-transplantation involves removal of organ, tissue or hematopoietic stem cells from a donor and placed into body of recipient
Autograft
organ, tissue or hematopoietic stem cells is transplanted within same person’s body
ex: veins from leg in a heart bypass surgery
Allograft
organ, tissue or hematopoietic stem cells harvested from one individual and placed into body of a different individual
alleles of MHC proteins on donor graft not normally present in recipient’s body (non-self-antigens)
recipient may have T cells that bind strongly to these foreign MHC proteins on the transplanted person
during negative selection process
T cells that bind to self MHC proteins too strongly are eliminated to avoid an immune response against own tissues
possible that both T helper cells and naive CTLs have TCRs that bind to foreign MHC proteins on transplanted organ or tissue very strongly and induce an immune response against them → host vs graft disease
if hematopoietic stem cells are transplanted into a recipient’s body with allograft → transplanted immune cells might recognize host’s MHC as foreign and mount an immune response against host’s cells, tissues, organs → graft vs host disease
-organs that have been successfully transplanted include
heart
kidney
liver
lungs
pancrease
intestine
thymus
uterus
-tissues that have been successfully transplanted are
bones
tendons
corneae
skin
heart valves
nerves
veins
-different people have different versions of MHC proteins on their cells
in transplantation → transplanted organs/tissues/hematopoietic cells from donor may have different proteins than those of recipient
-occurs when recipient’s T cells mount an attack against the donor organ
-activation of T helper cells has consequences
T helper cells infiltrate into graft → recruit and activate macrophages
activated macrophages secrete proteases and other inflammatory mediators that damage the graft
activated T helper cells also provide IL-2 that aids in activation of CTLs
-activated T helper cells also provide cytokine support to activated B cells that recognize foreign-MHC proteins
these B cells differentiate into plasma cells that secrete antibodies that bind to foreign cells
complement cascade is activated and membrane attack complex kills foreign cells
-CTLs that recognizes the foreign MHC class I proteins become activated CTLs and kills transplanted cells → graft rejection
-to improve chances of a successful transplant
donors are HLA matched as closely as possible to recipient
-identical twin is the best donor since all their genes are identical
grafts from identical twins are almost always accepted
close relative is the next choice since they have an increased likelihood of shared MHC alleles
-if there are differences in MHC alleles between donated tissue and recipient
necessary to prevent T cells from getting activated
use drugs — Cyclosporin A — to suppress T cell function
increases risk of viral infections since ability to kill virus-infected cells is also suppressed
Indirect Allorecognition
antigen presenting cells (APCs) from recipient take up and process MHC proteins from transplanted organ/tissue
recipient T cells recognize the presented peptide as foreign and mount a response
Direct Allorecognition
T cells become activated against graft through action of donor-derived antigen presenting cells
transplanted into recipient with donated organ
once in recipient’s body → donor-derived antigen presenting cells are able to move out of transplanted organ and interact with recipient’s T cells
recipient T cells recognize MHC proteins on these donor derived APCs as foreign and react strongly
-successful organ transplantation is dependent on host’s immune system accepting the organ or tissue
-matching MHC proteins are important for minimizing rejection of foreign grafts in recipient
-besides matching MHC proteins, other ways to improve graft acceptance are
drugs that suppress T cell function (cyclosporin A)
healthier and less damaged organs
better surgery techniques