ABSTRACT
The environment contains a large array of potential pathogens, such
as bacteria, viruses, parasites, fungi, chemicals, drugs, and pollen. To
protect themselves from potentially nefast foreign invaders, humans
have a laborious network of cells, molecules, and mechanisms
that collectively are referred to as the immune system, both
innate and adaptive. The direct aim of the immune system is to
differentiate between self and nonself and to neutralize and remove
the intruder.1,2
Of interest to this study is the innate immunity with which
an individual is born and is always present and available at very
short notice for protection from challenges by foreign invaders.1,3
It accomplishes a wide variety of activities within minutes after
invasion of the pathogen, including recognition and effector func-
tions. The former involves the recognition of structures present
in pathogens that are distinct from self. The effector functions
include the release of substances exerting direct antimicrobial
properties and production of cytokines and chemokines that recruit
inflammatory cells to the infection site. The innate responses
use cellular and molecular components, and the extent of the
reactions remains constant regardless of previous exposure to
the same pathogen. It was believed for many years that the
innate immune response is nonspecific and nonselective. This
dogma has been challenged by the discovery that innate immune
responses are triggered by cellular pattern recognition receptors
(PRRs) located on the plasma membrane or inside cells. They
recognize specific conserved structures of invading pathogens
called pathogen-associated molecular patterns (PAMPs).3 The most
important classes of PRRs are the toll-like receptors (TLRs) and
the lectin-like receptors. TLRs recognize a wide variety of microbial
structures, including lipopolysaccharide (LPS) of Gram-negative
bacteria (TLR4), lipoteichoic acid and lipoproteins of Gram-positive
bacteria (TLR2), bacterial DNA (TLR9), and viral RNA (TLR3,
TLR7 and TLR8).3,4 Lectin-like receptors are PRRs specialized in
the recognition of polysaccharide chains of bacterial pathogens,
including the mannans and glucans of pathogenic fungi.5,6
The cellular components of innate immunity comprise phago-
cytic cells, such asmacrophages, monocytes, and neutrophils, aswell
as cells that release inflammatorymediators, such as basophils, mast
cells, and eosinophils, in addition to natural killer cells. Phagocytic
cells of the innate immune system consist of certain types of
polymorphonuclear leukocytes (PMNs) and phagocytic monocytes
(macrophages). Upon activation, these cells release cytokines, which
have different effects on various cells. PMNs are a population of
cells also referred to as granulocytes. About 98% of the PMNs
are neutrophils, 1-2% eosinophils, and 0.1-0.2% basophils. The
neutrophils are the most important circulating phagocytes. They
form the body’s first line of defense against invading particles,
especially bacteria. PMNs migrate into the inflammatory site and
kill the invading microorganisms by releasing toxic peroxide and
superoxide radicals. Mononuclear phagocytes are cells giving rise
to the circulating phagocytic monocytes, ultimately maturing into
mobile or fixed macrophages, which, in turn, play an important role
in phagocytosis in tissue.1,2
Phagocytosis is defined as a defense mechanism of innate immunity,
mediated by specialized cells for ingestion and destruction of the
invading foreign particles. This process is an evolutionarily ancient
host cell endocytic response discovered by Elie Metchnikoff in the
nineteenth century. The process of phagocytosis includes several
steps: adhesion, or recognition of the particle as an initiation of
ingestion; invagination of the outer cell membrane and enclosure
of the particle within a phagocytic vacuole, the “phagosome”; and
internalization, fusion with the granules, or lysosomes, forming
a “phagolysosome,” which contains a mixture of active agents.7
In the phagolysosome, the pathogen is killed by exposure to
enzymes, antimicrobial peptides, and reactive oxygen species
(ROS).2 Digestion products are then released from the cell into
the environment. Phagocytosis is performed by blood monocytes,
neutrophils (i.e., PMNs), and tissue macrophages. Phagocytosis may
be enhanced by a variety of factors that make the foreign particle
an easier target by a process called opsonization, or recognition of
the foreign particle. Opsonization is the process whereby particles,
such as microorganisms, become coated with molecules, allowing
them to bind to receptors on phagocytes, facilitating recognition
and full acceptance by such cells. Antibodies (especially IgG) and
complement proteins, like C3b, can opsonize and are, therefore,
referred to as opsonins.1,2