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C3H/HeN mice were immunized to induce contrasuppressor T-cell (Tcs) activity, splenic T cells from these mice were fused with the BW5147 thymoma, and the resulting hybridomas were tested for their ability to produce a contrasuppressor T-cell factor (TcsF). Nine TcsF-producing hybridomas were preliminarily identified by their ability to inhibit the effect of antigen-specific suppressor T-cell factor (TsF) on the adoptive transfer of contact sensitivity. One of these hybrids, AF5.C6, was cloned, the production of a contrasuppressor factor confirmed, and the high-titred TcsF produced by this cloned hybrid characterized. Hybridoma-derived TcsF is antigen-specific and specifically binds its antigen, but does not bear immunoglobulin (Ig) determinants. Thus, hybridoma-derived TcsF is serologically and functionally identical to an antigen-specific contrasuppressor factor for contact sensitivity, whose production from splenocyte cell cultures has previously been described. The generation of a hybridoma secreting a contrasuppressor factor identical to that produced by spleen cells significantly strengthens the hypothesis that the phenomenon of T-cell contrasuppression is mediated by a specific subset of cells whose activity is contrasuppressive. The further advantages of employing T-cell hybridomas for functional, biochemical and molecular genetic analyses of contrasuppression are also discussed. [ABSTRACT FROM AUTHOR]

An antigen-specific suppressor factor (TSF) produced by mouse T lymphocytes prevents immune cells from conferring adoptive immunity on normal recipients. This TSF attaches easily to the macrophage surface, and these ‘armed’ macrophages in the presence of a corresponding antigen manufacture (in vitro) a non-specific macrophage suppressor factor (MSF) which impairs the activity of cells sensitized to homologous or heterologous antigens. Our experiments show that MSF is temperature- and trypsin-sensitive, and is not a prostaglandin. Its molecular weight is in the range of 10 kD. MSF is synthesized by macrophages de novo subsequent to triggering by TSF and antigen. MSF impairs only the activity of cells mediating contact sensitivity reaction (Ly 1) but has no influence on T-suppressor cells (Ly 23). The possibility that MSF is an enzyme is discussed. [ABSTRACT FROM AUTHOR]

Contact sensitization by epicutaneous application of picryl chloride causes in mice a significant reduction of the antibody responses to immunogenic TNP-conjugates. This split unresponsiveness is long-lasting. It was found that hapten applied on the skin became attached to the serum proteins and the transfer of such a serum into normal recipients, while not influencing the ability of these animals to become contact-sensitized to PC1, rendered them unable to mount the anti-TNP antibody response, Possible mechanisms of split unresponsiveness to the TNP determinant induced by PC1 treatment are suggested. [ABSTRACT FROM AUTHOR]

Alloxan diabetic mice do not easily develop anaphylactic shock, and formation of IgE antibodies to sensitizing antigen almost ceases in these animals. Also, mice sensitized as normoglycaemic and then made diabetic are to a great degree protected from anaphylaxis. although they form minute but measurable amounts of IgE antibodies. Immune cells transferred into diabetic mice lose their ability to form IgE, while cells from immune diabetic mice, which in the hypoinsulinaemic milieu of donors do not synthesize appreciable amounts of IgE, regain this ability upon transfer into normal recipients. We conclude that the IgE response is very insulin-dependent and that insulin deficiency affects IgE-forming cells directly or indirectly via its influence on T helper cells. In the current study we also considered whether hyperglycaemia may influence the effector stage of anaphylactic reactions. To test this, massive doses of glucose were given to normoglycaemic mice, which increased their blood glucose level to that seen in diabetic mice and prevented local anaphylactic reactions when these mice were injected with monoclonal IgE antibody and challenged locally with antigen. [ABSTRACT FROM AUTHOR]

Alloxan diabetic BALB/c mice with high hyperglycaemia levels (⩾ 600 mg/100 ml) when immunized either with T-dependent (SRBC) or T-independent (TNP-LPS) antigens show a significant decrease in the number of specific PFC when compared with normo-glycaemic controls. Moderate diabetes (> 350 mg/100 ml) does not affect the immune response and in some experiments a slight increase of anti-SRBC plaques was seen. In transfer experiments primed spleen cells of either diabetic or normal donors gave much better responses when transferred to normal rather than diabetic X-irradiated recipients. In Mishell-Dutton (MD) cultures the anti-SRBC response of CBA spleen cells was moderately reduced only when the blood glucose level of cell donors exceeded 500 mg/100 ml. Glucose added to MD cultures of normal spleen cells diminished significantly the number of SFC when in concentrations exceeding 600 mg/100 ml. The data indicate that in diabetic animals B-lymphocyte function may be affected but give no clear-cut answer to whether this is also true for T-helper cells. Disabled lymphocytes, whatever population they represent, may partially recover when transferred into normo-insulinic milieu. It may be inferred that under conditions tested neither hyperglycaemia nor excess of corticosteroid accounted significantly for the impaired humoral responses in diabetic animals. These experiments imply, however, that in hypoinsulinaemia the lack of saturation of insulin receptors on the lymphocyte, and possibly also macrophage, membranes renders these cells functionally inactive presumably due to accumulation of cyclic AMP in the cell membrane. [ABSTRACT FROM AUTHOR]

Alloxan-diabetic mice of Swiss, CBA and DBA/2 strains show a significant depression of contact sensitivity to oxazolone, as compared with normoglycaemic control animals, which is accompanied by the involution of the thymus and spleen. Insulin treatment partially restores the contact sensitivity in diabetic animals and also increases the weight of lymphatic organs. In contrast, the non-specific inflammatory response to oxazolone is not impaired in insulin-deficient mice. Further experiments have shown that neither sensitized lymphocytes of control animals given to diabetic mice, nor sensitized lymphocytes of diabetic mice injected into normoglycaemic recipients, were able to transfer passively any significant contact sensitivity. It is suggested that in alloxan-diabetic mice the function of T lymphocytes is affected. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Explains that the function E(N,Z) in the Thomas-Fermi approximations is the solution to the so called March equation. Substantial regularities in the dependence of the binding energy of atoms and atomic ions on the atomic number Z and the number of electrons N; Mathematical equations for the problem.

Abstract: Testicular macrophages (TMf) are located in the interstitial tissue of the male gonad. Highly purified TMf populations can be prepared either by the mechanical shaking of dispersed testicular tissues or by enzymatic digestion with collagenase followed by cell adherence, rosetting and gradient centrifugation. TMf obtained by the enzymatic procedure produced significantly more cytokines (IL-6, IL-10 and TNF-α) than TMf isolated by the mechanical method and this effect is long-lasting. Our results indicate that isolation of tissue macrophages by enzymatic digestion may influence their functional activity, and suggest that critical evaluation of the method used to obtain these cells should be the regular practice. [Copyright &y& Elsevier]

Gastrectomy in mice affects the cell-mediated (CMI) and humoral immunity in a diverse fashion, such as CMI (contact sensitivity reaction) is severely impaired and antibody response is enhanced. Both effects are transient and disappear several days after surgery. While suppression of contact sensitivity is mediated by non-specific Ly 1-2+, L-J+ suppressor T cells generated by surgical stress, the mechanisms of enhancement of antibody response is unknown. We assume that the split unresponsiveness induced by surgical trauma has a clear survival advantage. Increased antibody production is the major defence mechanism against bacterial infections, while decrease of CMI prevents autoimmune response against altered (damaged) self structures. [ABSTRACT FROM AUTHOR]