Flashcards in Transplant Rejection Deck (27):
Define autograft and give an example
self to self donation - like a skin graft
syngeneic between identical twins
a transplant between genetically different individuals of the same species
a transplant between two species - like a pig heart valve to humans
What's the major barrier to successful transplantation?
Is rejection a cell-mediated or antibody-mediated issue?
both can be involved
What two groups of antigens are most important in determining the likelihood of transplant rejection?
ABO antigens and MHC (HLA typing)
What are the four HLA loci that are most involved in transplant rejection?
HLA-A, HLA-B, HLA-C, HLA-DR
Describe the process of direct cellular rejection.
DONOR nor class 1 and 2 MHC antigens on APCs in the graft are recognized by host CD8+ cytotoxic T cells and CD4 T cells.
The CD4 cells produce cytokines which induce tissue damage by a delayed hypersensitivity reaction
the CD8 cells kill the graft cells
(so donor antigen is presented by donor APCs to host cells)
Describe the process of indirect cellular rejection
Graft antigens are picked up, processed and displayed on HOST APCs to activate CD4 T cells, which damage the graft by local delayed HSR and stimulate B lymphocytes to produce antibodies
(so donor antigen is presented by host APCs to host cells)
What are the major types of pre-formed alloantibodies
antibodies to ABO blood group antigens (naturally occurring)
pre-formed anti-HLA antibodies (after pregnancy, previous transfusion or previous transplant)
What type of rejection reaction occurs if there are preformed antibodies present?
hyperacute rejection reaction
Antibody-dependent acute humoral rejection is usually manifested in what?
afftects the vasculature and results in rejection vasculitis
What does pretransplant testing include?
1. ABO compatability of donor and recipient
2. HLA typing of donor and recipient
3. Detection of pre-formed anti-HLA antibodies in recipient's serum
4. Performance of a lymphocyte cross-match (recipients serum with donor lymphocytes)
What are the three types of rejection?
hyperacute, acute and chronic
What happens in hyperacute rejection?
immediately type II antibody-mediated hypersensitivity reaction with preformed anti-HLA antibodies or ABO incompatibility
you get vessel thrombi and ischemic necrosis within minutes to hours
(almost never happens - clerical error)
What happens in acute rejection?
It's a cell-mediated hypersensitivity reaction with host CD4 cells releasing cytokines, activation host macrophages and CD8 cells or from antibody-mediated hypersensitivity reactions
Occurs over days to weeks
What happens in chronic rejection?
it's both cell-mediated and antibody-mediated HSRs that occurs over months and years
What is the most common type of rejection in the US and why?
chronic - because immunosuppression mainly controls acute rejection
What are the two major complications of immunosuppressive therapy in the transplant setting?
increased susceptibility for opportunistic infections (and community acquired infections diseases too)
Increased risk of malignancies (squamous cell carcinoma of skin, kaposi sarcoma, etc.)
What is an autologous hematopoietic cell transplantation?
you use hemaotpoietic progenitor cells derived from the individual with the disorder - you use their own cells
What is an allogeneic hematopoietic cell transplantation?
you use the projenitor cells from someone else
What's the main risk in doing an allogeneic hematopoietic cell transplantaiton?
graft vs host disease: the immunocompetent T cells from the DONOR may recognize host cells as foriegn and attack the new host
How can GVHD be avoided?
Do appropriate HLA typing and irradiate the blood before transfusion
Describe what happens in acute GVHD? WHat organs are usually affected?
Arbitrarily occurs in the first 100 days
direct cytotoxicity by CD8 cells as well as injury from cytokines released by CD4 cells - typically skin, liver and GI tract epithelium most affected
Describe what happens in chronic GVHD? What organs are usually affected?
Arbitrarily occurs after the first 100 days - either a continuation of acute or a new onset
you get dermal fibrosis, chronic liver disease with jaundice and fibrous structures in the GI tract - malabsorption and chronic diarrhea. lungs may show obliterative bronchiolitis