Transplantation Immunity Flashcards
What aer the 3 primary roles of the immune system
- defense against infections
- defense against tumors
- response against foreign proteins including tissue grafts (can result in pathology/tissue damage)
What are the major targets of tissue allograft rejection?
- Major histocompatibility comples molecules ( MHC) also referred to as HUman leukocyte antigen (HLA)
- antigens of tissue allografts recognized by T cells are allogeneic MHC molecules that resemble peptide-loaded self MHC molecules that the T cells have been selected to respond (basically they are the MHC molecules of the graft. foreign MHC)
- Graft alloantigens are either directly presented to recepient T cells or are picked up and indirectly presented by self APCs
Explain the alleles of MHC. How many classes of MHC are there anf how many alleles are in each class and what are they?
- There are two classes of MHC, class I and class II
- there are 6 alleles in class I (HLA-A, B, C from each parent)
- 6 alleles in class II (HLA-DR, DQ, DP)
what are the 2 alleles of MHC that have proven to be less important in transplant bc they are less likely to serve as a target for rejection?
HLA-C and HLA-DP
Describe the importance of matching for hematopoietic stem cell transplant
- in some organ transplant bc we treat with immunosuppresive therapy before transplant it doesn’t matter, but for hematoipoetic transplant it does matter. MHC matching is important. C and DP are not important so the match is typically out of 8.
What are minor antigens?
they are polymorphic mutations that may lead to reactivity. a lot of them can add up and cause an effect, but they are considered much less important that major. also you can’t match for minors only for major
Describe Direct alloantigen recognition
- the donor allogenic MHC is directly recognized by multiple self T cells eliciting an immune response. self T cell and donor MHC bind TIGHT
WHat is an indirect alloantigen recognition reaction
- A self T cell recognizes processed peptide of allogenic MHC molecule that is bound to self MHC molecule on host APC
- IOW: Foreign MHC is chewed up into peptides and is presented to self T cells via a self APC/MHC
what is autologous
transplant from yourself to yourself
allogenic
foreign
xenogenic
another animal
What is chimerism?
a mixture of donor and host
what is a hyperacute rejection
- the major barrier to xenotransplantation; occurs within minutes, but not common in clinical transplantation
what is an acute rejection
humoral or cellular in nature. typically occurs within days to weeks in non-immune suppressed individuals or months-years in suppresed individuals
what is a chronic rejection
as treatments for acute rejection have improved, this has become the major cause of graft failure. occurs within months-years; vascular changes, interstitial fibrosis, loss of renal parenchyma; get renal ischemia due to loss of glomeruli, interstitial fibrosis and tubular atrophy. can involve antiboides
How do we prevent graft rejection?
Immune suppresive drugs-cyclosporine
What is hematopoietic stem cell transplantation (HSCT)
- therapy for hematopoietic and nonhematopoetic malignancies, aplastic anemia and immune deficiencies
- used to be from bone marrow. now also peripheral blood after mobilization by growth factors or chemokine receptor inhibitors or umbilical cord blood
- recipient treated with chemotherapy and/or irradiation to eliminate malignant cells or diseased hematopietic cells
- high doses of chemo creates “space” for the incoming hSCs which are now administered intravenousl
- graft rejection and host vs graft disease can occur in HSCT
What are the problems associated with transplantation of allogenic hematopoietic stem cells
- finding a suitable donor (histocompatibility)
- graaft vs. host disease (acute and chronic)
- risk for infection (immun deficiency)
- graft rejection (failure)
- malignant disease relapse
- slow immune recovery
WHat are the key tissues that are inolved in GVHD and how do we rate GVHD
skin, liver and GI tract
GVHD is rated in stages based upon least sever to most stages 1-4
What is a mixed lymphocyte reaction
testing donor and receiver in a dish to see if it will react. Models alloreactivity
What does it mean to say that in HSCT alloreactivity is bidirectional
host can attack the graft (graft rejection)
AND/OR
graf can reject the host (host vs. graft disease)
describe the importance of major and minor histocompatibility antigens in solid organ transplant and HSCT respectively
in solid really only major matters
in HSCT major and minor matter but major is the key player
the success of both solid organ transplant and HSCT is dependent upon…..
immune suppressive drugs
What is the graft vs. tumor effect?
donor T cells attack self tumor bc it sees it as foreign
aka GVL (graft vs leukemia)
