Page 513 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART VII Immunology
502
CD4-positive cell if it contacts a cell bearing class II major
histocompatibility complex (MHC) proteins but will dif-
surface proteins are different from those of thymus-derived
ferentiate into a CD8-positive cell if it contacts a cell bear-
lymphocytes. IELs cannot substitute for thymus-derived
lymphocytes because patients with DiGeorge’s syndrome
ing class I MHC proteins. (Mutant mice that do not make
class II MHC proteins will not make CD4-positive cells,
who lack a thymus (see Chapter 68) are profoundly immu-
indicating that this interaction is required for differentia-
The thymus involutes in adults, yet T cells continue to
tion into single-positive cells to occur.) The double-nega-
tive cells and the double-positive cells are located in the
be made. Two explanations have been offered for this
apparent paradox. One is that a remnant of the thymus
cortex of the thymus, whereas the single-positive cells are nodeficient and have multiple infections.
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remains functional throughout life and the other is that an
located in the medulla, from which they migrate out of the
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extrathymic site takes over for the involuted thymus. Indi-
thymus into the blood and extrathymic tissue.
Within the thymus, two very important processes called
viduals who have had their thymus removed still make T
thymic education occur:
(1) CD4-positive, CD8-positive cells bearing antigen
Origin of B Cells
receptors for “self” proteins are killed (clonal deletion)
by a process of programmed cell death called apoptosis
B-cell precursors differentiate into immunocompetent B
(Figure 58–2). The removal of these self-reactive cells, a
cells in the bone marrow; they do not pass through the
thymus. Analogous to T cells, B cells also undergo clonal
process called negative selection, results in tolerance to
our own proteins (i.e., self-tolerance) and prevents autoim-
for self proteins, a process that induces tolerance and
mune reactions (see Chapter 66).
reduces the occurrence of autoimmune diseases (see Chap-
For negative selection to be efficient, the thymic epithe- deletion (apoptosis) of those cells bearing antigen receptors
ter 66). Note that B cells bearing an antigen receptor for a
lial cells must display a vast repertoire of self proteins. A
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self protein can escape clonal deletion by a process called
transcriptional regulator called the autoimmune regulator
receptor editing. In this process, a new, different light
(AIRE) enhances the synthesis of this array of self proteins.
Mutations in the gene encoding the AIRE protein results in
tor so that it no longer recognizes a self protein. It is esti-
the development of an autoimmune disease called autoim-
mated that as many as 50% of self-reactive B cells undergo
mune polyendocrinopathy.
receptor editing. T cells do not undergo receptor editing.
(2) CD4-positive, CD8-positive cells bearing antigen
receptors that do not react with self MHC proteins
Origin of Natural Killer Cells
(See Figure 58–2) are also killed. This results in a positive
selection for T cells that react well with self MHC proteins.
Natural killer (NK) cells are large granular lymphocytes
These two processes produce T cells that are selected for
gen receptor, and do not bear CD4 or CD8 proteins. They
their ability to react both with foreign antigens via their
recognize and kill target cells, such as virus-infected cells
antigen receptors and with self MHC proteins. Both of that do not pass through the thymus, do not have an anti-
and tumor cells, without the requirement that the antigens
these features are required for an effective immune response
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be presented in association with class I or class II MHC
by T cells.
proteins. Rather, NK cells target those cells to be killed by
Note that MHC proteins perform two essential func-
tions in the immune response: one is the positive selection
the cell surface. This detection process is effective because
of T cells in the thymus, as just mentioned, and the other,
many cells lose their ability to synthesize class I MHC pro-
which is described later, is the presentation of antigens to
teins after they have been infected by a virus (see page 516).
T cells, the initial step required to activate those cells. MHC
proteins are also the most important antigens recognized in
Origin of Macrophages
the graft rejection process (see Chapter 62).
During their passage through the thymus, each double-
tiate from lymphoid stem cells, macrophages arise from
positive T cell synthesizes a different, highly specific anti-
myeloid precursors. Macrophages have two important
gen receptor called the T-cell receptor (TCR). The
rearrangement of the variable, diversity, and joining genes In contrast to T cells, B cells, and NK cells, which differen-
functions, namely, phagocytosis and antigen presentation.
(see Chapter 59) that encode the receptor occurs early in
They do not pass through the thymus and do not have an
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T-cell differentiation and accounts for the remarkable abil-
antigen receptor. On their surface, they display class II
ity of T cells to recognize millions of different antigens.
MHC proteins, which play an essential role in antigen pre-
Some T lymphocytes, perhaps as much as 40% of the
total, do not develop in the thymus but rather in the gut-
MHC proteins, as do all nucleated cells. The cell surface
proteins that play an important role in the immune
associated lymphoid tissue (GALT). These intraepithelial
response are listed in Table 58–2.
lymphocytes (IELs) are thought to provide protection
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