Transplantation Immunology Flashcards
What are the three types of rejection?
Hyperacute, acute and chronic
What is hyper-acute rejection?
Rejection that occurs in minutes to hours after transplantation (due to the presence of pre-formed antibodies in the blood stream that then mediate prompt attack)
What is acute rejection?
Rejection the occurs in one week to six months after transplantation
What is chronic rejection?
Rejection that occurs in the months to years following transplantation
What is the mechanism behind hyper-acute rejection?
The body has already been sensitised to an antigen that is present on the allograft and therefore on insertion, the antibodies will react and activate complement which activates endothelial cells and leads to coagulation.
What is the mechanism behind acute rejection?
Either acute cellular rejection (via macrophages and CD8+ T cells - direct damage) or acute antibody-mediated rejection (via antibodies which target the endothelium of arteries and capillaries)
How would you find out whether an individual with acute rejection has this because of an acute antibody-mediated resistance (rather than a cellular rejection)?
If the damage is as a result of acute antibody-mediated rejection, complement will be activated and this will lead to the deposition of C4d. Therefore, there must be evidence of C4d staining in the peritubular capillaries, acute renal injury on histology, and circulating anti-donor specific antibodies
What are the common causes of chronic rejection?
Damage to the kidney before transplantation, surgical complications, disease recurrence that affects the new kidney or unanticipated immune rejection
How can you prevent hyperacute rejection?
Matching blood antigens (ABO) and screen for the presence of pre-formed antibodies
How can you prevent acute rejection?
HLA matching and minimising ischaemia (as ischaemia leads to up regulation of adhesion molecules which can increase leukocyte adhesion which can cause non-specific damage)
How can you prevent chronic rejection?
Choose the best organ, minimise surgical damage, minimise acute rejection, minimise drug toxicity
Why is immune suppression required post-transplantation?
Shortly after allograft insertion the immune system will respond aggressively
What is the mechanism of immunosuppressants that are prescribed post-transplantation?
Prevent the action of T helper cells
What non-self molecules may antibodies be formed against that may affect transplanatation success?
ABO antigens, MHC antigens (class I and II), MHC class-I related chain A (MICA) and other antibodies
How does the immune system evolve/adapt to the allograft in kidney transplantation?
Eventually there is loss of the bone-marrow derived cells from the donor in the body, and therefore there are less non-self antigens for the body to respond to. There is also active regulation of the immune response via CD4+, CD25+ and FoxP3 T cells.
