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.

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 DISTINCT EVENTS IN THE IMMUNE RESPONSE ELICITED BY TRANSFERRED MARROW AND THYMUS CELLS

1969 ◽  
Vol 130 (6) ◽  
pp. 1243-1261 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Bone Marrow Cells ◽  
Second Step ◽  
Cell Divisions ◽  
Cellular Events ◽  
Antigen Complex ◽  
Fresh Bone ◽  
Thymus Cells ◽  
Marrow Cells

Marrow cells and thymocytes of unprimed donor mice were transplanted separately into X-irradiated syngeneic hosts, with or without sheep erythrocytes (SRBC). Antigen-dependent changes in number or function of potentially immunocompetent cells were assessed by retransplantation of thymus-derived cells with fresh bone marrow cells and SRBC; of marrow-derived cells with fresh thymocytes and SRBC; and of thymus-derived with marrow-derived cells and SRBC. Plaque-forming cells (PFC) of the direct (IgM) and indirect (IgG) classes were enumerated in spleens of secondary host mice at the time of peak responses. By using this two-step design, it was shown (a) that thymus, but not bone marrow, contained antigen-reactive cells (ARC) capable of initiating the immune response to SRBC (first step), and (b) that the same antigen complex that activated thymic ARC was required for the subsequent interaction between thymus-derived and marrow cells and/or for PFC production (second step). Thymic ARC separated from marrow cells but exposed to SRBC proliferated and generated specific inducer cells. These were the cells that interacted with marrow precursors of PFC to form the elementary units for plaque responses to SRBC, i.e. the class- and specificity-restricted antigen-sensitive units. It was estimated that each ARC generated 80–800 inducer cells in 4 days by way of a minimum of 6–10 cell divisions. On the basis of the available evidence, a simple model was outlined for cellular events in the immune response to SRBC.

scholarly journals THE ROLE OF THYMUS AND BONE MARROW CELLS IN DELAYED HYPERSENSITIVITY

1971 ◽  
Vol 134 (5) ◽  
pp. 1144-1154 ◽  
Author(s):  
David G. Tubergen ◽  
Joseph D. Feldman
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Cell Type ◽  
Skin Reactions ◽  
Lymph Node Cells ◽  
Thymus Cells ◽  
Marrow Cells

Adoptive transfer experiments were performed to define the immunological role of thymus and bone marrow cells in the induction of delayed hypersensitivity (DH). The results indicated the following, (a) Bone marrow from immune donors contained cells capable of being stimulated by antigen to initiate the expression of DH. (b) Bone marrow from nonimmune or tolerant donors contained cells that were needed to complete the expression of DH after the infusion of immune lymph node cells. (c) Normal bone marrow and thymus cells cooperated in the irradiated recipient to induce the most vigorous skin reactions to specific antigen; these reactions were seen only when the recipients were stimulated by antigen. Either cell type alone was ineffective. (d) In the presence of tolerant bone marrow cells, thymus cells from immune donors gave a more vigorous response than did thymus cells from normal or tolerant donors. (e) There was suggestive evidence that thymus cells were the source of trigger elements that initiated DH. (f) Antigen in the irradiated recipient was necessary to induce DH after infusion of bone marrow cells alone, or bone marrow and thymus cells together.

scholarly journals Cannabis, the Endocannabinoid System and Immunity—the Journey from the Bedside to the Bench and Back

2020 ◽  
Vol 21 (12) ◽  
pp. 4448 ◽  
Author(s):  
Osnat Almogi-Hazan ◽  
Reuven Or
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Immune System ◽  
Immune Surveillance ◽  
Endocannabinoid System ◽  
The Other ◽  
Clinical Use ◽  
Medical Cannabis ◽  
Pathological Conditions ◽  
Regulatory Properties

The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system. While Cannabis is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical Cannabis is currently limited. A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage. Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders. In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.

Cytokines and Antitumor Immunity

2003 ◽  
Vol 2 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Ludmila Müller ◽  
Graham Pawelec
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Antitumor Immunity ◽  
Essential Role ◽  
The Other ◽  
Current Status ◽  
Immune Selection ◽  
Danger Signals ◽  
Cytokine Milieu ◽  
Successful Immunotherapy

Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation (“danger”) signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy.

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

1969 ◽  
Vol 129 (1) ◽  
pp. 185-199 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz ◽  
R. L. Priore
Keyword(s):  
Immune System ◽  
Specific Antibody ◽  
Cellular Differentiation ◽  
Single Cells ◽  
Donor Cell ◽  
Cell Suspensions ◽  
The Other ◽  
Spleen Cells ◽  
Igg Antibody ◽  
Differentiated Cells

Spleen cell suspensions of primed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice 122–138 days after immunization. Following secondary stimulation with antigen (sheep erythrocytes), these precursors, called antigen-sensitive units (ASU), gave rise to progeny cells secreting specific antibody in the spleens of recipients. Single cells releasing IgM hemolysins (direct plaque-forming cells or PFC), IgG hemolysins (indirect PFC), and hemagglutinins (cluster-forming cells or CFC) were enumerated. By transplanting graded and limiting numbers of primed spleen cells, inocula were found which contained one or a few ASU reaching the recipient spleens. We estimated, thereby, the frequency of ASU detectable by our procedures in donor cell suspensions. The values obtained from direct and in-indirect plaque assays, and from cluster assays were 1 in ∼8.0 x 105, 1 in ∼4.4 x 105, and 1 in ∼5.9 x 105 nucleated spleen cells, respectively. The number of splenic ASU for direct PFC was not greater than that of unimmunized mice; however, immunization greatly increased the number of splenic ASU for indirect PFC and for CFC. By applying to each recipient spleen direct and indirect plaque tests and cluster tests, we found that positivity for each type of immunocyte was independent from that of the other two types. These results confirm the unipotent nature of splenic ASU in general, and document the commitment of ASU primed with SRBC to generate progeny cells secreting antibody of a single molecular (IgM or IgG) or functional (lysin or agglutinin) class. We concluded that splenic ASU are composed of relatively differentiated cells of the immune system of mice. With respect to specificity and class differentiation, ASU appear to be as specialized as antibody-producing cells themselves. Our results did not support the view that ASU-derived clonal populations shift from IgM to IgG antibody production.

scholarly journals Osteoimmunology: Interactions of the Bone and Immune System

2008 ◽  
Vol 29 (4) ◽  
pp. 403-440 ◽  
Author(s):  
Joseph Lorenzo ◽  
Mark Horowitz ◽  
Yongwon Choi
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Immune Cells ◽  
Bone Cells ◽  
The Other ◽  
Organ Systems ◽  
Health And Disease ◽  
The Many ◽  
And Function ◽  
Broad Overview

Abstract Bone and the immune system are both complex tissues that respectively regulate the skeleton and the body’s response to invading pathogens. It has now become clear that these organ systems often interact in their function. This is particularly true for the development of immune cells in the bone marrow and for the function of bone cells in health and disease. Because these two disciplines developed independently, investigators in each don’t always fully appreciate the significance that the other system has on the function of the tissue they are studying. This review is meant to provide a broad overview of the many ways that bone and immune cells interact so that a better understanding of the role that each plays in the development and function of the other can develop. It is hoped that an appreciation of the interactions of these two organ systems will lead to better therapeutics for diseases that affect either or both.

scholarly journals Moms, babies, and bugs in immune development

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2141
Author(s):  
Katie Alexander ◽  
Charles O. Elson
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Cells ◽  
Mucosal Immunity ◽  
The Other ◽  
Primary Role ◽  
Initial Development ◽  
Immune Development ◽  
The One

Bacteria and mammals have co-evolved with one another over millennia, and it has become impossible to interpret mucosal immunity without taking the microbiota into consideration. In fact, the primary role of the mucosal immune system is regulating homeostasis and the host relationship with the microbiota. Bacteria are no longer seen as simply invading pathogens, but rather a necessary component to one’s own immune response. On the one hand, the microbiota is a vital educator of immune cells and initiator of beneficial responses; but, on the other, dysbiosis of microbiota constituents are associated with inflammation and autoimmune disorders. In this review, we will consider recent advances in the understanding of how the microbiota influences host mucosal immunity, particularly the initial development of the immune response and its implications.

scholarly journals Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity

2020 ◽  
Vol 7 ◽  
Author(s):  
José João Name ◽  
Ana Carolina Remondi Souza ◽  
Andrea Rodrigues Vasconcelos ◽  
Pietra Sacramento Prado ◽  
Carolina Parga Martins Pereira
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Adequate Intake ◽  
High Demand ◽  
Comprehensive Overview ◽  
Disease Prognosis ◽  
Mucous Membranes ◽  
And Function

Some nutrients play key roles in maintaining the integrity and function of the immune system, presenting synergistic actions in steps determinant for the immune response. Among these elements, zinc and vitamins C and D stand out for having immunomodulatory functions and for playing roles in preserving physical tissue barriers. Considering the COVID-19 pandemic, nutrients that can optimize the immune system to prevent or lower the risk of severe progression and prognosis of this viral infection become relevant. Thus, the present review aims to provide a comprehensive overview of the roles of zinc and vitamins C and D in the immune response to viral infections, focusing on the synergistic action of these nutrients in the maintenance of physical tissue barriers, such as the skin and mucous membranes. The evidence found in the literature shows that deficiency of one or more of these three elements compromises the immune response, making an individual more vulnerable to viral infections and to a worse disease prognosis. Thus, during the COVID-19 pandemic, the adequate intake of zinc and vitamins C and D may represent a promising pharmacological tool due to the high demand for these nutrients in the case of contact with the virus and onset of the inflammatory process. Ongoing clinical trials will help to clarify the role of these nutrients for COVID-19 management.

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