Flashcards in Transplantation Immunology Deck (22):
What are the different types of transplant rejection? How are they classified?
Acute - 1 weeks to 6 months post transplantation
Hyper-acute - minutes to hours
Chronic - months to years
What are the 2 types of acute rejection?
Acute cellular rejection (cell mediated)
Acute antibody-mediated rejection (humoral)
What is the mechanism of action of acute cellular rejection?
- CD4+ (T helper lymphocytes) activate CD8+ (cytotoxic T cells) and macrophages via a cell mediated response
- CD8+ cells produce lymphocyte infiltration, interstitial tubulitis and endarteritis
What is endarteritis?
Tunica intima inflammation
What is the mechanism of action of acute antibody-mediated (humoral) rejection?
- CD4+ T cells activate B lymphocytes to produce antibodies via a humoral response
- Antibodies form against ABO antigens, MCH class 1 and 2 antigens and MICA
- Antibodies target the endothelium of arteries and capillaries
- C4D gets deposited in the endothelium as a product of the antigen-antibody complex forming complement
What is MICA?
MHC class 1 related chain a
Glycoprotein encoded by MICA gene in MHC
What can be used as a marker for rejection?
C4D levels (complement component 4)
How would you confirm an acute antibody-mediated (humoral) rejection?
Acute renal injury (histology)
Antibody activity (C4D staining in peritubular capillaries)
Circulating anti-donor specific abnormalities
What is the main different between acute cellular rejection and acute antibody mediated rejection?
There are more CD4+ cells between connecting cells in acute cellular rejection whereas there are more around the peritubular capillaries in acute antibody mediated rejection
When would hyper-acute rejection occur?
previous transplants/transfusion/pregnancy means pre-formed antibodies are already in circulation before transplant occurs
What is the mechanism of action of hyper-acute rejection?
Pre-formed antibodies in circulation bind to endothelium = activates complement = thrombosis occurs = tissue breaks down = infarction
In the 1st hour => there are neutrophils in the peritubular capillaries and glomeruli
12-24 hours => intravascular coagulation/cortical necrosis
When would chronic rejection occur?
From pre-transplantation graft damage, original disease recurring or rejection
How do you prevent acute rejection?
What is HLA?
Human body form of MHC
Presents the antigen peptide of the graft/foreign pathogen to the T cell receptors
Individual with several different MHCs will have an increased number of antigen peptides it can bind
What are the types of MHC?
Class I is on almost all nucleated cells
Class II is on APCs (HLA-DR is the most common, DR4)
Why would minimising ischemia be beneficial?
- Ischemia upregulates adhesion molecules
- increased adhesion during reperfusion after ischaemia
- non specific damage and acute rejection
- increases toxin levels and reactive species
How is hyper-acute rejection prevented?
Checking pre-formed anitbiotics
How is chronic rejection prevented?
- choose the best organ
- minimise surgical damage, acute rejection, drug toxicity
What is the relationship between the immune system and the graft?
Early on very aggressive and then reduces.
Why does the aggression between the immune system and the graft reduce over time
Bone marrow derived cells of the donor are lost
Develop an active regulation
What is the purpose of immunosuppression? Which ones are used?
Prevents activation of CD4+ cells
If CD4+ cell activated = secrete IL2 = clonal expansion