Chapter 15: The Innate Immune Response
The body can defend itself against infection using two types of immune response: the innate
and adaptive immune response. The innate immune response is available to us when we are
born and is immediately available. It is also nonspecific, it responds against any infection or
pathogen. The adaptive immune response is specific, it responds against a particular
pathogen. The adaptive immune response has the benefit of memory, which allows it to
remember any pathogen it reacted against in the past to respond quickly and powerfully if
that pathogen returns.
The innate immune response can be divided into two parts: barriers that prevent infectious
organisms from entering the body and mechanisms that destroy any infectious organisms
that manage to break through the barriers. Barriers are the first line of nonspecific host
defenses, destruction second.
Host innate immune responses are triggered when cell and tissue damage occur, a series of
chemical messages are sent out from the damaged site signaling injury. These messages can
be chemotactic, meaning they give off a chemical signal. Defense cells follow these signals to
the site of injury, they then release further chemicals that amplify the response.
Barrier defenses
These barriers can serve to mechanically block the entrance of microbes into the body or
produce chemicals that kill or affect the microbes’ ability to grow and divide. In addition to
mechanical and chemical barriers, we also have our human microbiota that help block the
colonization of pathogens by existing or producing bacteriocins.
1. Skin:
The skin is a semi-watertight barrier made up of the epidermis and dermis. The outer layer,
the epidermis, is composed of many layers of tightly packed dead and dying cells that contain
keratin, a tough protein that gives the cells strength and semi-waterproofs them. Aside from
the places where glandular structures and hair follicles are located, the epidermis is
impenetrable to most microorganisms. Because there is no access to blood or lymph any
intrusion will be localized and not systemic.
Entry through the epidermal layer requires breaking the barrier. Burns are the deadliest from
the perspective of infection, because large patches of the epidermis can be lost. The skin is
occupied by organisms such as staphylococcus and streptococcus. While these organisms
usually provide a benefit by blocking the growth of other microbes, loss of sections of this
barrier allows these organisms to enter the dermis and underlying tissue. The dermis and
underlying tissues are vascularized, the changes of systemic infection are increased.
2. Mucous membranes:
Mucous membranes are made of epithelial tissue and an underlying connective tissue. They
line body cavities that open to the outside environment. Although the primary function of
the mucus produced by these membranes is to keep tissue moist, it also traps
microorganisms. Mucus helps defend against intrusions through an elegant mechanism
1
,known as the mucociliary escalator. The lower respiratory tract for example is lined with
ciliated cells and goblet cells. The goblet cells produce mucus, which traps any
microorganisms that have entered the tract. Then the ciliated cells rhythmically move this
mucus up to the junction of the larynx and esophagus, where it is either swallowed or
expectorated.
Mucus also has a role in the gastrointestinal tract. Produced in copious amounts in the
stomach, it coats the stomach wall to protect against acidic fluids needed for digestion. Some
microorganisms use this mucus coating for their own purposes.
3. Lacrimal apparatus:
The eye is an immunologically protected site, meaning that the
immune system does not protect this site like it does other parts of
the body. Host defense is reduced, meaning that the eye should be a
good region for microbial entry, but in fact few infections occur
here. This is because of the lacrimal apparatus. Tears, produced in the lacrimal glands, flush
any foreign particles across the eye and into the lacrimal canal, which drains into the nasal
cavity. The lacrimal apparatus increases the flow of tears whenever any irritant enters the
eye. In addition, tears also contain three important components: immunoglobulin A (IgA), an
antibody that prevents microbial attachment and neutralizes toxins, lysozyme, an enzyme
that destroys bacterial cell wall by breaking the bonds between the NAG and NAM subunits
in peptidoglycan and lipocalin, which binds iron and has been shown to have antimicrobial
activity by inhibiting pathogens as they scavenge for iron.
4. Saliva:
Produced by the salivary glands of the mouth, saliva is similar to tears. The main functions
are to cleanse the teeth and mucous membranes of the mouth and prepare food for
digestion. Saliva also washes microbes down the esophagus into the stomach. However,
saliva can also inhibit microbial growth because it contains IgA and lysozyme. Saliva also
contains histatin, a peptide that has antifungal activity and has a role in wound repair.
5. Epiglottis:
The epiglottis is a flap of tissue at the back of the throat and is a barrier that keeps food from
entering the respiratory tract. In this way, organisms that come into the body through the
mouth are kept away from the respiratory tract. Liquids or foods aspirated into the lungs can
result in aspiration pneumonia.
6. Sebum:
The sebaceous glands are located in the skin and produce an oily secretion called sebum that
prevents hair from drying out and forms a protective film over the skin to moisturize it and
keep it from cracking. Sebum contains unsaturated fatty acids, which inhibit bacterial and
fungal growth and organic acids, which make the environment of the skin naturally acidic (pH
3-5) and inhibitory to bacterial growth. The combination of these chemical factors and dead
bacterial cells on the skin can cause body odor and influence certain skin conditions.
2
, 7. Perspiration:
Perspiration is produced by sweat glands located in the skin. It is a natural mechanism that
regulates the body temperature and eliminates wastes. The effect of perspiring is like the
flushing of the lacrimal apparatus. When we perspire profusely, this action is magnified.
Perspiration contains the enzyme lysozyme, is salty and acidic, both factors can inhibit
microbial growth.
8. Gastric juice:
Stomach acids and enzymes, collectively called gastric juice, break down the ingested
materials that enter the stomach. This combination of substances produces a harsh chemical
environment that is not conducive to microbial growth. However, bacteria hidden in food
particles are protected from this environment and can therefore thrive in other regions of
the digestive tract.
9. Urine and vaginal secretions:
The acidity of urine inhibits most microbial growth in the urinary tract and the flushing action
of this body fluid keeps microbes from attaching to tissues. Vaginal secretions coupled with
lactic acid proved by resident bacteria help make the vagina more acidic and therefore
prevent colonization by many pathogenic bacteria. Because low pH conditions allow fungal
organisms to grow, yeast infections are more common in women than men.
10. Transferrins:
Transferrins also bind iron as a defense mechanism. Many bacteria require iron for growth
and division. Human blood contains transferrins, and bacterial growth is completely inhibited
when the body’s transferrin molecules capture iron and prevent bacteria from using it.
Molecules of innate immunity
1. Toll-like receptors:
An antigen is any substance that triggers an immune response in a host body, and the host
defense provides protection against nonself antigens found on foreign invading organisms.
Toll-like receptors (TLR’s) are molecules associated with defense cells and are a required part
of the innate immune response. They bind to antigens called pathogen-associated molecular
patterns (PAMP’s) found on pathogens. The first TLR discovered was TLR-4, which recognizes
and binds with lipopolysaccharide.
Thirteen TLR’s have now been identified as part of the innate immune response, humans
express ten of them. These receptors are the way in which our defenses see the microbial
world and are used to activate the innate response.
A TLR is activated as soon as it binds to a target antigen. This activation triggers the host
defense cell associated with the TLR to release a variety of chemical messengers. It can also
stimulate dendritic cells to remodel their actin cytoskeleton, which mediates a transient
increase in antigen-dependent endocytosis. This increased importing of substances can
3
, enhance the ability of the dendritic cells to present antigens to other immune cells, which is
required for an adaptive immune response to develop.
2. Cytokines:
Cytokines are low-molecular-weight proteins that are released by a variety of cell types in the
body. There are two major families of cytokines: the hematopoietin, which includes growth
hormones and interleukins (IL’s) and the tumor necrosis factor (TNF). Both are involved in the
innate and adaptive immune response. When TLR’s recognize a pathogen, a variety of
cytokines are released in response.
Cytokines can affect the cells that produce them, neighboring cells or cells in other areas of
the body. Cytokines act through specific receptors on their target cells and alter the activity
of those cells. The action of a cytokine depends on the concentration of that cytokine.
Individual cytokines have overlapping functions and act as a network to either induce or
inhibit the effects of other cytokines.
Chemokines are cytokines that are released in the earliest part of the immune response and
attract defense cells to the site of infection. They also have a role in the destruction of
pathogens. Chemokines are released by many types of immune-system cells. Some
chemokines are also involved in building new blood vessels (angiogenesis) when the body is
repairing damaged tissues.
4
