Transplant Immunology Flashcards
Rejection
Recipient immune system attacking graft
3 types of rejection
Hyperacute
Acute
Chronic
How are types of classification defined
Time of occurence
When does hyperacute rejection occur
Minutes to hours
When does acute rejection occur
1wk - 6 months
When does chronic rejection occur
Months to yrs
2 rejection mechanisms
Acute cell mediated rejection
Acute antibody mediated rejection
What immune cells are involved in acute cell mediated rejection
Helper T lymphocytes
Cytotoxic T lymphocytes
Macrophages
Tubulitis
Lymphocytes infiltrate kidney tubules
Endarteritis
Lymphocytes infiltrate artery walls
Immune cells involved in antibody mediated rejection
Helper T lymphocytes
B lymphocytes
What antigens can antibodies be made against in antibody mediated rejection
ABO antigens
MHC antigens
MHC class I related chain A
other non self antigens
What structures are most commonly attacked in antibody mediated rejection
Artery endothelium
Capillary endothelium
Histological features of antibody mediated rejection
Neutrophils in peritubular capillaries
Thrombosis
Arteritis/fibrinoid necrosis of vessels
Haemorrhage
Infarction
C4d deposition
What does C4d complement bind to in antibody mediated rejection
Endothelial cell surfaces and matrix componenets
Criteria for acute antibody mediated rejection
Acute renal injury evidence on histology
Antibody activity evidence
Circulating anti donor specific antibodies
What immune cells are involved in hyperacute rejection
B lymphocytes
What causes hyperacute rejection
Host already presensitised to antigens on transplant and has antibodies
What can pre sensitise a host to a transplant causing hyperacute rejection
Previous transplant
Previous transfusion
Previous pregnancy
What can cause a graft to fail
Damaged before transplantation
Surgical complications
Recurrence of original disease
Rejection
Which type of rejection can be caused by pre transplant damage and surgical complications
Chronic
How can hyperacute rejection be prevented
ABO compatibility
Screen for pre formed antibodies
How are pre formed antibodies for a transplant screened for
Direct cross matching
2 techniques for direct cross matching
Complement dependent cytotoxicity
Complement flow cytometry
What are most preformed antibodies in hyperacute rejection specific for
HLA
How can acute rejection be prevented
HLA matching
Minimise ischaemia - prevent ischaemia reperfusion injury
When does warm ischaemia of a transplant occur
While artery clamped at normal temp
When does cold ischaemia of a transplant occur
While transplant on ice waiting to be put in donor
Ischaemia reperfusion injury
Non specific damage caused by ischaemia upregulating adhesion molecules and increasing adhesion of leucocytes during reperfusion
Preventing chronic rejection
Choosing best organ
Minimise surgical damage
Minimise acute rejection
Minimise drug toxicity
Why does the relationship between the recipient immune system and the graft become less aggressive over time
Loss of bone marrow derived cells from donor
Active regulation develops
2 types of allorecognition
Indirect allorecognition
Direct allorecognition
Which type of allorecognition is more aggressive
Direct
What do immunosuppressants do
Prevent activation of helper t lymphocytes
How can immunosuppressants act
Ablate T cells
Inhibit signal from antibody receptor
Prevent cytokine gene activation
Inhibit IL-2 receptor
Inhibit signal from IL-2 receptor
Inhibit T cell proliferation
