Nelson- Transplant Rejection Flashcards
Define autograft
self to self
skin graft
Define isograft
syngenic b/t 2 identical twins
define allograft
Between genetically different individuals of the same species
Define xenograft
between 2 species
porcine heart valve to human
Using one word, state the major barrier to successful transplantation.
REJECTION
recipient’s IS recognizes the graft as being foreign and attacks it
cell mediated or Ab mediated
State the two groups of antigens that are most important in determining the likelihood of transplant rejection.
ABO and HLA compatible grafts have better chance of avoiding rejection
ABO-endothelial cells
HLA- MHCI (all nucleated cells), MHC II (APCs)
*most impt are HLA-A, B, C, minor importance DR
What is cellular rejection? How does it vary?
T cell mediated graft rejection
Destruction of donated graft cells by recipient CD8 T cells
Delayed hypersensitivity rxns triggered by activated recipient CD4 T helper lymphocytes
**Rejection depends on differences in highly pleomorphic HLA alleles
What are the two pathways by which recepient’s T cells recognize the donor alloantigens?
Direct
Indirect
Explain direct cellular rejection.
- Donor MHC I and II antigens on APCs are recognized by host CD8 and CD4 T cells
- CD4 T cells> proliferate> produce IFNy> local delayed hypersensitivity reaction
- CD8T cells> CTLS> kill graft cells
Explain indirect cellular rejection and how does it relate to humoral rejection.
- Graft antigens are picked up and displayed by host APC.
- CD4 T cells are activated> proliferate> produce IFNy> local delayed hypersensitivity
- CD4 T cells stimulate B lymphocytes > produce Ab (humoral rejection
What are the major types of pre-formed alloantibodies?
Abs to ABO blood group antigens (naturally occurring
Preformed anti-HLA Abs (pregnancy, previous transfusion, prevoius transplant)
What type of rejection reaction is possible if preformed Abs are present?
Hyperactue rejection reaction
What is the rationale for pre-transplant testing?
Key immonological factors affect graft survival:
ABO compatibility
close matching of HLA loci
absence of preformed anti-HLA Abs
What does pretransplant testing include?
ABO compatibilty testing of donor and recipient
HLA typing of donor and recipient
detection of pre-formed anti-HLA ab in recipients serum
Lymphocyte cross match- react recipient serum against donor lymphocytes
What is the difference in terms of timing of hyperacute, actue and chronic rejection?
hyperacute- begins suddnely w/ in minutes-hrs of transplant
acute- days to wks
chronic- months/yrs
What is the immunological mechanism of hyperacute rejection? What type of sensitivity is this?
Incompatible ABO Ab or preformed anti HLA Ab bind endothelial Ag>
complement activation>
vessel thrombi and ischemic necrosis
Type II hypersensitivity
What is the immunological mechanism of acute rejection? What type of sensitivity is this?
Cell mediated hypersensitivity- host CD4 T cells release cytokines, activating host macrophages and CD8 T cells
Ab mediated hypersensitivity rxns- host CD4 T cells release cytokines which promote B cells to differentiatie into plasma cells> produce anti-HLA Abs that bind endothelial Ag
What is the immunological mechanism of chornic rejection? What type of sensitivity is this?
Often secondary to vascular injury
result of both cell-mediated and ab-mediated hypersensitivity rxns
Which type of rejection is the most common cause of renal graft failure?
Chronic rejection
What is seen pathologically w/ all three rejections? W/ which one is the deposition of C4d seen?
Hyperacute: vascular thrombosis> acute fibrinoid necrosis
Acute cell mediated: inflammatory cells in interstitium and b/t endothelial cells
Actue humoral: inflammatory cells and proliferating smooth muscle cells in blood vessel> vasculitis> thrombosis> fibrosis/narrowing> ischemic injury *C4d
Chronic: graft atherosclerosis (vascular lumen repleaced by cells)
What are the major complications associated w/ immunosuppresssive therapy in the transplant setting?
- Increased susceptibility to opportunistic infections/ common community required disease
- Increased risk of malignancies (EBV, SCC, KS)
What is a hematopoietic cell transplant? What is it used to treat? What are the two types?
Administration of hematopoietic cells from source to reconstitute BM
Malignancies, aplastic anemias, thalassemias, some immunodeficiencies
Autologous
allogenic
What is an autologous HCT?
HPC derived from individual w/ disorder
What is an allogenic HCT?
HPCs from someone else
What is GVHD?
Immunologically competent donor T cells recognize the recipients HLA antigens as foreign and react against them
Host is unable to mount IR against grafted lymphocytes
Allows graft lymphocytes to attack host
What is used to prevent GVHD and when is their no risk of GVHD?
HLA typing for allogenic HCT donor
Autologous HCT
What causes acute GVHD?
Occurs cytokines > cell injury
What organs are involved w/ acute GVHD?
skin- severe dermatitis
liver- destruction of bile ducts> jaundice
GI tract- mucosal ulceration > bloody diarrhea
What organs are involved in chronic GVHD?
> 100 days following allogenic HCT
skin-loss of appendages w/ dermal fibrosis
liver- chronic liver disease > cholestatic jaundice
GI tract- fibrous structures, malabsorption, chronic diarrhea
lungs- obliterative bronchiolitis
