Page 549 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART VII Immunology
538
MHC genes and proteins are also important in two
the donor cells. CD8-positive cytotoxic T cells do most of
other medical contexts. One is that many autoimmune
the killing of the allograft cells.
diseases occur in people who carry certain MHC genes (see
Chapter 66), and the other is that the success of organ
Foreign MHC proteins typically activate many more
T cells (i.e., they elicit a much stronger reaction) than do
transplants is, in large part, determined by the compatibil-
ity of the MHC genes of the donor and recipient (see later).
the response to foreign MHC proteins can be explained by
the observation that there are two processes by which the
TRANSPLANTATION 1 foreign proteins that are not MHC proteins. The strength of
recipient’s immune response is stimulated.
These processes are as follows:
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An autograft (transfer of an individual’s own tissue to
another site in the body) is always permanently accepted
(1) The direct process in which the donor’s antigen-
(i.e., it always “takes”). A syngeneic graft is a transfer of
tissue between genetically identical individuals (i.e., identi-
(APC) from the graft can present either the donor’s or the
1
cal twins) and almost always “takes.” A xenograft, a trans-
recipient’s proteins in association with their class I and class
fer of tissue between different species, is always rejected by
II MHC proteins and activate the recipient’s immune
an immunocompetent recipient.
response in the draining lymph node. This process results
1
An allograft is a graft between genetically different
in activation of the recipient’s cytotoxic T cells that kill
members of the same species (e.g., from one human to
the cells of the graft. This is the main mechanism of the
another). Allografts are usually rejected unless the recipient
is given immunosuppressive drugs. The severity and rapid-
teins can be recognized as foreign by the recipient’s immune
ity of the rejection will vary depending on the degree of the
cells (to which they would ordinarily be tolerant) when
differences between the donor and the recipient at the acute graft rejection process. Note that the recipient’s pro-
presented by a foreign MHC protein.
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MHC loci.
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(2) The indirect process in which the recipient’s anti-
gen-presenting cells present the donor’s proteins. The
donor’s self proteins and class I and class II MHC proteins
Allograft Rejection
Unless immunosuppressive measures are taken, allografts
APC that enter the graft. The APC then migrates to the
are rejected by a process called the allograft reaction. In an
draining lymph node where it activates the recipient’s
acute allograft reaction, vascularization of the graft is nor-
helper T cells and B cells. This process typically results in
mal initially, but in 11 to 14 days, marked reduction in
production of antibodies against the graft and is thought
circulation and mononuclear cell infiltration occurs, with
to be important in the chronic rejection process.
eventual necrosis. This is called a primary (first-set) reac-
A graft that survives an acute allograft reaction can nev-
tion. A T-cell–mediated reaction is the main cause of
ertheless become nonfunctional as a result of chronic rejec-
rejection of many types of grafts (e.g., skin), but antibodies
tion. This can occur months to years after engraftment. The
contribute to the rejection of certain transplants, especially
bone marrow. In experimental animals, rejection of most
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tion is atherosclerosis of the vascular endothelium. The
types of grafts can be transferred by cells, not serum. Also,
immunologic stimulus that causes chronic rejection is likely
T-cell–deficient animals do not reject grafts, but B-cell–
to be incompatibility of minor histocompatibility antigens
deficient animals do. The role of cytotoxic T cells in
which are allelic variants of normal proteins that differ in
allograft rejection is described on page 511.
the donor and recipient. The adverse effects of long-term
If a second allograft from the same donor is applied to a
use of immunosuppressive drugs are likely to play a role in
sensitized recipient, it is rejected in 5 to 6 days. This accel-
chronic rejection as well.
erated (second-set) reaction is caused primarily by presen-
In addition to acute and chronic rejection, a third type
sitized cytotoxic T cells.
called hyperacute rejection can occur. Hyperacute rejec-
The acceptance or rejection of a transplant is deter-
mined, in large part, by the class I and class II MHC pro-
due to the reaction of preformed anti-ABO antibodies in
teins on the donor cells, with class II playing the major
the recipient with ABO antigens on the surface of the endo-
role. The proteins encoded by the DR locus of class II are
thelium of the graft. Hyperacute rejection is often called the
especially important. These donor alloantigens activate tion typically occurs within minutes of engraftment and is
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“white graft” reaction, because the graft turns white as a
recipient T cells, both helper and cytotoxic, which bear
result of the loss of blood supply caused by spasm and
T-cell receptors specific for the alloantigens. The activated
occlusion of the vessels serving the graft. In view of this
and recipients must be matched and a cross-matching test
(see later) must be done. The laboratory tests used to deter-
1
Previously used synonyms for these terms include isograft (syngeneic
mine ABO blood groups are described in Chapter 64.
graft), heterograft (xenograft), and homograft (allograft).
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