Transplantation Flashcards
What is the indirect pathway of allorecognition?
Uses MHCII
- Donors MHC is processed in APC of the recipient.
- The donor MHC are presented as MHCII molecules
Which pathway is seen with chronic rejection?
Indirect pathway
What is hyper acute rejection?
- Minutes to hours
2. Via preformed anti donor anditbodies and complement factors
What is accelerated rejection?
- Occurs in days
2. Reactivation of sensitized T cells
What is an acute rejection?
- Occurs in days to weeks
2. Consists of primary activation f T cells
What is a chronic rejection?
- Occurs over months to years
- Caused by immunological and non-immunologic factors.
- Not manageable with immunosuppressants
Which type of cells cause cellular acute rejection?
Th1
What type of cells cause humoral acute rejection?
Th2
Explain what a hyper acute graft rejection is.
Pre-existing antibodies of the recipient (specific to the donor) already exist. Causing complement activation, endothelial damage, inflammation, thrombosis within minutes to hours.
What are different possibilities that can lead to hyperacute graft rejection?
- ABO blood group incomparable
- Recipient is sensitized to donor MHC (recipient T cells convert memory of previous exposure)
- Classical complement activation
- Endothelial death via complement
What cells have a primary role in acute graft rejection?
The donor DCs of passenger leukocytes
When is a primary immune response generated in an acute graft rejection and where does this occur?
- Primary immune response occurs when donor DC drain from the transplanted organ to the LN, and cause cell activation
What happens in acute graft rejection after the primary immune response is initiated?
- T cells migrate to donor organ and cause tissue damage.
2. Caused by CD4/CD8+ T cells
What are the 2 ways that tissue damage can occur in acute graft rejection after the primary immune response occurred?
- CTL generation
2. Induce delayed-type hypersensitivity reaction
What is a common cause of chronic rejection?
- Occlusion so far blood vessels causes organ ischemia
What are common non-immunologic factors contributing to chronic graft rejection?
- Ischemia-reperfusion damage
- Disease recurrence
- Nephrologist drug effect
What is the normal pathway activated with chronic rejection?
Indirect pathway, which normally includes Abs
What are key concepts of the graft tissue?
- Condition of the allograft
- Donor-host antigenic disparity
- Strength of host anti-donor response
- Immunosuppressive regiment
What acts as a non-immunological factor that increases local vascular permeability?
- Increase fibrinopeptides.
- From the clotting cascade and fibrin formation
- Also neutrophil and macropahge attractant
What are the early inflammatory processes that can cause allograft rejection if not properly managed?
- Fibrinopeptides to form clot
2. Production of bradykinin to cause vasodilation/ vascular permeability
What are the stages of the donor-recipient work up before transp;ant action?
- ABO blood group compatibility
- Tissue typing (HLA inspection)
- cross match recipient serums for preformed Abs against donor
- Mixed lymphocyte reaction determines donor cells proliferation of the recipient lymphocytes
Where is ABO blood matching not important?
- Cornea transplants
- Heart valve transplants
- Bone/tendon grafts
Why is ABO not contraindicated with stem cells?
No specificity has occurred yet in the stem cells
A red blood cell type A, will express which Abs, and which Ags?
Ab: Anti-B
Ag: A
A red blood cell with ABO type B express Ag/Ab of which kind?
Ag: B
Ab: anti-A
Group AB blood type will express what kind of Ag/Ab?
Ag: A and B
Ab: neither
Group O will express which kind of Ag/Ab?
Ag: none
Ab: Anti-A, Anti-B
What type of blood can A type receive?
Type A or O
What type of blood can Type B receive?
Type B and O
What type of blood can AB receive?
Can receive type A, B, O
What type of blood can type O receive?
Can only receive type O
What was the classical method of serological HLA testing?
Use of complement dependent serology (Like in micro with sheep RBC)
What is cross-matching used to test for?
Test’s the recipient serum for preformed ABs against the donor’s HLA’s which would cause rejection
What can be used to determine if the donor cells stimulate proliferation of teh recipient’s lymphocytes?
Mixed lymphocyte reaction (HLA II typing)
What is HLA II typing, mixed lymphocyte reaction?
- Determines the donor cells ability to stimulate proliferation of the recipient lymphocyte
When will no cell proliferation occur in a class II HLA typing reaction?
If the MHC II are the same then no proliferation will occur
When will cell proliferation occur in a HLA II typing mixed lymphocyte reaction?
If MHC II Ag are not the same, proliferation will occur
What type of response is a host versus graft?
Adaptive immune. When host attacks the donor tissue
What makes a host versus graft resposne rapid and dangerous?
Better than against a pathogen, bc of increased number of T cells recognizing foreign material.
What mechanisms have a large effect of activation of graft rejection?
- Humoral rejection (Th2: IL-4,-5,-10)
2. Cellular rejection (Th1: IL-2, IFN-gamma)
What is the primary role for chemotherapy while trying to generate hematopoietic stem cells?
- Prevent graft rejection
- Create niche for the HSC engraftment
- reduce tumor cells when stem cells are used to treat cancer
What is the direct pathway of allorecognition?
- The donor’s MHC molecules are recognized by the recipient’s T cells and cause activation
- Seen only with Type I MHC
