Transplantation Flashcards
What is an autologus graft (isograft)?
a graft transplanted from an individual to the same individual
What is a syngeneic graft?
a transplant between two genetically identical individuals
What is an allogeneic graft?
a transplant between two genetically dissimilar individuals of the same species
What is a xenogeneic graft?
a transplant between members of two different species
What are orthotopic grafts?
is a graft that is placed in its normal anatomic location
What is a heterotropic graft?
A transplant placed in an anatomically different site
What are first and second set rejections?
Basically first and second immune responses to grafts
What are immunologicall privileged sites?
locations in the body where an allogeneic transplant can be placed without risk of rejection
What are the three reasons for immunologically privileged sites?
- Extracellular fluid does not leave through lymph system
- TGF-beta released at these sites
- Fas ligand expressed on cells to induce T cell apoptosis
What is Sympathetic ophthalmia?
an eye disease that occurs when one eye is damaged by trauma and an autoimmune response to eye proteins ensues to threaten the undamaged eye
Are transplants between identical twins ever rejected?
Rarely
Are transplants between genetically dissimilar individuals rejected?
Almost always
Can children give grafts to parents or vice versa?
No
What are the molecules that are being rejected in grafts?
MHC class I and II
How fast do hyperacute rejections take place? What is the mechanism behind this?
within minutes, due to complement being activated by memory antibodies, and causing thrombosis
What are examples of hyperacute rejections?
Incorrect blood transfusions
How long do acute rejections take to develop?
1 month
What are the two mechanisms behind acute rejection?
- Acute humoral rejection d/t antibody and complement mediated lysis of graft tissue
- Acute cellular rejection caused by cell mediated lysis by CTLs
What is the treatment for acute rejections?
increased immunosuppression such as high dose steroid therapy or anti-T cell antibodies
How long does chronic rejection take place?
Over months / years
What is the pathogenesis of chronic rejection?
Not totally known, but there are fibrotic changes in the graft
What is the pathogenesis of graft rejection?
Host APCs present MHC proteins of graft as foreign molecules via the class II pathway.
How are CTLs activated against grafts, if the grafts do not have self MHC cells?
T cells recognize self peptide with foreign MHC. Basically fools T cells.
True or false: either dendritic cells from the donor (direct) or recipient (indirect) can be used to activate graft rejection
True
What are the three means through which grafts are destroyed in the acute rejection?
- CD8+ CTLs lyse graft cells
- CD4+ T cells recruit macrophages
- Alloantibodies activate complement
What are minor histocompatability antigens?
none MHC factors that may generate an immune response
What happens after dendritic cells present MHC molecules to host T cells?
CD4+ Th cells prodive IL-2 and IFN-gamma to activate CD8 T cells to produce CTLs
What are the three strategies used to reduce graft rejection?
- Select compatible graft
- Immunosuppression
- Deplete passenger leukocytes from graft
What is the effect of corticosteroids?
Lyse immature thymocytes, block release of cytokines from macrophages, inhibit leukocyte migration
What is the mech of action of cyclosporine?
Inhibits IL-2 and IFN-gamma
What is the major drawbacks of cyclosporin?
It’s nephrotoxic
What is anti-lymphocyte globulin and how does it work?
Horse immunogloin against human lymphocytes. Kills all human lymphocytes to prolong graft
What is graft-versus-host disease?
When bone marrow cells attack the rest of the body
What causes acute GVHD?
mature T cells responding to host alloantigens.
How can you remove the T cells from bone marrow transplants?
in vitro treatment with anti-CD3 monoclonal antibodies (along with Complement)
Why would you want to have some variation in HLA type for leukemia pts?
To kill CA
What is the chemical given to bone marrow donors to increase stem cells/ spill into blood?
Granulocyte colony-stimulating factor (G-CSF)
What are the three major mechanisms that prevent a mother’s body from killing a fetus?
- Trophoblasts cells do not express paternal MHC proteins
- Trophoblast cells secrete TGF-beta
- Y is broken down at fetal-materal interface, diabling T lymphocytes
Why does the liver carry an increased risk of GVHD?
Has a lot of donor lymphocytes
What is the function of HLA-G expressed by fetal trophoblast cells?
Inhibits NK cells
What are the three steps involved in the activation of CTLs against a graft?
- Dendritic cells present antigen to CD4+ T cells
- CD4+ T cells release IL-2 and IFN-gamma to stimulate CTLs.
- CTLs kill via CD8+/MHC I graft cells
What is the difference between direct and indirect stimulation of T cells in graft rejection?
Direct = using donor’s dendritic cells
Indirect = using recipients dendritic cells
What is the mechanism of action for cyclosporine?
Inhibits the expression of IL-2 and IFN-gamma, preventing CTL formation.
Cyclosporine is not good at inhibiting secondary immune responses. What is the effect of this?
Pts retains ability to fight off infections that he/she has already been exposed to.
