Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 3Immunity, Infection, & Inflammation 73

IMMUNOGLOBULINS

Circulating antibodies protect their host by binding to and
neutralizing some protein toxins, by blocking the attachment
of some viruses and bacteria to cells, by opsonizing bacteria
(see above), and by activating complement. Five general types
of immunoglobulin antibodies are produced by the lympho-
cyte–plasma cell system. The basic component of each is a sym-
metric unit containing four polypeptide chains (Figure 3–10).
The two long chains are called heavy chains, whereas the two
short chains are called light chains. There are two types of light
chains, k and λ, and eight types of heavy chains. The chains are
joined by disulfide bridges that permit mobility, and there are
intrachain disulfide bridges as well. In addition, the heavy
chains are flexible in a region called the hinge. Each heavy
chain has a variable (V) segment in which the amino acid se-
quence is highly variable, a diversity (D) segment in which the
amino acid segment is also highly variable, a joining (J) seg-
ment in which the sequence is moderately variable, and a con-
stant (C) segment in which the sequence is constant. Each light

chain has a V, a J, and a C segment. The V segments form part

of the antigen-binding sites (Fab portion of the molecule [Fig-

ure 3–10]). The Fc portion of the molecule is the effector por-

tion, which mediates the reactions initiated by antibodies.

Two of the classes of immunoglobulins contain additional

polypeptide components (Table 3–3). In IgMs, five of the

basic immunoglobulin units join around a polypeptide called

the J chain to form a pentamer. In IgAs, the secretory immu-

noglobulins, the immunoglobulin units form dimers and tri-

mers around a J chain and a polypeptide that comes from

epithelial cells, the secretory component (SC).

In the intestine, bacterial and viral antigens are taken up by

M cells (see Chapter 27) and passed on to underlying aggre-

gates of lymphoid tissue (Peyer’s patches), where they acti-

vate naive T cells. These lymphocytes then form B cells that

infiltrate mucosa of the gastrointestinal, respiratory, geni-

tourinary, and female reproductive tracts and the breast.

There they secrete large amounts of IgAs when exposed again

to the antigen that initially stimulated them. The epithelial

cells produce the SC, which acts as a receptor for and binds

the IgA. The resulting secretory immunoglobulin passes

through the epithelial cell and is secreted by exocytosis. This

system of secretory immunity is an important and effective

defense mechanism.

GENETIC BASIS OF DIVERSITY

IN THE IMMUNE SYSTEM

The genetic mechanism for the production of the immensely

large number of different configurations of immunoglobulins

produced by human B cells is a fascinating biologic problem.

FIGURE 3–9 Summary of acquired immunity. (1) An antigen-
presenting cell ingests and partially digests an antigen, then presents
part of the antigen along with MHC peptides (in this case, MHC II pep-
tides on the cell surface). (2) An “immune synapse” forms with a naive
CD4 T cell, which is activated to produce IL-2. (3) IL-2 acts in an auto-
crine fashion to cause the cell to multiply, forming a clone. (4) The ac-
tivated CD4 cell may promote B cell activation and production of
plasma cells or it may activate a cytotoxic CD8 cell. The CD8 cell can
also be activated by forming a synapse with an MCH I antigen-present-
ing cell. (Reproduced with permission from McPhee SJ, Lingappa VR, Ganong WF
[editors]: Pathophysiology of Disease, 4th ed. McGraw-Hill, 2003.)

MHC class II

CD4

TCR

IL-1

CD4

Activated

T cell

IL-2R IL-2

Inflammation

and delayed

hypersensitivity

Cytokine-

induced

activation

Activated B cell

Antibody-

producing cell

1

2

3

4

Macrophage

(antigen-

presenting

cell)

CD8

IL-2R

MHC class I

Cytotoxic

T cell

4

4

Cell death

FIGURE 3–10 Typical immunoglobulin G molecule. Fab, por-

tion of the molecule that is concerned with antigen binding; Fc, effec-

tor portion of the molecule. The constant regions are pink and purple,

and the variable regions are orange. The constant segment of the

heavy chain is subdivided into CH1, CH2, and CH3. SS lines indicate in-

tersegmental disulfide bonds. On the right side, the C labels are omit-

ted to show regions JH, D, and JL.

SS SS

SS

SS

Antigen-

binding

site

Complement

binding

Macrophage

binding

Fab

Fc

Hinge

VH

VL VL

VH

JL

JHD

CL

CH 1

CH 2

CH 3