scholarly journals EFFECT OF RECENT ANTIGEN PRIMING ON ADOPTIVE IMMUNE RESPONSES

1973 ◽  
Vol 138 (1) ◽  
pp. 143-162 ◽  
Author(s):  
J. Sprent ◽  
J. F. A. P. Miller
Keyword(s):  
Immune Responses ◽  
B Lymphocytes ◽  
Transient State ◽  
Antibody Responses ◽  
Partial Recovery ◽  
Cell Transfer ◽  
Spleen Cells ◽  
Experimental Conditions ◽  
Mesenteric Lymph ◽  
Normal Spleen

When spleen, mesenteric lymph node, or Peyer's patch cells from mice primed 24 h before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later were very low to the priming antigen but high to the other antigen. This was demonstrated either by measuring numbers of antibody-forming cells in spleen or levels of hemagglutinins in serum. Specific unresponsiveness of the transferred cells was evident in both the 19S and 7S responses. It was observed only when strict experimental conditions were followed: (a) the cell donors had to be primed with not less than 109 erythrocytes given intravenously; (b) the cells had to be transferred between 1 and 2 days after antigen priming; (c) antibody responses in the recipients were measured within 7 days of cell transfer, i.e., partial recovery was evident by 11 days; (d) the transferred cells had to be challenged in the recipients within 1 day after cell transfer: when challenge was delayed for 5 days or longer, responsiveness returned. The failure of cells from recently primed donors to respond to the priming antigen on adoptive transfer could be overcome by supplementing with normal spleen cells, but not with thymus alone or bone marrow alone. This implied that unresponsiveness occurred at the levels of both T and B lymphocytes, and was not due to a suppressive influence exerted by T cells. Further work is in progress to determine the mechanism of this transient state of specific unresponsiveness.

scholarly journals Isotype commitment in the in vivo immune responses. I. Antigen-dependent specific and polyclonal plaque-forming cell responses by B lymphocytes induced to extensive proliferation.

1982 ◽  
Vol 156 (3) ◽  
pp. 690-702 ◽  
Author(s):  
M Björklund ◽  
A Coutinho
Keyword(s):  
Immune Responses ◽  
B Lymphocytes ◽  
Antibody Responses ◽  
Regulatory Mechanisms ◽  
Transfer System ◽  
Spleen Cells ◽  
Serial Transfer ◽  
Specific Antibodies ◽  
Cell Responses

The random recombination and deletion hypothesis for the control of isotype commitment in antibody responses was directly tested in a serial transfer system in vivo. Normal or hyperimmune spleen cells were used in weekly serial transfers with antigen into irradiated recipients until clonal senescence was observed. Antigen-specific and -nonspecific plaque-forming cells of all isotypes were determined at each transfer time. No major changes in the isotypes of specific antibodies were observed for the whole life-span of the transferred cells (9-10 wk), and no indication was obtained for the accumulation of cells transcribing the most 3' members of the C-gene cluster with sustained proliferation. Rather, the dominant isotypes were found throughout the response to be IgG1, IgG2b, and IgG2a. The results imply isotype-specific regulatory mechanisms in the control of Ig class production. These appear to operate as well in the antigen-nonspecific component of the immune response.

scholarly journals Cell interactions in the suppression of in vitro antibody responses.

1976 ◽  
Vol 143 (6) ◽  
pp. 1421-1428 ◽  
Author(s):  
C E Calkins ◽  
S Orbach-Arbouys ◽  
O Stutman ◽  
R K Gershon
Keyword(s):  
B Lymphocytes ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Antibody Responses ◽  
Secondary Antibody ◽  
Spleen Cells ◽  
Homeostatic Mechanism ◽  
Normal Spleen ◽  
Cells Cultured

Normal T and immune B lymphocytes interact in a fashion that leads to suppression of the immune response. Normal spleen cells added to cultures of primed spleen cells specifically suppressed both the IgM and IgG secondary antibody response of the primed cells to less than 30% of the response of the immune cells cultured alone. Cell crowding as a possible in vitro artifact was ruled out. The suppression was specific for the priming antigen, even when the specific and nonspecific antigens were included in the same cultures. Suppression required both normal T and immune B cells to be present in culture. We suggest that the immune population produces a signal that can induce normal T cells to become specific suppressor cells. This form of interaction may represent an important regulatory (homeostatic) mechanism in the immune system.

scholarly journals EFFECT OF RECENT ANTIGEN PRIMING ON ADOPTIVE IMMUNE RESPONSES

1974 ◽  
Vol 139 (1) ◽  
pp. 1-12 ◽  
Author(s):  
J. Sprent ◽  
J. F. A. P. Miller
Keyword(s):  
Lymph Node ◽  
Immune Responses ◽  
Mesenteric Lymph Node ◽  
Antibody Responses ◽  
The Other ◽  
Spleen Cells ◽  
Antigen Concentration ◽  
Short Term ◽  
Mesenteric Lymph ◽  
Circulating Lymphocytes

When thoracic duct lymphocytes (TDL) or mesenteric lymph node (MLN) cells from mice primed 1 day before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later could not be detected to the priming antigen but were high to the other antigen. Furthermore, this unresponsiveness of TDL and MLN to the priming antigen could not be abrogated by delaying antigen challenge of the transferred cells for 1–2 wk. Previous work had shown that short-term priming with antigen also induced specific unresponsiveness in spleen cells on adoptive transfer. Unresponsiveness in these cells, however, was only of temporary duration, full recovery in the reactivity of the cells being observed when challenge with the priming antigen on transfer was delayed for 5 or more days. Since the present work showed that such recovery from initial unresponsiveness on transfer was unique to spleen cells and did not apply to TDL or MLN, it appeared that different mechanisms were responsible for the unresponsiveness in the three populations. It is proposed that the unresponsiveness detected in TDL and MLN cells in the present study resulted from a deficiency of antigen-reactive cells, these cells having been recruited to the spleen, i.e., a region of antigen concentration. This concept of antigen-induced selective recruitment of circulating lymphocytes was supported by evidence that 51Cr-labeled heterologous erythrocytes indeed localized largely in the spleen after intravenous injection but not in MLN.

scholarly journals SELECTIVE ROLES OF THYMUS-DERIVED LYMPHOCYTES IN THE ANTIBODY RESPONSE

1974 ◽  
Vol 140 (1) ◽  
pp. 239-252 ◽  
Author(s):  
Tomio Tada ◽  
Toshitada Takemori
Keyword(s):  
T Cells ◽  
B Cells ◽  
Antibody Response ◽  
Suppressive Effect ◽  
Antibody Responses ◽  
Cell Transfer ◽  
Spleen Cells ◽  
Igg Antibody ◽  
Igm Antibody

Passively transferred thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) exerted differential suppressive effect on IgM and IgG antibody responses of syngeneic recipients immunized with DNP-KLH depending primarily on the time when KLH-primed cells were transferred. This was demonstrated by the decrease in the numbers of DNP-specific direct and indirect PFC in the spleen of the recipients given KLH-primed cells at different times during primary and secondary immunization. Whereas the cell transfer simultaneously with or 2 days after the primary immunization produced only slight suppression of the peak IgM antibody response, it caused profound suppression of late IgM and IgG antibody responses. By contrast, the cell transfer 3 days after the immunization produced immediate suppression of the ongoing IgM antibody response resulting in its earlier termination, while being unable to prevent the induction of IgG antibody response. KLH-primed cells could moderately suppress the secondary anti-DNP antibody response, in which IgG antibody response was found to be slightly more sensitive than IgM antibody response to the suppressive influence of KLH-primed cells. The suppressive effect of the KLH-primed spleen cells was completely eliminated by the in vitro treatment of the cells with anti-θ and C before cell transfer, indicating that cells responsible for the suppression are, in fact, T cells. The suppression of DNP-specific antibody response by KLH-primed T cells was achieved only if the recipients were immunized with DNP-KLH but not with DNP-heterologous carrier, suggesting that direct interaction between T and B cells is necessary for the suppression of the antibody response. It is concluded that susceptibility of B cells to the specific suppressive influence of T cells is inherently different depending on the differentiation stage of B cells and on the immunoglobulin class they are destined to produce.

scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1968 ◽  
Vol 128 (3) ◽  
pp. 437-457 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz ◽  
Mary St. James Connell ◽  
R. L. Priore
Keyword(s):  
Cellular Differentiation ◽  
Sheep Erythrocyte ◽  
Donor Cell ◽  
Cell Suspensions ◽  
Antibody Responses ◽  
Primary Immune Response ◽  
Cell Populations ◽  
Spleen Cells ◽  
Experimental Conditions ◽  
Antibody Class

Spleen cell suspensions of unprimed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice. In the presence of antigen (sheep erythrocytes) these precursors, called antigen-sensitive units, gave rise to progeny cells secreting specific antibody. We studied quantitatively the production of cells releasing IgM hemolysins (direct plaque-forming cells), IgG hemolysins (indirect plaque-forming cells), and hemagglutinins (cluster-forming cells). We found that each of these immunocyte populations was distinct, i.e., that cells releasing agglutinins did not, as a rule, release hemolysins, and vice versa. We also found that cell populations secreting IgM hemolysins did not shift, under certain experimental conditions, to the production of IgG hemolysins during the primary immune response. By transplanting graded numbers of spleen cells, we succeeded in limiting to one or a few the number of antigen-sensitive units that reached the recipient spleen. We estimated thereby the frequency of antigen-sensitive units in donor cell suspensions and tested their potential for production of immunocytes of more than one type. Our results indicated that antigen-sensitive units were unipotent for they displayed in the spleens of unprimed donors the same restrictions of function and heterogeneity (antibody-specificity differentiation, antibody-class differentiation) found among antibody-forming cells. Furthermore, antigen-sensitive precursors for direct plaque-forming cells, indirect plaque-forming cells, and cluster-forming cells were detected in the spleens of unprimed mice in different frequencies, i.e., 1 in ∼ 106, 1 in ∼ 7 x 106, and 1 in ∼ 19 x 106 spleen cells, respectively. We concluded that relatively advanced differentiation of potentially competent cells occurs before sheep erythrocyte administration. The relevance of this finding for the broad spectrum of immunologic reactivities and for the heterogeneity of antibody responses to given antigens was discussed.

scholarly journals ANTIBODY RESPONSES TO ANTIGENIC DETERMINANTS OF INFLUENZA VIRUS HEMAGGLUTININ

1974 ◽  
Vol 140 (6) ◽  
pp. 1571-1578 ◽  
Author(s):  
Jean-Louis Virelizier ◽  
Anthony C. Allison ◽  
Geoffrey C. Schild
Keyword(s):  
Influenza Virus ◽  
Antibody Responses ◽  
Secondary Response ◽  
Antigenic Determinants ◽  
Memory Cells ◽  
Spleen Cells ◽  
Experimental Conditions ◽  
Influenza Virus Hemagglutinin ◽  
Kinetics Of ◽  
Antibody Secretion

Mice immunized sequentially with two related influenza virus hemagglutinins (HA) produced a secondary antibody response with two different specificities. Some antibodies were specific for determinants common to both HA's. Paradoxically, some antibodies were directed to determinants existing only in the HA first encountered. Primed spleen cells treated with anti-θ serum and complement were transferred from animals immunized with the first HA to either normal, irradiated, or thymus-deprived recipients. These memory cells were boosted in the recipients with either the homologous or the heterologous cross-reacting HA. B-memory lymphocytes were shown to be directly triggered by both HA's and to be able to secrete, independently of T lymphocytes, antibodies to both kinds of determinants. However, T cells were shown to modulate this secondary response by either enhancing or suppressing antibody secretion by B-memory cells, depending on experimental conditions. These results are discussed in terms of antigen recognition by B cells and of kinetics of development of immunological memory.

scholarly journals SURFACE ANTIGENS OF IMMUNOCOMPETENT CELLS

1970 ◽  
Vol 132 (6) ◽  
pp. 1181-1190 ◽  
Author(s):  
T. Takahashi ◽  
E. A. Carswell ◽  
G. J. Thorbecke
Keyword(s):  
Immune Responses ◽  
Spleen Cell ◽  
Surface Antigens ◽  
Lymphoid Cells ◽  
Secondary Response ◽  
Cell Transfer ◽  
Spleen Cells ◽  
Antigen Present ◽  
Thymus Cells

Spleen cell transfer studies were done in BALB/c strain mice in an attempt to define the role of θ-antigen-bearing lymphoid cells in immune responses to SE. Incubation with alloantiserum to θ-C3H and rabbit C' virtually completely abolished the ability of the cells to transfer both primary and secondary (IgM and IgG) responses to 650 R irradiated recipients. Normal thymus cells partially reconstituted the ability of such treated cells to transfer the primary but not the secondary response. The results are interpreted as showing immunological memory for SE in the θ-bearing thymus-derived cells. Incubation of the spleen cells with alloantiserum to the PC.1 antigen present on antibody-forming cells did not significantly affect the ability to transfer either primary or secondary response.

scholarly journals IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (4) ◽  
pp. 921-938 ◽  
Author(s):  
Carl W. Pierce ◽  
Judith A. Kapp ◽  
Susan M. Solliday ◽  
Martin E. Dorf ◽  
Baruj Benacerraf
Keyword(s):  
Immune Responses ◽  
Lymphoid Cells ◽  
Antibody Responses ◽  
Current Understanding ◽  
Spleen Cells ◽  
Sheep Erythrocytes ◽  
Selective Suppression ◽  
D Region ◽  
Stimulate Antibody

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.

Immune responses during the acute stages of infection with the intestinal trematode Echinostoma caproni

Parasitology ◽  
2000 ◽  
Vol 120 (6) ◽  
pp. 565-571 ◽  
Author(s):  
L. R. BRUNET ◽  
S. JOSEPH ◽  
D. W. DUNNE ◽  
B. FRIED
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Humoral Response ◽  
Spleen Cells ◽  
Echinostoma Caproni ◽  
Th2 Cytokine ◽  
Mesenteric Lymph ◽  
Cytokine Pattern ◽  
Th1 Cytokine ◽  
Ifn Γ

This study investigated the nature of the immune response of C57BL/6 mice infected with the trematode Echinostoma caproni. To determine the preferential development of either a Th1 or Th2 cytokine pattern during early stages of infection, cytokine production by spleen and mesenteric lymph node (MLN) cells during the first 3 weeks of infection was followed. Whereas spleen cells failed to respond to antigen stimulation, MLN cells produced IFN-γ and to a lesser extent IL-4. IL-5 levels were elevated throughout the period studied. The humoral response was consistent with a Th1 cytokine pattern as antigen-specific IgG2a antibodies were preferentially developed. We investigated whether IFN-γ is critical for establishment of E. caproni infection. Worm burden in infected mice treated with a single injection of anti-IFN-γ mAb was significantly reduced compared to that of animals treated with a control antibody.

scholarly journals Efficiency of pH-Sensitive Fusogenic Polymer-Modified Liposomes as a Vaccine Carrier

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Shinobu Watarai ◽  
Tana Iwase ◽  
Tomoko Tajima ◽  
Eiji Yuba ◽  
Kenji Kono
Keyword(s):  
Immune Responses ◽  
Ph Sensitive ◽  
Antibody Responses ◽  
Antigen Delivery ◽  
Spleen Cells ◽  
Delivery Vehicle ◽  
Spleen Lymphocytes ◽  
Vaccine Carrier ◽  
Specific Mrna

The usefulness of pH-sensitive fusogenic polymer-(succinylated poly(glycidol)-(SucPG-) modified liposomes as a vaccine carrier in the induction of immune responses was evaluated. Mice were intraperitoneally immunized with ovalbumin- (OVA-) containing SucPG-modified liposomes. After immunization, significant OVA-specific antibodies were detected in the serum. When sera were analyzed for isotype distribution, OVA-specific IgG1 antibody responses were noted in mice immunized with OVA-containing polymer-unmodified liposomes, whereas immunization with OVA-containing SucPG-modified liposomes resulted in the induction of OVA-specific IgG1, IgG2a, and IgG3 Ab responses. In spleen lymphocytes from mice immunized with OVA-containing SucPG-modified liposomes, both IFN-γ-(Th1-type-) and IL-4-(Th2 type-) specific mRNA were detected. Moreover, substantial production of IFN-γand IL-4 was demonstrated in spleen cells from OVA-containing SucPG-modified liposomesin vitro. These results suggest that the pH-sensitive fusogenic polymer-(SucPG-) modified liposomes would serve effectively as an antigen delivery vehicle for inducing Th1 and Th2 immune responses.

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