Transplant Immunology Flashcards
Isograft
syngraft
transfer of tissue between identical twins
autograft
transfer of one’s own tissue from one site to another
burn victims, coronary bypass
Allograft
transfer of tissue between genetically different members of the same species
Xenograft
heterograft
graft between members of different species
baboon heart
Orthotopic transplant
transplant into an anatomical normal recipient site
heart into chest
Heterotopic transplant
transplant into anatomically abnormal site
kidney into iliac fossa
what is transplant rejection due to?
recognition of foreign MHC antigens by T cells activation
What two transplants have low or no concern for rejection?
Corneas are not vascularized so can even transplant between unmatched individuals
RBC express no MHC but recipients still need to be matched for ABO and Rh blood types
Pig valves are not vascularized
what is a lifelong requirement of transplant recipients?
They will have to be immunosuppressed to prevent graft rejection
Agglutinogens
Antigens on the surface of RBCs that allow the immune system to recognize cell as self
Agglutinins
antibodies in the plasma
What does the H gene code for?
an enzyme that adds sugar fucose to the terminal sugar of a precursor substance
H antigen is the foundation upon which A and B antigens are built
A gene codes for enzyme (transferase)
that adds N-acetylgalactosamine to the terminal sugar of the H antigen
N-acetylgalactosaminyltransferase
B gene codes for an enzyme that adds
D - galactose to the terminal sugar of the H antigen
D-galactosyltransferase
forward typing
determines antigens on patients or donor’s blood
cells are tested with antisera reagents
reverse typing
determines antibodies in patients or donor serum or plasma
serum tested with reagent A cells and B cells
Reverse grouping is also known as back typing or serum confirmation
HLA forms part of
MHC
HLA found on what chromosome?
short arm of chromosome 6
What cells are MHC 1 found on?
Almost all nucleated cells
What cells is MHC II found on?
APCs, B cells
highly polymorphic genes
Genes of class Ia and class II
what are some genes that are not highly polymorphic?
Class Ib and class III
what are the most polymorphic HLAs?
class I HLA-B class II HLA-DR
Direct alloreactivity
Involves both CD8 and CD4 T cells
Donors APCs present to recipients Lymphocytes
self MHC recognizes the structure of an intact allogeneic MHC molecule
Indirect alloreactivity
donor MHC is processed and presented by recipient APC
so donor MHC is handled like any other foreign antigen
Involves only CD4 T cells
Antigen presentation by MHC II
Mixed Leukocyte Reaction
the higher the response
the higher the mismatch
to detect tissue incompatibilities by mixing leukocytes from potential donor with irradiated leukocytes from the potential recipient and vice versa
if mismatch donor leukocytes will proliferate and lyse host cells and vice versa
Hyperacute rejection
occurs hours to days after transplantation - once the anastomosis is complete
target is vascular endothelium -> immediate thrombosis
destruction within 24-48 hrs
Graft destruction by antibody mediated and complement dep -> coagulative necrosis
Acute rejection
most common seen
takes days to months after transplant (usually 3 months) - can 5 days or 6 months
classical, cell mediated rejection ( T cell mediated) - mostly CD4/8 T cells directed against donor MHC antigens
Target of current immunosuppression
Chronic rejection
small percent of patients
slow, indolent process months to years after transplantation
has immune and non immune components - poorly defined
causes Ischemic injury - characterized by arteriole thickening and interstitial fibrosis
untreatable
Hypersensitivity of Acute rejection
Type 2 and 4
see inflammation and swelling
Hypersensitivity of chronic rejection
Type 2 but maybe type 3 or 4
Graft vs. Host disease
seen with Bone marrow transplant
an immuno competent graft is transplanted into an immunology suppressed recipient
grafted cells survive and react against the host cells
GVH reaction is characterized by fever, pancytopenia, wt loss, rash, diarrhea, hepatosplenomegaly
What are some methods of prevention and treatment of allograft rejection?
Immunosuppression
Reduce immunogenicity of allografts
Induce donor specific tolerance
Immunosuppression is achieved by
drugs that inhibit or kill T lymphocytes
toxins that kill proliferating T cells
antibodies that deplete or inhibit T cells
anti inflammatory agents
Reduce immunogenicity of allografts by
ABO blood typing
HLA typing and matching
Induce donor specific tolerance through
Blood transfusions
