Showing papers on "Antigen processing published in 1973"
TL;DR: It is postulate that T lymphocytes are best triggered by cell-bound antigen and that after this step the activated T lymphocyte regulate the triggering of B cells with antigen.
Abstract: A detailed analysis of the role of determinant presentation in the process of triggering immunocompetent lymphocytes has been made utilizing cell-bound hapten-carrier conjugates to elicit secondary antihapten antibody responses, primarily in vitro. The results of these experiments demonstrate that: (a) hapten-protein conjugates will attach to the surface membranes of macrophages directly, in the absence of specific antibodies, in a highly immunogenic form; (b) such macrophage-bound conjugates serve as remarkedly efficient stimuli to trigger both thymus-derived (T) and bone marrow-derived (B) cells in a specific manner, lowering the optimal threshold antigen dose (in molar terms) by several logs as compared with soluble antigen; (c) the macrophage is not unique in this regard, since fibroblasts are essentially comparable in the capacity to present antigen in highly immunogenic form; (d) cell surface-bound antigen clearly favors secondary in vitro responses of the IgG as compared with the IgM antibody class; (e) in terms of triggering B or T cells, antigen bound to macrophages in the form of immune complexes does not appear to possess any appreciable advantage over equimolar quantities of directly attached antigen; (f) the increased immunogenicity of cell-bound antigen appears to reflect certain crucial, and undefined, features of cell surface membranes and not merely the stabilization of determinants on a relatively immobile surface; and (g) although the efficiency of lymphocyte triggering is markedly enhanced by cell-bound antigen, the presence of macrophages is apparently not an absolute requirement for eliciting secondary in vitro antibody responses to soluble hapten-protein conjugates. The relevance of these observations to the nature of the signal induced upon antigen interaction by specific lymphocytes and the sequential cellular events involved in the regulatory influence of activated T cells on B cell responses to antigen is discussed. We postulate that T lymphocytes are best triggered by cell-bound antigen and that after this step the activated T lymphocytes regulate the triggering of B cells with antigen.
161 citations
TL;DR: “Antigen binding” and “antigen processing” cells are discussed, which may potentially comprise all cells capable of phagocytosis or pinocytotic.
Abstract: Before discussing the topic on “antigen binding” and “antigen processing” cells, let us first define what we mean by these two terms:
1.
Antigen recognizing cells:
There are two main categories of cells which may recognize antigen: first, immunocompetent lymphocytes which bind antigen by means of actively synthesized receptors. These cells are believed to be clonally diverse with respect to the conformational specificity of their receptors for antigenic determinants.
A second main category of cells binds antigen passively via membrane adsorbed mediator substances, such as antibody (1) or complement. (2) Thus antigen may be bound by antibody to cells of the reticuloendothelial system, such as macrophages and reticulum cells. Antigen binding to a subpopulation of B-lymphocytes via complement factor C3 and antibody is a phenomenon of great interest the significance of which is yet unclear.
2.
Antigen processing cells:
Antigen processing cells may potentially comprise all cells capable of phagocytosis or pinocytosis.
4 citations
TL;DR: The recent work on the nature of retained antigen in lymph nodes and spleen showed that antigen at five hours after intravenous injection into rabbits was either partially degraded or unchanged, however, a small but significant amount of radioactivity was associated with cellular components to give high molecular weight complexes.
Abstract: The processing of an immunogenic molecule and the importance of this metabolic fate of foreign material in antibody synthesis, since Campbell * pointed out in 1957, have gained much attention not only from the standpoint of localization and retention, but also with respect to whether or not the activity depends upon retention of the native configuration or upon a modified form. The knowledge of whether or not the manner in which an immunogenic material is processed in vivo that could determine the ultimate nature of the host's reaction as to what type of immunity will be induced, for example, humoral or cellular, is of importance for understanding the basic mechanism of immune response. It is generally agreed that radioactive antigen, after injection, is commonly found in the liver, spleen, lung, lymph nodes, and the kidney, but little is known about the nature of the retained antigen material. Is it the original antigen, fragmented antigen, or processed antigen that differs from the original antigen? In particular, the question concerns the immunological activity of these retained antigens. Since methods of using organic solvents for the preparation of nucleic acids became available, attention was focused on the role of RNA in immunity. The transfer of immunity to skin homografts from one animal to another by crude RNA preparations from lymph nodes of sensitized animals was reported by Mannick and Egdal.' The RNA preparations containing radioactive antigen were reported 3 9 . ) to be found in liver and in urine of immunized rabbits. Later, Fishman and Adlers showed that there are two types of RNA responsible for the induction of antibody synthesis, one type of RNA was found to lack antigen, and the other RNA fraction is complexed with antigen. There is accumulating evidence that antigen-RNA plays an important role in antibody synthesis,GR but the precise role of these complexes in triggering a sequence of events in motion that finally lead to the appearance of antibody still remain obscure. Our recent work on the nature of retained antigen in lymph nodes and spleen showed that antigen, sulfanilate ( 36S)-azo-bovine serum albumin ( 35SBSA), at five hours after intravenous (i.v.) injection into rabbits was either partially degraded or unchanged. However, a small but significant amount of radioactivity was associated with cellular components to give high molecular weight complexes. Perhaps the most interesting finding of our studies was the highly degraded antigen fragments which conjugate to oligoribonucleotides
3 citations
TL;DR: Injections of antigen in less than 1 PCU causes plasma cells to decrease in number, and interrelation between antigen and plasma cells changes with time in different regions of the lymphatic system.
Abstract: The cellular activity of an antigen is understood as its power to cause plasma cells to accumulate in the regional lymph node. Two plasma cell units (PCU) is the dose causing one plasma cell addition (as compared with the “background”), whereas 1 PCU causes neither increase nor decrease in plasma cell number in the regional lymph node. Injections of antigen in less than 1 PCU causes plasma cells to decrease in number. Interrelation between antigen and plasma cells changes with time in different regions of the lymphatic system.
TL;DR: It is concluded that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.
Abstract: A number of recent studies have suggested that the main functional role of the product of the immune response (Ir) genes is in the process of antigen recognition by the T lymphocyte. The observation in the accompanying report that the interaction of macrophage-associated antigen with immune T lymphocytes requires that both cells share histocompatibility antigens raised the question as to whether the macrophage played a role in the genetic control of the immune response or even if the macrophage were the primary cell in which the product of the Ir gene is expressed. In the current study, parental macrophages were pulsed with an antigen, the response to which is controlled by an Ir gene lacking in that parent; these macrophages were then mixed with T cells derived from the (nonresponder x responder)F1 and the resultant stimulation was measured. No stimulation was seen when column-purified F1 lymph node lymphocytes were mixed with antigen-pulsed macrophages from the nonresponder parent. However, when the highly reactive peritoneal exudate lymphocyte population was used as the indicator cells, parental macrophages pulsed with an antigen whose Ir gene they lacked were capable of initiating F1 T-cell proliferation. The magnitude of stimulation was approximately 1/10 that seen when macrophages from either the responder parent or the F1 were used. In order to explain this observation, we hypothesize that antigen recognition sites on the T lymphocyte are physically related to a macrophage-binding site and both are linked to the serologically determined histocompatibility antigens. Thus, parental macrophages pulsed with an antigen, whose Ir gene they lack, activate F1 cells poorly because the recognition sites for the antigen are physically related to the macrophage-binding site of the responder parent while the main contacts between the cells are at the nonresponder binding sites. Experiments performed with alloantisera lend support to this hypothesis. Thus, when parental macrophages are pulsed with any antigen and added to F1 T cells, an alloantiserum directed against parental histocompatibility antigens reacts with both the lymphocyte and the macrophage and thereby inhibits macrophage-lymphocyte interaction and abolishes antigen-induced lymphocyte transformation. When the alloantisera are directed at determinants present solely on the T lymphocyte, they only inhibit the recognition of antigens controlled by the Ir gene linked to the histocompatibility antigen against which they are directed. We conclude from these studies that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.