Transplantation immunology Flashcards
3 classifications of rejection
Hyperacute
Acute Chronic
When does hyperacute rejection occur
Minutes or hours of transplantation
When does acute rejection occur
1 week to 6 months later
When does chronic rejection occur
Months to years
What mechanism happens in acute rejection
Acute cellular rejection
Acute antibody rejection
How does kidney appear in cell mediated rejection
Interstitital tuberlitis
Endothelialitis
Lumen compromised by presence of lymphocytes
What happens in acute cellular rejection
Helper T cell stimulates cytotoxic T cell to produce immune response
What is antibody mediated rejection
Help T cell produces B lymphocyte which produces antibodies
What is the primary target of antibodies in antibody mediated rejection
Endothelium of arteries adn capillaries
How does blood vessel appear histologically after antidboy mediated rejection
Inflammation
How is cell vs antibody mediated rejection differentiated
Antibody activates complement cascade
C4d forms covalent bonds with thio-ester groups on endothelial cell surfaces and these can be detected
What happens when you have complement mediated activation
C1 activated, then C2 and C4
C4d is lost
Criteria for acute AMR
1) Evidence of acute renal injury on histology
2) Evidence of antibody activity
3) Circulating anti-donor specific antibodies
Is antibody or cell mediated rejection more common
Cell
Is antibody or cell rejection more dangerous
Antibody
In what kind of person does a hyperacute rejection occur
A person who has been ‘immunologically primed’- they have had a previous transplant, transfusion or pregnancy
What kind of response is involved in hyperacute rejection
Antibody mediated
How does hyperactive rejection lead to endothelial damage
Preformed antibodies bind to the vessel lumen, activating the endothelium into pro-coagulant state
Leads to thrombosis and damage
Reasons why a graft can fail (4)
- It was damaged before transplantation
- Surgical complication
- Recurrence of original disease
- Rejection
Define rejection
Recognition and destruction by recipient immune system
How do grafts appear after chronic rejection
Lost majority of structure
Not as many tubules
Replaced in large measure by collagen- fibrotic process
Who can the following blood groups receive donated organs from
a) A
b) B
c) 0
d) AB
a) A or O
b) B or O
c) O
d) A, B or O
How do you prevent hyperacute rejection
Screen for the presence of preformed antibodies.
What are most preformed antibodies specific for?
HLA
How do you prevent acute rejection
HLA matching
Minimising ischaemia
What is the HLA molecule responsible for
Sampling all the proteins around the presenting the antigen on an antigen presenting cell for the T cell receptor
What is the advantage of an individual having several different MHC molecules
Increases the number of peptides that can be bound
What is the difference between MHC class 1 and class 2
MHC class 1 found on every cell MHC class 2 only found on antigen presenting cells
Why does ischaemia need to be minimised to prevent rejection
- Ischaemia upregulates adhesion molecules
- Increases adhesions of leucocytes during rreperfursion
- Increases non specific damage
How to prevent chronic rejection (4)
Choose best organ
Minimise surgical damage
Minimise acute rejection
Minimise drug toxicity
Why is the immune response to graft less aggresive over time
Loss of bone marrow derived cells of donor
Development of active regulation
What factors affect the ‘load’ (how much stress the kidney undergoes)
Hypertension Hyperlipidaemia CNI toxicity Senescence Alloimmune injury Hyperfiltration CMV
What can cause inflammation of the transplant (3)
Ischaemia reperfusion
CNI toxicity
Alloimmune injury
Where can imunosuppresants target
- Take out T cell receptor
- Calcineurin inhibitors which inhibit transduction of signal
- Steroids inhibit gene activation
- Anti IL-2
- Anti metabolites present cells from dividing
