scholarly journals SUPPRESSION OF MEMORY BY PASSIVE IMMUNIZATION LATE IN THE PRIMARY RESPONSE

1971 ◽  
Vol 133 (4) ◽  
pp. 857-863 ◽  
Author(s):  
Michael A. Axelrad

The acquisition of a capacity to respond well to sheep erythrocytes in the presence of anti-SRBC antibody was taken as an indication of the presence of immunological memory. By the use of passive immunization, both the primary IgG plaque-forming cell response and the establishment of memory were abolished, despite occurrence of a full peak IgM PFC response. Evidence for regarding the aquisition of memory and the IgM PFC and IgG PFC responses as three separate processes was presented. Antibody on day 3 of the response to 1.5 x 108 SRBC abolished formation of memory; this effect was less if passive immunization was further delayed and absent by day 10.

Development ◽  
1973 ◽  
Vol 29 (1) ◽  
pp. 73-85
Author(s):  
Gerald M. Kidder ◽  
Laurens N. Ruben ◽  
Jean M. Stevens

The heterologous red cell response of Xenopus laevis larvae and post-metamorphic toadlets was investigated by means of the immuno-cytoadherence (ICA) technique. Sheep erythrocytes (SRBC) were employed as immunogen. Toadlets responded to a single injection of immunogen within 4 days, and exhibited a peak level of rosette-forming cells (RFC) in their spleens at 8 days post-injection. Toadlets immunized against sheep erythrocytes gave only a very slight response when tested against rat erythrocytes. A secondary response, much greater in magnitude than the primary response, was evident within 2days when previously immunized toadlets were reinjected with the same immunogen. It was concluded that the ICA technique provides a quantitative measure of an acute immune response in these animals. Larvae which had passed through stage 50 of Nieuwkoop & Faber exhibited substantial increases in RFC in the spleens when tested 6–10 days after injection with sheep erythrocytes. Significantly increased frequencies of RFC in thymi were also noted in these larvae, but the numbers involved were very low and varied considerably. Histological observations of these larvae revealed lymphoid maturation of the spleens and thymi to be essentially complete. Larvae which had not reached stage 50 according to external morphological criteria, but whose lymphoid organs had matured to a degree equivalent to stage 50, also exhibited strong anti-SRBC response in the spleens. Response in the thymi was low and not statistically significant. Larvae injected at a stage when lymphocytic differentiation was complete in the thymi but had not begun in the spleens did not exhibit an elevated splenic RFC frequency when tested after the spleens had matured. These data suggest that the heterologous red cell response in the larval spleen is dependent upon antigenic challenge to spleens which have reached the stage 50 equivalent in their histogenesis.


1965 ◽  
Vol 121 (5) ◽  
pp. 683-695 ◽  
Author(s):  
Donald A. Rowley ◽  
Frank W. Fitch

An active immune response to sheep erythrocytes was demonstrated in rats made "tolerant" to sheep erythrocytes by twice-weekly antigen injections beginning on the day of birth. Groups of tolerant rats were sacrificed 4 days after they had received 5 to 42 antigen injections; spleens were sampled for plaque-forming (antibody-releasing) cells and sera were titrated for antibody to sheep erythrocytes using a sensitive "plate hemolysin" technique. During the 3rd week of life and after the 5th antigen injection, the tolerant rats had an immune response equivalent to that of rats of similar age which had received a single antigen injection, but spleens contained only about one-tenth as many plaque-forming cells as adults animals receiving similar antigen injections. Continued antigen injections produced a marked decline and stabilization of this relatively small population of antibody-forming cells; however, the number of plaque-forming cells in the tolerant rats remained considerably elevated above the numbers of plaque-forming cells present in the spleens of non-immunized animals. The sera from all but 1 tolerant rat had demonstrable antibody to sheep erythrocytes in low titer. A progressive recovery of the plaque-forming cell response and rise in antibody titers occurred in adult tolerant rats when the interval between the last 2 antigen injections was increased from 3 days to 14 or 28 days. The decline and stabilization of numbers of plaque-forming cells occurring with continued injections after the 3rd week of life paralleled a similar decline and stabilization in rats receiving similar antigen injections as adults. Also, the recovery of the plaque-forming cell and antibody response of tolerant animals paralleled the recovery observed when the interval between injections was increased in rats receiving similar antigen injections as adults. These findings suggested that the same mechanism controlled numbers of antibody-forming cells in tolerant and normally responsive adult animals. Repeated closely spaced antigen injections presumably interfered with either cell division or maturation of antibody-forming cells. As the interval between injections was increased, additional antibody-forming cells matured or were formed through cell division. Relatively constant antigenic stimulation provided a mechanism for controlling or limiting the response of antibody-forming cells. The mechanism controlling or limiting the response of antibody-forming cells would not account for the stabilization of numbers of antibody-forming cells at high levels for normal animals and at low levels for the tolerant animals. Passive immunization of growing rats with homologous anti-sheep erythrocyte serum markedly inhibited the plaque-forming cell response of growing rats. It was proposed that antibody produced by the small population of antibody-forming cells in the tolerant rats provided a feedback or homeostatic mechanism which inhibited transformation of potential antibody-forming cells to antibody-forming cells. Thus, tolerance to sheep erythrocytes was induced and maintained by two mechanisms. One mechanism, dependent on relatively constant antigenic stimulation, limited or controlled the numbers of antibody-forming cells. The other, dependent on the production of small quantities of antibody by a few antibody-forming cells, limited or controlled the transformation of potential antibody-forming cells to antibody-forming cells.


2006 ◽  
Vol 74 (8) ◽  
pp. 4538-4548 ◽  
Author(s):  
Dennis M. Lindell ◽  
Megan N. Ballinger ◽  
Roderick A. McDonald ◽  
Galen B. Toews ◽  
Gary B. Huffnagle

ABSTRACT Cell-mediated immunity plays an important role in immunity to the pathogenic fungus Cryptococcus neoformans. However, the antigen specificity of the T-cell response to C. neoformans remains largely unknown. In this study, we used two approaches to determine the antigen specificity of the T-cell response to C. neoformans. We report here that a diverse T-cell receptor (TCR) Vβ repertoire was maintained throughout the primary response to pulmonary C. neoformans infection in immunocompetent mice. CD4+ T-cell deficiency resulted in relative expansion of all CD8+ T-cell subsets. During a secondary immune response, preferential usage of a TCR Vβ subset in CD4+ T cells occurred in single individuals, but the preferences were “private” and not shared between individuals. Both CD4+ and CD8+ T cells from the secondary lymphoid tissues of immunized mice proliferated in response to a variety of C. neoformans antigens, including heat-killed whole C. neoformans, culture filtrate antigen, C. neoformans lysate, and purified cryptococcal mannoprotein. CD4+ and CD8+ T cells from the secondary lymphoid tissues of mice undergoing a primary response to C. neoformans proliferated in response to C. neoformans lysate. In response to stimulation with C. neoformans lysate, lung CD4+ and CD8+ T cells produced the effector cytokines tumor necrosis factor alpha and gamma interferon. These results demonstrate that a diverse T-cell response is generated in response to pulmonary C. neoformans infection.


1968 ◽  
Vol 128 (1) ◽  
pp. 171-187 ◽  
Author(s):  
J. D. Wakefield ◽  
G. J. Thorbecke

White-pulp cells and whole spleen from donor mice immunized with sheep erythrocytes were transferred intravenously to heavily irradiated mice. The numbers of plaque-forming cells and the amount of hemagglutinating antibody produced after reexposure to antigen were measured. When reexposure to sheep erythrocytes was delayed, a much greater response occurred in the transferred cells. Peak responsiveness was reached at 24 hr after transfer. This "lag effect" was greatly reduced by repeated injections of 5-bromodeoxyuridine into the recipient mice prior to challenge with antigen. It was therefore concluded that much of the increase in responsiveness was due to a proliferation of "primed" cells after cell transfer. The fact that a significant response was given by the transferred cells in spite of 5-bromodeoxyuridine treatment suggested that some of the primed cells were nondividing. White pulp was a much richer source of responsive cells than was whole spleen.


1977 ◽  
Vol 145 (2) ◽  
pp. 372-389 ◽  
Author(s):  
B Merchant ◽  
J K Inman

Immunization of rabbits or mice with a single, chemically defined hapten elicits populations of plaque-forming cells (PFC) detectable not only on sheep erythrocytes (SRBC) bearing the immunizing hapten, but also on SRBC bearing structural analogues of the immunizing hapten. Most of these analogue-reactive PFC preferentially lyse analogue-conjugated SRBC and cannot be detected on erythrocytes bearing the immunizing hapten. Thus, they represent heretofore largely unstudied components of the secretory B-cell response to haptenic immunization, and they have been termed alloreactive PFC. Such alloreactive PFC are detectable using either classical small haptens or tripeptide-enlarged counterparts of these classical haptens. They are present in large numbers both in direct and in indirect PFC assays, and they are elicited in response to both thymic-dependent and thymic-independent antigens. Relatively few alloreactive PFC can be attributed to cells producing hapten-carrier or "bridge area"-specific antibodies. Since the antibodies released by alloreactive PFC can also be detected by passive hemagglutination, their presence does not appear attributable to vagaries of complement activation. Numerous coexisting alloreactive PFC populations are detectable after haptenic immunization. In early direct PFC responses it is not nucommon for a single alloreactive PFC population to outnumber the population of PFC detectable on SRBC bearing the actual immunizing hapten. These alloreactive PFC may be the source of at least some of the new "nonspecific" Ig which is formed at the time of immunization but about which little is known for lack of available techniques. Some possible implications of these findings on the specificity of B precursor cell activation are discussed.


1971 ◽  
Vol 133 (4) ◽  
pp. 846-856 ◽  
Author(s):  
Gordon N. Radcliffe ◽  
Michael A. Axelrad

The immune responses to sheep erythrocytes of mouse spleen cell suspensions from immune and nonimmune donors were compared in vitro. In vivo immunity was only transiently reflected in vitro, and 8 wk after in vivo immunization the responses of cultures from immunized and nonimmunized mice were virtually identical. There appeared to be two mechanisms for an antibody response to sheep erythrocytes. The first was responsible for the early primary response and is unmodified in the immune animal though contributing little to subsequent in vivo responses due to its suppressibility by specific antibody. The second was expressed in the in vivo secondary response but not on in vitro challenge of spleen cells from mice immunized many weeks previously; spleen cell cultures from such immune mice, freed from the antibody of the in vivo environment, once again demonstrate a pure primary-type response.


1974 ◽  
Vol 140 (2) ◽  
pp. 333-348 ◽  
Author(s):  
S. J. Black ◽  
C. J. Inchley

The kinetics of the generation of primed IgM and IgG antibody-forming cell precursors, and of helper T-cell populations, were analyzed in mice whose primary responses to high and low doses of SRBC were arrested at intervals by the immunosuppressive agents cyclophosphamide monohydrate and specific antibody. The extent to which immunological memory was established in these animals before blockade of the primary response was assessed by the hemolytic plaque assay following challenge 12 wk after priming. The presence of IgG B-memory cells and T-memory cells in suppressed mice was further investigated by the transfer into these animals of syngeneic SRBC-stimulated thymocytes or anti-θ-treated spleen cells. It was found that the progenitors of secondary IgM-synthesizing cells were primed almost immediately after injection of antigen, and that early blockade of the primary response resulted in a raised IgM response after challenge. On the other hand, priming for a secondary IgG response took at least 4 days, and was dose-dependent, although helper T populations for a secondary IgG response appeared 3 days after antigen injection. It appeared that both IgM and IgG memory cells may be considered as Y cells in terms of the X-Y-Z scheme of lymphocyte activation, but that the two populations are generated at different times after exposure to antigen. The size of either Y-cell population at any given time is dependent upon the amount of antigen available to provoke differentiation to antibody-forming Z cells, and the IgM Y-cell population in particular is likely to be depleted during the course of a normal 1° response. When IgM Y cells were maintained for long periods as a result of immunosuppression, their secondary antibody response was independent of the primed T cells necessary for a secondary IgG response.


Hybridoma ◽  
1995 ◽  
Vol 14 (3) ◽  
pp. 209-216 ◽  
Author(s):  
M. ALFONSO ◽  
A.M. VÁZQUEZ ◽  
A. CARR ◽  
T. HAERSLEV ◽  
L.E. FERNÁNDEZ ◽  
...  

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