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Cellular immune responsiveness, as measured by lymphocyte transformation in one-way mixed leucocyte cultures (MLC) and in phytohaemagglutinin (PHA) stimulated cultures was evaluated in forty patients with systemic lupus erythematosus (SLE) and in seventy-four normal controls. The effect produced by sera from these subjects on in vitro lymphocyte reactivity was tested on autologous cells and on homologous responding cells from a constant panel of ten healthy volunteers. The reactivity of lymphocytes from SLE patients to PHA and to a battery of allogeneic cells was significantly lower than that of normal controls. Sera from some SLE patients inhibited the MLC reactions, while in other cases a distinct stimulatory effect was found. It is suggested that virus-induced modifications of normal histocompatibility antigens cause the appearance of blocking antibody that might bind to the surface of T lymphocytes, impairing their function. [ABSTRACT FROM AUTHOR]

The cross-reactivity of heterologous erythrocytes was measured at the level of the B and the T cell. B cells produced antibody with restricted cross-reactivity as compared with the cross-reactivity of T cells, assayed by their ability to help B cells in a primary anti-sheep erythrocyte immune response. Helper function was maximally elicited with low antigen doses. The data suggest that the T-cell antigen receptors for erythrocyte antigens differ in specificity from those of B cells and that the sensitivity of T cells to antigen may be very great. [ABSTRACT FROM AUTHOR]

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]

Both the humoral and cellular immune response to haemocyanin was measured in normal subjects and patients with liver disease including primary biliary cirrhosis, other forms of cholestasis, and cryptogenic cirrhosis. Significant differences in antibody titre were found 2 weeks after immunization being highest in normal subjects, less in cryptogenic cirrhosis and least in primary biliary cirrhosis. The incidence of positive skin tests, indicating the development of delayed hypersensitivity to haemocyanin, was significantly less in patients with primary biliary cirrhosis and cryptogenic cirrhosis than in those with cholestasis or the normal subjects. It is suggested that the poor antibody response seen in primary biliary cirrhosis, could be related to impaired T cell function and hence lack of the T and B cell co-operation necessary for antibody formation to some antigens. The presence of delayed hypersensitivity to haemocyanin as measured by the skin test was compared to other tests of delayed hypersensitivity including the tuberculin skin test, DNCB sensitization and PHA-stimulated in vitro lymphocyte transformation. Of twenty patients with primary biliary cirrhosis the results of all four tests correlated in nine but did not agree in the remaining eleven patients. These results emphasize the importance of using a number of indices when assessing the degree of energy of any one patient. [ABSTRACT FROM AUTHOR]

Cell-mediated immunity was assessed in man by summation of positive delayed hypersensitivity (DHS) responses to five test antigens, Candida, mumps, trichophyton, tuberculin and streptokinase-streptodornase (Varidase). The study included forty-four controls comprising healthy persons and hospital inpatients with minor illnesses, forty-five aged persons, twenty-four patients with active chronic hepatitis (ACH), nine with systemic lupus erythematosus (SLE) and fourteen patients with rheumatoid arthritis. For controls and the group with ACH, cell-mediated immunity was assessed also by transformation of blood lymphocytes with phytohaemagglutinin (PHA). The incidence of positive DHS responses to all antigens fell with advancing age, and responsiveness was significantly lower in all three groups of immunopathic disease, particularly ACH. Prednisolone was not associated with significantly depressed DHS reactions, but combined prednisolone and azathioprine were. Weak DHS responses were associated significantly with low titres of natural antibody to flagellin and with lower humoral immune responses to flagellin. Lymphocyte transformation in response to PHA in ACH was significantly less than in healthy controls. Thus certain autoimmune diseases show an immunological imbalance in the form of depressed cell-mediated immunity to extrinsic antigens and 'hyperactive' humoral immune responses to 'self' antigens and selected extrinsic antigens. [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]

In Sjögren's syndrome (SS), the earliest glandular infiltration by lymphoid cells surrounds the salivary ducts, which are also the target of the organ-specific antisalivary duct (ASD) autoantibody found in some patients with this disorder. A sensitizing antigen localized in ductal epithelial cells may elicit both humoral and cellular immune responses. In a study using coded specimens from twenty-five patients with SS and eight with rheumatoid arthritis, sera were tested for ASD, and lip biopsies were graded for the degree of lymphoid infiltration and destruction of labial salivary glands. Significantly less cellular infiltration was found in SS patients who had ASD compared to those who lacked this antibody. In SS, the group of ASD-negative patients had greater gland destruction and more severe xerostomia. The possible role of ASD as a blocking antibody is suggested. [ABSTRACT FROM AUTHOR]

Anti-erythrocyte autoantibodies of two distinct antigenic specificities can be recovered from immunoglobulin-coated NZB erythrocytes. These autoantibodies react with either exposed (X) or hidden (HB) antigenic determinants on murine red cells and both types can be neutralized by mouse plasma. Antibody neutralization by plasma is dependent on two distinct plasma activities which appear to be soluble analogues of the erythrocyte surface autoantigens X and HB. The soluble erythrocyte antigens SEA-X and SEA-HB can be separated by molecular exclusion chromatography, with approximate sizes of 2 × 105 for SEA-X and ⩾ 5 × 106 for SEA-HB. The presence of these soluble erythrocyte autoantigens in the plasmas of 'autoimmune' NZB mice has to be considered in relation to the immunologic homeostasis of these autoantibody responses and pathogenesis of both the autoimmune haemolytic anaemia and the autologous immune complex disease of these mice. Individual anti-erythrocyte autoantibodies of both anti-X and anti-HB types exhibit discrete and individually distinctive differences in affinity for autoantigen and also in respect to antigenic determinant specificity. These results suggest that factors which control the genetic selection of these responses in an inbred strain do not prescribe a single specific B lymphoid cell clone; but rather it appears that a number of different autoimmunocompetent B lymphocyte clones with differing affinity and determinant specificity for given autoantigen molecules may be derepressed by other events in the recruitment of the autoantibody responses. [ABSTRACT FROM AUTHOR]

Guinea-pigs were immunized with an emulsion of human thyroglobulin (Tg) and BCG vaccine in Freund's incomplete adjuvant. Peripheral blood lymphocytes binding Tg and purified protein derivative of mammalian tuberculin (PPD) labelled with 125I were demonstrated with an autoradiographic technique. The percentage of these cells was compared with the size of the delayed hypersensitivity (DH) skin reactions to Tg and PPD, and Tg antibody titres at intervals up to 35 days after immunization. The individual responses to Tg showed the time course of primary immune reactions although they did not parallel each other closely. By contrast, a depression of cutaneous DH to PPD was observed in spite of the presence of substantial numbers of 125I-PPD-binding peripheral blood lymphocytes. In non-immune guinea-pigs, approximately 2-8% of peripheral blood lymphocytes bound 125I-PPD whereas <0-l% bound 125I-Tg. The significance of antigen-binding lymphocytes in the immune response is discussed, and it is suggested that the presence of a substantial pool of antigenbinding lymphocytes in unprimed animals may be of importance in the induction of DH. [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]

Mice were immunized with an. allogeneic tumour antigen using various adjuvants and were subsequently challenged with live tumour cells. Immunization using certain adjuvants led to accelerated destruction of the subsequent tumour alto- graft, whilst the use of Freund's complete and incomplete adjuvant (CFA and IFA) led to enhanced tumour growth and eventual death of the mice. Pretreatment with Freund's complete adjuvant without antigen also resulted in enhanced tumour growth. Enhancing antibody was not detected in the sera or on the tumour cells, though some of the sera were able to inhibit cell-mediated cytotolysis of tumour cells. The mice pretreated with CFA, with or without antigen, showed a depressed cell-mediated cytotoxicity against tumour cells when compared with untreated mice. [ABSTRACT FROM AUTHOR]

The macrophage migration inhibition test was employed to show reactivity of maternal peripheral blood leucocytes to placental antigens. Four to 5 days after delivery, all of forty-one postpartum women tested had leucocytes in their blood that reacted with pooled antigens from five placentas. When antigens from a single placenta were used leucocytes from only the woman who donated that placenta and one of nine unrelated postpartum women were reactive. Leucocytes from seventeen-control subjects, including nulligravidous women, were non-reactive with either the single or the pooled placental antigens. The results indicated that the mothers may be specifically sensitized, as far as the cell mediated immune response is concerned, by the placenta during pregnancy. [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]

The mitogenic selectivity of four phytomitogens, phytohaemagglutinin (PHA), concanavalin (ConA), lentil mitogen (LM) and pokeweed mitogen .(PWM), and a series of heterologous antilymphocyte sera (ALS) for mouse T and B lymphocytes has been investigated using thymidine uptake as a measure of proliferative activity. The results show that PHA, ConA and LM stimulate T but not B cells whereas PWM activates both T and B cells. Of six mitogenically active ALS, five were T cell specific and one B cell specific. Cortisone resistant (T) cells within the thymus showed a much greater response to all mitogens than unselected thymocytes. However, ConA and LM activated a considerable response in the latter population. Selective activation of T and B cells by aspecific means may be useful both as a clinical tool and as an approach to gaining an understanding of antigen induction of immune responses. [ABSTRACT FROM AUTHOR]

The human secondary immune response to the protein antigen Keyhole limpet haemocyanin (KLH) was studied in thirteen normal adults. For secondary immunization and for measurement of delayed hypersensitivity, 100 μg of KLH was given intradermally to each individual between 81 and 375 days after primary immunization. Immunity was assessed by delayed hypersensitivity skin testing and measurement of antibody formation and KLH stimulated in vitro lymphocyte blastogenesis. Twelve of the thirteen subjects had positive KLH delayed hypersensitivity reactions. Prior to secondary immunization all thirteen had circulating lymphocytes responsive in vitro to KLH and all had circulating haemagglutinating antibody. After secondary immunization there was no further increase in the mean KLH-stimulated blastogenesis while the KLH haemagglutinin titre rose due to increased 7S antibody formation. Primary immunization with small doses of KLH was as effective in inducing immunological memory and a subsequent secondary response as immunization with large doses of the antigen. [ABSTRACT FROM AUTHOR]

The proliferative response of human blood lymphocytes to homologous cells in vitro (i.e. the mixed lymphocyte reaction) has been used as a model of cell-mediated immune responses to investigate the nature of the antigen receptor site involved in the initiation of these reactions. Pretreatment of lymphocytes with the Fabγ monomer of rabbit antisera to human immunoglobulin light chain determinants effectively suppressed subsequent responsiveness to antigen without impairing lymphocyte viability or response to phytohaemagglutinin. Experiments in which the dose of antigen and the time of addition of antigen relative to antiserum were varied suggested that anti-light chain antibodies compete with antigen for the receptor site. These results are discussed in relation to the problem of the chemical nature of the receptor site for transplantation reactions and delayed hypersensitivity. [ABSTRACT FROM AUTHOR]

A 46-year-old woman with repeated skin infections, sore throats, laryngitis and abscesses was investigated because of low gammaglobulin on serum electrophoresis. When tested for ability to form antibodies to several antigens the patient did not respond to primary antigenic stimuli with Salmonella H or O antigens, or with keyhole limpet haemocyanin (KLH). However, she had a good secondary response to numerous agents with which she had previous contact (tetanus, diphtheria, polio and specific blood group substances). The selective impairment of cells capable of giving a primary immune response in the presence of intact memory cells gives support to the concept of a qualitative difference between these two types of cells. [ABSTRACT FROM AUTHOR]

Studies were continued on the mode of action of a methanol-insoluble moiety (methanol-extraction residue) of attenuated tubercle bacilli which enhances the immune response. We analysed the effects of treatment with this material on the primary and secondary immune responses of mice to two antigens, sheep red blood cell and T2 phage. Pretreatment with methanol-extraction residue enhanced the primary response to sheep red blood cells, accelerating the formation of both 19S and 7S plaque-forming cells and of circulating haemagglutinins, and prolonging high levels of 19S and 7S plaque-forming cells. Methanol-extraction residue delayed the secondary response to sheep red blood cells when administered between primary and secondary immunization. Methanol- extraction residue administration subsequent to immunization did not affect an ongoing primary response to this antigen. Administration of methanol-extraction residue before primary immunization with T2 phage, or between primary and secondary immunizations, enhanced both the primary and secondary circulating antibody responses to this antigen. The findings are discussed in relation to possible sites of action of methanol-extraction residue. [ABSTRACT FROM AUTHOR]

At least two different types of plaque-forming cells (PFC) participating in the Immune response of mice to sheep red blood cells (SRBC) are identified. This is demonstrated by (a) two PFC-peaks appearing at different times in response to the same low dose of antigen; (b) the morphology of the PFC in each of the two peaks is different; (c) the PFC in each peak respond differently to the suppressive effect of anti-S RBC serum. [ABSTRACT FROM AUTHOR]

The article presents a study that studied immunoglobulin classes of antibodies produced in the primary and secondary responses in man. A method, radio-immunoprecipitation, is described which measures the antibody in the different classes in whole sera by its antigen binding capacity. In nineteen of twenty-four individuals immunized with Limulus polyphemus haemocyanin, haemagglutinating antibodies were produced in the primary response, but in only five were amounts significant enough to measure by radio-immunoprecipitation. In these live individuals, the primary response was characterized by an early appearance of IgM and IgA antibodies: IgG antibody was detectable but only in small amounts and not before the 18th day after immunization.

The article presents information on a study regarding the role of phagocytosed antigen in the production of antibody to bacteriophage T4. The ability of mice to give an antibody response to this antigen was first impaired either by splenectomy or by X-irradiation, and then restored by injection of syngeneic lymphoid cells given at various times relative to the injection of T4. T4 bacteriophage is rapidly cleared from the circulation by the reticulo-endothelial system in both normal and irradiated mice. It was found that the bulk of phage particles which are taken up by Kupffer cells are inactivated and degraded at a faster rate than is the relatively small amount phagocytosed by spleen macrophages.

The article presents information on a study regarding the relationship between lymphocyte transformation and immune responses. The data reported in this study show that a correlation exists in general between antigen-induced blast transformation and other immunological manifestations. Rabbits with strong immune responses usually showed more intense transformation reactions than those with immunity against the same antigens. Strong immune responses were induced in the present experiments by use of adjuvant emulsion.

The article focuses on the response to dinitrophenyl in mice as general methods for the study of cells and serum during the immune response. Two new methods for antibody assay are reported: one for antibody in solution, the other for individual cells releasing antibody. They depend on the use of an immunoabsorbent-bound antigen to absorb the antibody, and radioactively-labeled anti-immunoglobulin antibody (anti-Ig) for its detection. In the first method immunoabsorbent was added to the solution containing antibody, washed free of serum components other than the bound antibody, treated with radio labeled anti-Ig, and the uptake of radioactivity assessed by gamma-ray counting.

The article cites a study conducted by the author, which tested the inhibition of immune responses to sheep red cells in rats pre-immunized with heterophilic antigen. After immunization of rats with heterophilic antigen, their immune responses to sheep red cells were constantly depressed, whereas those to heterophilic antigen were increased, as compared with controls. The suppression of immune response to sheep red cells in rats immunized with heterophilic antigen may represent an animal model paralleling the interference with Rh immunization of ABO incompatibility in man.

The article cites a study conducted by the authors, which tested the immune response in hybrid mice. The study was made of the immune response of hybrid (BW) mice against H antigen of Salmonella, sheep red blood cells, bovine serum albumin and allogeneic tumour cells. The responses of old BW mice having autoimmune glomerulonephritis were compared with those of young healthy mice. It was found that the mice develop immune depression concurrently with the autoimmune process. It was suggested that the ability to respond to foreign antigens was probably depressed by the competition provided by autoantigens.

This article reports that the formation of antibodies represents a special case of induced cell differentiation. It has been recently reported that the complex series of events triggered by the injection of antigen includes dramatic changes in activities of several enzymes of nucleotide metabolism in the spleen. It is informed that a specific immune response can be suppressed by passive transfer of the corresponding antibody. To get additional information on the mechanism of this inhibition, researchers studied effects of the passive transfer of antibodies upon changes in activity of these enzymes induced by different doses of antigen. The study conducted showed that the specific activity of uridine kinase and thymidine kinase increased in the particle-free extract of mouse spleen after primary and secondary injections of sheep red blood cells.

The article presents information on a study that focuses on immunocyto-adherence by spleen cells and tissue antigens in normal and carbon tetrachloride-treated rats. The immunocyto-adherence test with sheep red cells coated with rat liver mitochondrial antigen shows that rat spleen cells form more rosettes with the coated cells than with sheep cells alone. The rise in the anti-tissue antibody level after carbon tetrachloride injection is accompanied by an increase in the number of rosette forming cells. This evidence adds substantial support to the likely immune nature of the anti-tissue antibody response.

The article focuses on the effect of phytohaemagglutinin on the immune response in vitro. Phytohaemagglutinin (PHA) was found to suppress both the primary and secondary immune response to mammalian and avian erythrocytes in rats and mice. Effective suppression of humoral antibody production occurred when PHA was administered prior to or a few hours after immunization. Animals used in this study were inbred Wistar rats and inbred strains of mice. Mice were immunized with a variety of bacterial antigens.

This article presents information on the criteria of immunological tolerance to tissue antigens. Fresh surgical specimens of human renal carcinoma and adjacent normal kidney were used without pooling with specimens from other patients to avoid the complication of individual antigenic differences. Material was grossly separated into normal kidney, tumor, and marginal tissue comprising both normal and tumor. Immunodiffusion, which has sometimes been the only method employed, cannot detect non-diffusible antigens or non-precipitating reactions. Immunofluorescence overcomes these deficiencies and, in the present study, permitted the demonstration of diverse immunological responsiveness in rabbits presumptively tolerant by immunodiffusion tests.