36 - Transport Immunology Flashcards
How long does hyper acute rejection of organ occur
Minutes to hours
What causes a hyper acute rejection
previous transplant
previous transfusion
previous pregnancy
(individual that has been immunologically primed - pre-existing immune responses mediated by antibodies)
Mechanism of hyperacute rejection
- Antibodies bind to the graft
- Activate endothelial cells+ complements
- Activated endothelial cells are pro-coagulant (causes thrombosis, haemorrhage and infarction)
1 hour after hyper acute rejection
Neutrophils in peritubular capillaries and glomeruli
12 -24 hours after hyper acute rejection
Intravascular coagulation and cortical necrosis
What may you see in vascular and glomerular lesions (hyper acute)
- IgM
- Complement
How long after does acute rejection of transplant occur
1 week - 6 months occasionally later (adaptive response)
What can cause acute rejection
CD4 T cells
Cell mediated rejection
Antibody mediated rejection
Helper (CD4) T cell acute rejection
T cell mediated rejection (CD8 cells) cause direct organ damage
B lymphocytes produce antibody mediated reaction
Cell mediated rejection
Aka acute cellular rejection
- Tissue is inflamed with lymphocytes
What is Endarteritis
Type 2 rejection
Inflammation of innter lining of artery
(Acute cell mediated rejection)
Antibody mediated rejection
Antibodies against any non-self-molecules (ABO, MHC, MICA most common)
- Endarteritis is v common
- Much more severe
How can antibody-mediated rejection be detected
Complements are activated and this allows to differentiated with cell mediated
What do antibodies activate
C1 –> C2 –> C4 and C4 is deposited (C4 is what is detected)
What does CD4 correlate with
Donor specific antibodies
Covalently bonds with thio-ester groups on endothelium
Criteria for acute AMR
Evidence of acute renal injury on histology
Evidence of antibody activity (CD4 staining in peritubular capillaries)
Circulating anti-donor specific antibodies
CMR or AMR more common?
CMR is more common than AMR
AMR has higher graft loss than CMR
When does chronic transplant rejection occur
Months to years
What can you do in chronic rejection
Impossible to do anything as a lot of pathology
Other reasons for graft loss (not rejection issues)
Graft was damaged before transplantation
Surgical complications
Recurrence of origin disease
How to prevent hyper acute rejection
Should not occur in the first place as you could detect beforehand
- ABO compatibility
- Screen for presence of pre-formed antibodies (direct cross-match) to see if any binding of antibodies
How do you prevent acute rejection?
HLA matching
Minimising ischaemia
What is HLA matching
HLA is the molecule which holds up the antigen on the antigen-presenting cell
Immune system recognises our own and the HLA molecule of others
(Mismatch in HLA causes less chance of survival)
Which MHC classes are peptides
Class I, II and III
