Chapter 16 Flashcards
Transplantation of tissues from one individual to a
genetically nonidentical recipient leads to?
a specific immune response called rejection that can
destroy the graft. The major molecular targets in
allograft rejection are allogeneic class I and class II
MHC molecules.
Allogeneic MHC molecules may be presented on
donor APCs to recipient T cells (the direct
pathway), or who else?
the alloantigens may be picked up by
host APCs that enter the graft or reside in draining
lymphoid organs and be processed and presented
to T cells as peptides associated with self MHC
molecules (the indirect pathway)
The frequency of T cells capable of recognizing
allogeneic MHC molecules is very high, explaining what?
why the response to alloantigens is much stronger
than the response to conventional foreign antigens.
Graft rejection is mediated by what?
T cells, including
CTLs that kill graft cells and helper T cells that
cause cytokine-mediated inflammation resembling DTH reactions, and by antibodies.
Several effector mechanisms cause rejection of
solid organ grafts, and each mechanism may lead
to a histologically characteristic reaction. Preexisting antibodies cause what?
hyperacute rejection characterized by thrombosis of graft vessels. Alloreactive
T cells and antibodies produced in response to the
graft cause blood vessel wall damage and parenchymal cell death, called acute rejection
Chronic
rejection is characterized by what?
fibrosis and vascular
abnormalities (graft vasculopathy), which may represent blood vessel damage and ischemic injury
to parenchyma due to a T cell- and cytokinemediated inflammatory reaction in the walls of
arteries.
Graft rejection may be prevented or treated how?
immunosuppression of the host and by minimizing the immunogenicity of the graft (by limiting
MHC allelic differences). Most immunosuppression is directed at T cell responses and entails the
use of cytotoxic drugs, specific immunosuppressive agents, or anti–T cell antibodies
A widely
used immunosuppressive agent is cyclosporine which does what?
which blocks T cell antigen receptor signaling
linked to cytokine synthesis. Immunosuppression
is often combined with anti-inflammatory drugs
such as corticosteroids that inhibit cytokine synthesis by macrophages and other cells.
Patients receiving solid organ transplants may
become what?
immunodeficient because of their therapy
and are susceptible to viral infections and malignant tumors.
Xenogeneic transplantation of solid organs is
limited by what?
the presence of natural antibodies to
carbohydrate antigens on the cells of discordant
species that cause hyperacute rejection, antibodymediated acute vascular rejection, T cell–mediated
immune response to xenogeneic MHC molecules,
and prothrombotic effects of xenogeneic endothelium on human platelets and coagulation
proteins.
The ABO blood group antigens are a set of what?
polymorphic carbohydrate structures present on blood
cells and endothelium that limit transfusions and
some solid organ transplantations between individuals
Preexisting natural anti-A or anti-B IgM
antibodies are present in individuals who do not
express what?
s A or B antigens on their cells, respectively,
and these antibodies can cause transfusion reactions and hyperacute allograft rejection
Hematopoietic stem cell transplants are susceptible
to rejection, and recipients require what?
intense preparatory immunosuppression. In addition, T lymphocytes in the bone marrow graft may respond
to alloantigens of the host and cause GVHD
Acute
GVHD is characterized by what?
epithelial cell death in
the skin, intestinal tract, and liver; it may be fatal.
Chronic GVHD is characterized by fibrosis and
atrophy of one or more of these same target organs
as well as the lungs and may also be fatal. Bone
marrow transplant recipients also often develop
severe immunodeficiency, rendering them susceptible to infections.
