Human Physiology, 14th edition (2016)

The Immune System 511

people are related, the closer the match between their histocom-

patibility antigens.

Interactions Between

Antigen-Presenting Cells

and T Lymphocytes

The major histocompatibility complex of genes produces two

classes of MHC molecules, designated class 1 and class 2, that

are found on the cell surface. Class-1 MHC molecules are pro-

duced by all the cells of the body except red blood cells, and

present polypeptides derived from proteins in the cell’s cyto-

plasm and nucleus. That is, the MHC class-1 molecules normally

present “self ” antigens, but they can present foreign antigens that

have entered the cell (as from a virus, discussed shortly). By con-

trast, class-2 MHC molecules are produced only by antigen pre-

senting cells—dendritic cells, macrophages, and B lymphocytes.

These cells take in foreign proteins through endocytosis, process

them, and move the foreign polypeptide antigens to the surface.

There, they present the foreign polypeptide antigens together

with their MHC class-2 molecules to helper T lymphocytes.

The helper T lymphocytes can only be activated by anti-

gens presented to them in association with class-2 MHC mol-

ecules. Killer (cytotoxic) T lymphocytes, by contrast, can be

activated to destroy a victim cell only if the cell presents anti-

gens to them in association with class-1 MHC molecules. The

different requirements for class-1 or class-2 MHC molecules

result from the presence of coreceptors, which are proteins

associated with the T cell receptors. The coreceptor known as

CD8 is associated with the killer T lymphocyte receptor and

interacts only with the class-1 MHC molecules; the corecep-

tor known as CD4 is associated with the helper T lymphocyte

receptor and interacts only with the class-2 MHC molecules.

These structures are illustrated in figure 15.14.

For example, the epidermis contains dendritic cells called
Langerhans cells, which are derived in the bone marrow and
make up 3% to 5% of the cells in the epidermis (not counting the
cornified layers), where they occupy spaces between the keratino-
cytes. These cells engulf protein antigens by pinocytosis, partially
digest these proteins into shorter polypeptides, and then move
these polypeptides to the cell surface. At the cell surface, the for-
eign polypeptides are associated with molecules called histocom-
patibility antigens (discussed in the next section). This allows the
antigen-presenting cells to activate the T lymphocytes ( fig. 15.13 ).
In order to interact with the correct T lymphocytes (those
that have specificity for the antigen), however, the dendritic
cells must migrate through lymphatic vessels to the second-
ary lymphoid organs, where they secrete chemokines to attract
T lymphocytes. This migration affords the antigen-presenting
cells the opportunity for a close encounter with the correct
T lymphocytes. A T lymphocyte that does not encounter its
antigen will not spend more than 24 hours in a lymph node, but
this time will increase to 3 to 4 days when it becomes activated
by the dendritic cells that bear its antigen. Activated T cells
divide to first produce effector T cells (those that perform their
specific functions), and then produce memory T cells.

Histocompatibility Antigens

Tissue that is transplanted from one person to another contains
antigens that are foreign to the host. This is because all tissue
cells, with the exception of mature red blood cells, are genetically
marked with a characteristic combination of histocompatibility
antigens on the membrane surface. The greater the variance in
these antigens between the donor and the recipient in a trans-
plant, the greater will be the chance of transplant rejection. Prior
to organ transplantation, therefore, the “tissue type” of the recipi-
ent is matched to that of potential donors. Because the person’s
white blood cells are used for this purpose, histocompatibility
antigens in humans are also called human leukocyte antigens
(HLAs). They are also called MHC molecules, after the name of
the genes that code for them.
The histocompatibility antigens are proteins that are coded by
a group of genes called the major histocompatibility complex
(MHC), located on chromosome number 6. These four genes
are labeled A, B, C, and D. Each of them can code for only one
protein in a given individual, but because each gene has multiple
alleles (forms), this protein can be different in different people.
Two people, for example, could both have antigen A3, but one
might have antigen B17 and the other antigen B21. The closer two

Clinical Investigation CLUES

Timmy’s mother treated his wound so that the infection

would not spread.

• What is it called if the infection spreads and stimulates
  a systemic inflammation, and what are its dangers?


• How is this condition produced, and what are its
  symptoms?

Figure 15.14 Coreceptors on helper and killer

T cells. A foreign antigen is presented to T lymphocytes in

association with MHC molecules. The CD4 on helper T cells, and

CD8 coreceptors on killer T cells, permit each type of T cell to

interact only with a specific class of MHC molecule.

CD4

coreceptor

T cell receptor

Class-2 MHC

molecule

Foreign antigen

Class-1 MHC

molecule

CD8

coreceptor

Antigen-presenting cell Target cell

Helper T cell Killer T cell