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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 alternative complement pathway.
Ways in Which Microorganisms Can Resist Body Defenses by
Circumventing the Complement Pathways
Bacterial
capsules can interfere with the complement pathways in a number of
ways.
-
Some capsules prevent
the formation of C3 convertase, an early enzyme in the
complement pathways. Without this enzyme, the opsonins C3b and
C4b, as well as the other beneficial proteins are not produced.
-
Other capsules, rich in
sialic acid, a common component of host cell glycoprotein, have an
affinity for serum protein H, a complement regulatory protein
that leads to the degradation of the opsonin C3b by factor I
and the formation of C3 convertase. (Serum protein H is what
normally leads to the degradation of any C3b that binds to host
glycoproteins so that we don't stick our own phagocytes to our own
cells with C3b.)
-
Some capsules simply cover the C3b that
does bind to the bacterial surface and prevent the C3b receptor
on phagocytes from making contact with the C3bThis is seen with
the capsule of Streptococcus pneumoniae
.
-
Capsules can resist unenhanced attachment by preventing the
endocytic pattern recognition receptors on phagocytes from
recognizing the bacterial cell wall components and mannose-containing
carbohydrates
An outer membrane molecule of Neisseria
gonorrhoeae
called Protein II and the M-protein of Streptococcus pyogenes
allow these bacteria to be more resistant to phagocytic engulfment.
The M-protein of S. pyogenes
,
for example, binds factor H of the complement pathway and this
leads to the degradation of the opsonin C3b by factor I and the
formation of C3 convertase. S. pyogenes also produces a
protease that cleaves the complement protein C5a.
A Yersinia protein
degrades C3b and C5a.
Some gram-negative bacteria attach sialic
acid to the LPS O antigen and this prevents the formation of the
complement enzyme C3 convertase that is needed for the eventual
formation of all the beneficial complement proteins such as C3b, C5a,
nd MAC. Blood-invasive strains of Neisseria gonorrhoeae
,
as well as Bordetella pertussis
and Hemophilus influenzae
are examples of Gram-negative bacteria that are able to alter their
LPS in this maner. Other gram-negative bacteria, such as Salmonella
,
lengthen the LPS O antigen side chain and this prevents the
formation of MAC. Neisseria meningitidis
and Group B Streptococcus
,
on the other hand, produces capsular polysaccharides composed of
sialic acid and as mentioned above, sialic acid prevents MAC
lysis.
In addition,
some viruses adsorb to complement receptors on body cells to
begin their life cycle. The Epstein-Barr virus (EBV), for example,
adsorbs to CR2 complement receptors found on B-lymphocytes and
epithelial cells.
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