Shawk Transplantation After reading this chapter you should be able to describe your current understanding to transplantation discuss some of the characteristics of the most commonly transplanted tissues ID: 935739
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Slide1
2021-2022Dr. Refif S. Al-Shawk
Transplantation
After reading this chapter, you should be able to:
describe your current understanding to transplantation
discuss some of the characteristics of the most commonly transplanted tissues
understanding of primary and secondary immune responses to create a sequence for the immune events that occur during the sensitization and effector phases of allograft rejection
discuccs
the immunologic processes governing graft rejection
Slide2Transplantation: the process of taking cells, tissues, or organs from one individual and placing them into a different individual or different site of the same individual
Graft: transplanted cells, tissues, or organs.
Donor:
the individual who provides the graft.
Recipient:
the individual who receives the graft. Also called the host.
Slide3Different types of transplants:
Autograft
Self tissue transferred from one part of body to another(
skin,blood
vessel)
Isograft
Tissue transferred between genetically identical individuals(
syngeneic
)
Allograft
Tissue transferred between genetically different members of same species
Most of our transplants
Xenograft
Tissue transferred between different species
{Antigenic similarity between donor and recipient improves transplant success}
Slide4Slide5Transplantation of cells or tissues from one individual to a genetically non-identical individual invariably leads to rejection of the transplant due to an
adaptive immune response.
Slide6Major
histocompatibility antigens (MHC molecules) are expressed on all nucleated cells (class I) and on B cells APC,cells
,
monocytes
/macrophages (class II) They are targets for rejection,Minor histocompatibility antigens: They are peptides derived from polymorphic cellular proteins bound to MHC class I moleculesOther alloantigens :Human ABO blood group antigens and Some tissue specific antigens
ADAPTIVE IMMUNE RESPONSES TO ALLOGRAFTS
What is the target for rejection?
Slide7Schematic diagrams of the process of graft acceptance and rejection.
(Specificity & Memory)
Slide8Recognition of Alloantigens by T Cells
Allogeneic MHC molecules of a graft can be presented
for recognition by the recipient’s T cells in two different ways:
Direct presentation (or direct recognition) of
alloantigens.In the case of direct recognition, intact MHC molecules displayed by cells in the graft are recognized by recipient T cells without a need for processing by host APCs.Direct allorecognition can generate both CD4+ and CD8+ T cells that recognize graft antigens and contribute to rejection.
Indirect Recognition of
Alloantigens
In the indirect pathway, donor (allogeneic) MHC molecules are captured and processed by recipient APCs, and peptides derived from the allogeneic MHC molecules are presented in association with self MHC molecules
Indirect presentation may result in allorecognition by CD4+ T cells because
alloantigens
are acquired by host APCs primarily through the endosomal vesicular pathway (i.e., as a consequence of phagocytosis) and are therefore presented by class II MHC molecules.
Slide9Slide10Activation and Effector Functions of Alloreactive T Lymphocytes
When lymphocytes recognize alloantigens, they become activated to proliferate, differentiate, and perform effector functions that can damage grafts. Through:
1)sensitization
2)Effector Functions
of Alloreactive T Cells
Slide11Sensitization
Doner APCs express donor MHC molecules as well as costimulators. migrate to regional lymph nodes and present, on their surface, unprocessed allogeneic MHC molecules to the recipient’s T cells
or
Host dendritic cells from the recipient may also migrate into the graft, pick up graft alloantigens, and transport these back to the draining lymph nodes, where they are displayed
Slide12Slide132) Effector Functions of Alloreactive T Cells(Alloreactive CD4+ and CD8+ T cells) and B cells that are activated by graft alloantigens cause rejection by distinct mechanisms
CD8+ CTLs that are generated by direct
allorecognition of donor MHC molecules on donor APCs can recognize the same MHC molecules on parenchymal cells in the graft and kill those cells by CTL-mediated killing of graft cells.CD8+ CTLs that are generated by the indirect pathway are self MHC restricted, and they will not be able to kill the foreign graft cells because these cells do not express self MHC alleles displaying allogeneic peptides. both CTLs and helper T cells generated by either direct or indirect alloantigen recognition can cause cytokine-mediated damage to grafts.
(the principal mechanism of rejection is
inflammation caused by the cytokines produced by the effector T cells
.
Slide14Activation of Alloreactive B Cells and Production and Functions of Alloantibodies.
Antibodies against graft antigens also contribute to rejection.
Most high-affinity alloantibodies are produced by helper
T cell–dependent activation
of alloreactive B cells, much like antibodies against other protein antigens(donor HLA molecules, including both class I and class II MHC proteins).Engage effector mechanisms, including complement activation
, and targeting and activation of
neutrophils
,
macrophages
, and
NK
cells through Fc receptor binding.
Slide15Slide16Clinical Manifestations of Graft Rejections: different classes of allograft rejection phenomena are classified according to their time of activation & the type of
effector mechanism that predominates. These are:
Hyperacute
Within
hours: Hyperacute rejection is characterized by thrombotic occlusion of the graft vasculature that begins within minutes to hours after host blood vessels are anastomosed (joined) to graft vessels and is mediated by preexisting antibodies in the host circulation that bind to donor endothelial antigens
Slide17Clinical Manifestations of Graft Rejection
Hyperacute
Pre-existing recipient antibodies
Graft never become vascularized
Slide18AcuteWithin weeks:
Acute rejection is a process of injury to the graft parenchyma and blood vessels mediated by alloreactive T cells and antibodies.Acute Cellular Rejection
:The principal mechanisms of acute cellular rejection are
inflammation
caused by cytokines produced by helper T cells and CTL-mediated killing of graft parenchymal cells and endothelial cells Acute Antibody-Mediated Rejection: Alloantibodies cause acute rejection by binding to alloantigens, mainly HLA molecules, on vascular endothelial cells, causing endothelial injury and intravascular thrombosis that results in graft destruction
Slide19Slide20Chronic As therapy for acute rejection has improved, the major cause of the failure of vascularized organ allografts has become chronic rejection.
A dominant lesion of chronic rejection in vascularized grafts is arterial occlusion
as a result of the proliferation of intimal smooth muscle cells, and the grafts eventually fail mainly because of the resulting ischemic damage HOW?
Months to years . Due to various mechanisms: cell-mediated, deposition of antibodies or antigen antibody complexes with subsequent obliteration of blood vessels and interstitial fibrosis
Slide21What is graft versus Host Reaction ?
When grafted tissue has mature T cells, they will attack host tissue leading to GVHR.Major problem for bone marrow transplant.
Because it is the source of
pluripotent
hematopoietic stem cells, it can be used to reconstitute myeloid, erythroid, & lymphoid cells in a recipient who has lost these cells as a result of malignancy or chemotherapeutic regimens. Because B.M. is a source of some mature T lymphocytes, it is necessary to remove these cells before transplantation to avoid the appearance of graft-versus-host disease in the recipient. In this special case of rejection, any mature T cells remaining in the B.M. inoculums can attack allogeneic MHC-bearing cells of the recipient & cause widespread epithelial cell death accompanied by rash, jaundice, diarrhea, & gastrointestinal hemorrhage.
Slide22GVHD – Graft versus Host Disease, watch this video:
https://www.youtube.com/watch?v=Rmx11JpKLGA
Slide23Slide24References :Immunology , Kuby, eighth edition 2019
Cellular and Molecular Immunology, Abul K. Abbas, 8th edition.