18. Tissue Transplants (Rejection) Flashcards
Graft rejection occurs based on
immunological principles
How is the degree and type of immune response varied?
with type and source of grafted tissue
Name four types of graft possible:
- Autograft
- Isograft
- Allograft
- Xenograft
What two types of graft are usually accepted?
Autograft and isograft
Autograft
self-tissue grafted to another self area (skin, blood vessels)
Isograft
transplant between two genetically identical individuals (inbred strains of mice, identical twins)
Allograft
tissue transferred between genetically different members of the same species (majority of transplants)
Xenograft
tissue transferred between different species (baboon heart into a human)
First set rejection
complete 12-14 days after the first graft; memory of the anti-graft response is generated
Second set rejection
complete much faster, within 5-6 days; due to memory response generated after first set rejection
What is the role of T cells in graft rejection?
T cells mediate graft rejection; primarily CD4+ T cells, but CD8+ also play a small role
Explain what happens when splenic T cells from a first set rejection mouse (necrosis of tissue) are placed into a first skin graft mouse.
second set rejection induced
Histo-compatible
tissues which are antigenically similar
Histo-incompatible
tissues which are antigenically dissimilar
Which loci are most likely to lead to rejection in transplantation scenarios?
MHC genes
What percent chance do siblings have of MHC match?
25%
What percent chance do parent to offspring transplants have of MHC match? Why?
50% due to always having one MHC haplotype in common
Blood group and AG differences have what effect on transplants:
They produce the most intense graft rejections
What compatibility is first checked in donor/recipient matching?
Blood group Ag found on RBCs, epithelial and endothelial cells
What compatibility is checked second in donor/recipient matching?
MHC compatibility
What would allow organ transplant between mismatched people?
Anti-rejection drugs
List the four steps of the Sensitization Stage.
- CD4+ and CD8+ T cells recognize alloantigens expressed on foreign graft cells
- The T cells proliferate in response
- Recognize the donor MHC molecules directly
- Memory T cells generated
List the three components of the Effector Stage.
- Variety of mechanisms participate in effector stage of graft rejection
- Heavy infiltration of recipient cells into graft tissue, similar to a DTH reaction
- Production of antibodies against donor HLA molecules or endothelial Ag
Acute Rejection is mediated by what type of response?
T cell response
Which type of rejection occurs through mechanisms described for effector stage?
acute rejection
Which type of rejection induces a massive infiltration of lymphocytes and macrophages, which leads to proliferation of T cells?
acute rejection
One year kidney graft survival rates were what percentage in US in 2008?
97%
Ten year kidney graft survival rates were what percentage in US in 2008?
60%
Chronic rejection mechanisms include both humoral and cell-mediated recipient responses. T or F?
TRUE
When does Chronic Rejection occur?
months or years after acute rejection reactions have subsided
Immunosuppressive therapy can be either ___________ or _____________.
general or target specific
Monoclonal antibodies achieve what desired effect?
immunosuppressive
How might T cells be depleted prior to transplant? Why?
monoclonal antibodies to CD3; to suppress immune response and increase chances for graft acceptance
Soluble CTLA-4 fusion proteins can induce what in T cells?
anergy
Ideal Specific Immunosuppressive Therapy would be:
specific
Some “immunologically privileged sites” are characterized by what components?
Allografts in such areas are less likely to experience rejection, while some organs are more amenable to clinical transplantation than others or easier to obtain surgically. In some cases, harvest cells may be transferred.
What are some examples of “immunologically privileged sites”?
- Corneal transplants are highly successful (no lymphatics)
- Cartilage, heart valves
Is immune tolerance to allografts favored in certain instances?
Yes; Tregs
-Presence and activities of TREG cells found in clinical operational tolerance cases
-Situations where grafts are tolerated after complete removal of anti-rejection drugs
-Involvement of TREG cells and their cytokines in prevention of rejection is an area of active research
