Immunology 5 - Transplants Flashcards
What is an autologous transplant?
Tissue returning to individual after period outside the body
What is an syngeneic transplant?
Between twins (also called isograft)
What is an allogenic transplant?
Non-identical members of the same risk of species
What is an xenogeneic transplant?
Different species (highest risk of rejection)
What are the criteria for solid organ transplantation?
Disease must not recur
Good evidence damage is irreversible
No alternate therapy
How is rejection chance minimised?
ABO compatability
Recipient must not have anti-donor HLA antibodies
Must be as close HLA as possible
Patient take immunosuppressives
What transplant does not require immunosuppressants?
Corneal transplant (not vascularised)
What is hyperacute rejection?
Within hours
Antibodies binding either to ABO or HLA class 1 on graft
Type 2 hypersensitivity reaction
Damage via thrombosis
How is hyperacute rejection prevented?
HLA and ABO crosstyping
What is acute rejection?
Type 4 (delayed) hypersensitiity HLA incompatibility the main cause
What is acute antibody mediated rejection?
Antibodies form after grafting and cause vascular injury leading to a thrombus
What is chronic rejection?
Months - years post-transplant
T-cell mediated
Can recur pre-existing autoimmune disease
What is tolerance?
Unresponsiveness of immune system to the body’s own cells
Function mimicked by immunosuppressives
Outline the pathology of graft rejection?
Afferent phase: donor MHC molecules on dendritic cells recognised by host CD4+ cells
Effector phase: CD4+ recruit macrophages, CD8, NK and B cells to reject
What are the mechanisms for graft rejection?
Direct alloantigen recognition (T-cell recognises foreign free antigen)
Indirect alloantigen recognition (Foreign antigen processed then presented)
How are tissues ‘typed’?
HLA typing HLA cross matching (A, B and DR loci) ABO compatibility T lymphocytes
What are the different types of stem cell transplant?
Autologous SCT
Allogenic SCT
Outline the process, pros and cons of autologous SCT?
Marrow removed, frozen and reinfused post-chemotherapy
Minimum risk
Outline the process, pros and cons of allogenic SCT?
Can be used in blood cancers or primary immunodeficiencies
Risk of Graft vs host disease
High mortality
What are the sources of stem cells?
Bone marrow
Peripheral blood (post colony-stimulating factors)
Cord blood
What is the role of conditioning for stem cells?
High dose RT/chemotherapy to destroy host stem cells for engraftment
What is Graft Vs Host disease?
Where donor T cells attack the allogeneic antigens HLA mismatch antigens Prevented with immunosuppressives 70% mortality risk Skin, gut, liver, lungs affected
What are the main groups of immunosuppressives?
Corticosteroids
T-cell Signalling Blockade (Cyclosporine/Tacrolimus)
IL-2 blockade
Antiproliferatives
Give 3 side effects of Cyclosporine?
Increased risk infections, cancers
Nephrotoxicity
Diabetes
Hypertension
Give 3 side effects of Rapamycin?
Raised lipds, cholesterol Hypertension Anaemia Diarrhoea Thrombocytopenia
What issues are associated with xenotransplants?
Galactose-a1,3-galactose present on non-primate cells
Recipient antibodies bind to this and activate complement
Hyperacute rejection
Outline how Corticosteroids work?
Inhibit antigen-presenting cells and T cells at higher doses (used early)
Outline how Cyclosporine/tacrolimus work?
Interact with intracellular T-cell signalling cascade
Outline how Monoclonal antibodies work to suppress the immune system?
IL-2 Blockade
Used in acute rejection
Outline how Rapamicin works?
IL-2 Blockade
Prevents graft rejection
Outline how Antiproliferatives work?
(Azathioprine, methotrexate)
Inhibit DNA production
Prevent lymphocyte proliferation
Suppress the bone marrow
