Lecture 15: Immunological Aspects of Renal System (Part 2) Flashcards
What is the difference between autografts, isografts, allografts and xenografts?
autografts: graft exchange within same individual
isograft: graft exchange within identical genetic constitutions (twins)
allograft: graft exchange witihin same species
xenograft: graft exchange between members of different species
What must match to prevent graft rejection?
HLAs
What factors affect successful transplantation?
condition of allograft
donor-host antigenic disparity
strength of host anti-donor response
immunosuppressive regimen
Why should a transplant take place within 36 hours of the donor’s death?
longer will lead to graft damage > release DAMPS > activation of clotting cascade (fibrin, fibrinopeptides) & kinin cascade (bradykinin) > immune cell infiltration and incresed vascular permeability
*All leads to hyperacute allograft rejection
is ABO compatibility necessary for kidney transplants?
Yes (w/o solid immunosuppression)
With what type of transplants is ABO compatibility non important?
Non-vascularized tissue:
- corneal transplantation
- heart valve transplantation
- bone and tendon grafts
Exercise: What type of blood can an A type recipient get?
O and A (no anti A antigens in these types)
How do you perform the Microcytotoxicity Test for for Preformed Antibodies? When do you need to do this?
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
to see if there are pre-existing antigens in the recipient’s blood
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 (Microtoxicity Test for Class I HLA)?
Take lymphocytes from recipient and donor
Take antisera with antibodies to certain HLA
Abs will bind Ags and activate complement and lyse the cells
If both types of cell are lysed = they both have that HLA = match
What happens if there is no compatibility when testing for Class I HLA compatibility?
Only donor cells will be lysed because it has that HLA. Recipient cell does not lyse since it does not have that HLA
Why is class II HLA compatibility not too important?
Class II only present on antigen presenting cells
What is mixed lymphocyte Response test for Class II HLA?
Mix recipient and donor cells (donor cells treated with 3H-thymidine so it does not proliferate)
If R cell proliferates = mismatch since it’s the first time the R cell has “met” that HLA because it’s not in the R’s cells
What is a host versus graft disease?
How does immune memory relate to this type of rejection?
Recipient’s T cells attack new organ
more robust response if you get 2nd graft from the same donor
What is the difference between direct and indirect allorecognition?
Direct: T cell recognize intact foreign HLA on graft cells
Indirect: T cell recognizes degraded HLA peptide on presenting MHC
Cellular effectors of graft rejection
Humoral effectors of graft rejection
TH1 by releasing IL2, IFN-Y
TH2 by releasing IL4,5 and 10
Describe hyperacute rejection. Onset Mechanism Presentation What type of hypersensitivity?
Onset: Immediate
Mechanism: Preformed antibodies in recipient immediately attacks donor tissue
Presentation: Normally in accidental ABO incompatibility
Type II
Describe acute rejection. Onset Mechanism Presentation What type of hypersensitivity?
Onset: Weeks to months
Mechanism: Donor DC cells activate recipient lymphocytes > cytotoxic T cells generation and induction of delayed type hypersensitivity reaction (Type IV)
Presentation: Inflammation and leukocyte infiltration of graft vessels
Type IV
Describe chronic rejection
Onset
Mechanism
Presentation
Onset: Months to years
Mechanism: graft gets damaged (injury, ischemia, drugs) > body senses damage and induces macrophage and smooth muscle proliferation
Presentation: Intimal thickening and fibrosis of graft vessels
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 cell either by Fas-FasL or perforins
What type of transplantation do graft versus host response normally occur?
Small bowel
Lung
Liver
What is an acute graft versus host response?
symptoms?
Epithelial cell death in skin, liver, or GI
-rash, jaundice, diarrhea, GI hemorrhage
What is an chronic graft versus host response?
symptoms?
Fibrosis and atrophy of affected organ
-dysfunction of affected organ, small airway obliteration
What type of hypersensitivity is graft versus host response?
Type IV
