Immunology of Transplantation Flashcards
what is the major histocompatibility complex called in humans
histocompatilibilty locus antigen (HLA)
function of HLA
molecules which imprint individuality on cells (mark them as your own cells)
what class of HLA molecules are expressed by most somatic cells
class 1
function of HLA class I molecules
present peptides from internally processed proteins
which cells express HLA class II molecules
antigen presenting cells that are constantly sampling their microenvironment
function of HLA class II molecules
present antigenic peptides derived from digested material (including pathogen, abnormal or foreign cells)
what happens if a HLA class I molecule is associated with a virus derived protein
it is recognised as infected and killed by cytotoxic t cells
what happens if a HLA class II molecule displays a peptide derived from a foreign cell/pathogen
t cell immune response stimulated
if someone rejects a tranplant and gets a second similar one how would the body respond
rejected more quickly due to memory cells
what is HLA profiling used for
allocating kidneys that best match individuals
why is HLA not as important in liver transplant compared to kidney
liver is less immunogenic
how is HLA mismatch reported
0-0-0 mismatch if all of HLA-A, -B and DR loci are the same
2-2-2 mismatch if all different - less good match
immunosuppression drugs
corticosteroids
calcineurin inhibitors
anti-proliferative agents
various antibodies
MoA of corticosteroids for immunosuppression
kills lymphocytes
interferes with T cell activation and gene transcription
anti-inflammatory agents
immunosuppression drugs
corticosteroids
calcineurin inhibitors (CNIs)
anti-proliferative agents
various antibodies
MoA of CNIs for immunosuppression
inhibit T cell activation by interfering with intraelluus signalling pathwy
MoA of anti-proliferative agenst for immunosuppression
inhibit clonal expansion of T cells
what investigations need to be done befroe transplantation
exercise ECG
myocardial perfusion studies
angiography - need decent vessels for anasatomosis
urodynamic dstudis
tumour markers
DCD vs DBD cardaveric Tx meaning
donated after cardiac/brain death
do live or dead donor kidneys have better long term outcomes
living
where may a patient acquire cytotoxic Abs to many HLA antigens
previous transfusions
pregancies
previous transplantation
what investigation can be used to detect HLA antibodies
luminex HLA antibody detection
what type of transplant rejection shouldn’t happen now
hyperacute rejection
when does hyperacute rejection occur
when the transplant carries antigens to which the recipient is already sensitised
signs/presentation of acute transplant rejection
rise in creatinine
reduce urine output
tender transplant
fever
differential diagnosis of acute transplatn rejection
dehydration
renal obstruction
vascular catastrophe
drug toxicity
AKI
treatment of acute rejection
high dose steroids to kill lymphocytes and reduce inflammation
more potent immunosuppression or increased dose
anti-t cell antibody
plasma exchange for severe Ab mediated rejection
progressive renal dysfunction
interstitial fibrosis and vascular disease on renal biopsy
are signs of
chronic rejection
what type fo trasnplant is ideal for diabetcis
pancreas adn kidney
risk factors for chronic rejection
increased HLA mismatch
previous acute rejection
poor drug compliance
prolonged cold iscahmeia time of kidney prior to surgery
causes of graft failure
delayed graft function
infection
afge o donor
poor blood pressure control
porteinuria
msanagemnt of chronic rejection
eventaully dialysis or anothr transplant
optimise immunosupprssion
treat BP, lipids, proteinuria
what are you at increawsed risk of when on immunosuppresion
infection
cancer
diabetes
hypertension
osteoporosis
