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chapter
3 5
Molecular Immunology
Cells and proteins that participate in the innate immune re-
sponse recognize generic “marker” molecules (e.g., com-
plex polysaccharides) on foreign microbes and other sub-
stances that are generally not found in the host. Attack on
the “marked” invading microorganisms by phagocytes en-
gulf and destroy the infectious organisms. These phago-
cytic cells kill infectious microbes by releasing reactive
oxygen species and nitric oxide that are produced by the
phagocyte and by releasing enzymes that initiate pro-
grammed cell death (apoptosis). Organisms that are too
large for phagocytosis, such as large parasites or worms,
are attacked by a specialized leukocyte, the eosinophil,
which is capable of injecting toxic substances into the or-
ganism to kill it.
The phagocytic cells, i.e., neutrophils, monocytes,
macrophages, and dendritic cells, are myeloid cells that
actively participate in innate immunity and are one lin-
eage of stem cell differentiation (Table 35-1). Mutations
in myeloid cells are one of the causes of the
myelocytic
leukemias.
The proteins of the complement system provide a sec-
ond line of defense for the infected host.
Complement
pro-
teins are so named because they complement the action of
the phagocytes and antibodies. However, antibodies are
not involved in the action of complement in innate im-
mune response. Complement proteins, which are present
in the circulating blood, attach covalently to bacterial cells
and undergo a series of proteolytic reactions that activate
the complement system and enhance the innate immune
response. Binding of the complement activation products
C3b and C4b and another plasma protein, CRP (C-reactive
protein, one of a group of proteins called acute phase
reactants) to the surface of foreign organisms is a pro-
cess called
opsonization.
This process labels the organism
as nonself and promotes adhesion of phagocytes to the
invading microbes, resulting in phagocytosis of the op-
sonized organisms. The terminal product of complement
activation, the membrane attack complex (MAC), creates
a pore in the organism, making the microbe permeable
to water and other solutes and ultimately causing the mi-
crobe to lyse. The MAC is composed of components C5b,
C
6
,
Cl,
C
8
, and C9 (see Table 35-3). Fragments pro-
duced during complement activation also act as chemo-
tactic and inflammatory agents and attract phagocytes to
the sites of invasion and injury and to the opsonized mi-
crobes. These potent products of complement activation
cause blood vessel dilation and facilitate the movement
of phagocytic cells from the bloodstream into the sur-
rounding tissues where the infectious organisms may be
located. The innate immune response involves only one
of three pathways by which complement is activated, i.e.,
the “alternative pathways of complement activation” (see
complement).
35.2 Acquired or Adaptive Immunity
The general mechanisms responsible for innate immunity
are inadequate to deal with all types of organisms, e.g., dif-
ferent strains of bacteria and viruses. These inadequacies
are compensated for by the specific abilities of the acquired
or adaptive immune system. Leukocytes, i.e., white blood
cells (specifically B and T lymphocytes), are the agents of
acquired immunity. B cells are so designated because they
mature in the bone marrow; T cells because they mature in
the thymus. B and T cells perform several biological pro-
cesses that are uniquely responsive to repeated infection
by foreign organisms. Adaptive immune responses that are
responsible for these unique properties of the immune sys-
tem occur in specialized regions (germinal centers) of the
lymph nodes, the spleen, and mucosal lymphoid tissues,
e.g., tonsils and adenoids.
Adaptive immunity provides a defence against some of
the pathogens that avoid the innate immune system and
can mount an attack against the evolving and ever chang-
ing characteristics of disease-causing organisms, e.g., dif-
ferent strains of bacteria and viruses, such as those that
cause influenza.
Preexisting B-lymphocytes are present from birth and
can recognize and bind antigens, more specifically
epi-
topes
(restricted portions of the antigen), on infectious
agents or foreign macromolecules. The receptors on a B-
cell surface that recognize these epitopes are antibody
molecules that are synthesized by the B cell. After en-
docytosis and processing of the bound antigen by the
B cell, the B cells are stimulated to divide and produce
more B cells. This is a cooperative interaction between
the B cells and specific T cells and signaling molecules
called
cytokines
that result in cooperative interactions
with T cells is B-cell proliferation and differentiation.
Some of the stimulated and proliferating B cells undergo
a change to a specialized variety of B cell, called a
plasma
cell.
The plasma cells synthesize large amounts of a spe-
cific antibody that recognizes an epitope on the antigen
to which the B cell was originally bound. The antibod-
ies are secreted into the extracellular fluid where they
provide a highly specific line of defense against current
and future disease-causing agents. Other stimulated B
cells differentiate to become very long-lived cells called
memory cells.
The antibodies secreted by plasma cells are distributed
to blood, lymph, and interstitial fluid where they are ca-
pable of binding to the infectious organism. Once these
antibodies react with cell surface antigens on the in-
fectious organism or foreign macromolecule, the cell
or macromolecule has a “signal” that attracts circulat-
ing complement proteins. This antibody-based component
of acquired immunity is commonly designated
humoral
