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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 the 3 pathways of the complement system.
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 lectin pathway.
The
Lectin Pathway
The lectin pathway is
mediated by mannan-binding lectin (also known as mannan-binding
protein or MBP). MBP is a protein that binds to the mannose
groups found in many microbial carbohydrates but not usually found
in the carbohydrates of humans. The MBP is equivalent to C1q in the
classical complement pathway.
Activation of the
lectin pathway begins when mannan-binding protein (MBP)
binds to the mannose groups of microbial carbohydrates. Two more
lectin pathway proteins called MASP1 and MASP2 (equivalent to
C1r and C1s of the classical pathway) now bind to the MBP This forms an enzyme similar to C1 of the
classical complement pathway that is able to cleave C4 and C2 to
form C4bC2a, the C3 convertase capable of enzymatically
splitting hundreds of molecules of C3 into C3a and C3b.
The beneficial results
are the same as in the classical complement pathway above:
-
trigger
inflammation (C5a>C3a>c4a);
-
chemotactically
attract phagocytes to the infection site (C5a);
-
promote the
attachment of antigens to phagocytes via enhanced attachment or
opsonization (C3b>C4b);
-
serves as a second
signal for the activation of naive B-lymphocytes (C3d);
-
cause lysis of
gram-negative bacteria and human cells displaying foreign
epitopes (MAC); and
-
remove harmful
immune complexes from the body (C3b>C4b).
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