scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1969 ◽  
Vol 130 (3) ◽  
pp. 467-480 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz ◽  
R. L. Priore

Thymocytes and marrow cells of unprimed donor mice were mixed in vitro and transplanted into X-irradiated syngeneic mice. 18 hr later, sheep erythrocytes were injected to induce immune responses. Splenic plaque-forming cells (PFC) secreting IgM (direct PFC) or IgG (indirect PFC) hemolytic antibody were enumerated at the time of peak responses. By transplanting graded and limiting numbers of thymocytes with 4 x 107 marrow cells, inocula were found which contained one or a few thymic antigen-reactive cells (ARC) reaching the recipient spleens, interacting with marrow cells, and inducing PFC formation. The frequency values of ARC inferred from direct and indirect plaque assays were very similar, 1 in ∼107 thymocytes. Furthermore, statistical analysis indicated that the formation of direct PFC was not independent of the formation of indirect PFC. This was interpreted to mean that ARC were not specialized themselves and did not determine the molecular class of antibody to be secreted after interaction with marrow cells. Spleens of thymus-marrow grafted mice containing one or two ARC and non-limiting numbers of marrow precursors of PFC (P-PFC), had direct and indirect PFC clustered in several focal areas. Assuming that each focal area represented the progeny of one P-PFC that had interacted with ARC, these results confirmed the statistical evidence for lack of class differentiation in thymic ARC, and also indicated that each ARC or its progeny cells interacted with more than one P-PFC of either class.

1969 ◽  
Vol 130 (3) ◽  
pp. 481-492 ◽  
Author(s):  
G. Cudkowicz ◽  
G. M. Shearer ◽  
R. L. Priore

Marrow cells and thymocytes of unprimed donor mice were mixed in vitro and transplanted into X-irradiated syngeneic hosts. 18 hr later sheep erythrocytes were injected to induce immune responses. Splenic plaque-forming cells (PFC) secreting IgM (direct PFC) or IgG (indirect PFC) hemolytic antibody were enumerated at the time of peak responses. By transplanting graded and limiting numbers of marrow cells with 5 x 107 thymocytes, inocula were found that contained few precursors of PFC (P-PFC) reaching the recipient spleens, interacting with thymocytes, and generating PFC. However, the frequency of responses in relation to the number of grafted marrow cells did not follow Poisson statistics, presumably because the interaction of marrow cells with thymocytes was more complex than a single or a one-to-one cell event. The frequency of direct PFC responses was greater than that of indirect PFC responses in 13 of 15 groups of mice tested. This was interpreted as evidence for the existence of two classes of P-PFC, each of which was restricted to generate either direct or indirect PFC. The precursors of direct PFC were ∼ 15 times more frequent than those of indirect PFC. Since thymic antigen-reactive cells were not differentiated for antibody class, it follows that antigen-sensitive units reactive to sheep erythrocytes owe their class restriction to specialized marrow cells. Specialization of P-PFC may have arisen within marrow cell lines by differentiation, or may have been conferred upon P-PFC by interaction with other cells, including those of the irradiated host.


Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 575-577 ◽  
Author(s):  
N. A. Mitchison

Only a few years ago parasite immunology looked an unattractive subject better left to the dogged specialists. Parasites and hosts had been playing chess together for a million years, and there seemed little prospect of perturbing matters in favour of the host immune system. All that has changed, for three reasons. Firstly, we have learned how to grow at least some parasites in vitro, and prospects of doing so with others are encouraging. Secondly, progress in cellular immunology has revealed the sort of loopholes in the host defence system which parasites are likely to exploit: we are learning the questions which matter about parasites as antigens. Thirdly, and most importantly, molecular genetics is being brought to bear on parasites: we can now see a real, though long-term, prospect of manufacturing practicable vaccines through bio-engineering, and more immediately it gives us the tools needed to probe the host immune responses in the form of cloned antigens.


2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Ilse Van Brussel ◽  
Zwi N. Berneman ◽  
Nathalie Cools

Earlier investigations have revealed a surprising complexity and variety in the range of interaction between cells of the innate and adaptive immune system. Our understanding of the specialized roles of dendritic cell (DC) subsets in innate and adaptive immune responses has been significantly advanced over the years. Because of their immunoregulatory capacities and because very small numbers of activated DC are highly efficient at generating immune responses against antigens, DCs have been vigorously used in clinical trials in order to elicit or amplify immune responses against cancer and chronic infectious diseases. A better insight in DC immunobiology and function has stimulated many new ideas regarding the potential ways forward to improve DC therapy in a more fundamental way. Here, we discuss the continuous search for optimal in vitro conditions in order to generate clinical-grade DC with a potent immunogenic potential. For this, we explore the molecular and cellular mechanisms underlying adequate immune responses and focus on most favourable DC culture regimens and activation stimuli in humans. We envisage that by combining each of the features outlined in the current paper into a unified strategy, DC-based vaccines may advance to a higher level of effectiveness.


1971 ◽  
Vol 133 (3) ◽  
pp. 494-505 ◽  
Author(s):  
Margot N. Pearson ◽  
Sidney Raffel

Sheep erythrocytes ingested by guinea pig peritoneal macrophages in vitro, and permitted to undergo digestion for various periods, were found after some hours to lose the capacity to induce antibodies while gaining the ability to invoke delayed hypersensitivity. These observations may be related to the known predilection of small molecular immunogens to act as good inducers of delayed reactivity and poor stimulators of antibody. They may be related also to the activity of mycobacterial adjuvant as a vehicle for the induction of delayed hypersensitivity on the basis that this melange activates macrophages to phagocytose and enzymatically degrade macromolecular antigens rapidly. The thesis that small fragments of antigenic molecules may preferentially invoke hypersensitivity can be interpreted on the basis of current concepts of multicellular involvements in immune responses.


1990 ◽  
Vol 2 (3) ◽  
pp. 263 ◽  
Author(s):  
MP Hedger ◽  
JX Qin ◽  
DM Robertson ◽  
Kretser DM de

Immune responses within the mammalian gonads, and in particular the testis, are deficient in spite of adequate lymphatic drainage and the presence of lymphocytes and MHC II+ macrophages. There is considerable evidence from in vivo and in vitro studies that this 'suppression' of the immune system may be due, at least in part, to localized inhibition or regulation of normal lymphocyte and/or macrophage functions within the gonads. In the testis, both steroidal and non-steroidal products of the Leydig cells, including androgens, endorphins, and inhibin-related proteins, have been implicated in mediating this activity. In turn, a number of immune cell cytokines affect steroidogenic cell function in vitro. The studies described in this paper indicated that [3H]-thymidine incorporation by adult rat thymocytes in vitro was inhibited by conditioned medium collected from short-term incubations of Percoll-purified adult rat Leydig cells, but stimulated by testicular interstitial fluid and by conditioned medium collected from short-term incubations of adult rat seminiferous tubules. The factors responsible for these effects on thymocyte function appeared to be of large molecular weight, as they were retained by ultrafiltration membranes with exclusion limits of 10,000 or 30,000 daltons. It is hypothesized that an 'immunosuppressive' mechanism, principally mediated by non-steroidal factors secreted by the steroidogenic cells of the gonadal interstitial tissue, exists within the gonads in order to prevent activation of the immune system by germ cell antigens and growth factors associated with germ cell proliferation and differentiation. This mechanism probably acts in parallel with normal antigen-specific tolerance mechanisms operating at the gonadal level. As immune responses to germ cells are believed to be a significant causative factor in infertility, particularly in men, this represents an important area for further study.


1969 ◽  
Vol 129 (5) ◽  
pp. 935-951 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz

Marrow cell suspensions of unprimed donor mice have been transplanted into X-irradiated syngeneic hosts. 5–46 days later, bone cavities and spleens contained regenerated cells of the immune system which required interaction with thymocytes (from intact donors) and antigen (SRBC) to form antigen-sensitive units (ASU) and to generate mature immunocytes. These cells were capable of differentiating either into direct or indirect hemolytic plaque-forming cells (PFC). The precursors of PFC regenerated earlier than the other cell type necessary for immunocompetence, the antigen-reactive cell (ARC). The latter was not found until 10 or more days after transplantation. Availability of ARC was inferred from PFC responses elicited by grafted mice challenged with SRBC at varying intervals. In a second series of experiments, graded numbers of marrow cells (ranging from 107 to 5 x 107) were transplanted with 5 x 107 or 108 thymocytes into irradiated mice, and SRBC were given 18 hr later. After 9–12 days the recipient spleens contained all or some of the following immunocytes: direct and indirect PFC, and hemagglutinating cluster-forming cells. The frequency of each immune response varied independently of the others, but in relation to the number of marrow cells grafted. This was interpreted to indicate that ASU formed in irradiated mice by interaction of marrow and thymus cells were similar to those of intact mice. In particular, they were specialized for the molecular class (IgM or IgG) and function (lysis or agglutination) of the antibody to be secreted by their descendent immunocytes. Hence, class-differentiation appeared to be conferred upon ASU by their marrow-derived components.


1970 ◽  
Vol 132 (6) ◽  
pp. 1122-1137 ◽  
Author(s):  
Harold C. Miller ◽  
Gustavo Cudkowicz

Graded numbers of marrow cells and 5 x 107 thymocytes were mixed in vitro and transplanted into X-irradiated (C3H x C57BL/10)F1 mice. Upon injection of sheep or chicken erythrocytes, splenic plaque-forming cells secreting IgM (direct PFC) or IgG (indirect PFC) hemolytic antibody were enumerated at the time of peak responses. Anti-sheep and anti-chicken primary PFC responses elicited by nonimmune marrow cells differed sharply from each other under the conditions of limiting dilution assays. The frequencies of anti-chicken responses in recipients of different numbers of marrow cells conformed to the predictions of the Poisson model, while the frequencies of anti-sheep responses did not. Hence, the function of certain marrow-derived cells was expressed differentially during the two immune responses, to exclude that the same precursor units generated anti-sheep or anti-chicken PFC. The former precursor cells or units were functionally more heterogeneous than the latter. Immunization of marrow donors against sheep erythrocytes did not alter the population of cells engaged in anti-chicken responses, since limiting dilution assays with immune and nonimmune marrow cells gave identical results. However, anti-sheep immunization altered specifically the cell population engaged in anti-sheep responses, in two ways: (a) potentially immunocompetent marrow cells underwent antigen-dependent differentiation or maturation, to become functionally homogeneous. Consequently, the frequencies of PFC responses in limiting dilution assays conformed to the Poisson model; the changes occurred independently in class-restricted precursors of direct and indirect PFC. (b) marrow cells capable of inhibiting precursors of direct anti-sheep PFC arose in primed mice. The inhibition, which was specific, could have been effected directly by marrow cells or by a diffusable product such as IgG antibody. Results indicated that potentially immunocompetent cells of mouse marrow with distinct functions were antigen specific and antigen sensitive.


2004 ◽  
Vol 19 (3) ◽  
pp. 213-220
Author(s):  
F. Battaini ◽  
D. Besusso ◽  
L. Sfondrini ◽  
A. Rossini ◽  
D. Morelli ◽  
...  

Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiating immune responses to antigens. It is also well documented that cancer patients often experience anergy against tumor antigens. In this study we selected the best protocol for inducing the production of antibodies against the HER2 oncoprotein using DCs to overcome anergy. Murine DCs were pulsed in vitro, using different protocols, with recombinant HER2 fused to a human Fc (in order to improve DC antigen uptake) and were used to vaccinate mice. The obtained results indicate that antigen-pulsed DCs can induce an antibody response and that adding CpG after antigen pulsing greatly increases anti-HER2 antibody production.


Author(s):  
Diah Wulandari Rousdy ◽  
Rahmawati Rahmawati ◽  
Rikhsan Kurniatuhadi

<p>Peat soil is a type of soil that dominates the island of Borneo. Typical compounds in peat soil is shumic acid. Various in vitro studies performed have shown peat subtropical humic compounds can stimulate the immune system. However, in vivo study on animal has not been done. This study aimed to determine the effect of humic acid extracted from peat soil of Kalimantan against the immune system, both of non-specific and specific immunity Wistar rats (<em>Rattus novergicus</em>). Research using a completely randomized design with five treatments and five replicates, the normal controls, a positive control (isoprinosine), humic acid 125; 250; 500 mg/kg. Humic acid was administered orally for 10 days. The results showed humic acid adduction did not significantly affect levels of hemoglobin, erythrocytes and hematocrit. Humic acid adduction of 125 mg/kg significantly affects the total leukocyte count and differential leukocyte. Humic acid 125 mg/kg also showed increased phagocytic index better than normal controls. All humic acid treatments do not provide a significant effect on the total amount of antibody. The results of this study can be used for the development of Borneo tropical peat resources as natural imunostimulant.</p><p><strong>How to Cite</strong></p><p>Rousdy, D. W., Rahmawati, R. &amp; Kurniatuhadi, R. (2016). Immune Responses of Wistar Rat (<em>Rattus novergicus</em>) on Adduction of Humid Acid from Borneo Peat Soil. <em>Biosaintifika: Journal of Biology &amp; Biology Education</em>, 8(3), 401-406. </p>


1974 ◽  
Vol 140 (4) ◽  
pp. 921-938 ◽  
Author(s):  
Carl W. Pierce ◽  
Judith A. Kapp ◽  
Susan M. Solliday ◽  
Martin E. Dorf ◽  
Baruj Benacerraf

The effects of alloantisera against leukocyte alloantigens on plaque-forming cell (PFC) responses to sheep erythrocytes and the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) by mouse spleen cells in vitro have been investigated. Polyspecific antibodies against both H-2 and non-H-2 alloantigens on responding spleen cells suppressed both IgM and IgG PFC responses; antisera against alloantigens coded for by the K and I regions, but not the D region, of the H-2 complex also effectively suppressed PFC responses. The suppression was not due to cytotoxicity to the spleen cells or anti-immunoglobulin activity in the sera and was directly related to the amount of antiserum added to the cultures. The suppression was specific for spleen cells against which the alloantiserum was directed. The alloantisera suppressed responses most effectively when present during the first 24 h of incubation, and although not rendering lymphoid cells incapable of developing PFC responses after removal of noncell-bound antibody, did act by interfering with successful initiation of the PFC response. The alloantisera suppressed both IgM and IgG PFC responses when directed against alloantigens only on macrophages, but selectively suppressed IgG responses when directed against alloantigens only on lymphoid cells. The alloantisera did not interfere with the ability of macrophages to bind GAT or to support the viability of the lymphoid cells, but did interfere with the ability of macrophage-associated antigen to effectively stimulate antibody responses by the lymphoid cells. Possible mechanisms for the effects of alloantisera on macrophages and the selective suppression of IgG responses when the antisera are directed against alloantigens on lymphoid cells are discussed with reference to our current understanding of genetic restrictions governing cell interactions in the development of antibody responses in mice.


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