TID Flashcards
What was the first transplanted material?
→cornea
What is the difference between autologous and syngeneic donor relationships?
→autologous= within same individual →syngeneic= donor with a genetically identical
What is allogenic transplant?
→Donors and recipients are from the same species but genetically different
What is xenogeneic transplant?
→Donor and recipient are different species
What are immune responses to transplant mainly due to?
→differences the antigens forming the major histocompatibility complex
Where are HLA genes found?
→chromosome 6
What may be foreign in transplants?
→both the MHC protein and the peptide in its binding groove may be foreign
What is the outcome of indirect allorecognition of self HLA and non-self peptide?
→Tcell activation
What is the outcome of direct allo-recognition of non-self HLA in a donor cell?
→Unmatched HLA + peptide = T-cell activation
What needs to be matched to reduce likelihood of problems with transplants?
→match 4/6 MHC class II loci
Compare live and dead donors
→Organs from deceased donors are also likely to be in inflamed condition due to ischemia
→Transplant success is less sensitive to MHC mismatch for live donors
What are the types pf graft rejections?
→Hyperacute rejection
→Acute rejection
→Chronic rejection
When does hyperacute rejection occur?
→Within a few hours of transplant
What type of transplants commonly see hyperacute rejection?
→highly vascularised organs (e.g. kidney)
What is the blood group implicated in hyperacute rejection?
→ABO
→MHC-I
How can antibodies to MHC arise?
→pregnancy
→blood transfusion or previous transplants
How do antibodies cause damage to transplanted tissue?
→Recognition of Fc region leading to -
→Complement activation
→Antibody dependent cellular cytotoxicity -(Fc Receptors on NK cells)
→Phagocytosis- (Fc Receptors on macrophages)
Describe the process of hyperacute rejection
→Antibodies bind to endothelial cells
→complement fixation
→accumulation of innate immune cells
→Endothelial damage, platelets accumulate, thrombi develop
→
What cells are activated in acute rejection?
→organ’s resident dendritic cells
Why is there a Tcell response in acute rejection?
→MHC mismatch
Describe the process of direct allorecognition of foreign MHC
→Inflammation results in activation of organ’s resident dendritic cells
→DC migrate to secondary lymphoid tissue where they encounter circulating effector T cells
→Macrophages and CTL increase inflammation and destroy transplant
What happens in chronic rejection?
alloantibodies recruit inflammatory cells to blood vessel
→Blood vessel walls thickened, lumina narrowed – loss of blood supply
→Correlates with presence of antibodies to MHC-I
What is the main cause of chronic rejection?
→indirect allorecognition of foreign MHC
Describe the process of indirect allorecognition of foreign MHC
→Membrane fragments containing donor MHC are taken up by host DC
→Donor MHC is processed into peptides which are presented by host MHC
→T cell and antibody responses is generated to the peptide derived from processed donor MHC
What type of transplant is haematopoietic stem cell transplant?
→autologous
Where do
transplanted HSCs regenerate?
→bone marrow
How are HSCs preserved?
→cyropreserved
What is graft vs host disease?
→donor immune cells attacking the host
What is one way of reducing GVHD?
→Removing T cells from transplant
→suppressing their function
When are GVHD beneficial, and how?
→removing original leukemia
→Graft sees leukeamia is non-self
→may prevent disease relapse
What are three classes of immunosuppressants for transplants?
→General immune inhibitors (e.g. corticosteroids)
→Cytotoxic – kill proliferating lymphocytes (e.g. mycophenolic acid, cyclophosphamide, methotrexate)
→Inhibit T-cell activation (cyclosporin, tacrolimus, rapamycin)
What is cyclosporin?
→Blocks T cell proliferation and differentiation
What is involved in combination immunosuppressive regimes?
→Steroids – e.g. prednisolone
→(2) Cytotoxic – e.g. mycophenolate motefil
→(3) Immunosuppressive specific for T cells – e.g. cyclosporin A, FK506
Describe the induction stage of immunosuppression regime
→Antibody induction therapy
→Triple drug regimen
What is involved in triple drug regimen?
→a calcineurin inhibitor, an antiproliferative agent, and corticosteroid
eg. Tacrolimus, mycophenolate mofetil, and prednisone is the most common regimen
What is involved in the maintenance stage of immunosuppression regime?
→Triple drug regimen at lower doses- tapering off as time goes on
→No antibody regimen
How is Tcell mediated rejection treated?
→ATG and steroids (eg, methylprednisolone 250-1000 mg per dose)
How is Bcell mediated rejection treated?
→Intravenous immunoglobulin or anti-CD20 antibody and steroids.
What are different types of immunosppressants?
→calcineurin inhibitors- inhibit IL-2 production
→antiproliferative- inhibit Tcell and Bcell proliferation
→corticosteroids
→mTOR inhibitors- blocks Tcell activation
→mAb antibodies- costimulation blockers
→IL-2 receptor antagonist
→antithymocyte globulins- inhibits and deplete Tcell
What condition is cyclosporin liked with?
→nephrotoxicity
Why is FMT used in immunosuppressed patients?
→promote effective anti-cancer immune responses
