Ganong's Review of Medical Physiology, 23rd Edition

panel of monoclonal antibodies. Most cytotoxic T cells display
the glycoprotein CD8, and helper T cells display the glycoprotein
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 readily
converted to effector cells by a later encounter with the same
antigen. This ability to produce an accelerated response to a second
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 receptors
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 appropriate
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 reactive
with self antigens are normally deleted. This results in immune
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
CHAPTER 3 Immunity, Infection, & Inflammation 71
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 histocompatibility
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 function.
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 25to
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 synthesized
within cells. The peptides to which the host is not
tolerant (eg, those from mutant or viral proteins) are recognized
by T cells. The digestion of these proteins occurs in
α 1
C
β2m
FIGURE 3–6 Structure of human histocompatibility antigen
HLA-A2. The antigen-binding pocket is at the top and is formed by the
α1 and α2 parts of the molecule. The α3 portion and the associated β2 microglobulin (β2m) are close to the membrane. The extension of the C
terminal from α3 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
N
C
α 2
α3