Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 3Immunity, Infection, & Inflammation 71

panel of monoclonal antibodies. Most cytotoxic T cells display
the glycoprotein CD8, and helper T cells display the glycopro-
tein CD4. These proteins are closely associated with the T cell
receptors and may function as coreceptors. On the basis of
differences in their receptors and functions, cytotoxic T cells
are divided into αβ and γδ types (see below). Natural killer
cells (see above) are also cytotoxic lymphocytes, though they
are not T cells. Thus, there are three main types of cytotoxic
lymphocytes in the body: αβ T cells, γδ T cells, and NK cells.

MEMORY B CELLS & T CELLS

After exposure to a given antigen, a small number of activated B
and T cells persist as memory B and T cells. These cells are readi-
ly converted to effector cells by a later encounter with the same
antigen. This ability to produce an accelerated response to a sec-
ond exposure to an antigen is a key characteristic of acquired
immunity. The ability persists for long periods of time, and in
some instances (eg, immunity to measles) it can be lifelong.
After activation in lymph nodes, lymphocytes disperse
widely throughout the body and are especially plentiful in
areas where invading organisms enter the body, for example,
the mucosa of the respiratory and gastrointestinal tracts. This
puts memory cells close to sites of reinfection and may
account in part for the rapidity and strength of their response.
Chemokines are involved in guiding activated lymphocytes to
these locations.

ANTIGEN RECOGNITION

The number of different antigens recognized by lymphocytes
in the body is extremely large. The repertoire develops initially
without exposure to the antigen. Stem cells differentiate into
many million different T and B lymphocytes, each with the
ability to respond to a particular antigen. When the antigen
first enters the body, it can bind directly to the appropriate re-
ceptors on B cells. However, a full antibody response requires
that the B cells contact helper T cells. In the case of T cells, the
antigen is taken up by an antigen-presenting cell and partially
digested. A peptide fragment of it is presented to the appropri-
ate receptors on T cells. In either case, the cells are stimulated
to divide, forming clones of cells that respond to this antigen
(clonal selection). Effector cells are also subject to negative
selection, during which lymphocyte precursors that are reac-
tive with self antigens are normally deleted. This results in im-
mune tolerance. It is this latter process that presumably goes
awry in autoimmune diseases, where the body reacts to and
destroys cells expressing normal proteins, with accompanying
inflammation that may lead to tissue destruction.

ANTIGEN PRESENTATION

Antigen-presenting cells (APCs) include specialized cells
called dendritic cells in the lymph nodes and spleen and the

Langerhans dendritic cells in the skin. Macrophages and B

cells themselves, and likely many other cell types, can also

function as APCs. In APCs, polypeptide products of antigen

digestion are coupled to protein products of the major histo-

compatibility complex (MHC) genes and presented on the

surface of the cell. The products of the MHC genes are called

human leukocyte antigens (HLA).

The genes of the MHC, which are located on the short arm

of human chromosome 6, encode glycoproteins and are

divided into two classes on the basis of structure and func-

tion. Class I antigens are composed of a 45-kDa heavy chain

associated noncovalently with β 2 -microglobulin encoded by a

gene outside the MHC (Figure 3–6). They are found on all

nucleated cells. Class II antigens are heterodimers made up of

a 29- to 34-kDa α chain associated noncovalently with a 25-

to 28-kDa β chain. They are present in antigen-presenting

cells, including B cells, and in activated T cells.

The class I MHC proteins (MHC-I proteins) are coupled

primarily to peptide fragments generated from proteins syn-

thesized within cells. The peptides to which the host is not

tolerant (eg, those from mutant or viral proteins) are recog-

nized by T cells. The digestion of these proteins occurs in

FIGURE 3–6 Structure of human histocompatibility antigen

HLA-A2. The antigen-binding pocket is at the top and is formed by the

α 1 and α 2 parts of the molecule. The α 3 portion and the associated β 2 -

microglobulin (β 2 m) are close to the membrane. The extension of the C

terminal from α 3 that provides the transmembrane domain and the small

cytoplasmic portion of the molecule have been omitted. (Reproduced with

permission from Bjorkman PJ et al: Structure of the human histocompatibility

antigen HLA-A2. Nature 1987;329:506.)

N

C

C

N

α 1 α 2

β 2 m

α 3