Immune Defense against Bacterial Pathogens: Innate Immunity (page 5)
(This chapter has 6 pages)
© Kenneth Todar, PhD
When invading parasites penetrate the tissues the inflammatory
previously described, is immediately brought into play. Part of this
leads to the recruitment of phagocytes to the site of inflammation. Phagocytes
are a class of cells which are capable of ingestion (engulfment) and
of microorganisms that are responsible for inciting the inflammatory
First to accumulate around the invaders and initiate the phagocytic
are neutrophils. Later, local and blood-borne macrophages
also migrate to the tissue site and initiate phagocytosis. Neutrophils
(also known as polymorphonuclear leukocytes, polymorphism or Pans) and
sometimes referred to as professional phagocytes for their
in this process.
Properties of Neutrophils
Neutrophils have their origin in multi-potential stem cells
the bone marrow. They differentiate in the marrow and are released in a
mature form, containing a full complement of bactericidal agents. They
are short-lived cells which constitute 30-70% of the circulating white
blood cells (leukocytes).
During differentiation in the marrow (2-3 days) the nucleus of the
becomes multilobed (hence the name polymorphonuclear leukocyte),
cell division ceases, and mitochondria and endoplasm reticule
from the cytoplasm. At the same time the cell becomes motile and
phagocytic. Cytoplasmic granules are formed from the Golgi apparatus.
granules are called lysosomal and contain the various
and digestive enzymes which can destroy bacterial cells after
The contents of lysosomal granules include lysozyme, cationic proteins,
acid hydrolyses, protease's, peroxidase and lactoferrin. Neutrophils
contain large stores of glycogen. Since they derive most of their
energy from glycolysis, they can function efficiently in anaerobic
Some additional properties of neutrophils are:
-Only half the neutrophils in human circulation are detectable in
blood; the rest adhere to vessel walls.
-For every circulating neutrophils, approximately 100 near mature
are held in reserve in the bone marrow pool.
-Once a neutrophils enters the tissues, intestinal tract or
tract, it never returns to the circulation.
Properties of Macrophages
Macrophages (also called mononuclear phagocytes) also
arise from bone marrow stem cells which give rise to monocytes which
develop into monocytes that are released into the blood stream.
Monocytes make up 3-7% of the circulating white blood cells. The
is actively phagocytic and bactericidal. Within 2 days or so, the
stream monocytes (sometimes called wondering macrophages) emigrate into
the tissues where they settle down, enlarge and become fixed
(tissue histiocytes), which also have phagocytic potential. Macrophages
are more active in phagocytosis than monocytes and develop many more
containing hydrolytic enzymes. New macrophages can develop by cell
under inflammatory stimuli, but most macrophages are matured blood
The total pool of macrophages is referred to as the system of
phagocytes. The system is scattered throughout connective tissue,
membranes of small blood vessels, liver sinusoids, spleen, lung ,
marrow and lymph nodes. Monocytes from the blood migrate into virtually
every organ in the body where they mature into fixed macrophages. In
lymph nodes, macrophages function as scavengers to remove foreign
Compared to neutrophils, macrophages are long-lived cells. As
neutrophils play a more important role in the acute stages of an
while macrophages are principally involved in chronic types of
Neutrophils circulate in the blood stream, and during an acute
response they migrate through the endothelial cell junctions as part of
the inflammatory exudate. They migrate to the focus of the infection
ingest or phagocytose foreign agents, Neutrophils which have become
engorged with bacteria usually die and largely make up the material of
pus. Macrophages, which are also attracted to the area during an
response, are slower to arrive and become increasingly involved in
infections. They, too, are actively phagocytic and will engulf and
foreign particles such as bacteria. However, macrophages have another
function in host defense: they "process" the antigenic components of
agents and present them to lymphocytes, a process that may usually
for the initiation of immunological responses of the host.
Macrophages and related dendritic cells are
among an elite corps of antigen-presenting cells or APC's.
The Phagocytic Process
Phagocytosis and destruction of engulfed bacteria involves
following sequence of events:
1. Delivery of phagocytic cells to the site of infection
2. Phagocytic adherence to the target
3. Ingestion or engulfment of the target particle
4. Phagolysosome formation
5. Intracellular killing
6. Intracellular digestion (and egestion, in the case of
These steps involved in the phagocytic process in
are illustrated below.
Figure 6. Phagocytosis by a
Macrophage. A bacterium, which may or may not be opsonized, is engulfed
by the process of endocytosis. The bacterium is ingested in a
vesicle called the phagosome. Digestive granules (lysosomes) merge with
phagosome, release their contents, and form a structure called the
The killing and digestion of the bacterial cell takes place in the
The macrophage egests debris while processing the antigenic components
of the bacterium, which it returns to its surface in association with
II for antigen presentation to TH cells.
Delivery of phagocytic cells to the site of
The delivery of phagocytic cells, monocytes or neutrophils, to
site of microbial infection involves two processes:
Diapedisis: the migration of cells across vascular walls
is initiated by the mediators of inflammation (kinins, histamine,
Chemotaxis. Phagocytes are motile by ameboid action.
is movement of the cells in response to a chemical stimulus. The
concentration of phagocytes at a site of injury results from
response by the phagocytes which is analogous to bacterial chemotaxis.
A number of chemotactic factors (attractants) have been identified,
for neutrophils and monocytes. These include bacterial products, cell
tissue debris, and components of the inflammatory exudate such as
derived from complement.
Phagocytosis is initiated by adherence of a particle to the surface
of the plasma membrane of a phagocyte. This step usually involves
types of surface receptors on the phagocyte membrane. Three major
on phagocytes recognize the Fc portion of IgG: one is for monomeric IgG
and the others are for antigen-crosslinked IgGs. Another receptor binds
a complement factor C3b. Other phagocyte receptors bind fibronectin and
mannose-terminated oligosaccharides. Under certain circumstances of
bacteria or viruses may become coated or otherwise display on their
one or another of these substances (i.e., IgG, C3b, fibronectin or
Such microbes are said to be opsonized and such substances as
or complement C3b bound to the surface of microbes are called opsonins.
(Opsonin comes from a Greek word meaning "sauce" or "seasoning": they
the microbe more palatable and more easily ingested by the
Opsonins provide extrinsic ligands for specific receptors on the
membrane, which dramatically increases the rate of adherence and
of the pathogen. Opsonized bacteria can be cleared from the blood by
many types of non opsonized bacteria cannot be cleared.
Less firm attachments of a phagocyte to a particle can take place in
the absence of opsonization. This can be thought of as nonspecific
which might be due to net surface charge on the phagocyte or particle
hydrophobicity of the particle.
Lastly, in the absence of any specific interaction between the phagocyte and microbe
phenomenon called surface phagocytosis may take place: a
can simply trap an organism against a surface and initiate ingestion.
phagocytosis may be an important pre-antibody defense mechanism which
determines whether an infection will become a disease and how severe the
disease will become.
After attachment of the phagocyte to its target, some sort of signal
generation, which is poorly understood, results in physical or chemical
changes in the cell that triggers ingestion. Ingestion is an engulfment
process that involves infolding or invagination of the cell membrane
the particle and ultimately releasing it into the cytoplasm of the cell
within a membrane vesicle. The end result of ingestion is entry of the
particle enclosed in a vesicle derived from the plasma membrane of the
cell. This structure is called the phagosome.