Benutzer:Anjen0815/Transplantationsimmunologie
Die Transplantationsimmunologie ist ein Teilgebiet der Immunologie. Sie beschäftigt sich mit den immunologischen Vorgängen, die an der Abstossung oder der Akzeptanz von Transplantaten beteiligt sind. Als Grundlage für die Transplantationsimmunologie gilt die vom späteren Nobelpreisträger Joseph Edward Murray[1] 1954 erste erfolgreiche Organtransplantation bei eineigen Zwillingen, bei der keine immunologische Abstossungsreaktion auftrat. Alle kernhaltigen menschlichen (und tierischen) Zellen exprimieren Zelloberflächenmoleküle, genannt Haupthistokompatibilitätskomplex (Abk. MHC vom engl. Major Histocompatibility Complex) von denen verschiedene Genvarianten, Allele genannt, existieren. Von den MHC-Molekülen gibt es Klasse I und II und bei Menschen heißen MHC-Moleküle auch HLA (Abk. vom engl. human leukocyte antigen). Die Anzahl an nicht zu einander passenden Allelen von Organspender zu Organempfänger korreliert mit der Geschwindigkeit und Schwere der Transplantatabstoßung.
Ziel der Transplantationsimmunologie
[Bearbeiten | Quelltext bearbeiten]Immunologic mechanisms of rejection
Rejection is an adaptive immune response via cellular immunity (mediated by killer T cells inducing apoptosis of target cells) as well as humoral immunity (mediated by activated B cells secreting antibody molecules), though the action is joined by components of innate immune response (phagocytes and soluble immune proteins). Different types of transplanted tissues tend to favor different balances of rejection mechanisms. Immunization
An animal's exposure to the antigens of a different member of the same or similar species is allostimulation, and the tissue is allogenic. Transplanted organs are often acquired from a cadaver (usually a host who had succumbed to trauma), whose tissues had already sustained ischemia or inflammation.
Dendritic cells (DCs), which are the primary antigen-presenting cells (APCs), of the donor tissue migrate to the recipient's peripheral lymphoid tissue (lymphoid follicles and lymph nodes), and present the donor's self peptides to the recipient's lymphocytes (immune cells residing in lymphoid tissues). Lymphocytes include two classes that enact adaptive immunity, also called specific immunity. Lymphocytes of specific immunity T cells—including the subclasses helper T cells and killer T cells—and B cells.
The recipient's helper T cells coordinate specific immunity directed at the donor's self peptides or at the donor's Major histocompatibility complex molecules, or at both. Immune memory
When memory helper T cells' CD4 receptors bind to the MHC class II molecules which are expressed on the surfaces of the target cells of the graft tissue, the memory helper T cells' T cell receptors (TCRs) can recognize their target antigen that is presented by the MHC class II molecules. The memory helper T cell subsequently produces clones that, as effector cells, secrete immune signalling molecules (cytokines) in approximately the cytokine balance that had prevailed at the memory helper T cell's priming to memorize the antigen. As the priming event in this instance occurred amid inflammation, the immune memory is pro-inflammatory. Cellular immunity
As a cell is indicated by the prefix cyto, a cytotoxic influence destroys the cell. Alloreactive killer T cells, also called cytotoxic T lymphocytes (CTLs), have CD8 receptors that dock to the transplanted tissue's MHC class I molecules,which display the donor's self peptides. (In the living donor, such presentation of self antigens helped maintain self tolerance.) Thereupon, the T cell receptors (TCRs) of the killer T cells recognize their matching epitope, and trigger the target cell's programmed cell death by apoptosis. Humoral immunity
Developed through an earlier primary exposure that primed specific immunity to the nonself antigen, a transplant recipient can have specific antibody crossreacting with the donor tissue upon the transplant event, a secondary exposure. This is typical after earlier mismatching among A/B/O blood types during blood transfusion. At this secondary exposure, these crossreactive antibody molecules interact with aspects of innate immunity—soluble immune proteins called complement and innate immune cells called phagocytes—which inflames and destroys the transplanted tissue. Antibody
Secreted by an activated B cell, then called plasma cell, an antibody molecule is a soluble immunoglobulin (Ig) whose basic unit is shaped like the letter Y: the two arms are the Fab regions, while the single stalk is the Fc region. Each of the two tips of Fab region is the paratope, which binds a matching molecular sequence and its 3D shape (conformation), altogether called epitope, within the target antigen. Opsonization
The IgG's Fc region also enables opsonization by a phagocyte, a process by which the Fc receptor on the phagocyte—such as neutrophils in blood and macrophages in tissues—binds the antibody molecule's FC stalk, and the phagocyte exhibits enhanced uptake of the antigen, attached to the antibody molecule's Fab region. Complement cascade
When the paratope of Ig class gamma (IgG) binds its matching epitope, IgG's Fc region conformationally shifts and can host a complement protein, initiating the complement cascade that terminates by punching a hole in a cell membrane. With many holes so punched, fluid rushes into the cell and ruptures it.
Cell debris can be recognized as damage associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), on membranes of phagocytes, which thereupon secrete proinflammatory cytokines, recruiting more phagocytes to traffic to the area by sensing the concentration gradient of the secreted cytokines (chemotaxis).
- ↑ Transplant doc, Nobel winner Murray dies in Boston. Abgerufen am 27. November 2012 (englisch).