Immunology 3: Transplantation Flashcards
Why does the cornea fail?
degenerative disease, infections, trauma
Why does Skin/Composite fail?
burns, trauma, infections, tumours
Why does Kidney fail ?
diabetes, hypertension, glomerulonephritis, hereditary conditions
Why does liver fail?
cirrhosis, acute liver failure
Why does the heart fail?
coronary artery or valve disease, cardiomyopathy, congenital defects
Why does the bone marrow fail?
tumours, hereditary diseases
What are the 5 different types of transplantation?
-Autografts
within the same individual
-Isografts
between genetically identical individuals of the same species
-Allografts
between different individuals of the same species
-Xenografts
between individuals of different species
e.g pig heart valves
-Prosthetic graft
plastic, metal
Who are the different types of donors?
DECEASED DONORS
a) –> donor after brainstem death
- death conformed using neurological criteria
b) –> donor after circulatory death
- death confirmed via cardio-respiratory criteria
- exclude viral infections / malignancy / drug abise
- time limit for kidney = 60 h
LIVING DONORS
- -> kidney, bone marrow, liver
- -> may be genetically related / unrelated
How is transplant allocated ?
- transplant selection
- transplant allocation
what are the 2 most relevant protein variations in clinical transplantation ?
- ABO blood group
- -> A + B proteins = on RBC / Endothelial cells
- BUT you can remove antibodies int eh receipients via Plasma exchange - HLA
- -> cell surface proteins
- variability of HLA = important against defense against infection + neoplasia
- recognizes peptides from infectious disease
- APC take up protein –> present as fragment on cell memb - T cell detects APC on HLA Molecule (HAS TO SEE CHICKEN ON A PLATE - on top of HLA molecule) –> mounts Delayed T cell response
Class I (A/B/C) Class II (DR, DQ,DP)
no. of mismatched in HLA = identified –> used to determine organ allocation
What are the different types of rejection in transplantation ?
- hyperacute rejection
- acute rejection
- chronic rejection
-4. T-cell mediated rejection
–> recognizes antigens on endothelial cells
+ also chemokine /
- recruit macrophages / cytotoxic T cells (infiltration)
- antibody-mediated rejection
- -> antibodies against graft HLA + AB Antigen
- -> antibodies formed against the graft
- antibodies can arise pre/protrasplantation
- usually intravascular
How would you diagnose rejection of transplantation?
How would you treat rejection of transplantation?
Diagnose = histological examination of graft biopsy
treatment =
immunosuppressive drugs
Post transplantation, how would you monitor for rejection?
a) deteriorating graft function
e.g
Kidney transplant: Rise in creatinine, fluid retention, hypertension
Liver transplant: Rise in LFTs, coagulopathy
Lung transplant: breathlessness, pulmonary infiltrate
b) subclinical
- heart –> clinically silent
- kidney
How do immunosuppressive drugs work?
By:
- Targeting T cell activation and proliferation
- Targeting B cell activation and proliferation, and antibody production
Post transplantation infections
Increased risk for conventional infections
Bacterial, viral, fungal
Opportunistic infections – normally relatively harmless infectious agents give severe infections because of immune compromise
Cytomegalovirus
BK virus
Pneumocytis carinii (jirovecii)