Transplantation Immunity (Lec 11 & 12) Flashcards
Transplant tourism
- 10% of transplants
- practice of individuals traveling from one country to another to undergo an organ transplant, often due to long waiting times, legal or ethical issues, or the availability of organs in the destination country
Ischemia
deprivation of blood to organs and tissue damage due to inflammation
Solid organ transplants
medical procedures in which a diseased or failing organ is replaced with a healthy organ from a donor
Why do transplants of corneas have high success rates?
- because eyes are immunologically privileged sites
- no HLA matching required because there is no rejection response generated
HLA (Human Leukocyte Antigen) matching
- helps determine the compatibility between a donor’s and a recipient’s immune systems
- more closely the HLA markers match, the lower the risk of transplant rejection
- looks at matches between HLA molecules which are proteins found on surface of cells that help immune system recognize what is “self” and “‘non-self”
Benefits of Blood Transfusions
- blood can be donated regularly with no health effects
- Simple and inexpensive
- Only required temporarily
- NO HLA molecules that cause
incompatibility but do have HLA
antigens
ABO antigens
- carbohydrates on RBCs (erythrocytes)
- determine blood compatibility between the donor and recipient
Alloantigens
- present in one individual but are recognized as foreign by the immune system of another individual of the same species
- antigens that differ between unrelated members of a species
Alloantibodies
antibodies produced by an individual’s immune system in response to the presence of alloantigens (foreign antigens from another individual of the same species)
ABO incompatibility mirrors..
type II hypersensitivity
allergy responses
A and B antigens resemble…
commensal bacteria antigens
Rhesus D (RhD) Antigens
- blood group antigen
- complicate compatibility
- have the D antigen on their red blood cells are Rh-positive (Rh⁺)
- D antigen are Rh-negative (Rh⁻)
Histocompatibility
degree to which the tissues of a donor and recipient are immunologically compatible—meaning the recipient’s immune system will not recognize the donor’s cells as foreign and attack them
Autograft
transfer of tissue from
one site to another (same individual)
Syngenic or isogenic transplant
between genetically identical
individuals
Allogenic transplant or allograft
between two genetically different
individuals
Xenograft
between two different
species
Hyperacute rejection
- Minutes to hours after transplantation
- Cause: Pre-formed antibodies in the recipient against donor antigen
- Highly vascularized organs would get attacked by the immune system rapidly
Acute rejection
- Days to weeks after transplant
- Cause: Recipient immune system recognizes the donor’s antigens as foreign
- Transplantation causes inflammatory environment that leads to immune cell activation and infiltration
-Typically prevented with
immunosuppressive drugs
Chronic rejection
- Months to years after transplant
- caused by immune complexes
- causes failure of more than half of transplants within 10 years
- Treatment is Rituximab
(anti-B cell antibodies)
Cross-match test
- assessment of patient serum for antibodies towards donor blood
2 ways:
1. put recipient serum, donor lymphocytes and compliment in tube - no donor-specific HLA antibodies in recipient serum = no antibody binds, negative crossmatch and no cell lysis
- donor specific HLA antibodies in recipient serum= antibody binds and complement activated, positive cross match and cell lysis
2. recipient serum + 100 beads which each has unique dye signature and unique HLA antigen on surface - HLA antibody in recipient serum to specific bead
- detection antibody binds which captures reporter dye
- dual laser beam detects bound reporter dye and identifies specific bead
T Cell Reactions to Allogenic MHC
- central to the immune response in organ transplantation, especially in acute and chronic rejection
- when recipient T cells recognize donor MHC molecules as foreign, leading to immune activation
- happens because T cells are never negatively selected for allogenic MHC molecules
Direct pathway of Allorecognition
donor DCs interact with recipient
T cells (CD4 and CD8) leading to killing of donor DCs
Indirect pathway of allorecognition
- apoptosis of donor DCs leads to recipient DCs presenting alloantigens
- leads to alloreactive T cell activation in lymph nodes and alloantibody production
- has a smaller contribution to
transplant rejection than direct pathway - Results in Treg activation if patient has received blood
transfusion with same HLAs = transfusion effect
