284
UNIT IV
Infection, Inflammation, and Immunity
organisms. Both types of cells rely on the recognition of spe-
cific PAMPs associated with the microorganism cell type.
NK cells are a heterogeneous population of innate
lymphocytes that mediate spontaneous cytotoxicity against
infected cells.
16
They resemble large granular lymphocytes
and are capable of killing some types of tumor and/or infected
cells without previous exposure to surface antigens. NK cells
were given their name because of their ability to mediate spon-
taneous cytotoxicity during both innate immune responses.
However, they have been shown to play an equally important
role in limiting the spread of infection and assisting in the
development of adaptive immune responses through the pro-
duction of cytokines.
16
NK cells assist in dendritic cell matu-
ration and innate immune control of viral infections. These
cells are capable of directly killing host cell infected with
intracellular (viral) or bacterial pathogenic organisms. They
comprise approximately 10% to 15% of peripheral blood lym-
phocytes but do not bear T-cell receptors (TCR) or cell surface
immunoglobulins (Igs). Two-cell surface molecules have been
identified, CD16 and CD56, which are widely used to iden-
tify NK cell activity. CD16 serves as a receptor for the IgG
molecule, which provides NK cells with the ability to lyse
IgG-coated target cells.
NK cells can be divided into two main subsets based upon
their ability to excrete proinflammatory cytokines. In addition,
they differ in their expression of inhibitory versus activating
receptors. Cells that express activating receptors (
i.e.,
NKG2D)
are induced in response to pathogen-infected or stressed cells,
whereas the inhibitory receptors on NK cells recognize patterns
(major histocompatibility complex [MHC]-I, lectins) on normal
host cells and function to inhibit the action of the NK cells.
16
This assures that only “foreign” cells are destroyed (see Fig.
13.2). In addition to their role as phagocytes, NK cells assist in
T-cell polarization, DC maturation, and innate immune control
of viral infection through the secretion of immune modulators
and antiviral cytokines.
16
Current research is investigating the
utilization of these properties of NK cells for the development
of vaccines that can modulate and direct the immune response
through enhanced cytokine activity.
Pathogen Recognition
The innate immune response plays a crucial role in the proin-
flammatory response to infection and relies upon the ability
of host defenses to differentiate self from nonself so that only
invading organisms are targeted. The leukocytes involved in
this response recognize certain evolutionarily retained pat-
terns present on the surface of pathogens and in response bind
to the membrane and destroy the invading organism through
the process of phagocytosis (Fig. 13.3).
Pattern Recognition
Invading pathogens contain conserved structures in their cell
membranes termed
pathogen-associated molecular patterns
(PAMPs
), which are recognized by the cells of the innate
immune system because they possess a limited number of
marrow into the bloodstream where they migrate into tissues
and mature into macrophages and dendritic cells where they
participate in the inflammatory response and phagocytize for-
eign substances and cellular debris. Macrophages have a long
life span, reside in the tissues, and act as the first phagocyte
that invading organisms encounter upon entering the host.
13
Neutrophils and macrophages work in concert with each other
and are crucial to the host’s defense against all intracellular
and extracellular pathogens.
13
Macrophages are essential for the clearance of bacteria
that breach the epithelial barrier in the intestine and other
organ systems.
14
They also have remarkable plasticity that
allows them to efficiently respond to environmental signals
and change their functional characteristics.
14
This makes them
more efficient phagocytic cells than the more abundant neutro-
phils. Once activated, these cells engulf and digest microbes
that attach to their cell membrane. The ability of these phago-
cytic cells to initiate this response is dependent upon the rec-
ognition of pathogenic surface structures known as PAMPs
or PRRs of which the TLRs have been the most extensively
studied.
3
Phagocytosis of invading microorganisms helps to
limit the spread of infection until adaptive immune responses
can become fully activated.
In addition to phagocytosis, macrophages and dendritic
cells process and present antigens in the initiation of the
immune response acting as a major initiator of the adaptive
immune response.
1
These cells secrete substances that initi-
ate and coordinate the inflammatory response or activate lym-
phocytes. Macrophages can also remove antigen–antibody
aggregates or, under the influence of T cells, they can destroy
malignant host or virus-infected cells.
Dendritic Cells
Dendritic cells (DCs) are specialized, bone marrow–derived
leukocytes found in lymphoid tissue and are the bridge
between the innate and adaptive immune systems. DCs take
their name from the dendrites within the central nervous sys-
tem because they have surface projections that give them a
similar appearance. DCs are relatively rare cells that are found
mainly in tissues exposed to external environments such as
the respiratory and gastrointestinal systems.
1
They are pres-
ent primarily in an immature form that is available to directly
sense pathogens, capture foreign agents, and transport them
to secondary lymphoid tissues.
15
Once activated DCs undergo
a complex maturation process in order to function as key
antigen-presenting cells (APCs) capable of initiating adaptive
immunity.
15
They are responsible for the processing and
presentation of foreign antigens to the lymphocytes. DCs, like
macrophages, also release several communication molecules
that direct the nature of adaptive immune responses.
Natural Killer Cells and Intraepithelial
Lymphocytes
NK cells and intraepithelial cells (IELs) are other cell types
involved in the innate immune response. NK cells are so
named because of their ability to spontaneously kill target
