Transplantation Flashcards
Alloimmunity
Immune response due to different/other tissue of the same species.
3 immune responses to genetically dissimilar tissue
- Transient neonatal alloimmunity
- Transfusion reactions
- Transplant rejection
Transient neonatal alloimmunity
Fetal Ag/Maternal Ab
- Hemolytic disease of the newborn
- Neonatal alloimmune Thrombocytopenia
Maternal autoimmune disease
When is hemolytic disease of the newborn of concern
If mom is - and dad is + and then baby is positive.
Concern after first birth. After the placenta has pulled away from uterine walls and the mom’s body has been exposed to fetal blood.
What medication to take to prevent HDTN
Rhogam. Administer twice.
Neonatal alloimmune thrombocytopenia
Low levels of thrombocytes (platelets)
Like HDN, only with platelets
Up to 60% of cases occur during first pregnancy.
Mortality 10%. Usually do not screen for this.
Resolves in 2-3 weeks without treatment.
Involves IgG from mom that degrade over time.
Transient neonatal alloimmunity caused by maternal autoimmune disease
Material antibodies can cross the placenta (type II) and react with material Age that are in the fetus. Elicit an immune response.
Effects are usually transient.
Seen in maternal patients with SLE, Myasthenia gravis, and graves.
Antigens on red blood cells
Carbohydrate antigens. Individuals produce Abs to blood type antigens they lack.
ABO incompatibility results in which hypersensitivity response
Type II by complement mediated lysis.
Organ transplant criteria
- Irreversible organ damage
- No alternative treatment options
- Non recurring disease. Infection? ok. But HSK? no, will continue to flare up over time.
- Transplant compatibility
- Priority based on organ needed
- ABO compatibility
- Haplotype matching (arrangement of genes on Chr)
HLA Class I molecules
HLA A, B , and C
HLA Class II molecules
HLA DR (most important to match! Less flexible)
HLA DQ
HLA DP
Siblings with same parents have __ % chance of having matching haplotypes
20%
Minor HLA differences
Associated proteins from the donor with different amino acid sequences. Encoded by genes outside HLA region Not detected by standard tissue typing techniques.
Can cause graft rejection in up to 1/3 of transplants.
Transplant rejection is mediated by?
Cells mainly.
How are transplant rejections classified?
According to time
Hyper acute: Minutes to hours
Acute: First days to weeks
Chronic: years
5 causes of transplant rejection
MHC I MHC II ABO Endothelial antigens Minor HLA
What causes hyper acute transplant rejection?
Pre-existing host serum ABs specific for alloantigens.
Ag-Ab complex settles in donated tissue activating PPS= leukocyte infiltration = blood clots = ischemia = “white graft”
Preventable with careful ABO and HLA matching.
Maybe seen in patients with history of many transplants or women who have been pregnant with many different men. Exposed to lots of non-self Ags.
What causes acute transplant rejection?
Mismatched HLA antigens. Leads to activation of T cells by Cell mediated (90%) or humoral destruction (10%)
Cell mediated: Recepient T cells directed at the MHC on donor cell antigen presenting cells. Can be minimized with immunosuppressants. Damage to endothelial cells is reason for rejection.
Humoral destruction/ Ab mediated: Ab against HLA antigens. B cells and complement activated. Causes clotting in recipient blood vessels.
What causes chronic transplant rejection?
Humoral and cell mediated (mechanism poorly known)
Proliferation of fibroblasts and vascular cells cause slow loss of organ function.
Result in arteriosclerosis of donor vessels- thickening due to collagen deposit.
Graft vs host disease
Side effect of bone marrow or cord blood transplant. Major HLA is matched, but minor HLA is not matched and causes antigens.
Treat by immunosuppressant therapy.
Cornea transplant survival %
90
____: Clinical goal of transplantation
Tolerance. Host tolerating foreign tissue..
What is the role of immunosuppressant drugs?
Allow for imperfect matches.
Important in controlling the MHC antigen rejection.
Bad bc it can dampen appropriate immune responses.
Anterior chamber associated immune deviation (ACAID) in cornea transplants
Before transplant, intentionally trigger an immune response in the anterior chamber by sticking a needle with Ag to increase T cells. AS response, body will suppress immune response because they don’t want immune cells in the eye.
Key risk factor in cornea transplant
Corneal vascularization.
What is the line of rejection in a cornea transplant
A line of actual immune cells. Usually along with corneal edema and vascularization.
Future of transplantation
Xenotransplantation- between species.
regenerative medicine using stem cell
Artificial organs by biomedical replacement
