scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1969 ◽  
Vol 130 (3) ◽  
pp. 481-492 ◽  
Author(s):  
G. Cudkowicz ◽  
G. M. Shearer ◽  
R. L. Priore
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cell Lines ◽  
Cellular Differentiation ◽  
Marrow Cell ◽  
Sheep Erythrocytes ◽  
Poisson Statistics ◽  
Antibody Class ◽  
Marrow Cells

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.

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
Keyword(s):  
Immune System ◽  
Statistical Analysis ◽  
Immune Responses ◽  
Cellular Differentiation ◽  
Statistical Evidence ◽  
Sheep Erythrocytes ◽  
Focal Area ◽  
Marrow Cells

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.

scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1970 ◽  
Vol 132 (4) ◽  
pp. 623-635 ◽  
Author(s):  
G. Cudkowicz ◽  
G. M. Shearer ◽  
T. Ito
Keyword(s):  
Cellular Differentiation ◽  
Genetic Factors ◽  
Strain Differences ◽  
Immunocompetent Cells ◽  
Antibody Specificity ◽  
Poisson Statistics ◽  
Accessory Cells ◽  
Antibody Class ◽  
Marrow Cells

Marrow cells and 5 x 107 thymocytes of unprimed (C57BL/6 x DBA/2)F1, (C57BL/10 x WB)F1 and (C3H x C57BL)F1 donor mice were mixed in vitro and transplanted into X-irradiated syngeneic hosts. Upon injection of sheep erythrocytes, splenic plaque-forming cells (PFC) secreting IgM (direct PFC or IgG (indirect PFC) hemolytic antibody were enumerated at the time of peak responses. By grading the numbers of marrow cells, inocula were found that contained few immunocompetent cells reaching the recipient spleens, interacting with thymocytes or other accessory cells (or both), and generating PFC. The frequency of responses in BDF1 mice conformed to Poisson statistics, indicating that immunocompetent marrow cells participated in a single-hit interaction limiting PFC responses. The marrow cells assayed were not restricted for the antibody class (IgM versus IgG) to be secreted by mature PFC. Unrestricted marrow cells could have been either the precursors of PFC or accessory cells. Different results were obtained in BWF1 and C3BF1 mice. The frequency of responses in relation to the number of marrow cells grafted did not follow Poisson statistics, and the limiting cells were restricted for antibody class. Presumably, immunocompetent cells of these strains were more heterogeneous than those of BDF1 mice and participated in a multiplicity of cell-to-cell interactions. The strain differences reflected inherent properties of marrow cells and not influences of the environment in which PFC were produced. The results confirmed for bone marrow the heterogeneity of immunocompetent cells reported by others for spleen, and suggested that genetic factors such as "immune response" genes regulate cellular differentiation also for functions other than those related to antibody specificity.

scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1969 ◽  
Vol 129 (5) ◽  
pp. 935-951 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Cellular Differentiation ◽  
Marrow Cell ◽  
The Other ◽  
Cell Type ◽  
Series Of Experiments ◽  
And Function ◽  
Thymus Cells ◽  
Marrow Cells

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.

Lidocaine depresses splenocyte immune functions following trauma-hemorrhage in mice

2006 ◽  
Vol 291 (5) ◽  
pp. C1049-C1055 ◽  
Author(s):  
Takashi Kawasaki ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
Kirby I. Bland ◽  
Irshad H. Chaudry
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Immune Responses ◽  
Cytokine Production ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Sham Operation ◽  
Mapk Activation ◽  
Midline Laparotomy ◽  
Marrow Cells

Traumatic and/or surgical injury as well as hemorrhage induces profound suppression of cellular immunity. Although local anesthetics have been shown to impair immune responses, it remains unclear whether lidocaine affects lymphocyte functions following trauma-hemorrhage (T-H). We hypothesized that lidocaine will potentiate the suppression of lymphocyte functions after T-H. To test this, we randomly assigned male C3H/HeN (6–8 wk) mice to sham operation or T-H. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× shed blood volume in the form of Ringer lactate). Two hours later, the mice were killed and splenocytes and bone marrow cells were isolated. The effects of lidocaine on concanavalin A-stimulated splenocyte proliferation and cytokine production in both sham-operated and T-H mice were assessed. The effects of lidocaine on LPS-stimulated bone marrow cell proliferation and cytokine production were also assessed. The results indicate that T-H suppresses cell proliferation, Th1 cytokine production, and MAPK activation in splenocytes. In contrast, cell proliferation, cytokine production, and MAPK activation in bone marrow cells were significantly higher 2 h after T-H compared with shams. Lidocaine depressed immune responses in splenocytes; however, it had no effect in bone marrow cells in either sham or T-H mice. The enhanced immunosuppressive effects of lidocaine could contribute to the host's enhanced susceptibility to infection following T-H.

An appraisal of survival strategies

Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 575-577 ◽  
Author(s):  
N. A. Mitchison
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Survival Strategies ◽  
Host Immune System ◽  
Cellular Immunology ◽  
Host Immune Responses ◽  
Host Defence System ◽  
Bio Engineering

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.

scholarly journals Anti-K562 cell monoclonal antibody RTF8X recognizes tumor-associated antigen of erythroid lineage

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1487-1491 ◽  
Author(s):  
T Sakurai ◽  
H Hara ◽  
K Nagai
Keyword(s):  
Monoclonal Antibody ◽  
Cell Lines ◽  
Surface Antigen ◽  
K562 Cell ◽  
K562 Cells ◽  
Erythroid Differentiation ◽  
Enzyme Treatment ◽  
Normal Peripheral Blood ◽  
Marrow Cells

Abstract A new anti-K562 cell monoclonal antibody, RTF8X, a cytotoxic IgM, recognized a surface antigen on erythroblasts from patients with erythroleukemia and polycythemia vera. RTF8X, which is highly specific to K562 cells, did not react with the other 14 hematopoietic cell lines and the seven nonhematopoietic cell lines. RTF8X antigen was not detected in normal peripheral blood, but was found in less than 1% of normal marrow cells. RTF8X did not inhibit in vitro colony formation of CFU-E and BFU-E in a complement-dependent cytotoxicity assay. Cell- sorting analysis showed that, morphologically, the RTF8X-positive marrow cells from the patients and normal volunteers contained more than 60% erythroblasts and that CFU-E and BFU-E were not demonstrated in cells with RTF8X antigen. Enzyme treatment suggested that RTF8X antigen was a sialoglycolipid. These results indicate that RTF8X may recognize the surface antigen found increasingly in association with tumors of erythroid lineage. RTF8X should be useful for studies of erythroid differentiation and proliferation in patients.

scholarly journals Calcium ionophore but not phorbol ester promotes eicosanoids release by proliferating interleukin-3-dependent bone marrow cells

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1586-1592 ◽  
Author(s):  
Y Shibata ◽  
PG McCaffrey ◽  
H Sato ◽  
Y Oghiso
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Phorbol Ester ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Calcium Ionophore ◽  
Mouse Bone Marrow ◽  
Ionophore A23187 ◽  
Interleukin 3 ◽  
Marrow Cells

Abstract Eicosanoid release during multilineage hematopoiesis was assessed using freshly isolated mouse bone marrow cells cultured in the presence of interleukin-3 (IL-3) (10% WEHI-3 culture-conditioned medium). Cells that could release prostaglandin E2 (PGE2) when stimulated with calcium ionophore A23187, but not with phorbol ester (PMA), appeared within 4 days. The cells harvested on day 10 released 42 ng of PGE2/10(6) cells/mL after A23187 stimulation. Leukotriene B4 (LTB4) (4 ng/mL) was also detected after A23187 stimulation, but there was no detectable LTC4 (less than 0.5 ng/mL). Nonadherent bone marrow cells were isolated from 28-day cultures and cloned. All clones were strongly IL-3- dependent. Although other growth factors such as granulocyte colony- stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and CSF-1 failed to promote survival or support proliferation of the cells, three clones (11–1-A6, 3–2-D5, and 11–1-A1) showed significant increases in 3H-thymidine incorporation, respectively, after PMA treatment for 24 hours. Surviving cells displayed dominantly myeloid type morphology and phenotypic characteristics. The data suggest that IL-3 is important in the formation of PGE2-producing cells. In contrast to many macrophages (MO), neither the IL-3-dependent cell lines nor the IL-3-cultured bone marrow cells released significant amounts of PGE2 when stimulated with PMA or IL-3, although PMA and IL-3 both induced translocation of protein kinase C (PKC) to the membrane fraction. The lack of production of PGE2 and other eicosanoids by the PMA- and IL-3- stimulated cell lines was confirmed by measuring the release of 3H- arachidonic acid. The data suggest that in IL-3-dependent bone marrow cell lines the activation of eicosanoid metabolism requires elevated cellular Ca2+; PKC activation alone does not appear to be a sufficient stimulus.

scholarly journals The effects of tumor-promoting phorbol esters on human granulopoiesis in vitro

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 526-533 ◽  
Author(s):  
R Sullivan ◽  
RA Brodie ◽  
NE Larsen ◽  
PJ Gans ◽  
LA McCarroll
Keyword(s):  
Peripheral Blood ◽  
Colony Formation ◽  
Phorbol Esters ◽  
Marrow Cell ◽  
Adherent Cells ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Light Density ◽  
Marrow Cells

Abstract In order to determine whether the tumor-promoting phorbol esters are capable of inducing normal human committed granulocytic-monocytic progenitor cells (CFUc) to proliferate and differentiate in the absence of granulocyte-monocyte colony-stimulating activity (CSA), we studied the effects of these compounds on human granulopoiesis in vitro. We found that when light-density human marrow cells or peripheral blood leukocytes were depleted of adherent cells and then incubated in semisolid tissue culture medium under conditions optimal for CFUc growth, phorbol myristate acetate (PMA) and its congeners produced no measurable stimulatory effect on the proliferation of CFUc in the absence of added CSA. Likewise, when light-density marrow cells that had not been depleted of adherent cells were plated in the cultures, no stimulation of CFUc colony growth resulted from the addition of PMA. However, when light-density peripheral blood leukocytes were used as a target source of CFUc without first subjecting them to adherence separation, enhanced proliferation and differentiation of CFUc were noted in cultures that contained PMA. To investigate the possibility that CSA production by monocytes in these cultures in response to activation by PMA might account for the enhanced colony formation that we observed, we incubated isolated peripheral blood monocytes in short- term liquid suspension cultures and found that in the presence of PMA, large quantities of CSA were secreted into the surrounding medium. Finally, we noted that when marrow cell suspensions were suboptimally stimulated by low concentrations of CSA added to the cultures, the effects of PMA on CFUc proliferation were unpredictable, enhancing colony formation in some cases and inhibiting it in others. Our data indicate that although the tumor-promoting phorbol esters do not appear capable of directly stimulating the proliferation or differentiation of human CFUc in the absence of CSA, they may do so indirectly by causing auxiliary cells such as monocytes to secrete CSA.

scholarly journals Optimizing Dendritic Cell-Based Immunotherapy: Tackling the Complexity of Different Arms of the Immune System

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Ilse Van Brussel ◽  
Zwi N. Berneman ◽  
Nathalie Cools
Keyword(s):  
Immune System ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Cellular Mechanisms ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
New Ideas ◽  
And Function

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.

scholarly journals MACROPHAGE-DIGESTED ANTIGEN AS INDUCER OF DELAYED HYPERSENSITIVITY

1971 ◽  
Vol 133 (3) ◽  
pp. 494-505 ◽  
Author(s):  
Margot N. Pearson ◽  
Sidney Raffel
Keyword(s):  
Immune Responses ◽  
Guinea Pig ◽  
Peritoneal Macrophages ◽  
Delayed Hypersensitivity ◽  
Sheep Erythrocytes

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.

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