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Plaque-forming cell responses and antibody titres to sheep red cells (SRC) were elevated in normally-fed irradiated adult mice reconstituted with spleen cells from young mice which had received a 4% albumin diet, compared with those given cells from normally-fed littermates. This was independent of the dose of cells transferred (5 × 106-4 × 107), the day of assay (3–10) and the duration of protein-deficiency (1 or 3 weeks). It suggests that the depressed responses produced by protein-deficient (donor) mice reported in earlier papers resulted from an impairment of reticuloendothelial function or a shortage of protein reserves, not directly associated with the spleen. As protein-deficiency (of the donor) accelerated the initiation of the adoptive response and increased the cell yields of the recipients it is considered likely that an enhancement of cell proliferation during the first 3-5 days after transfer was responsible for the elevated responses. [ABSTRACT FROM AUTHOR]

This paper describes the induction of immunosuppression by multiple injections of carrageenan-lambda (cgn) in BALB/c mice. While cgn alone induced non-specific suppression that persisted for up to 25 days, priming with sheep red blood cells (SRBC) of mice within l0 days of cgn treatment prolonged the suppressive state. Also, antigen (SRBC)-specific suppression was observed when these mice were siren a secondary challenge 25–30 days after priming. Thus multiple cgn treatment along with priming SRBC generated non-specific and specific suppressive states which were transferable by Thy-l+ Lyt-2+ splenocytes. [ABSTRACT FROM AUTHOR]

Red cells sensitized with naturally occurring or 'immune' fowl antibody were lysed by fresh fowl serum. This fowl complement could not be replaced by that of human, rabbit or guinea pig. Both naturally occurring and 'immune' antibodies to red cells in the mammalian species tested did not lyse with fowl complement. Lysis by fresh fowl serum of sheep red cells sensitized with mammalian antibody is due to the presence of naturally occurrent antibody to these cells in the fowl serum; the enhancement of this lysis by the mammalian antibody will be described more fully in the next paper. Naturally occurring antibody to sheep red cells present in turkey serum and 'immune' antibody to fowl red cells were not lytic with fresh turkey serum, with fowl complement, with guinea-pig complement or with any combination of these. Some properties of fowl complement are given. [ABSTRACT FROM AUTHOR]

The effect of an horse anti-mouse thymocyte globulin (ALG) preparation on the primary and secondary immune responses to sheep erythrocytes (RBC) was studied in 2-3-month-old male A/HeJ, C57B1, BALB/c, DBA/1, CBA and C3H mice. A wide variation in the primary and secondary responses of the individual strains was noticed but in ail cases these were significantly suppressed by ALG pretreatment. The capacity of the ALG to suppress the primary immune response was not overcome by increasing the antigen dose from 3 × 107 to 3 × 109 sheep RBC. [ABSTRACT FROM AUTHOR]

Irradiated (NZB × BALB/c)F1 mice were injected with syngeneic bone marrow cells, syngeneic or parental thymus cells, and sheep red cells. The antibody plaque-forming cell response depended on the number of sheep cells and the age and strain of the thymus cells. Young or adult BALB/c thymus, and young hybrid thymus, responded best to low numbers of sheep cells; with higher numbers they became tolerant. Adult hybrid thymus, and young or adult NZB thymus, responded better to high numbers of sheep cells. Hybrid mice irradiated and restored with BALB/c bone marrow developed thymus cells with the reactivity of BALB/c thymus. It is argued that NZB mice, and older hybrids, may develop autoimmunity because of an abnormality of tolerance induction manifested in their thymus cells, but of bone marrow origin. [ABSTRACT FROM AUTHOR]

Normally circulating human leucocytes were found to consistently lyse rabbit erythrocyte (RRBC) target cells within 24 hr in culture. The reaction is referred to as the naturally-occurring cell-mediated cytotoxic, or NOCC, reaction. Characteristics of this cytotoxic reaction are as follows. (i) The cytotoxic reaction described here can be distinguished from the antibody-dependent cellular cytotoxic (ADCC) reaction as conventional Fc receptors do not appear to play a role. Although the cytotoxic reaction occurs optimally in medium fortified with normal human serum to a final concentration of 1%, neither antibodies nor immunoglobulins in general appear to play a role. Agamma human serum or purified human Serum albumin without detectable immunoglobulins are as capable of facilitating and sustaining the NOCC cytotoxic reaction as is normal human serum. Furthermore, foetal calf serum, which promotes the ADCC cytotoxic reaction, inhibits the NOCC cytotoxic reaction. (ii) The NOCC reaction is not a phagocytic one as phagocytosis of the RRBC could not be detected during the culture period. (iii) Monocytes and neutrophils, but not lymphocytes, are capable of lysing the target cells in the NOCC reaction. The effector mononuclear cell is a monocyte with receptors for Fc and C′3. (iv) The NOCC cytotoxic reaction is dependent upon direct effector cell-target cell contact and not upon soluble mediators secreted by the effector cells since third-party bystander erythrocytes are not lysed in the presence of rabbit erythrocyte target cells and human mononuclear cells. Supernatants from lysed RRBC target cells could not lyse fresh RRBC. It is concluded that the NOCC cytotoxic reaction utilizing rabbit erythrocytes as target cells permits the identification of cytotoxic subclasses of monocytes and neutrophils. [ABSTRACT FROM AUTHOR]

Anti-red blood cells (RBC) and anti-hapten antibody synthesis were studied in the goldfish, Carassius auratus. Spontaneous haemagglutination titres were found against all the antigens tested. A weak secondary response was observed in RBC-primed fish boosted during the end-phase of the primary antibody production. However, when the second antigenic challenge was performed during the early exponential phase of a primary stimulation, an important amplified response was obtained. The antibody production and immunological memory can be dissociated: no antibody synthesis occurred in glutaraldehyde-fixed RBC (F-RBC) primed animals but a characteristic amplified response was obtained when untreated or F-RBC were given to F-RBC primed animals. The amplified response to sheep red blood cells (SRBC) was significantly inhibited when fish were primed with a mixture of SRBC and Xenopus red blood cells (SRBC). demonstrating an antigenic competition phenomenon. Studies on anti-trinitrobenzene responses confirm the efficiency of E. coli lipopolysaccharide as a carrier for fish anti-hapten immunization. The kinetics and regulation of antibody synthesis in fish are discussed in relation to the described results. [ABSTRACT FROM AUTHOR]

The appearance of antibody responsiveness against sheep red blood cells (SRBC) was studied in young mice treated with hydrocortisone hemisuccinate (HHC) either during gestation or around delivery (last 5 days of gestation or day of birth). The plaque forming cell (PFC) response was normal at 2 weeks and depressed at 4 weeks in animals treated during the last 10 days of pregnancy. Conversely, when HHC was only given around delivery. PFC response was depressed at 2 weeks and normal at 4 weeks. The presence of suppressor cells in unimmunized 1-2-week-old spleen cells was evaluated by co-culturing them with adult spleen cells from mice immunized against SRBC. Suppressive activity was found at high level at 8 days, and had already declined at 15 days in non-treated mice. Spleen cells from mice treated with HHC around delivery showed reduced suppressive activity at 8 days but this activity was very high on the 15th day, greater than in normal mice. Such highly suppressive activity correlated with a high level of Lyt123 T cells. These data on suppressor cells indicate that the paradoxical effect of HHC in mice treated during gestation or around birth is probably explained by the differential effect of HHC on the kinetics of suppressor cells in ontogeny. [ABSTRACT FROM AUTHOR]

After immunization of carp with sheep red blood cells, the spleen accounts for only 5% of the total number of plaque-forming cells (PFC). In addition, thymus, peripheral blood and heart contained low numbers of PFC (« 0.5, 1 and 0.5%, respectively). Pronephros and mesonephros were the major antibody-forming organs (53 and 40% of total PFC, respectively). The temperature dependence of the antibody-forming cell response in spleen, pronephros and mesonephros was studied in animals kept at 12–24°. Lowering temperatures induced a delay in the peak of the primary response but had no effect on the magnitude of the response. The temperature-peak day relationship indicated that there are steps in the primary immune response of carp differing in temperature sensitivity. The anamnestic character of the secondary response was clearly demonstrated at 24 and 20° but lost at 18°. [ABSTRACT FROM AUTHOR]

Erythrocytes labelled with chromium51 were injected into embryos and young chicks and a similar challenge given soon after the majority of the initial dose had been eliminated. While tolerance was the typical response in embryos and chicks up to 3 days of age, immunity could be induced in most chicks from this time onwards. The intensity of the immune response increased rapidly until the 12th day of age. No maternal antibody could be detected. Pretreatment of the embryo with testosterone impaired the immune response of 14-day-old chicks. [ABSTRACT FROM AUTHOR]

Cell kinetics of the 2,4,6-trinitrophenyl (TNP)-erythrocyte response in non-immune, immune, and vinblastine-treated immune BDF1 mice were studied by measuring hapten- and carrier-RFC and hapten- and carrier-PFC responses at various time intervals. Injection of a single dose of horse red blood cells alone enhances the anti-TNP response. [ABSTRACT FROM AUTHOR]

Incorporation of [³H]thymidine into the spleens of intact mice during the primary and secondary responses to SRC has been studied. In both responses, auto-radiographs show a well marked increased incorporation of [³H]thymidine by cells in the peri-arteholar zone during days 1 and 2. The degree of labelling indicated that many of these cells were in S phase in preparation for mitosis. A similar response occurred in cells situated in the mantle layer on day 3 to day 4 of the primary response, but was much less evident in the secondary response. This was in keeping with the results of scintillation counting which showed that increased uptake of [³H]thymidine was more sustained in the primary than in the secondary response to SRC. Many lightly labelled cells indicating metabolic turnover of DNA developed in the red pulp of the spleen at times which coincided with the maximum development of antibody-producing cells (PFC) which occurred about 24 hours earlier in the secondary than in the primary response. Germinal centres showed many lightly labelled nuclei. In both primary and secondary responses these areas enlarged, becoming maximal in size after the peaks of PFC were achieved. It was concluded that the enlargement of germinal centres was the result of trapping of cells in the areas rather than proliferation. From these studies it appears that metabolic turnover of DNA occurred in areas of the spleen intimately associated with antibody formation. The possible role of this process in antibody synthesis is discussed in the light of these observations. [ABSTRACT FROM AUTHOR]

The present report describes the morphology of lymphoid tissues and the humoral antibody response during primary and secondary immune responses to sheep erythrocytes (SRBC) in Snell-Bagg hereditary pituitary dwarf mice. It has been found that while 19S primary response was depressed to a great extent, 7S secondary response reached practically normal levels. Histological studies of the peripheral lymphoid tissues have shown patterns of cellular depletion in nonthymus-dependent areas in dwarfs killed during primary response, while these areas appeared markedly cellular after a second antigenic stimulation. It is suggested that the cell systems involved in antibody production during primary and secondary responses to SRBC may be separate and different. As a result, the endocrine imbalance of the dwarf mice affects only the primary response to SRBC. [ABSTRACT FROM AUTHOR]

Lepisosteus osseus possesses high titres of natural agglutinins to human group A (HuA) erythrocytes and to Salmonella typhosa 'O' (STO) antigens. Moderate natural haemagglutinin titres to sheep red blood cells (SRBC) were noted. Cold agglutinin (4°) titres exceeded agglutinin titres recorded at 25°. Immunization with STO antigen resulted in a marked increase in corresponding anti-STO agglutinins, as well as increases in anti-HuA and anti-SRBC agglutinins. Animals immunized with SRBC antigen produced elevated anti-SRBC agglutinin titres, while immunization with HuA erythrocytes produced no changes in agglutinin levels. Immunization with STO following previous injections with HuA resulted in increases of corresponding anti-STO agglutinins, as well as marked increases in anti-HuA agglutinins. Absorption studies indicated that anti-STO agglutinins were not cross reactive against HuA antigens. Natural and immune antibodies were all of the same macromolecular class. Rises in antibody titres were reflected in both cold and warm agglutinins. Animals maintained for long periods at low temperatures exhibited preferential ability for increased synthesis of cold agglutinins to HuA. Natural haemolytic titres, as measured by an SRBC indicator system, were also elevated as compared to mammalian systems. These titres increased with stimulation with SRBC. Results suggest that the high levels of natural haemolytic and agglutinin activity in this species are of immunogenic origin. [ABSTRACT FROM AUTHOR]

Initiation of an immune response to sheep erythrocytes by the transplantation of spleen cells into irradiated recipients is thought to involve an interaction between two functionally different lymphoid cells. If such populations actually exist, it should be possible to separate them from each other and to study the properties of each type of cell. To this end, mouse spleen cells have been fractionated using equilibrium centrifugation in density gradients of Ficoll. Two functionally different populations of spleen cells were obtained. Neither population was active in initiating an immune response by itself on transplantation into irradiated mice, but mixtures of the two populations were. One population of spleen cells was also active when transplanted together with normal mouse bone marrow and the other population was active when mixed with thymus cells from normal mice. These results indicate that two different spleen cells must interact to initiate an immune response in vivo. The specificity of the cell that synergizes with thymus ceils was investigated further and shown to have antigen-specific receptors on its surface. These cells can be recognized by their ability to make rosettes with erythrocyte antigens. Thus, the ‘background’ rosette-forming cells found in unimmunized mice are actually progenitors of antibody-producing cells. [ABSTRACT FROM AUTHOR]

The role of macrophages in the immune response against SRBC in spleen cell suspension cultures obtained from mice was studied. 1. The presence of macrophages increases the number of PFC against SRBC in spleen cell cultures. 2. The ratio peritoneal exudate cells to spleen cells is very critical. Two × 105 peritoneal exudate cells preincubated with sheep red blood cells stimulate 1 × 107 mouse spleen cells to an optimal response. This reaction is suppressed when 2 × 106 peritoneal cells are used. 3. Spleen cell populations which had lost the capability of producing antibodies by elimination of cells adhering to glass yielded a strong immune response upon addition of 2 × 105 peritoneal exudate cells. The significance of macrophages for the induction of the immune response is discussed. [ABSTRACT FROM AUTHOR]