Transplantation Immunology II Flashcards
Allograft rejection
- one of the leading cause of graft loss
- two types: T cell-mediated vs Antibody-mediated
T cell-mediated rejection
- APCs encounter allograft
- Donor and recipient APCs migrate to secondary lymphoid organs
- APCs meet T cells in lymphoid organs
- Effector T cells migrate to graft = graft loss (cytolytic granules, Fas/ Fas-L pathway)
Antibody-mediated rejection
- APCs encounter allograft
- Donor and recipient APCs migrate to secondary lymphoid organs
- APCs meet T cells in lymphoid organs
- T cell provide help to B cells = develop into plasma cells
- Effector T cells migrate to graft
- Plasma cells in bone marrow produce HLA antibodies
- HLA antibodies enter blood and reach graft = graft loss (complement-mediated cytotoxicity AND antibody-dependent cell-mediated cytotoxicity)
What is detected during antibody-mediated rejection ?
CD4 deposition in micro vascular endothelium
Hyper acute rejection
- Pre-formed antibodies bind to the graft endothelium directly after transplantation
- Takes minutes to hours
- Very rare
= complement activation, endothelial damage, inflammation, thrombosis
Acute cellular rejection
- T cells destroys the graft parenchyma (and vessels) by cytotoxicity and inflammatory reactions
- Early (weeks) or delayed (months; typically <1 year) onset
Acute humoral rejection
- Antibodies damage graft vasculature
- Early (weeks; often memory response!) or delayed (months onset; memory response vs. de novo antibodies)
T or F: The higher a patient’s cPRA, the more difficult it is to find an organ donor
TRUE; The higher a patient’s cPRA (ie. 80%), the more difficult it is to find an organ donor
- patient’s sensitized to HLA A2 are already limited by 50%
Immunological memory
- ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously
- Also applies to HLA antigens!
= Secondary immune response is larger and faster than primary immune response
What causes immunological memory for HLA antigens ?
- transfusions
- pregnancy
- previous transplants
- cross-reactivity (ie. vaccines)
- any human tissue allografts
Danger of memory
When testing for HLA antibodies, patient patient may not have active antibodies BUT have memory B cells = testing negative, potentially exposing patient to a sensitized antibody
NOTE: female patient pregnant 30 years ago..
Chronic rejection
- Caused by both humoral and cellular immunity
- Intimal thickening and fibrosis of graft vessels as well as graft atrophy
- Late (months to years) onset
How to diagnose allograft rejection
-
Initially non-specific clinical manifestation:
— malaise, lethargy, apathy, general weakness, vague discomfort, low creatinine clearance (kidney Tx), proteinuria (kidney Tx), shortness of breath (lung Tx), cough with or without sputum production (lung Tx), etc - chronic rejection can be asymptomatic
- Diagnosis based on biopsy, blood test results, and HLA antibody testing
NOTE: clinical dysfunction usually already occurs before rejection is detected
