286
UNIT IV
Infection, Inflammation, and Immunity
inflammatory process including acute-phase proteins, lec-
tins, and complement. Components of the adaptive immune
response can also act as opsonins. For example, when the
humoral response is activated, IgG and IgM antibodies can
coat cellular particles on pathogens and bind to Fc receptors
on neutrophils and macrophages, enhancing the phagocytic
function of innate cells.
Inflammatory Cytokines
Cytokines are low molecular weight proteins that serve as sol-
uble chemical messengers and which mediate the interaction
between immune and tissue cells. They are part of an integrated
signaling network with extensive functions in both the innate
(nonspecific) and adaptive immune defenses. The cytokines
involved in innate immunity include TNF-
α
and lymphotoxin;
interferons (IFN-
γ
, IFN-
α
, IFN-
β
); the interleukins IL-1, IL-6,
and IL-12; and chemokines (see Table 13.2). These substances
modulate innate immunity by stimulating the development of
cells involved in both innate and adaptive immunity, produc-
ing chemotaxis within leukocytes, stimulating acute-phase pro-
tein production, and inhibiting viral replication. Once an innate
immune phagocyte is activated via PRR–PAMP with a patho-
gen, cytokines are released into the surrounding tissues where
they exert their effect. If large numbers of cells are activated,
then cytokines may be able to stimulate inflammatory processes
in tissues far from the initial site of infection. Under normal
circumstances, the duration of activity of cytokines is relatively
short so that a prolonged immune response does not occur.
gram-negative bacteria. TLR2 binds to peptidoglycan, which
is an essential component of the cell wall of gram-positive
bacteria. Finally, TLR5 can recognize the protein flagellin
found in flagellated bacteria. In addition to their role in the
immune response, TLRs have been shown to have a patho-
logic role in disorders such as atherosclerosis, allergies, and
certain autoimmune diseases.
21,22
Soluble Mediators of Innate
Immunity
While cells of the innate immune system communicate critical
information about invading microorganisms and self–nonself
recognition through cell-to-cell contact, soluble mediators are
also essential for many other aspects of the innate immune
response. Development of innate immune response is very
much dependent upon the secretion of soluble molecules such
as opsonins, cytokines, and acute-phase proteins.
Opsonins
Opsonins are molecules that coat negatively charged par-
ticles on cell membranes and as a result enhance the recog-
nition and binding of phagocytic cells to microorganisms.
The process by which the cellular particles on microbes
are coated is called
opsonization
. Once the opsonin binds
to the microbe, it is able to activate the phagocyte after
attachment to a PRR on the phagocytic cell. There are sev-
eral opsonins important in innate immunity and the acute
B
cell
B-cell receptor
Plasma
cell
Antibody
Characteristics
Recognition
Different
microbes
Identical
mannose
receptor
Different
microbes
Distinct
antibodies
Receptors
Cellular
expression
Self–nonself
discrimination
Effector cell types express identical receptors (e.g.,
neutrophils express Toll-like receptors).
Yes, by recognizing molecules unique to pathogen,
NK cells recognize MHC-I self-recognizing molecules.
Each clone of lymphocytes expresses unique
receptors.
Yes, lymphocytes use MHC-I and -II and foreign
peptides (e.g., microbial peptides in recognition).
Innate immunity
Adaptive immunity
Molecular patterns common to microbes
Specific microbial molecules
Limited diversity expressed by germline genes
Toll-like receptor
Mannose receptor
Great diversity expressed through
recombination of somatic genes
FIGURE 13.3
•
Recognition systems of innate and adaptive immunity.
