grafting/transplants - immunology

• grafting refers to the transfer of tissues or organs from donor to patient
• grafting procedures aim to replace or repair damaged or non-functional tissues in the recipients body
• various types of graft/transplant methods:

  • autograft
  • allograft
  • xenograft
  • isograft
• autograft - transfer of tissue from one site to another within the same individual
• autografts are most commonly used in those who are burn victims and this procedure has the lowest likeliness for rejection
• allograft - transplant/graft between individuals of the same species with different genetic make ups
• mojority of organ transplants count as allografts
• in allografts organ/tissue comes from genetically different but immunogically compatible donor
• xenograft - transfer of organ/tissue between different species
• xenografts have high rejection rates due to immunological barriers
• isograft - transfer between genetically identical individuals i.e. identical twins
• synthetic grafts are also known as artificial grafts
• synthetic grafts involve the use of man -made materials rather than biological materials
• synthetic materials may be used in procedures such as vascular grafts or artificial joint replacement
• composite tissue transplantation - the transplantation of multiple tissues or structures such as the face or hand which involves the transplant of various nerve, skin, muscle and bone tissues
• graft rejection occurs when the hosts immune system recognises the gaft as foreign, triggering an immune response
• graft rejection involves both cellular and humoral immune responses
• types of graft rejection:

  • hyperacute
  • acute
  • chronic
• hyperacute rejection is immediate and severe form of rejection occuring within minutes to hours of the transplantation
• hyperacute rejection occurs due to pre-existing antibodies going against donor antigens, leading to rapid blood clotting in the graft's blood vessels
• hyperacute rejection can lead to necrosis
• necrosis - cell death caused by lack of oxygen or other toxins
• acute rejection is the most common type occuring within days to months post-transplantation
• acute rejection is primarily t-cell mediated response involving the recognition of donor antigens as foreign
• acute rejection can lead to the inflammation and damage of the tissue
• chronic rejection is slow and progressive occuring over months to years post-transplantation
• immunological mechanisms:

  • MHC - major histocompatibility complex
  • antibody mediated reaction
  • cell response
• main target for immune response after graft rejections is MHCs on the donor cells
• during graft rejection, disparities in MHC molecules are the main reason drivers of the graft rejection
• post-transplant, the host T-cells recognise the foreign MHCs on the donor tissue, activating and carrying out am immune response as a result leading to the destruction of the graft
• stratergies to minimise graft rejection:

  • matching donor and recipient
  • immunosuppresive drugs
  • tolerance induction
• to minimise graft rejection, improving matching of the donor and recipent tissues can reduce the likelihood of rejection of the donor tissue as the MHCs are less likeliy to be detected as foreign
• to minimise graft rejection but giving the recipient immunosuppresant drugs it can prevent rejection
• Commonly used immunosuppresants include calcineurin inhibitors anf corticosteroids
• inducing tolerance in the recipient to the transplant tissue has been considered a way to reduce rejection and does not require the long-term need of immunosuppression
• inducing tolerance is still being researched today
• compatibility testing for grafting and transplants:

  • histocompatibility testing
  • crossmatching
  • blood type matching
  • PRA testing - panel reactive antibody
• HLA - human leukocyte antigen
• HLA testing determines the compatibility between donor and recipient and the likelihood of rejection - the closer the match the lower the risk of rejection
• HLA testing evaluates specific types of proteins on the cell surface that regulates the immune system's response