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Innate immunity refers to antigen-nonspecific defense mechanisms that
a host uses immediately or within several hours after exposure to an
antigen
.
This is the immunity one is born with and is the initial response
by the body to eliminate microbes and prevent infection.
Unlike
adaptive immunity, innate immunity does not recognize every possible
antigen. Instead, it is designed to recognize a few highly
conserved structures present in many different microorganisms. The
structures recognized are called pathogen-associated molecular
patterns and include LPS from the gram-negative cell wall,
peptidoglycan, lipotechoic acids from the gram-positive cell wall, the
sugar mannose (common in microbial glycolipids and glycoproteins but
rare in those of humans), bacterial DNA, N-formylmethionine found in
bacterial proteins, double-stranded RNA from viruses, and glucans from
fungal cell walls. Most body defense cells have pattern-recognition
receptors for these common pathogen-associated molecular patterns
and so there is an immediate response against the invading
microorganism. Pathogen-associated molecular patterns can also be
recognized by a series of soluble pattern-recognition receptors in the
blood that function as opsonins and initiate the complement pathways.
In all, the innate immune system is thought to recognize approximately
103 molecular patterns. All of this will be discussed in
greater detail in upcoming sections.
The innate immune responses
involve:
-
phagocytic
cells (neutrophils, monocytes, and macrophages);
-
cells that
release inflammatory mediators (basophils, mast cells, and
eosinophils);
-
natural
killer cells (NK cells); and
-
molecules
such as complement proteins, acute phase proteins, and cytokines.
Examples of
innate immunity include anatomical barriers, mechanical removal,
bacterial antagonism, pattern-recognition receptors, antigen-nonspecific
defense chemicals, the complement pathways, phagocytosis, inflammation,
and fever. In the next several sections we will look at each of these
in greater detail.
We will now
take a closer look at phagocytosis.
An Overview of Phagocytic Defense
Phagocytosis is the
primary method used by the body to remove free microorganisms in the
blood and tissue fluids. The body's phagocytic cells are able to
encounter these microorganisms in a variety of ways:
a. Infection or tissue injury stimulates
cells such as mast cells and basophils to release vasodilators
to initiate the inflammatory response (discussed later in
this unit). As a result of vasodilation and increased capillary
permeability, phagocytic white blood cells (neutrophils,
monocytes/macrophages, eosinophils) and other white blood cells
enter the tissue around the injured site and are chemotactically
attracted to the area of infection. In other words,
inflammation allows phagocytes to enter the tissue and go to the
site of infection. Neutrophils are the first to appear and are
later replaced by macrophage.
b.
Lymph nodules are unencapsulated masses of lymphoid tissue
containing fixed macrophages and ever changing populations of
B-lymphocytes and T-lymphocytes. They are located in the
respiratory tract, the liver, and the gastrointestinal tract and
are collectively referred to as mucosa-associated lymphoid
tissue or MALT. Examples include the adenoids and tonsils in
the respiratory tract and the Peyer's patches on the small
intestines. Organisms entering these systems can be
phagocytosed by fixed macrophages and dendritic cells and
presented to B-lymphocytes and T-lymphocytes to initiate adaptive
immune responses. In addition, beneath the skin surface is
skin-associated lymphoid tissue (SALT) that contains
phagocytic cells for killing microbes and sampling antigens on the
skin in order to start adaptive immune responses against them.
c. Tissue fluid
picks up microbes and then enters the lymph vessels as lymph.
Lymph vessels carry the lymph to regional lymph nodes .
Lymph nodes contain many reticular fibers that support fixed
macrophages and dendritic cells as well as everchanging
populations of circulating B-lymphocytes and T-lymphocytes.
Microbes picked up by the lymph vessels are filtered out and
phagocytosed in the lymph nodes by these fixed macrophages and
dendritic cells and presented to the circulating B-lymphocytes
and T-lymphocytes to initiate adaptive immune responses. The lymph
eventually enters the circulatory system at the heart to maintain
the fluid volume of the circulation.
In addition, dendritic cells are
located throughout the epithelium of the skin, the respiratory
tract, and the gastrointestinal tract where in their
immature form they are attached by long cytoplasmic processes.
Upon capturing antigens through pinocytosis and
phagocytosis and becoming activated by proinflammatory cytokines,
the dendritic cells detach from the epithelium, enter lymph
vessels, and are carried to regional lymph nodes. By the
time they enter the lymph nodes, they have matured and are now
able to present antigen to the everchanging populations of
naive T-lymphocytes
located in the cortex of the lymph nodes.
d. The
spleen contains many reticular fibers that support fixed
macrophages and dendritic cells as well as everchanging
populations of circulating B-lymphocytes and T-lymphocytes. Blood
carries microorganisms to the spleen where they are
filtered out and phagocytosed by the fixed macrophages and
dendritic cells and presented to the circulating B-lymphocytes
and T-lymphocytes to initiate adaptive immune responses.
e. As
mentioned above under fixed macrophages, there are also
specialized macrophages and dendritic cells located in the brain (microglia),
lungs (alveolar macrophages), liver (Kupffer cells), kidneys (mesangial
cells), bones (osteoclasts), the gastrointestinal tract (peritoneal
macrophages), and the skin and mucous membranes (Langerhans' cells).
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