Transplantation Immunology Flashcards
autograft
from one part of the body to another (e.g trunk to arm)
isograft
btwn genetically identical individuals (e.g. monozygotic twins or inbred)
allograft
between different members of the same species (e.g. tom and paul)
xenograft
between members of different species (e.g. pig to human)
most transplanted organ
kidney and liver
failure of skin grafting caused by an inflammatory reaction is called
rejection
graft rejection is a result of an
adaptive immune response
transplantation of cells or tissues from one individual to a genetically nonidentical individual invariably leads to rejection of the transplant because of an _______
adaptive immune response
Which are not rejected?
A. Cells or organs transplanted between genetically nonidentical people
or members of two different inbred strains of a species
B. The offspring of a mating between two different inbred strains e.g. an (A
× B) F1 animal accepting grafts from an A or B strain animal ( violates HSC transplantation)
C. A graft derived from the offspring of a mating between two different
inbred strains of animal a graft from e.g. an (A × B) F1 animal onto a A or B strain animal
D. Cells or organs transplanted between genetically identical individuals
(identical twins or members of the same inbred strain of animals)
B. The offspring of a mating between two different inbred strains e.g. an (A
× B) F1 animal accepting grafts from an A or B strain animal ( violates HSC transplantation)
D. Cells or organs transplanted between genetically identical individuals
(identical twins or members of the same inbred strain of animals)
Which are rejected?
A. Cells or organs transplanted between genetically nonidentical people
or members of two different inbred strains of a species
B. The offspring of a mating between two different inbred strains e.g. an (A
× B) F1 animal accepting grafts from an A or B strain animal ( violates HSC transplantation)
C. A graft derived from the offspring of a mating between two different
inbred strains of animal a graft from e.g. an (A × B) F1 animal onto a A or B strain animal
D. Cells or organs transplanted between genetically identical individuals
(identical twins or members of the same inbred strain of animals)
A. Cells or organs transplanted between genetically nonidentical people
or members of two different inbred strains of a species
C. A graft derived from the offspring of a mating between two different
inbred strains of animal a graft from e.g. an (A × B) F1 animal onto a A or B strain animal
syngeneic graft is …
Not rejected
Fully allogeneic is ….
rejected
graft from inbred parental strain is … by F1 hybrid
not rejected
graft from F1 hybrid is …. by inbred parental strain
rejected
Negative selection is ….
the process that
eliminates developing lymphocytes
whose antigen receptors bind strongly
to self-antigens present in the generative lymphoid organs.
The cell death (Apoptosis) is due to a combination of
factors, including:
- Failure to productively rearrange the TCR β chain gene and thus to fail the preTCR/β,
- Failure to be positively selected by self MHC molecules in the thymus,
- Self antigen–induced negative selection
The polymorphic class I and class II MHC molecules
are the ones whose function is to display peptide
antigens for recognition by
CD8+ and CD4+ T cells
t/f The products of different MHC alleles bind and display
different peptides, different individuals in a
population may present different peptides even from
the same protein antigen.
true
3 class I MHC genes
- HLA-A
- HLA-B
- HLA- C
3 class II MHC genes
- HLA-DP
- HLA-DQ
3.HLA-DR
MHC haplotype
set of MHC alleles present on each chromosome
In humans, the MHC is located on the short
arm of chromosome __ and occupies a large
segment of DNA, extending about ____
kilobases (kb)
6, 3500
T cells of a graft recipient recognize intact, unprocessed MHC
molecules in the graft is called what?
Direct alloantigen
recipient’s MHC molecules must be presenting peptides
derived from allogeneic donor MHC proteins to recipient T
cells is called what?
indirect alloantigen
characterization of Hyperacute rejection
thrombotic occlusion of the graft vasculature that begins within minutes to hours after host blood vessels are anastomosed to graft vessels and is mediated by preexisting antibodies
in the host circulation that bind to donor endothelial
antigens
T/F complement activation, endothelial damage, inflammation and thrombosis occurs in hyperacute rejection
true
mechanism of acute cellular rejection
CTL-mediated killing of graft parenchymal cells and endothelial cells and inflammation caused by cytokines produced by helper T cells
Treg inhibits …
dendritic cell
naive T cell
effector T cells
B cells
NK cells
Tregs appear to suppress immune responses at
- Production of the immunosuppressive cytokines IL10 and TGF
β. - Reduced ability of APCs to stimulate T cells.
- Consumption of IL2
what interleukin maintain Treg?
IL2
The major barrier to grafting embryonic
stem cells is …
alloantigenicity and rejection by the recipient’s immune system.
Solutions of using iPS cells (3) using adult somatic tissues by transduction of certain genes, derive from somatic cells harvested from the pt and remove MHC gene from allogeneic embryonic stem cells by CRISPR-Cas genome editing technology
- using adult somatic tissues by transduction of certain genes
- derive from somatic cells harvested from the pt
- remove MHC gene from allogeneic embryonic stem cells by CRISPR-Cas genome editing technology
t/f Allogeneic HSCs are rejected by even a minimally immunocompetent
host, and therefore, the donor and recipient must be carefully matched
at all MHC loci.
true
t/f GVHD is caused by the reaction of grafted mature T cells in the HSC inoculum with alloantigens of the host.
true
t/f The consequence of immunodeficiency is that HSC transplant recipients are susceptible to viral infections, especially
cytomegalovirus, bacterial and fungal infections. Also EpsteinBarr virus–provoked B cell lymphomas
true
N-acetylgalactosamine is present in which blood type?
A
there’s more galactose in which blood group?
B
antibody/antigen in blood group A
B/A
antibody/antigen in blood group B
A/B
antibody/antigen in blood group AB
No antibody/antigen A & B
antibody/antigen in blood group O
antibody A & B, none
T/F immune synapse is the site of signaling machinery of the T cell, the TCR complex, coreceptors, costimulatory receptors and adaptors
true
functions of immune synapse
- facilitates prolonged and effective T cell signaling through TCR
- ensures delivery of secretory granule contents and cytokines from a T cell to APCs or to targets in contact w/ the T cell
- important site for turnover of signaling molecules
Antigen presenting cells (APCs)
dendritic cells, macrophages and B cells
T/F Matching of major histocompatibility complex
(MHC) alleles between the donor and recipient
significantly improves renal allograft survival.
true
T/F Alloantibodies cause acute rejection by binding to alloantigens mainly HLA molecules, on vascular
endothelial cells, leading to endothelial injury and
intravascular thrombosis that result in graft destruction
True
Functions of Alloantibodies (4)
- cause acute rejection by binding to alloantigens, mainly HLA molecules, on vascular endothelial cells, leading to endothelial injury and intravascular thrombosis that result in graft destruction.
- triggers local complement activation, which causes
lysis of the cells, recruitment and activation of neutrophils,
and thrombus formation. - engage Fc receptors on
neutrophils and NK cells, which then kill the endothelial
cells. - may directly alter endothelial function by inducing intracellular signals that enhance surface expression of proinflammatory and procoagulant molecules.
t/f graft vasculopathy (arterial change) is a result of chronic rejection
true
_________ is frequently seen in failed cardiac and renal
allografts and can develop in any vascularized organ transplant within 6 months to a year after transplantation
Graft vasculopathy
mechanism of occlusive vascular lesions of chronic rejection
activation of alloreactive T cells and secretion of
IFNγ and other cytokines that stimulate proliferation of vascular
smooth muscle cells.
___ stimulates the survival, proliferation, and differentiation of
T lymphocytes, acting as an autocrine growth factor, leading to the generation of
effector and memory cells.
IL-2
corticosteroids decrease what inflammatory cells
dendritic cell, macrophage, mast cell,T lymphocyte, eosinophil
corticosteroids decrease what in epithelial cells
cytokines , mediators
corticosteroids decrease what in endothelial cells
leak
corticosteroids decrease what in mucus gland
mucus secretion
corticosteroids decrease and increase what in airway smooth muscle
increase B2 receptors
decrease cytokines
corticosteriods suppresses what inflammatory stimuli?
IL-1B, TNF-a
inflammatory gene
GM-CSF, COX-2
site of action of cyclosporine and tacrolimus
calcineurin
site of action of glucocorticoids
glucocorticoid response elements in DNA (regulate gene transcription)
site of action of muromonab-cd3
t cell receptor complex (blocks antigen recognition)
site of action of azathioprine
DNA
site of action of mycophenolate
inosine monophosphate dehydrogenase (inhibits activity)
site of action of daclizumab (basilixiimab)
IL-2 receptor (block IL-2 mediated T cell activation)
site of action of of siroliums
protein kinase involved in cell cycle progression (mTOR) (inhibits activity)
