CHAPTER 10
Lymphoid System
185
Figure 10-4A.
A representation of T-lymphocyte maturation.
H&E,
3
19 (thymus);
3
200 (spleen)
T cells
are derived from
pro–T lymphocytes
, which migrate from the bone marrow to the thymus where they undergo cell division to generate
a large number of developing lymphocytes (
thymocytes
). As thymocytes undergo the differentiation process, they begin to express
TCR
and
other cell-surface proteins. Some of the maturation markers of T cells help them to recognize and interact with
MHC
molecules. In order to
survive and mature, thymocytes must negotiate both
positive
and
negative selection processes
.
Positive selection
involves promoting survival
of only those thymocytes that are able to interact at an appropriate level with
self-MHC molecules
, a capacity essential to their ability to
mount effective immune responses.
Negative selection
involves destruction of thymocytes that have too strong an interaction with
self-MHC
molecules
; these cells have the potential to contribute to autoimmune disease, and they are removed by macrophages. Positive selection occurs
in the cortex of the thymus and negative selection mainly in the medulla. It has been estimated that only 1% to 2% of thymocytes survive
these selection processes and complete differentiation to become immunocompetent T cells (naive T cells). Naive T cells leave the medulla
of the thymus through the circulation and migrate to the speciF c regions of the secondary lymphoid organs where they may encounter the
foreign antigen
that they are programmed to recognize. If antigen stimulation occurs, virgin T cells become active, undergo cell division, and
give rise to clones composed of both
memory T cells
and
effector T cells
. Memory T cells can be found in the paracortex of the lymph nodes
and may migrate to infl ammatory sites and give rise to effector T cells. Effector cells include
helper T cells
,
cytotoxic T cells
, and
regulatory (sup-
pressor) T cells
. Each effector cell has either
CD4
or
CD8
as a surface marker. Effector cells participate in
cell-mediated immune responses
.
Figure 10-4B.
A representation of helper T-cell and cytotoxic T-cell maturation markers.
Each
T lymphocyte
has in its plasmalemma numerous
TCRs
, each with the same antigen recognition site. Each T cell also has either
CD4
or
CD8 molecules
that act as essential
coreceptors
with the TCR. In the early stages of T-cell development, each thymocyte has both CD4
+
and
CD8
+
markers, and mature T cells have either CD4 or CD8 markers, but not both.
CD8
+
cells
have the capacity to recognize and react to their
speciF c antigen only if it is presented by another cell in association with MHC class I. All nucleated cells of the body express MHC class I
and present fragments of internally synthesized peptides on their surface MHC class I molecules. If any cell in the body becomes infected
by a virus and synthesizes viral proteins, fragments of these viral proteins are presented as foreign antigens by the cell’s surface MHC class I
molecules. If such a virus-infected cell is encountered by a cytotoxic T cell (CD8
+
cells) that bears TCRs that recognize one of the viral antigens,
the cytotoxic T cell will become activated and destroy the virus-infected cell.
CD4
+
cells
recognize their speciF c antigen only if it is presented
by another cell in association with MHC class II. MHC class II is expressed by antigen-presenting cells. If an antigen-presenting cell presents
antigen to a CD4
+
(helper T cell) that recognizes the antigen, the helper T cell will become activated to provide signals that promote activation
of other lymphocytes. The illustration on the left shows helper T cells with TCR and surface marker CD4. TCR is an antigen receptor that
is speciF c to the peptide that is attached to the groove of the MHC II molecule on the macrophage. This peptide presents a foreign antigen
to helper T cells. The illustration on the right shows TCR and CD8 markers on the cytotoxic T cells’ surface. TCR of the cytotoxic T cell
responds to antigen presented in association with MHC I molecules of the infected cells. Once a cytotoxic T cell recognizes a nonself antigen,
it releases
perforins
and
enzymes
from granules to kill the infected cells as well as some tumor cells, grafted cells, and virus-infected cells.
MHC I
Cytotoxic T cells
CD8
CD8
TCR
Virus-infected cell
MHC II
Peptide
Helper
T cells
CD4
CD4
TCR
Antigen-presenting cell
(macrophage)
Perforins
B
Circulation
PALS
PALS
PALS
Pro–T lymphocytes
in bone marrow
Pro–T lymphocytes develop
into lymphoblasts in thymus
Migrate to T–cell regions
(example of PALS in spleen)
Memory T Cell
(CD 4 and CD 8 cells)
Pro–T lymphocytes
Pro–T lymphocytes
CD8
CD4
CD4
TCR
TCR
TCR
Cytotoxic
T cells
Virgin/naive T cells
(medulla)
Activated effector T cells
Helper
T cells
Regulatory
(suppressor) T cells
Thymocytes
Thymocytes
(cortex)
(cortex)
Thymocytes
(cortex)
Pro–T lymphocytes
A
T Lymphocytes
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