Transplantation Immunology
Told to know these for “passage of the exam”
Autograph- skin transplant; no immunosuppression
Syngenic or Isograft- identical twins
Allograft/Homograft- genetically different of same species; need immunosuppression
Xenograft/Heterograft- 2 different species
Primary and Secondary Allograft rejection
- T cell mediated – memory and specificity
First set rejection- (7-30 days)- organ and tissue allografts are rejected by non sensitized recipients in an acute fashion
Second set acute rejection or accelerated rejection- (2-10 days) faster rejection when given from same individual
Hyperacute allograft rejection- within min or hours after vascularization due to presensitivity
If immunosuppressed, Chronic allograft rejection (mths to years) can develop. THE OLY WAY TO RECOGNIZE: is histologically due to thickening of the vessel walls.
ON TEST: T cells are only ones capable of allograft rejection.
Mechanism of Allograft Rejection
“understand process, don’t memorize”
3 distinct steps in Rejection
1. rolling
- once vascularization has occurred, leukocytes “roll” though the vessel lumen. The “rolling” allows for greater interaction between the vessel wall and the surface of the leukocyte.
- a family of molecules called selectins on the endothelium of the vessel binds to the carbohydrate ligands (sialylated Lewis) on the surface of the leukocyte
- The “rolling” also enhances chemo-exposure to chemoattractants such as IL-8 which increases the expression of othe integrins by the leukocyte.
2. firm attachment
a. the “firm attachment” of leukocytes to endothelial cells involves an interaction between the integrins and very late antigen-4 of the leukocyte with the intracellular adhesion molecule (ICAMs) and vascular cell adhesion molecule (VCAMs) on the endothelial cell
3. migration
a. destruction can now occur
Direct recognition- T cells directly recognize alloantigens
Indirect presentation- APC-Class II presentation to alloantigen-specific T cells
Allograft rejection is induced by:
1. MHC complex antigens
2. minor histocompatibility (mH) antigens (everything but MHC)
- MHC polymorphism is the reaseon it is so difficult to find a perfect match between donor and recipient for tissue transplantation in humans.
Transplant Tolerance
Definition- reduced or altered immune response towards an allograft, allowing a long-term survival WITHOUT the necessity for continuous nonspecific immunosuppression
Mechanisms of Transplatation tolerance
1. Clonal Deletion
- occurs when alloantigen-specific-T cells are physically eliminated
2. Clonal Anergy
- occurs when alloantigen-specific- T cells are temporarily functionally inactivated, but not eliminated
3. Suppression
- occurs when response of one T cell population (T regulatory cells) inhibits another T cell population which is involved in allograft rejection
Necessity of treatment with Immunosuppressive Drugs to prevent Allograft rejection
- No clinical protocol, yet
- must treat daily with immunosuppressive drugs to inhibit alloreactive T lymphocytes and to prevent allograft rejection
- all have drawbacks; toxicity and other various side effects
The following immunosuppressive drugs are used in clinical transplantation
1. Cyclosporine- most widely used; blocks production of IL-2, IFN-g, IL-4, and other cytokines by T helper lymphocytes
2. Tacrolimus- acts like cyclosporine (predominantly used for liver transplantation)
3. Sirolimus- (Ripamycin)- unknown mechanism; inhibits cytokine signal transduction
4. Azathioprine- inhibits primary immune responses
5. Corticosteroids
6. anti-lymphocyte serum- (ALS)- used shortly after transplant
7. murine monoclonal Ab- lowers numbers of circulating lymphocytes
HLA typing
Immunological Testing for Organ Transplantation
1. Standard ABO blood group matching
Blood Type Can donate to type Remember Rh groups
O O,A,B,AB
A A,AB
B B,AB
AB AB
2. HLA antigen matching between donor and recipient is performed for HLA-A, HLA-B, and HLA-DR antigens
3. Recipient cross-matching is performed for the presence of recipient anti-donor pre-sensitivity by testing for anti-donor HLA antibodies
Tags: alloantigen specific, Allograft rejection, Azathioprine, Corticosteroids, Cyclosporine, endothelial cell, Endothelium, Hyperacute Allograft rejection, immunosuppression, Immunosuppressive drugs, Isograft, leukocytes, polymorphism, sialylated Lewis, Sirolimus, Syngenic, Tacrolimus, transplant, vascularization
