The Serum Hemolysin Response in Intact and Splenectomized Rabbits following Immunization by Various Routes

Draper, Laurence R.; Sussdorf, Dieter H.

doi:10.1093/infdis/100.2.147

“…Some investigators have concluded that anti-endotoxin antibodies represent the primary underlying mechanism (1); others have concluded that they play no demonstrable role (2)(3)(4)(5)(6). It is well establislhed that when small quantities of insoluble anti-gens are administered i.v., the spleen constitutes the major site of antibody formation, particularly during the initial week of immunization (7)(8)(9). Since these are the conditions under which endotoxin tolerance is generally studied, splenectomy was employed in the present investigations as a means of suppressing anti-endotoxin antibodv production.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of endotoxin tolerance. The role of the spleen.

Greisman¹,

Young²,

Workman³

et al. 1975

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A B S T R A C T Splenectomy markedly impaired the production of circulating anti-endotoxin antibodies during the initial 10 days after i.v. administration of a Boivin preparation of Escherichia coli endotoxin (ET) lated to fall between 1/10 and 1/100 of those used in the splenectomized subjects. The impairment of latephase pyrogenic tolerance after splenectomy appeared to be the result of the concomitant suppression of antiendotoxin antibody production rather than the loss of splenic reticuloendothelium required to clear and inactivate the ET. This was evidenced by: (a) the significant retardation in appearance of humoral factors in the splenectomized rabbits capable of transferring high levels of specific tolerance; (b) the inability to impair the late phase of tolerance in human volunteers with intact spleens until the immunizing doses of endotoxin were reduced to levels that virtually eliminated circulating anti-endotoxin antibody production; (c) the unimpaired development of tolerance in partially hepatectomized rabbits lacking more functional reticuloendothelium than splenectomized animals, but capable of normal anti-endotoxin antibody synthesis.

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“…Attempts to resolve this problem are under way, and therefore one can only speculate. Since antibody formation can be elicited primarily in cells in the thymus (11), spleen (12)(13)(14), or draining lymph node (15)(16)(17)(18)(19)(20), depending on the route of administration of the antigen (intrathymic, intravenous, and foot pad, respectively), it would appear that the potential AFC already reside in the lymphoid organs, and that the presence of antigen at these sites constitutes one of the determining factors concerned with the initiation of the local immune response. Recent findings (3-7) indicate that the committed antigen-reactive cells (ARC) vacate the bone marrow following interaction with the antigen (activated antigen-reactive cells) and migrate to one or more of the lymphoid organs, where they probably transfer activated antigen to the antibody-forming cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cells involved in the immune response: XI. Identification of the antigen-reactive cell as the tolerant cell in the immunologically tolerant rabbit

Abdou¹,

Richter²

1970

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Previous investigations have disclosed that normal allogeneie bone marrow cells can transfer antibody-forming capacity to irradiated rabbits (1-5). On the other hand, "primed" bone marrow (bone marrow obtained from a donor rabbit 24 hr following intravenous administration of the specific antigen) could not transfer antibodyforming capacity to the antigen with which the marrow donor had been immunized, but could transfer immunocompetence to other antigens (3, 4). It was also demonstrated that the antibody-forming cell in the marrow recipient is of host, not donor, origin (5), thus supporting the conclusion that the immunoeompetent cell in the bone marrow is the antigen-reactive cell and that the bone marrow does not contain any antibody-forming cells (4--7). Furthermore, it was demonstrated that antigenreactive cells, isolated by passage of the normal bone marrow cell suspension through an antigen-sensitized glass bead colnmn, followed by elution of retained cells from the column (eluate), could transfer antibody-forming capacity to an irradiated rabbit, but only toward the antigen used to sensitize the glass beads (2). In contrast, the cells which passed through the antigen-sensitized glass bead column (effluent) lost the capacity to transfer immtmoeompetence with respect to the antigen used to sensitize the beads, but not with respect to other non-cross-reacting antigens (2).These findings suggested a means of indentifying which of the cell types concerned with the mediation of the humoral immune response in the rabbit--the antigen-reactive cell or the antibody-forming ceil--is the tolerant cell in the immunologicaily tolerant rabbit. As shown below, it would appear that the antigen-reactive cell is the one which is unresponsive in the latter animal. Materials and MethodsNew Zealand white rabbits were used throughout this study. The antigens used were human serum albumin (HSA) (Ityland Laboratories, Los Angeles, Calif.) and bovine gamma

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“…Attempts to resolve this problem are under way, and therefore one can only speculate. Since antibody formation can be elicited primarily in cells in the thymus (11), spleen (12)(13)(14), or draining lymph node (15)(16)(17)(18)(19)(20), depending on the route of administration of the antigen (intrathymic, intravenous, and foot pad, respectively), it would appear that the potential AFC already reside in the lymphoid organs, and that the presence of antigen at these sites constitutes one of the determining factors concerned with the initiation of the local immune response. Recent findings (3-7) indicate that the committed antigen-reactive cells (ARC) vacate the bone marrow following interaction with the antigen (activated antigen-reactive cells) and migrate to one or more of the lymphoid organs, where they probably transfer activated antigen to the antibody-forming cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cells Involved in the Immune Response

Abdou

¹

,

Richter

²

1969

The Journal of Experimental Medicine

7

0

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Previous investigations have disclosed that normal allogeneie bone marrow cells can transfer antibody-forming capacity to irradiated rabbits (1-5). On the other hand, "primed" bone marrow (bone marrow obtained from a donor rabbit 24 hr following intravenous administration of the specific antigen) could not transfer antibodyforming capacity to the antigen with which the marrow donor had been immunized, but could transfer immunocompetence to other antigens (3, 4). It was also demonstrated that the antibody-forming cell in the marrow recipient is of host, not donor, origin (5), thus supporting the conclusion that the immunoeompetent cell in the bone marrow is the antigen-reactive cell and that the bone marrow does not contain any antibody-forming cells (4--7). Furthermore, it was demonstrated that antigenreactive cells, isolated by passage of the normal bone marrow cell suspension through an antigen-sensitized glass bead colnmn, followed by elution of retained cells from the column (eluate), could transfer antibody-forming capacity to an irradiated rabbit, but only toward the antigen used to sensitize the glass beads (2). In contrast, the cells which passed through the antigen-sensitized glass bead column (effluent) lost the capacity to transfer immtmoeompetence with respect to the antigen used to sensitize the beads, but not with respect to other non-cross-reacting antigens (2).These findings suggested a means of indentifying which of the cell types concerned with the mediation of the humoral immune response in the rabbit--the antigen-reactive cell or the antibody-forming ceil--is the tolerant cell in the immunologicaily tolerant rabbit. As shown below, it would appear that the antigen-reactive cell is the one which is unresponsive in the latter animal. Materials and MethodsNew Zealand white rabbits were used throughout this study. The antigens used were human serum albumin (HSA) (Ityland Laboratories, Los Angeles, Calif.) and bovine gamma

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The Serum Hemolysin Response in Intact and Splenectomized Rabbits following Immunization by Various Routes

Cited by 21 publications

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Mechanisms of endotoxin tolerance. The role of the spleen.

Mechanisms of endotoxin tolerance. The role of the spleen.

Cells involved in the immune response: XI. Identification of the antigen-reactive cell as the tolerant cell in the immunologically tolerant rabbit

Cells Involved in the Immune Response

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