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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 anatomical barriers, mechanical removal, intraepithelial T-lymphocytes
and B-1 cells, and
bacterial antagonism.
Anatomical Barriers, Mechanical Removal,
Intraepithelial T-lymphocytes
and B-1 cells, Bacterial Antagonism by Normal Flora, and
Antigen-Nonspecific Antimicrobial Molecules Produced by the
Body
1.
Anatomical barriers are tough, intact barriers that prevent
the entry and colonization of many microbes. Examples include the
skin, the mucous membranes, and bony encasements.
a. the
skin
The skin,
consisting of the epidermis and the dermis, is dry, acidic, and
has a temperature lower than 37 degrees Celcius (body
temperature). These conditions are not favorable to bacterial growth.
Resident normal flora of the skin also inhibit potentially
harmful microbes. In addition, the dead, keratinized cells that
make up the surface of the skin are continously being sloughed
off so that microbes that do colonize these cells are
constantly being removed. Hair follicles and sweat glands produce
lysozyme and toxic lipids that can kill bacteria. Finally,
beneath the skin surface is skin-associated lymphoid tissue
(SALT) that contains cells for killing microbes and sampling
antigens on the skin to start adaptive immune responses against them.
b. the
mucous membranes
Mucous
membranes line body cavities that open to the exterior, such as the
respiratory tract, the gastrointestinal tract, and the genitourinary
tract. Mucous membranes are composed of an epithelial layer that
secretes mucus, and a connective tissue layer. The mucus is a
physical barrier that traps microbes. Mucus also contains
lysozyme to degrade bacterial peptidoglycan, an antibody called
secretory IgA that prevents microbes from attaching to
mucosal cells and traps them in the mucous, lactoferrin to
bind iron and keep it from from being used by microbes, and
lactoperoxidase to generate toxic superoxide radicals that kill
microbes. Resident normal flora of the mucosa also inhibit
potentially harmful microbes. In addition, the mucous membrane, like
the skin, is constantly sloughing cells to remove microbes
that have attached to the mucous membranes. Beneath the mucosal
membrane is mucosa-associated lymphoid tissue (MALT) that
contains cells for killing microbes and sampling antigens on the
mucosa to start adaptive immune responses against them.
c. bony
encasements
Bony
encasements, such as the skull and the thoracic cage, protect vital
organs from injury and entry of microbes.
2.
Mechanical removal is the process of physically flushing microbes
from the body. Methods include:
a.
mucus and cilia
Mucus
traps microorganisms and prevents them from reaching and colonizing
the mucosal epithelium. Mucus also contains lysozyme to
degrade bacterial peptidoglycan, an antibody called secretory IgA
that prevents microbes from attaching to mucosal cells and traps
them in the mucus, lactoferrin to bind iron and keep it from
from being used by microbes, and lactoperoxidase to generate
toxic superoxide radicals that kill microbes. Cilia on the
surface of the epithelial cells propels mucus and trapped
microbes upwards towards the throat where it is swallowed. This
is sometimes called the tracheal toilet.
b. the
cough and sneeze reflex
Coughing
and sneezing removes mucus and trapped microbes.
c.
vomiting and diarrhea
These
processes remove pathogens and toxins in the gastrointestinal tract.
d. the
physical flushing action of body fluids
Fluids
such as urine, tears, saliva, perspiration, and blood from injured
blood vessels also flush microbes from the body.
3.
Intraepithelial T-lymphocytes and B-1 cells
a. Intraepithelial
T-lymphocytes
are found in the epidermis
of the skin and the mucosal epithelia. These T-lymphocytes, known as
gamma delta T-cells, have a limited diversity of antigen
receptors for microbes often encountered on the skin and mucous
membranes. As such they function
more as effector cells for innate immunity rather than
adaptive immunity.
b.
B-1 cells are B-lymphocytes with a limited
diversity of antigen receptors that initially produce a class of
antibody called IgM against common polysaccharide and lipid antigens
of microbes. As such they function more as effector
cells for innate immunity rather than adaptive immunity.
Antibodies produced by B-1 cells are often called natural antibodies.
4. Bacterial Antagonism by Normal
Flora
Approximately 100 trillion bacteria and other microorganisms reside in
or on the human body. These normal body flora keep potentially harmful
opportunistic pathogens in check and also inhibit the colonization of
pathogens by:
a.
producing metabolic products (fatty acids, bacteriocins, etc.)
that inhibit the growth of many pathogens;
b.
adhering to target host cells thus covering them and
preventing pathogens from colonizing;
c.
depleting nutrients essential for the growth of pathogens; and
d.
nonspecifically stimulating the immune system.
Destruction of normal bacterial flora by the use
of broad spectrum antibiotics may result in superinfections or
overgrowth by antibiotic resistant opportunistic normal flora. The
yeast Candida, that causes infections such as vaginitis and
thrush, and the
bacterium Clostridium difficile, that causes potentially severe
antibiotic-associated colitis , are opportunistic flora normally held
in check by normal flora bacteria. Antibiotic-associated colitis
is especially common in older adults. It is thought that C.
difficile survives the exposure to the antibiotic by sporulation
. After the antibiotic is gone, the endospores germinate and C.
difficile overgrows the intestinal tract and secretes toxin A that
has a cytotoxic effect on the cells. Fortunately, C. difficile
does itself respond to certain antibiotics so antibiotic-associated
colitis is treatable.
5.
Antigen-Nonspecific Antimicrobial Molecules Produced by the Body
There are
many antigen-nonspecific antimicrobial chemicals produced by the host
that play roles in innate body defense. Examples include the following.
a.
Hydrochloric acid and enzymes found in gastric secretions
destroy microbes that are swallowed.
b.
Lysozyme , found in in tears, mucous, saliva, plasma, tissue
fluid, etc., breaks down peptidoglycan in bacteria causing osmotic
lysis.
c.
Human beta-defensins are short peptides found in blood plasma
and mucous. They forms pores in the cytoplasmic membrane of a
variety of bacteria causing leakage of cellular needs.
d.
Lactic and fatty acids, found in perspiration and sebaceous
secretions , inhibit microbes on the skin.
e. Lactoferrin and
transferrin, found in body secretions, plasma, and tissue fluid,
trap iron for use by human cells while preventing its use by
microorganisms.
f.
Cytokines are low molecular weight, soluble proteins that are
produced in response to an antigen and function as chemical
messengers for regulating the innate and adaptive immune systems.
They are produced by virtually all cells involved in innate and
adaptive immunity, but especially by T helper (Th) lymphocytes. The
activation of cytokine-producing cells triggers them to synthesize
and secrete their cytokines. The cytokines, in turn, are then able
to bind to specific cytokine receptors on other cells of the immune
system and influence their activity in some manner.
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