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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:
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phagocytic cells (neutrophils,
monocytes, and macrophages);
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cells that release
inflammatory mediators (basophils, mast cells, and eosinophils);
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natural killer cells (NK
cells); and
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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.
The complement system
refers to a series of proteins circulating in the blood and bathing
the fluids surrounding tissues. The proteins circulate in an inactive
form, but in response to the recognition of molecular components of
microorganism, they become sequentially actived, working in a cascade
where in the binding of one protein promotes the binding of the next
protein in the cascade.
There are 3 complement
pathways that make up the complement system: the classical
complement pathway, the lectin pathway, and the alternative complement
pathway. The pathways differ in the manner in which they are
activated and ultimately produce a key enzyme called C3
convertase:
We will now take a closer
look at the alternative complement pathway.
The
Alternative Complement Pathway
The alternative
complement pathway is mediated by C3b, produced either by the
classical or lectin pathways or from C3 hydrolysis by water. (Water
can hydrolize C3 and form C3i, a molecule that functions in a manner
similar to C3b.)
Activation of the
alternative complement pathway begins when C3b (or C3i) binds to
the cell wall and other surface components of microbes. C3b can
also bind to IgG antibodies. Alternative pathway protein Factor B
then combines with the cell-bound C3b to form C3bB. Factor
D then splits the bound Factor B into Bb and Ba, forming
C3bBb. A serum protein called properdin then binds to the
Bb to form C3bBbP that functions as a C3 convertase capable of enzymatically splitting hundreds of
molecules of C3 into C3a and C3b. The alternative complement pathway
is now activated.
Some of the C3b
subsequently binds to some of the C3bBb to form C3bBb3b, a C5
convertase capable of splitting molecules of C5 into C5a and C5b
The beneficial results
are the same as in the classical complement pathway above.
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trigger
inflammation (C5a>C3a>c4a);
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chemotactically
attract phagocytes to the infection site (C5a);
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promote the
attachment of antigens to phagocytes via enhanced attachment or
opsonization (C3b>C4b);
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serves as a second
signal for the activation of naive B-lymphocytes (C3d);
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cause lysis of
gram-negative bacteria and human cells displaying foreign
epitopes (MAC); and
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remove harmful
immune complexes from the body (C3b>C4b).
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