Lecture 14: Immunological Aspects of Renal System (Part 2) Flashcards
What are autografts?
Grafts exchanged from one part of body to another part in the same individual
What are isograts?
Grafts exchanged b/t different individuals of identical genetic constitutions (e.g. identical twins)
What are allografts?
Grafts exchanged between nonidentical membrane of same species (e.g. human to human)
What are xenografts?
Grafts exchanged between members of different species (e.g. pig to human)
- more susceptible to rapid attack
- can insert human genes to donor animals to increase chance of successful transplant
Why should a transplant take place within 36 hours of the donor’s death?
Trauma to the donor tissues can have the higher potential to release DAMPs, leading to immediate tissue damage
- Clotting cascade: generates fibrin, which is a chemoattractant for immune cells
- Increases local vascular permeability for immune cells to accumulate
- Bradykinin: increase vasodilation and vascular permeability
*All leads to hyperacute allograft rejection
is ABO compatibility necessary for kidney transplants?
Yes (w/o solid immunosuppression)
With what transplants is ABO compatibility non important?
Non-vascularized tissue:
- corneal transplantation
- heart valve transplantation
- bone and tendon grafts
How do you perform the Microcytotoxicity Test for for Preformed Antibodies?
1) Recipient serum with antibodies added to donor cells
2) Complement added after washing
3) Dye Added
4) If existing antibodies already existed, they are present
Why is HLA matching important?
Prevents graft rejection
What are convenient sources of lymphocytes for HLA typing
Cadaver: spleen or lymph node
Peripheral blood
How do you test for Class I HLA compatibility?
1) In separate dishes, antibodies to a specific antigen are added to donor are recipient cells.
2) Complement is added after washing –> Macs form pores in cells
3) Dye is added
4) Accumulation of dye in both cells mean there is compatibility
What happens if there is no compatibility when testing for Class I HLA compatibility?
Only donor cells will develop pores due to MAC complex and have dye accumulated in cells
Why is class II HLA compatibility not too important?
Class II only present on antigen presenting cells
What is mixed lymphocyte response?
1) Donor cells undergo radiation and do not proliferate.
2) These donor cells are mixed with recipient cells and 3H-thymidine.
3) If there is compatibility, proliferation of recipient cells does not occur.
What is a host versus graft disease?
Recipient rejects donor tissue
- adaptive immune response: very strong
- High frequency of T cells
- immune memory plays role
What is direct allorecognition?
Donor APC cells present to recipient T cells
-recipient recognizes unprocessed allogeneic MHC molecules on graft APCs
What is indirect allorecognition?
Donor alloantigens recognized by recipient class II molecules after they are processed by recipient APC
How does host versus graft response occur?
1) DAMPs activate endothelial cells
2) T cells eventually enter allograft
3) T cells release cytokines, activating greater immune response
Humoral rejection of transplants utilize what effector mechanism?
Th2 cells
-releases cytokines IL-4, IL-5, IL-10
Cellular rejection of transplants utilize what effector mechanism?
Th1 cells
-releases IL-1, IFN-γ
Describe hyperacute rejection.
Onset: Immediate
Mechanism: Preformed antibodies in recipient immediately attacks donor tissue
Presentation: Normally in accidental ABO incompatibility
What type of hypersensitivity are hyperacute rejections?
Type II
Describe acute rejection.
Onset: Weeks to months
Mechanism: Donor DC cells migrate to lymph nodes, triggering immune response in recipient —> leads to T cell mediated process. Also activation of classical complement pathway.
Presentation: Inflammation and leukocyte infiltration of graft vessels
Describe chronic rejection
Onset: Months to years
Mechanism: T-cell mediated process - foreign MHC similar to self MHC carrying antigen. Macrophages infiltrate tissue
Presentation: Intimal thickening and fibrosis of graft vessels
What type of hypersensitivity are acute and chronic rejections?
Type IV
What is a graft versus host disease?
Donor tissue rejects recipient
How does graft versus host response occur?
Mostly occurs in immunocompromised patients
-donor cytotoxic T cells attack allo-antigens of host either by Fas-FasL or perforins
Where do graft versus host response normally occur?
Small bowel
Lung
Liver
What is an acute graft versus host response?
Epithelial cell death in skin, liver, or GI
- rash
- jaundice
- diarrhea
- GI hemorrhage
What is an chronic graft versus host response?
Fibrosis and atrophy of affected organ
-dysfunction of affected organ
What type of hypersensitivity is graft versus host response?
Type IV
