Transplantation Immunology Flashcards
What is rejection
- rejection implies that there is something active that is attacking the graft, this is usually the immune system that attacks the graft and causes it to loose function
what are the three types of rejection that you can have
- hyperacute
- actue
- chronic
describe the time periods that the three types of rejection can occur in
Hyperacute:minutes to hours
Acute:- one week to six months occasionally later
Chronic: months to years – can see the change in the biopsy after a small number of months
How does acute rejection happen
- this is by activation of the adaptive immune system
name the two types of acute rejection
- acute cellular rejection
- acute antibody mediated rejection
Describe how acute cellular rejection happens
this involves the activation of the helper T lymphocyte
- this causes the activation of cytotoxic T lymphocyte and macrophage
what can be caused by acute cellular rejection
endarteritis
describe how acute antibody mediated rejection occurs
- the Helper T lymphocyte becomes activated
- this causes the B lymphocyte to become activated and produce antibodies
what is the primary target for the antibodies in acute anitbody mediated rejection
endothelium of the arteries and capillaries
List the antibodies that can be activated in antibody mediated rejection
ABO antigens
MHC antigens (class I, II)
MHC class I-related chain A (MICA)
others (including anti-AT1 receptor)
What are the histological features of antibody mediated rejeciton
Neutrophils (or mononuclear cells) in peritubular capillaries
Thrombosis
Severe arteritis/fibrinoid necrosis of vessels
This results in
Haemorrhage and Infarction
describe the classical pathway of complement activation
- antibody - antigen complex activates C1
- the activate C1 causes activation of C2 and C4
- this produces C3
and this also produces C4d which is clinically important as it shows up and can show that antibodies have been activated
what correlates with antibody activation
C4d
what is the criteria for acute antibody mediated rejection
1, Evidence of acute renal injury on histology
2, Evidence of antibody activity C4d staining in peritubular capillaries
3. Circulating anti-donor specific antibodies
Suspicious if 2 out of 3 are present
what is it important to define the mechanism of acute rejection between acute cellular rejection and acute antibody mediated rejection
because. ..
- projection is different
- treatment is different
what is more common acute cellular rejection or antibody mediated rejection
acute cellular rejection
Why is it harder to treat acute antibody mediated rejection
= harder to treat as you can remove the antibodies but you cannot remove the b cells which will carry on producing antibodies
what is hyperacute rejection
- this happens within minutes and house
- these people have been previously primed and sensitiesed to the antibodies
describe the 3 mechanisms of hyperacute rejection
previous transplant
previous transfusion
previous pregnancy
what causes hyperactue rejection
1 hour – neutrophils in peritubular capillaries and glomeruli
why does chronic acute rejection happen
It was damaged before transplantation
Surgical complications
Recurrence of original disease
Rejection
what factors lead to chronic rejection
- pre-transplant damage and surgicial complciations
- immune mediated damage
how do you prevent hyperacute rejection
- test ABO compatibility
how do you screen for hyperactue
Direct cross-match
- complement flow cytometry
- complement cytoxicity
Most preformed antibodies are specific for HLA
describe how complement flow cytometry works
Add serum form the potential recipietnt and add a second layer antibody that will shine in the dark when a laster is pointed at it
If there is a antibody that is specific to the layer – then the flueroqueine will shine
If the antibody is not present then there will be now fluroeine near the cell and it will be negative
describe how complement cytoxcitiy works
add complement and the complement destroys the cell – it will be activated adjacent to the cell if there is a serum that is antigen that is linked to the antibody of the cell
Continually screening patients
why do we get an immune response
This is why get an immune response because if the difference between the donor and recipient is not a peptide but part of HLA the T cell will assume the difference is the same as a viral infection and will attack the graft
how do you prevent rejection in acute rejection
HLA matching
Minimising ischaemia
- Ischaemia upregulates adhesion molecules
- Increases adhesion of leucocytes during re-perfusion
- Increases non-specific damage
- Also increases acute rejection
= ISCHAEMIA-REPERFUSION INJURY
- therefore you should perfuse it with fusions that reduce the risk of ischaemia reperfusion injury
how do you prevent chronic rejection
Choosing best organ
Minimising surgical damage
Minimising acute rejection
Minimising drug-toxicity
why do we get rejection
allorecognition direct
- CD8 nad CD4 cells
allorecgonition indirect
- CD8 and CD4 cells from an APC reaction
How does a T cell become activated
- T cell recongises the antigne as well as a non specific antigen whcih sends signals to the nucleus
- this causes cytokine activation
- IL2 is produced
- this causes other T lymphocytes to become proliferated
What sites do immunosupressive agents work at
1, calcineurin inhibits – inhibits signalling to the nucleus to release cytokines
2, Corticoisteroids- inhibit cytokine release
3 , antiproliferative drugs(azathioprine, MMF) – stop the nucleus dividing
