Ganong's Review of Medical Physiology, 23rd Edition

70 SECTION I Cellular & Molecular Basis for Medical Physiology
responses, such as endothelial and epithelial cells. The activated
cells produce their effects via the release of cytokines, as
well as, in some cases, complement and other systems.
An important link in innate immunity in Drosophila is a
receptor protein named toll, which binds fungal antigens and
triggers activation of genes coding for antifungal proteins. An
expanding list of toll-like receptors (TLRs) have now been
identified in humans. One of these, TLR4, binds bacterial
lipopolysaccharide and a protein called CD14, and this initiates
a cascade of intracellular events that activate transcription of
genes for a variety of proteins involved in innate immune
responses. This is important because bacterial lipopolysaccharide
produced by gram-negative organisms is the cause of septic
shock. TLR2 mediates the response to microbial lipoproteins,
TLR6 cooperates with TLR2 in recognizing certain peptidoglycans,
and TLR9 recognizes the DNA of certain bacteria.
ACQUIRED IMMUNITY
As noted previously, the key to acquired immunity is the ability
of lymphocytes to produce antibodies (in the case of B
cells) or cell-surface receptors (in the case of T cells) that are
specific for one of the many millions of foreign agents that
may invade the body. The antigens stimulating production of
T cell receptors or antibodies are usually proteins and
polypeptides, but antibodies can also be formed against nucleic
acids and lipids if these are presented as nucleoproteins and
lipoproteins, and antibodies to smaller molecules can be produced
experimentally if the molecules are bound to protein.
Acquired immunity has two components: humoral immunity
and cellular immunity. Humoral immunity is mediated by
circulating immunoglobulin antibodies in the γ-globulin fraction
of the plasma proteins. Immunoglobulins are produced
by differentiated forms of B lymphocytes known as plasma
cells, and they activate the complement system and attack and
neutralize antigens. Humoral immunity is a major defense
Bone marrow
lymphocyte
precursors
Thymus
T lymphocytes
B lymphocytes
Bursal equivalent
(liver, bone marrow)
Helper T cells
(CD4 T cells)
FIGURE 3–5 Development of the system mediating acquired immunity.
against bacterial infections. Cellular immunity is mediated by
T lymphocytes. It is responsible for delayed allergic reactions
and rejection of transplants of foreign tissue. Cytotoxic T cells
attack and destroy cells that have the antigen which activated
them. They kill by inserting perforins (see above) and by initiating
apoptosis. Cellular immunity constitutes a major defense
against infections due to viruses, fungi, and a few
bacteria such as the tubercle bacillus. It also helps defend
against tumors.
DEVELOPMENT OF THE IMMUNE SYSTEM
During fetal development, and to a much lesser extent during
adult life, lymphocyte precursors come from the bone marrow.
Those that populate the thymus (Figure 3–5) become
transformed by the environment in this organ into T lymphocytes.
In birds, the precursors that populate the bursa of
Fabricius, a lymphoid structure near the cloaca, become transformed
into B lymphocytes. There is no bursa in mammals,
and the transformation to B lymphocytes occurs in bursal
equivalents, that is, the fetal liver and, after birth, the bone
marrow. After residence in the thymus or liver, many of the T
and B lymphocytes migrate to the lymph nodes.
T and B lymphocytes are morphologically indistinguishable
but can be identified by markers on their cell membranes. B
cells differentiate into plasma cells and memory B cells.
There are three major types of T cells: cytotoxic T cells,
helper T cells, and memory T cells. There are two subtypes
of helper T cells: T helper 1 (TH1) cells secrete IL-2 and γinterferon
and are concerned primarily with cellular immunity;
T helper 2 (TH2) cells secrete IL-4 and IL-5 and interact
primarily with B cells in relation to humoral immunity. Cytotoxic
T cells destroy transplanted and other foreign cells, with
their development aided and directed by helper T cells. Markers
on the surface of lymphocytes are assigned CD (clusters of
differentiation) numbers on the basis of their reactions to a
Memory
T cells
Memory
B cells
Cytotoxic
T cells
(mostly CD8
T cells)
Plasma
cells
Cellular
immunity
IgG
IgA
IgM
IgD
IgE
Humoral
immunity