MICB 212 Chapter 16 Notes

Graft Rejection and Transplantation

-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

Organ Rejection

Host vs Graft Disease

-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

Summary

-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

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