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The purpose of this study was to determine whether suppression of acquired. cell-mediated immunity occurred during the course of cutaneous leishmaniasis of the guinea-pig. In order to do this, groups of animals were infected with amastigotes of Leishmania enriettii in doses ranging from 101 to 2 × 108 organisms. The clinical course of primary and metastatic infection was followed for up to 30 weeks and the immunological response was examined by skin tests of hypersensitivity to soluble leishmanial antigens. by detection of circulating antibody, and by determining the resistance of animals to reinfection with fresh organisms. With increasing inoculum size the incubation period (for the establishment of a primary lesion) diminished from 4 weeks (101 organisms) to 1 week (2 × 108 organisms). Large inocula (2 × 108) led to large ulcerated primary lesions with widespread metastases and death of sonic animals in the group. But no evidence of visceralization. With increasing dose of organisms, there was increasingly rapid development of delayed hypersensitivity and of antibody as detected by immunofluorescence: thus there was no evidence that high inocula produced immunological tolerance. With inocula > 105, a characteristic and selective depression of delayed hypersensitivity occurred when primary lesions were well developed and when metastatic infection was well advanced. Surviving animals recovered their delayed hypersensitivity as primary and metastatic lesions healed. After healing of the primary lesions, animals in all groups were fully resistant to reinfection, even though some of them bore persistent metastases. It was concluded that the immunosuppressive effects of heavy infecting inocula were due to desensitization of rapidly acquired, cell-mediated immunity rather than to the induction of immunological tolerance. It is suggested that this mechanism might underlie certain features of disseminated leishmaniasis in man. [ABSTRACT FROM AUTHOR]

Partial purification of soluble products of guinea-pig lymphocyte activation (LAP) was undertaken by fractional precipitation with ammonium sulphate, ion-exchange and Sephadex chromatography, and by immune precipitation of inducing antigen and of contaminating serum protein. During these purification steps the activity of macrophage migration-inhibition factor (MIF) was concentrated up to 1300-fold and separated from inducing antigen and serum protein. An endpoint assay was devised for expressing antigen-induced MIF activity of LAP fractions as weights of material giving 30% inhibition of migration (MI30 doses). MIF activity precipitated between 50% and 80% saturated ammonium sulphate and eluted from DEAE-cellulose at pH 7-9 at intermediate salt concentrations (0-03-0-2 M phosphate). On Sephadex gel filtration MIF activity was concentrated in fractions of molecular weight range 56,000-82,000 with a smaller amount of activity eluting from 20,000-56,000. After immune precipitation of extraneous protein and elution from DEAE-cellulose, LAP material was found to have an MI30 dose of 0-4 /μg. Materials representative of antigen and serum protein-depleted MIF were selected for intralymphatic injection in order to determine whether MIF-rich LAP fractions were able to induce paracortical distension in guinea-pig lymph nodes (see following paper). [ABSTRACT FROM AUTHOR]

Peripheral blood lymphocytes of twenty-three subjects with grass pollen allergy were cultured with grass pollen antigen for 3 days. After harvesting, the culture supernatants were added to fresh autologous lymphocytes which were maintained in culture for 6 days. Cellular uptake of [³H]thymidine was measured during the sixth day of culture, and revealed that the lymphocyte culture supernatants stimulated greater thymidine uptake than expected from the lymphocyte transformation response to corresponding amounts of antigen. The supernatant factor which mediated this effect was termed `lymphocyte mitogenic factor' by analogy with a similar response of lymphocytes in clinical and experimental delayed hypersensitivity. Lymphocyte culture supernatants were also tested for migration- inhibition factor by their ability to inhibit the migration of guinea-pig macrophages. [ABSTRACT FROM AUTHOR]

Complement-fixing and precipitating antibodies to mitochondrial and lysosomal fractions of rat liver were induced in rabbits. The incubation of these subcellular fractions with ferritin-labelled antibody revealed localization of the antibody on mitochondria and lysosomes, but no specific morphological effect of antibody and complement. Incubation of the cell fractions with antibody and complement did not impair the efficiency of mitochondrial oxidative phosphorylation or affect the latency and sedimentation characteristics of lysosomal acid phosphatase. The results are discussed in relation to the action of antibody and complement on cells and to possible mechanisms of tissue damage in autoimmunity. [ABSTRACT FROM AUTHOR]

This communication describes the use of micro-electrophoresis in studying the changes in ascites tumour cells exposed to antibodies and complement. Treatment of the cells with rabbit antibody led to a change in electrophoretic mobility consistent with a surface adsorption of γ-globulin. The addition of complement led to a reduction in this electrophoretic effect of antibody. Treatment of the cells with neuraminidase, which produced a marked fall in their electrophoretic mobility, did not alter the effect of rabbit antibody and complement on the cells. Incubation with iso-antibody, in the presence or absence of complement, did not alter the mobility of the ascites cells measured at pH 7.0. The addition of 0.01 M calcium chloride to the electrophoresis medium produced a fall in mobility of the cells exposed to either antibody preparation in the presence of complement. Therefore, although iso-antibody and complement did not produce direct changes in cell mobility, changes in the cell surface could be detected by electrophoresis in the presence of calcium ions. The possibility is discussed that, during immune cytolysis, unmasking of phosphate groups of phospholipids might take place in the cell surface. [ABSTRACT FROM AUTHOR]

The injection of rat liver and rat brain in Freund's complete adjuvant into rabbits led to the production of complement fixing autoantibodies against rabbit tissue. The autoantibody response following the injection of rabbit liver and brain was much smaller. The autoantibody response to rat liver occurred even when Freund's incomplete adjuvant was used. The injection of rabbit liver in Freund's complete adjuvant into rabbits which had produced autoantibody after the injection of rat liver did not increase the level of autoantibody to rabbit liver. In most, but not all, rabbits the natural antibody found in the sera taken before immunization was destroyed by heating the sera at 65°. After immunization with rat liver in Freund's complete adjuvant the levels of serum antibody to rabbit liver stable at 56° rose by day 5; however, autoantibody stable at 65° was not detectable until between days 7 and 14. [ABSTRACT FROM AUTHOR]

This paper describes the course of infection and the immunological response in thymus-deprived and normal CBA mice after intradermal inoculation with promastigotes of L. tropica. Infection of normal mice resulted in the development of a cutaneous ulcer healing within 12 weeks. As the infection progressed and the draining lymph nodes increased in weight, changes in the paracortical and follicular regions were accompanied by the development of delayed hypersensitivity and the production of antibodies detectable by immunofluorescence and a parasite agglutination test. Lesions in thymectomized irradiated mice healed more slowly and the draining lymph nodes were smaller than in normal mice. Follicular reactions were feeble and paracortical activity depressed. The most noticeable feature of these lymph nodes was a persistent and intense macrophage infiltration. Delayed hypersensitivity and antibodies detectable by immunofluorescence were correspondingly low; but parasite agglutinating antibody was not depressed. The course of infection and immunological response of a control group of sham thymectomized, irradiated mice resembled that of normal mice. These experiments indicate that thymus-dependent cell populations play an important role in the response of mice to infection with L. tropica. [ABSTRACT FROM AUTHOR]

Intradermal inoculation of the guinea-pig with Leishmania enriettii results in a self-healing cutaneous lesion which provides a laboratory model of human cutaneous leishmaniasis and which is dominated by cell-mediated immunological responses (Bryceson et al, 1970). In this study we sought to design experimental situations resembling non-healing forms of cutaneous leishmaniasis in man and to determine whether these experimental situations were accompanied by abnormalities in the immunological response to infection. This paper describes three procedures which impair the resistance of guinea-pigs to leishmanial infection: (i) induction of partial immunological tolerance to leishmanial antigen; (ii) systemic injection of anti-lymphocyte serum (ALS); and (iii) regional antigenic competition produced by multiple injections of bacterial adjuvants. Injection of soluble leishmanial antigen (PSA) during the third week of foetal life suppressed resistance to neonatal infection with L. enriettii; local infections were severe and were accompanied by metastatic spread and by impaired development of delayed hypersensitivity (DH). Injection of PSA into the 6-week foetus and into the adult guinea-pig led to impaired DH after leishmanial infection, but resistance to infection was only slightly suppressed. Transient impairment of DH was induced by a short injection course of adult animals with ALS during the first 3 weeks of infection, which resulted in large primary lesions with temporary metastatic spread. Multiple regional injections of tubercle- and corynebacterial-adjuvant emulsions markedly suppressed resistance to subsequent leishmanial infection; large ulcerative lesions were accompanied by widespread nodular metastases, the unusual appearance of haemagglutinating antibody, and death of some animals. [ABSTRACT FROM AUTHOR]

Inhibition of buffy layer peripheral leucocyte migration by tuberculin purified protein derivative (PPD) from micro-capillaries mounted in small tissue culture chambers correlates in all cases with a positive Mantoux test. This quick and reproducible test of cellular hypersensitivity in man requires only 5-15 ml of blood and is applicable for study in children and in clinical situations where repeated monitoring of cellular immunity may be required. [ABSTRACT FROM PUBLISHER]