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It has been shown that CBA mouse lymphocytes cultured in the presence of allogeneic fibroblasts or syngeneic polyoma virus-induced tumour cells became specifically immunized. These immunized lymphocytes, however, are by themselves non-cytotoxic and only cause target cell killing when mixed with normal macrophages. The reaction is immunologically specific and seems to depend on the antigenic differences between lymphocytes and target cells. The mechanism of the interaction between the immunized lymphocytes and the normal macrophages in the cytotoxic killing of target cells is discussed. [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]

Mice infected with Mycobacteriurn lepraemurium showed marked histological changes in the thymus and lymph nodes. In the thymus there was a progressive depletion of lymphoid cells and replacement by macrophages, many of which contained bacilli in the advanced stages of the disease. In lymph nodes there was depletion. of paracortical immunoblasts and accumulation of macrophages. Infected mice showed impaired cell-mediated immune responses, including delayed rejection of skin grafts and depression or absence of contact sensitivity. Humoral immune responses to bovine serum albumin and sheep erythrocytes in infected mice were normal. The defect in cell-mediated immune responses is thought to be secondary to the massive infection, and is discussed in relation to impaired immune responses in human lepromatous leprosy. [ABSTRACT FROM AUTHOR]

Lymph node and spleen cells from normal mice were cultured for 3 days with polyoma virus-induced tumour, Ehrlich's ascites turnout or leukaemia L 1210 cells. This resulted in in vitro immunization of the lymphocytes, which were then transferred to irradiated target cells labelled with 51Cr. Normal, i.e. non-immune thioglycollate-stimulated peritoneal macrophages were also added to some tubes. Non-immune macrophages mixed with immunized lymphocytes showed a significantly increased ability to destroy tumour ceils as compared with macrophages in the absence of immunized lymphocytes. The immunized lymphocytes were almost entirely inactive alone. When the number of macrophages was kept constant the cytotoxicity was dependent on the number of viable immunized lymphocytes placed on the target cells. Immunized lymphocytes, in the presence of macrophages, only exhibited strong killing of the target cells against which they had been immunized; some lysis of ‘bystander’ cells was, however, seen provided specific target cells were present. Macrophage monolayers exposed to immunized lymphocytes upon contact with specific antigen became ‘armed’ and showed a significant cytotoxicity for specific target cells. When immunized lymphocytes and normal macrophages were treated with actinomycin D and puromycin, cytotoxicity was inhibited in the immunized lymphocytes but not in the macrophages. The possible mechanism of normal macrophage cooperation with immunized lymphocytes in the cytotoxic killing reaction is discussed. Results presented in this paper favour the view that immunologically specific cytophilic factor (presumptive cytophilic antibody) is involved in the macrophage-mediated cytotoxicity in the system studied. [ABSTRACT FROM AUTHOR]

Contact sensitivity was produced in mice by applying an alcoholic solution of picryl chloride or 2-phenyl-4-ethoxymethylene oxazotone (oxazolone) to the abdominal wall. It was assessed by painting the ear with the contact sensitizing agent dissolved in olive oil and measuring the increase in ear thickness 24 hours later. Contact sensitivity to picryl chloride was depressed by pre-treatment with the sulphonic acid derivative of picric acid. Complete depression was obtained when either two large doses or multiple small doses were given and in the former case this complete depression was still present 6 weeks after the last injection of the sulphonic acid. Similar pre-treatment with oxazolone depressed contact sensitivity to oxazolone in some but not all mice. Pre-treatment with the folic acid antagonist amethopterin before and during sensitization almost completely abolished contact sensitivity, while a single larger dose given 48 hours before sensitization only had a small effect. Mice whose immune response to picryl chloride had been depressed by pretreatment with sulphonic acid and methotrexate were used to study restoration of immune competence by normal lymphoid cells. No restoration was observed when unirradiated recipients were used. However, a mixture of lymph node and bone marrow cells and, to a lesser extent thymus and bone marrow cells, restored immune competence to picryl chloride in irradiated recipients. It was concluded that irradiation favoured the restoration of immune competence by normal lymphoid cells and that a mixture of lymph node and possibly thymus cells with bone marrow cells was able to cause restoration. [ABSTRACT FROM AUTHOR]

Mice sensitized to oxazolone show contact sensitivity which can be assessed by painting oxazolone on the ear and measuring the increase in ear thickness at 24 hours. Contact sensitivity can be transferred passively by peritoneal exudate, lymph node and bone marrow cells. When CBA mice are challenged immediately after transfer, at a 3:1 donor recipient ratio, the peritoneal exudate cells give bigger transferred reactions than lymph node cells. The converse is true on challenge at 6 days after transfer, at which time the lymph node cells give bigger transferred reactions than the peritoneal exudate cells. These results suggest that different types or functional states of cells are involved in these two types of transfer. The possibility that the successful transfer with delayed challenge by lymph node cells was due to active sensitization by antigen transferred with the cells, was made unlikely by passive transfer into ‘tolerant’ recipients. Mice first show contact sensitivity when challenged at 3 days (about 72 hours) after sensitization. The lymph nodes develop the ability to transfer contact sensitivity with delayed challenge at the same time but the bone marrow only acquires this activity at 5 days. [ABSTRACT FROM AUTHOR]

Ear swelling in mice was measured with a micrometer and used to quantify 24-hour skin reactions. Specific contact sensitivity occurred in mice immunized with picryl chloride, 2-phenyl-4-ethoxymethylene oxazolone, dinitrofluorobenzene and tetramethyl-p-phenylenediamine as shown by ear swelling 24 hours after challenge. In some mice sensitized with oxazolone significant swelling occurred 4 hours after challenge. It was possible to induce tolerance in adult mice and contact sensitivity to dinitrochlorobenzene was diminished by prior treatment with dinitrobenzenesulphonic acid. There was some evidence of delayed hypersensitivity to protein antigens. Twenty-four-hour skin reactions to PPD (purified protein derivative of tuberculin) occurred in mice immunized with live BCG or dead tubercle bacilli in Freund's adjuvant. In most experiments the swelling at 24 hours was greater than at 4 hours. Similar reactions to egg albumin and bovine y-globulin were seen in mice immunized with these antigens in Freund's complete adjuvant and one group of mice showed greater swelling at 24 hours after challenge than at 4 hours. Contact sensitivity was readily transferred in inbred mice by peritoneal exudate cells when the challenge was undertaken immediately after transfer. Variable and usually inferior passive transfer was obtained with lymph node cells. Attempts to transfer contact sensitivity in outbred mice were unsuccessful. [ABSTRACT FROM AUTHOR]