions was that of lowest molecular weight, but far humoral responses immunogenicity ran parallel with increasing molecular weight with the exception of the polymer of highest molecular weight, which was almost insoluble. [ABSTRACT FROM AUTHOR]

The experiments described in this paper extend the observations of previous work in vitro demonstrating a decrease in the frequency of antigenreactive units specific for horse RBC in spleen cells from mice primed with KLH. It was observed that the addition of lymphoid cells having T-cell function reconstituted the anti-HRBC response to normal values. Significant enhancement of the response beyond the normal values could be evoked using two dissimilar methods, (i) addition of allogeneic thymus cells, and (ii) restimulation in vitro with the priming antigen. The latter type enhancement was elicited by the addition of small doses of KLH to cultures of spleen cells from mice recently primed with KLH, including cultures otherwise demonstrating antigen-induced suppression. The stimulus required to enhance the response to HRBC in these cultures was specific for the priming antigen, KLH. These results are discussed in the light of current theories of 'antigenic competition' and specific heterologous enhancement. [ABSTRACT FROM AUTHOR]

A specific antibody has been prepared in the rabbit against purified rat alveolar macrophages. Immunofluorescent and absorption tests show that rat alveolar macrophages are carriers of specific antigen(s) that are not visible in rat rnonocytes and free tissue macrophages (peritoneal). On the other hand, rat fixed tissue macrophages from different organs such as liver, spleen, thymus, and lymph node show high percentages of cross-reaction with the antialveolar macrophage antibody, thus revealing the presence of very similar or the same antigen(s). A certain number (about 20 per cent) of bone marrow cells also give positive reactions but their identity as either fixed tissue macrophages or precursors has not been established. A survey of the distribution of rat alveolar macrophage antigen(s) in cells of the mononuclear phagocytic system in four other animal species revealed a high degree of species specificity. [ABSTRACT FROM AUTHOR]

Preparations of poly-(glycyl-L-prolylglyc ine), poly-(glycyl-L-prolylL-pr oline), and poly-(β-alanyl-L-pro lylglycine) via the corresponding tripeptide 4-nitrophenyl ester hydrobromides are described. A series of polypeptide antigens of structure H-(L-Ala-Gly-L-Pro)n -OH with graded molecular weights were also prepared. The four low molecular weight members (n = 1, 2, 3 and 4) were obtained by stepwise classical condensation of tripeptide derivatives. Fractionation by gel filtration on Bio-Gel P-150 eluted with 50 per cent acetic acid was used to obtain five narrow fractions from a polydisperse preparation: these had single chain weight average molecular weights of approximately 2000, 3000, 6000, 11000 and 15000 respectively. The high molecular weight fractions possessed an ordered associated structure presumed to be a collagen-like triple helix, which was stable in 50 per cent acetic acid at room temperature. [ABSTRACT FROM AUTHOR]

Two antigens of human wart tissue, a nuclear and a cell surface antigen, were isolated from whole tissue homogenates by elution from antibody-Sepharose immunoadsorbents. Neither antigen was a structural component of purified human papilloma virus. The antigens were detected by immunofluorescence in warts, squamous cell carcinomas, fetal skin, and psoriatic epidermis, but not in normal skin or basal cell carcinomas. They could be detected in concentrated extracts of normal skin by agar gel diffusion. The antigens belong to the growing class of substances that are readily detected in tumors and in fetal tissues, but are present only in minute quantities in normal adult tissue. [ABSTRACT FROM AUTHOR]

Experimental animal tumors caused by papova viruses contain cellular antigens which relate to tumor rejection. A similar mechanism may account for the spontaneous resolution of human warts. We examined the antigenic composition of human wart tissue using rabbit antisera prepared to crude wart homogenates. The antisera were absorbed with pooled human plasma and liver extract prior to indirect immunofluorescent experiments. The absorbed antisera produced fluorescent staining of the nucleii and cell surfaces of epidermal cells in warts obtained from different patients, and did not react with normal skin. A single band of precipitation was detected when the antisera was reacted in agarose gel diffusion with an aqueous extract of wart tissue. The antisera also reacted with the nuclei and cell surfaces of keratoacanthomas and sqamous cell carcinomas but not based cell carcinomas. All immunological reactivity was eliminated after exhaustive absorption with pooled extracts of normal epidermis. These studies demonstrate cellular antigens of human wart tissue which are present in normal tissue and markedly increased in warts and certain epidermal tumors. These antigens appear to be organspecific and similar in distribution to the epidermal antigen of pemphigus. [ABSTRACT FROM AUTHOR]

Analyzes the biochemistry of antigens that influence histocompatibility. Properties of major histocompatibility loci; Application of an assay system to purify the substance; Location of the histocompatibility antigens according to tissue distribution, subcellular distribution and stabilization techniques.

The O-antigenic lipopolysaccharides and the acidic polysaccharides isolated from Escherichia coli strains O8:K87(B ?) :H45 were compared with respect to chemical composition and serological specificity. The O-specific polysaccharide moiety of the lipopolysaccharide from E. coli 08:K87(B?):H19 contains mannose as the sole sugar constituent, whereas the (032)-specific polysaccharide moiety of the lipopolysaccharide from E. coli (032):K87(B?):H45 consists of glucose, galactose, glucuronic acid, N-acetylglucosamine, and N-acetyl-L-fucosamine in the molar ratios of 1:1:1:1:1. From both strains, an acidic polysaccharide can be isolated which consists of glucose, galactose, glucuronic acid, N-acetylglucosamine, and N-acetyl-L-fucosamine in the molar ratios of 1:1:1:1:1. Both acidic-polysaccharide preparations, as well as the (032)-specific polysaccharide moiety of the lipopolysaccharide from E. coli (032):K87(B?):H45, have the same structure and, upon partial acid hydrolysis, yield the same oligosaccharides. With the aid of bacterial agglutination, passive hemagglutination, and immune precipitation in homologous and absorbed immune sera, as well as inhibition studies of these reactions with oligosaccharides, serological identity of the acidic polysaccharide and the (032)-specific polysaccharide moiety of the lipopolysaccharide from E. coli (032):K87(B ?):H45 was shown. It is concluded that the acidic polysaccharide, which has been shown to be the K antigen of E. coli 08 :K87(B ?):H19, is also responsible for O-specificity in strain (032):K87(B ?):H45. [ABSTRACT FROM AUTHOR]

A procedure is described for the preparation of liposomes with either lecithin or sphingomyelin in the presence of various Salmonella minnesota S and R form lipopolysaccharides (antigens). These liposomes release trapped glucose marker when incubated with an appropriate rabbit antiserum (as source of antibodies) and native, is. unheated, guinea pig serum (as source of complement). The extent of marker loss is dependent on the amount of antigen added; treatment of R or S form lipopolysaccharide with alkali markedly reduces the amount necessary for half-maximal sensitization, I e. half-maximal glucose release. The alkali-treated lipopolysaccharides are also effective in "passive" sensitization of liposomes. In this procedure (in contrast to the above which has been designated "active" sensitization), the liposomes are first generated in the absence of any antigen and subsequently incubated with lipopolysaccharide, Both actively and passively sensitized liposomes lose a greater percentage of their trapped glucose when prepared with lecithin than with sphingomyelin. The properties of the lipopolysaccharide liposomes are compared with those containing various ceramide antigens as described previously. [ABSTRACT FROM AUTHOR]

Cell-mediated immunity to varicella-zoster antigen was assessed by lymphocyte transformation in fourteen patients with acute herpes zoster and in a group of twelve healthy controls. There was a significant dimunition in cell-mediated immunity to this antigen in the patient group when compared to the controls but no definite difference was observed in the responses to phytohaemagglutinin and PPD measured at the same time. It was suggested that this lack of cell-mediated immunity contributes to the evolution of the disease. [ABSTRACT FROM AUTHOR]

The cellular response to HL-A antigens has been studied in thirty-one patients who had received a renal allograft from either a cadaveric or living donor, utilizing the leucocyte migration technique. The results indicate that inhibition of migration develops prior to or during the onset of a clinical rejection episode. This inhibition of migration reverts to non-inhibition in autologous serum when the rejection crisis is reversed. Inhibition of migration is still noted in allogeneic serum following this clinical reversal, but after varying time intervals the inhibition reaction also decreases in this serum. The abrogation of inhibition in autologous serum is specific to the HL-A antigens of the donor. These observations suggest that survival of human renal allografts depends on a blocking substance in the serum initially; subsequently, the loss of inhibition of migration with HL-A antigens in both autologous and allogeneic serum suggests an inactivation of specific antigen sensitive cells to the histocompatibility antigens of the donor. [ABSTRACT FROM AUTHOR]

F1 mice with chronic GVH disease were studied to investigate the hypothesis that non-specific stimulation of helper T cells, such as might be seen in graft-versus- host (GVH) disease, results in autoantibody production. Antinuclear antibody (ANA) was detected significantly more frequently in F1 mice with GVH disease than in control animals. The antigenic specificities of the ANA indicate that it is of host origin and, since it reacts with syngeneic nuclei, it can be considered a true autoantibody. The pattern of development, intensity, prevalence and sex distribution of ANA reactions differed notably in experiments with A x CBA F1s compared to those with C57B1/6 x BALB/c F1s suggesting that these parameters of ANA formation are influenced significantly by the genotype of the animal with GVH disease. [ABSTRACT FROM AUTHOR]

Isografts of foetal small intestine, implanted under the kidney capsules of adult mice grow normally and, despite the lack of intraluminal antigenic stimulation, are populated by thymus-dependent and thymus-independent lymphocytes. The Peyer's patches in these grafts are very small, lack germinal centres and can be shown to have small thymus-dependent areas. Quantitative intraepithelial lymphocyte counts were carried out in normally sited small intestine of immunologically intact and thymus-deprived mice, and in grafts implanted in intact and thymus-deprived mice. Counts were also performed in a group of neonatally thymectomized and control mice. The results show a significant depletion of intraepithelial lymphocytes in neonatally thymectomized mice, and a profound reduction in numbers of intraepithelial lymphocytes in grafts, deprived of antigen, when compared with normally sited intestine of the same age. [ABSTRACT FROM AUTHOR]

Haemagglutination inhibition experiments were used to study the interaction of several well-defined rheumatoid factors with pFá fragments ( = Cγ2 homology regions) prepared from all four IgG subclasses. The results suggest that rheumatoid factors interact with antigens located in both homology regions of the Fc fragment. A minimum of four reactive regions is suggested-one in the Cγ3 region and three more in the Cγ2 region. This multiplicity of IgG antigens may contribute to the formation of rheumatoid factor-IgG complexes and therefore play a role in the complement-fixing activity of such complexes. [ABSTRACT FROM AUTHOR]

Peritoneal exudate cells from old NZB/Bl mice were found to be more active in taking up I125 labelled bovine serum albumin than similar cells from age matched BALB/c, C57B1 and CBA mice. The cells from both young and old NZB/Bl mice were markedly less able to degrade the ingested antigen than cells from the other strains. These observations are discussed in relation to the development of autoimmune phenomena in the NZB/Bl strain, [ABSTRACT FROM AUTHOR]

Antigenic stimulation of the rat spleen to initiate a secondary response to tetanus toxoid (tet. tox.) has been found to have two effects on the recirculating lymphocytes which are migrating through the splenic pulp. Firstly, specific antigen-sensitive cells were selected from a population of immune lymphocytes during migration through an isolated, perfused spleen which was stimulated with tet. tox. This was supported by the substantial, and mostly specific, depression in the ability of such migrated cells to mediate a secondary response to tet. tox. and by the large secondary response produced by transplanted fragments of the perfused spleen without further exposure to antigen. Secondly the i. v. injection of tet. tox. into rats which had been previously transfused with labelled immune lymphocytes or alternatively labelled non-immune lymphocytes was followed by a transient retention of both populations in the spleen at the expense of the lymph nodes. Any surplus retention of the immune population in the stimulated spleen was not detected which suggests with certain reservations that only a small minority of even the immune population were antigen-sensitive cells. [ABSTRACT FROM AUTHOR]

Presence of soluble immune complexes was investigated in sera from persons with a well documented clinical diagnosis of leprosy. The complexes were detected by their reactivity with the Clq component of complement. More than 70% of the studied patients with lepromatous-leprosy had immune complexes demonstrable by this method (39/51), while only a small proportion of the healthy control group (1/35 or about 3%) had precipitable complexes. Two out of nine sera from patients with tuberculoid leprosy reacted when tested with Clq component. The presence of free-antibody to mycobacterial antigens was determined as well. The possible relationship between the presence of such immune complexes and the pathology of some reactional states of the disease is discussed. [ABSTRACT FROM AUTHOR]

Rats injected with syngeneic chondrocytes or cartilage shavings develop autoreactivity as assayed by the leucocyte migration inhibition test. It is suggested that chondrocyte specific differentiation antigen(s), normally sequestered from the immune system, once exposed experimentally by enzyme treatment or in some human pathological situations are recognized as foreign immunogens and induce a lymphocyte response. [ABSTRACT FROM AUTHOR]

The rate of elimination of soluble protein antigen injected intravenously difl"ers in different inbred strains of mice previously immunized to the antigen. This difference is apparently related to the affinity of the antibody they produce. Animals producing high affinity antibody eliminate antigen more effectively than those producing low affinity antibody. Passive transfer of antibody shows that the difference of antigen elimination is a property of the antibody, rather than the cellular mechanisms involved. The immunopathological significance of these findings is discussed. [ABSTRACT FROM AUTHOR]

Experimental autoimmune thyroiditis, characterized by thyroid antibodies (precipitating, haemagglutinating and complement fixing) and infiltration of the gland with mononuclear cells, was induced in inbred and randomly bred strains of mice, using thyroid extract from the same (syngeneic) or different (allogeneic) strains emulsified in sonicated Freund's complete adjuvant. The syngeneic antigen was much less efficacious than the allogeneic in inducing thyroid antibody and lesions. The subcutaneous route was more effective than intradermal immunization and pertussis vaccine decreased the incidence of the disease. Thyroid lesions and antibodies were found 9-14 days after immunization and were still present 3 months later. Differences, genetically determined, were observed in various inbred strains of mice in the degree of thyroid lesions as well as in the titre of thyroid antibody. [ABSTRACT FROM AUTHOR]

Sera from 760 subjects with and without inflammatory bowel disease (IBD) were studied selectively using both primary and secondary antibody assay techniques and different cow's milk antigens. Techniques which demonstrate anti- body-antigen binding revealed that the incidence, amount and immunoglobulin class of detectable antibody to bovine serum albumin (BSA) were not significantly different among IBD and control subjects. Only 13 of the 138 sera with the most anti-BSA by primary binding techniques had the capacity to precipitate spontaneously either BSA or antigens in raw (RSM) and pasteurized (PSM) skimmed milk. In passive haemagglutination studies, 41% of these 138 sera had the capacity to agglutinate BSA-coated erythrocytes, while the respective figures for RSM and PSM were 56% and 77%. Only in studies employing the passive haemagglutination of RSM-coated erythrocytes were high titres found more frequently in sera from patients with IRD than in sera from control subjects. Taken as a whole, this study fails to provide evidence for the pathogenetic significance of milk antibodies in lBD. [ABSTRACT FROM AUTHOR]

Antibody activity against HSA and KLH was present in all five immunoglobulin classes of BALB/c mice. Bordetella pertussis vaccine was more effective in stimulating antibody production against HSA than against KLH and IgG1 and IgG2b antibody were affected more than the antibody present in the other immunoglobulin classes. The results are discussed in relation to the differing thymic dependence of these two antigens. [ABSTRACT FROM AUTHOR]

Two liver-specific antigens are known: a water soluble protein (LP-2) and a water insoluble macromolecular low density lipoprotein (LP-1). In this paper the relative role of the two antigens in the development of experimental immune hepatitis has been investigated. Immunization of rabbits with a human preparation containing both antigens, led in all animals to lesions characteristic of an immune hepatitis. Immunization of the animals with a purified water soluble liver protein proved less efficient: only two out of six animals developed characteristic lesions which were less severe than those in the first group. It was deduced that although not a prerequisite, the liver-specific lipoprotein plays an important supportive role in the development of immune hepatitis, [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]

Plasma membrane fractions isolated from cells of an aminoazo-dye-induced rat hepatoma were solubilized by limited papain digestion. DEAE-cellulose chromatography yielded a discrete component retaining tumour-specific antigen as measured by its capacity to neutralize antibody in tumour-immune sera, which reacts in immunofluorescence tests with the plasma membrane of intact hepatoma cells. Solubilized plasma membrane fractions also elicited a tumour-specific humoral antibody response in syngeneic rats. The relative inefficiency of antigen isolation procedures would seem to preclude the use of solubilized antigen for immunotherapy, but these preparations are important in studying the nature of tumour antigen expression during chemical carcinogenesis and for analysing the involvement of antigen-antibody complexes in tumour immunity. [ABSTRACT FROM AUTHOR]

Decomplementation with cobra venom factor had no effect on eosinophil accumulation into the site of IgG,-mediated PCA reactions in the guinea-pig. Eosinophil and neutrophil accumulation also followed PCA reactions in animals partially or totally deficient in C4. The effect of intradermal injections of re-formed antigen-antibody complexes prepared from guinea-pig igG, or lgG2 were not affected by ecomplementation with cobra venom. The lesions produced with either immunoglobulin complex were similar in appearance in decomplemented and normal animals and were followed by comparable tissue accumulation of eosinophils and neutrophils. [ABSTRACT FROM AUTHOR]