scholarly journals THE IMMUNE RESPONSE TO SHEEP ERYTHROCYTES IN THE MOUSE

1967 ◽  
Vol 126 (1) ◽  
pp. 15-33 ◽  
Author(s):  
David Eidinger ◽  
Hugh F. Pross

The direct and indirect plaque technique for the detection of antibody-forming cells against sheep erythrocytes was utilized for the investigation of a number of biological parameters of the primary and secondary immune response on a cellular level. The sequential pattern of 19S followed by 7S antibody formation was elicited in the primary response after a latent period of at least 1–2 days and 2–3 days respectively. The secondary response initiated 140 days after primary immunization, in contrast, was characterized by the simultaneous appearance of 19S and 7S antibody-forming cells after an observed latent period of 2–3 days. The cellular dynamics of the recruitment phase of the respective immunoglobulins in the primary and secondary response was interpreted as evidence for the derivation of the two classes of immunoglobulins from separate progenitors. The 19S antibody-forming cells were derived predominantly by a process of transformation and maturation and 7S antibody formers by a process of cellular division with a doubling time of about 12 hr. The draining lymph node exhibited maximal immunological reactivity due to its capacity to retain the particulate antigen. This capacity was considerably enhanced in the sensitized draining lymph node. Minimal cellular activity was also noted in distal lymphoid tissues which included the thymus. Focal cellular activity was observed in the draining lymph node for 60 days after immunization. Subsequently, very low level plaque-forming cellular activity was observed in association with persistence of maximal antibody activity. The appearance at 120 days of a generalized peak of cellular activity in lymphoid tissues throughout the host was considered an explanation for this discrepancy. The change in distribution of cellular antibody-forming activity, from a local to a generalized lymphatic response during the late phase of the immune response, implied a fundamental alteration in homeostatic mechanisms associated with maintenance of immune reactivity. Further manifestations of such an alteration were indicated by the appearance of 2-ME-sensitive 7S antibody nearly 3 months after primary intradermal immunization, which in the ensuing 5 months was associated with, and inversely related to, two major fluctuations in 2-ME-resistant 7S antibody. Evidence for the existence of immunological memory in the 19S system was not established in the present work. 19S anamnesis, for which evidence was derived from measurements of circulating antibody levels, was interpreted from cellular studies as the result of the substantial activity of previously uncommitted 19S lymphoid cells in distal lymphoid tissue associated with previously committed 19S cells contained in the draining lymph node.

1972 ◽  
Vol 136 (2) ◽  
pp. 353-368 ◽  
Author(s):  
Alberto J. L. Macario ◽  
Everly Conway de Macario ◽  
Claudio Franceschi ◽  
Franco Celada

We have cultivated lymph node microfragments from ß-D-galactosidase (Escherichia coli) primed rabbits and have measured their secondary response directed towards the whole molecule (precipitating antibodies) and to a single determinant (activating antibodies) of the antigen. By decreasing the size of the fragments to 105 cells, we began to observe heterogeneity among identical cultures in terms of positivity of response, antibody specificity, and titers. The affinity of "early" activating antibodies was inversely proportional to the dose of challenge. While no maturation was seen in low and excessive challenge, in all cultures receiving intermediate doses the association constant was raised several orders of magnitude within periods of 20 days. The relevance of these data to the mechanism of affinity selection of antigen-sensitive cells is discussed.


2006 ◽  
Vol 203 (8) ◽  
pp. 1903-1913 ◽  
Author(s):  
Brian Webster ◽  
Eric H. Ekland ◽  
Lucila M. Agle ◽  
Susan Chyou ◽  
Regina Ruggieri ◽  
...  

Lymph nodes grow rapidly and robustly at the initiation of an immune response, and this growth is accompanied by growth of the blood vessels. Although the vessels are critical for supplying nutrients and for controlling cell trafficking, the regulation of lymph node vascular growth is not well understood. We show that lymph node endothelial cells begin to proliferate within 2 d of immunization and undergo a corresponding expansion in cell numbers. Endothelial cell proliferation is dependent on CD11c+ dendritic cells (DCs), and the subcutaneous injection of DCs is sufficient to trigger endothelial cell proliferation and growth. Lymph node endothelial cell proliferation is dependent on vascular endothelial growth factor (VEGF), and DCs are associated with increased lymph node VEGF levels. DC-induced endothelial cell proliferation and increased VEGF levels are mediated by DC-induced recruitment of blood-borne cells. Vascular growth in the draining lymph node includes the growth of high endothelial venule endothelial cells and is functionally associated with increased cell entry into the lymph node. Collectively, our results suggest a scenario whereby endothelial cell expansion in the draining lymph node is induced by DCs as part of a program that optimizes the microenvironment for the ensuing immune response.


1968 ◽  
Vol 128 (4) ◽  
pp. 855-874 ◽  
Author(s):  
W. J. Martin ◽  
J. F. A. P. Miller

In this series of papers it has been shown that the immune response of mice to sheep erythrocytes requires the participation of two classes of lymphoid cells. Thymus-derived cells initially react with antigen and then interact with another class of cells, the antibody-forming cell precursors, to cause their differentiation to antibody-forming cells. Antilymphocyte globulin depressed the ability of mice to respond to sheep erythrocytes. This effect was more marked when the antigen was injected intraperitoneally than intravenously, and occurred only when the antilymphocyte globulin was given before or simultaneously with antigen. Injection of thymus cells restored to near normal the ability to respond to an intravenous injection of sheep erythrocytes. Spleen cells from antilymphocyte globulin-treated mice gave a weak adoptive immune response in irradiated recipients. The addition of thymus cells however enabled a response similar to that given by normal spleen cells. When thymectomized irradiated recipients were used, normal spleen cells continued to give a higher response to a challenge of sheep erythrocytes at 2 and 4 wk postirradiation than did spleen cells from ALG-treated donors. This result is more consistent with the notion that thymus-derived target cells are eliminated, rather than temporarily inactivated, by antilymphocyte globulin. These findings suggest that, in vivo, antilymphocyte globulin acts selectively on the thymus-derived antigen-reactive cells.


1961 ◽  
Vol 154 (956) ◽  
pp. 398-417 ◽  

An attempt has been made to study the cellular inheritance of the induced state of cellular differentiation associated with a secondary immune response. Lymphoid cells have been transferred from donor mice immunized against a protein antigen (bovine gamma globulin) into lethally X -irradiated recipients of the same inbred strain. Evidence is discussed which has led to the assumption that the cells capable of producing a secondary response divide in an irradiated environment. The experiments described here have been designed to show the effect of cell division on the capacity of these cells to produce antibody. The rate of anti­body production in an immune response has been measured by means of the antigen-elimina­tion technique. This technique has been calibrated in passive immunization experiments using an antiserum prepared in outbred mice. The amount of division by the transferred immunized cells before challenge was varied in two ways. First, mice were challenged at different intervals after the transfer of the same number of immunized cells into each recipient mouse. Secondly, different numbers of cells were injected into mice, and these left for a time sufficient for the smallest inoculum used to recolonize the host completely. In the first type of experiment, the results showed that the capacity to produce a secondary response steadily declined with increasing time. Control experiments showed that such a decline can occur after active immunization in non-irradiated mice. In the second type of experiment, the rate of antibody production was directly proportional to the size of the original inoculum of immunized cells. It seems that the rate of antibody production is not increased by cell division. The results are prob­ably, therefore, incompatible with those hypotheses which postulate that all of the mechan­ism responsible for antibody synthesis is capable of replication.


1962 ◽  
Vol 116 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Harold F. Dvorak ◽  
Byron H. Waksman

Normal Dutch rabbit lymph node and spleen minces, lymph node cell suspensions, and residues from lymph node cell suspensions were cultured in Millipore chambers with slices of autologous or homologous (New Zealand) ear skin. for varying time intervals. Lymphoid cells exposed to New Zealand ear skin for more than 4 days were found capable of producing typical "transfer reactions" in the specific New Zealand ear skin donor, similar in every way to reactions produced by cells from lymph nodes sensitized in the intact Dutch animal. Heat-killed cells and cells exposed to New Zealand ear skin for less than 4 days (in chambers or in the intact animal) or to Dutch ear skin for any period of time were incapable of eliciting such reactions. It is concluded that normal lymphoid tissues undergo primary sensitization when exposed to homografts in Millipore chambers for suitable periods of time.


2018 ◽  
Author(s):  
Franciele Carolina Silva ◽  
Vinicius Dantas Martins ◽  
Felipe Caixeta ◽  
Matheus Batista Carneiro ◽  
Graziele Ribeiro Goes ◽  
...  

AbstractAn association between increased susceptibility to infectious diseases and obesity has been described as a result of impaired immunity in obese individuals. It is not clear whether a similar linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity in the immune response to cutaneous L. major infection, we studied the ability of C57BL/6 mice submitted to a high fat and sugar diet to control leishmaniasis. Mice with diet-induced obesity presented thicker lesions with higher parasite burden and more inflammatory infiltrate in the infected ear when infected with L. major. We observe no difference in IFN-γ or IL-4 production by draining lymph node cells between control and obese mice, but obese mice presented higher production of IgG1 and IL-17. A higher percentage of in vitro-infected peritoneal macrophages was found when these cells were obtained from obese mice when compared to lean mice. In vitro stimulation of macrophages with IL-17 decreased the capacity of cells from control mice to kill the parasite. Moreover, macrophages from obese mice presented higher arginase activity. Together our results indicate that diet-induced obesity impairs resistance to L. major in C57BL/6 mice without affecting the development of Th1 response.Author SummaryThe obesity is a public health problem and it is reaching extraordinary numbers in the world and others diseases are being involved and aggravated as consequence of obesity. What we know is that some diseases are more severe in obese people than in normal people. We did not know how obesity changes the profile of immune response to infectious agents, leading to the more severe diseases. That‘s why we decided to investigate how obese mice lead with Leishmania major infection. Leishmaniasis is a protozoa parasite infection considered a neglected disease. To try our hypothesis we gave a hipercaloric diet to induce obesity in C57BL/6 mice. After that, we injected L. major in the mice ear and followed the lesion for 8 weeks. We observed a ticker lesion and the cells from draining lymph node from obese mice produced more IL-17 than cells from normal mice. We also infected in vitro, macrophages from obese mice and stimulated the cells with IL-17, and we observed that the macrophages from obese mice are more infected by the L. major and it is worst in the presence of IL-17. Our results suggest that diet induced obesity decrease the resistance to infection.


Author(s):  
Kelli A. Connolly ◽  
Manik Kuchroo ◽  
Aarthi Venkat ◽  
Achia Khatun ◽  
Jiawei Wang ◽  
...  

1970 ◽  
Vol 131 (4) ◽  
pp. 675-699 ◽  
Author(s):  
J. F. A. P. Miller ◽  
G. F. Mitchell

Collaboration between thymus-derived lymphocytes, and nonthymus-derived antibody-forming cell precursors occurs during the immune response of mice to sheep erythrocytes (SRBC). The aim of the experiments reported here was to attempt to induce tolerance in each of the two cell populations to determine which cell type dictates the specificity of the response. Adult mice were rendered specifically tolerant to SRBC by treatment with one large dose of SRBC followed by cyclophosphamide. Attempts to restore to normal their anti-SRBC response by injecting lymphoid cells from various sources were unsuccessful. A slight increase in the response was, however, obtained in recipients of thymus or thoracic duct lymphocytes and a more substantial increase in recipients of spleen cells or of a mixture of thymus or thoracic duct cells and normal marrow or spleen cells from thymectomized donors. Thymus cells from tolerant mice were as effective as thymus cells from normal or cyclophosphamide-treated controls in enabling neonatally thymectomized recipients to respond to SRBC and in collaborating with normal marrow cells to allow a response to SRBC in irradiated mice. Tolerance was thus not achieved at the level of thelymphocyte population within the thymus, perhaps because of insufficient penetration of the thymus by the antigens concerned. By contrast, thoracic duct lymphocytes from tolerant mice failed to restore to normal the response of neonatally thymectomized recipients to SRBC. Tolerance is thus a property that can be linked specifically to thymus-derived cells as they exist in the mobile pool of recirculating lymphocytes outside the thymus. Thymus-derived cells are thus considered capable of recognizing and specifically reacting with antigenic determinants. Marrow cells from tolerant mice were as effective as marrow cells from cyclophosphamide-treated or normal controls in collaborating with normal thymus cells to allow a response to SRBC in irradiated recipients. When a mixture of thymus or thoracic duct cells and lymph node cells was given to irradiated mice, the response to SRBC was essentially the same whether the lymph node cells were derived from tolerant donors or from thymectomized irradiated, marrow-protected donors. Attempts to induce tolerance to SRBC in adult thymectomized, irradiated mice 3–4 wk after marrow protection, by treatment with SRBC and cyclophosphamide, were unsuccessful: after injection of thoracic duct cells, a vigorous response to SRBC occurred. The magnitude of the response was the same whether or not thymus cells had been given prior to the tolerization regime. The various experimental designs have thus failed to demonstrate specific tolerance in the nonthymus-derived lymphocyte population. Several alternative possibilities were discussed. Perhaps such a population does not contain cells capable of dictating the specificity of the response. This was considered unlikely. Alternatively, tolerance may have been achieved but soon masked by a rapid, thymus-independent, differentiation of marrow-derived lymphoid stem cells. On the other hand, tolerance may not have occurred simply because the induction of tolerance, like the induction of antibody formation, requires the collaboration of thymus-derived cells. Finally, tolerance in the nonthymus-derived cell population may never be achieved because the SRBC-cyclophosphamide regime specifically eliminates thymus-derived cells leaving the antibody-forming cell precursors intact but unable to react with antigen as there are no thymus-derived cells with which to interact.


Vaccine ◽  
2014 ◽  
Vol 32 (21) ◽  
pp. 2420-2427 ◽  
Author(s):  
Sunita Awate ◽  
Heather L. Wilson ◽  
Baljit Singh ◽  
Lorne A. Babiuk ◽  
George Mutwiri

1955 ◽  
Vol 102 (4) ◽  
pp. 379-392 ◽  
Author(s):  
James C. Roberts ◽  
Frank J. Dixon

A secondary immune response to the soluble foreign protein antigens I*BSA and I*BGG has been demonstrated when lymph node cells, largely lymphocytes with a few reticulo-endothelial and plasma cells, from previously immunized rabbits were transferred to x-radiated recipient rabbits, and the recipients then challenged with antigen. The total specific antibody synthesized by the transferred cells during the first 8 days of the secondary response amounted to approximately ⅔ of the wet weight of the transferred cells. In an attempt to elicit a primary response, lymph node cells were obtained from normal, non-immunized donors, and transferred to x-radiated recipients. No immune response was observed upon antigenic stimulation. When normal or previously immunized lymph node cells were incubated with antigen for periods up to 1 hour, washed and injected into recipients, no antibody production was observed.


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