Transplantation Flashcards
DIfference between class I and II HLAs
Class I
- Expressed on somatic cells
- Present peptides from internally processed proteins ( viral etc.)
Class II
- Expressed by APCs eg. DCs that sample their microenvironment
- Used to present antigenic peptides derived from digested material ( including pathogens, abnormal or foreign cells)
Pathogenic or foreign peptides will stimulate a T cell immune response
What immune suppression is given for kidney transplants
- Standard is Triple Immune Suppression (first three below)
- Corticosteroids
- Kill lymphocytes
- Interfere with T cell activation and gene transcription
- Powerful anti-inflammatory agents
- Suppress cytokines
- Corticosteroids
- Calcineurin inhibitors (CNI) eg. Tacrolimus
- Inhibit T cell activation by interfering with intracellular signalling pathways
- Anti-proliferative agents eg. mycophenolate motefil
- Inhibit clonal expansion of T cells
What is Immunological X-match negative, checking for antibodies or antigens
Serum of recipient does not have HLA antibodies for antigen on donor lymphocytes
What is a hyperacute rejection, symptoms?
Total destruction of the transplant on the table, Occurs when Tx carries antigens to which recipient is already sensitised, will cause purpura
Acute rejection and its symptoms/ histological features
Acute rejection ⇒ Cell or Ab mediated
- Features :
- Rise in creatinine (often only an indication)
- Reduced urine output
- Tender transplant due to inflammation, AKI
- Tubulitis
What staining can be used for Antibody mediated rejection
C4d staining which indicates where the Antibody is bound
Treatment of acute rejection
- High dose methyl prednisolone ( anti-inflammatory, kills lymphocyte etc.)
- Change to more potent immunosuppressive agent or increased dose
- Anti- T cell antibody (but higher risk of infectionn, tumours)
- Plasma exchange (severe acute Ab mediated rejection)
Features of chronic rejection of kidney
- Progressive renal dysfunction
- Interstitial fibrosis and vasculopathy on renal biopsy
- Vasculopathy ⇒ endothelium gets attacked early on, inflammation
Management of chronic rejection
- No specific treatment
- Will mostly require dialysis and further transplant
- Optimise immunosuppression
- Proactive treatment of BP, lipids, proteinuria etc.
What are bacterial risks of immunosuppression
UTI, chest infection
What are viral risks of immunosuppression? Prophylaxis??
- CMV, Herpes, Parvo, BK (causes renal dysfunction)
- BK only causes problems with transplantation
- Treatment is to reduce immunosuppression to facilitate anti-viral immunity
- Need prophylatic valagancyclovir for 6 months if recipient CMV -ve and donor CMV +ve
Tb may also need prophylaxis
Tumour related disorder after tranplant
- ost Tx Lymphoproliferative Disorder (PTLD)
- Secondary to infection with EBV ⇒ may have reinfection of EBV→ Lymphoma
- Need to reduce immunosupression
- Secondary to infection with EBV ⇒ may have reinfection of EBV→ Lymphoma
Side effects of anti rejection drugs
- Calacineurin inhibitors are nephrotoxic
- Need to measure plasma levels of tacrolimus
- Increased risks of diabetes ⇒ steroid and tacrolimus
- Hypertension (steroids and CNI)
- Osteoporosis (steroids)
which HLA antigens are important in transplants
AB, DR
causes of chronic rejection
- Increased HLA mismatch
- Previous acute rejection
- Poor drug compliance (low tacrolimus levels ⇒ immune recognition will occur)
- Prolonged CIT of kidney prior to surgery
