Barriers (MT1)

Name the three types of barriers

Mechanical
Chemical
Microbiological

Give examples of mechanical marriers

Epithelial cells joined by tight junctions, movement of mucus by cilia, tears, nasal cilia, flow of air/fluid in the body

Define: Epithelium

The physical barrier between the external environment and the host. (Skin, linings of organs, nasal cavity, mouth etc)

True or False: Sepsis is the leading cause of death among fire victims

True, the loss of our protective barrier increases the risks of infection.

Define: Epithelial Tight Junctions

Cell-cell adhesion that creates an impermeable barrier that even ions are incapable of entering

Describe the layout of skin epithelium

Old, dead skin sits on the topmost surface that bacteria can slough off as skin sheds, tight junctions sit a few layers below, even further below is a watertight lipid layer.

Define: Stratum Granulosum, what it it's significance?

Watertight lipid layer deep below skin surface, significant since most pathogens are found in aqueous environments

Define: Cilia

Active hair-like structures on the surface of airway epithelium, "sweeps" particles and mucus up and out of the airway

How does cilia dysfunction affect individuals, what causes it?

Loss of cilia function leads to an increased risk of airway infections. Dysfunction is often due to smoking (yes all types), the more you smoke the more prone you are to infections since cilia cannot effectively remove mucus containing pathogens

Define: Mucus

Viscous coating comprised of glycoprotein and water, provides thin layer of protection to underlying epithelium from pathogens (dust/particulate in airways) and digestive/antimicrobial molecules (so we don't digest ourselves)

What is the result of mucus dysfunction?

A lack of Cl- ions results in an ability for mucus to absorb water, resulting in excessively viscous mucus that doesn't clear out of airways. (Cystic fibrosis)

Give examples of chemical barriers

Fatty acids
Low pH (acidity)
Enzymes in tears and saliva (lysozyme) and in digestive tract (pepsin)

Define: Chemical Barriers

Non-physical barriers added to physical barriers as an additional layer of defense. Includes:
Stomach acid (pH=2) is toxic to many pathogens
Skin (ph=5) produces acidic sweat, fatty acids
Salts in sweat make it hypertonic which leads to dehydration of pathogens
Intestinal-bile is alkaline (pH=7+) which affects some microbes

Give an example of an enzymatic barriers

Lysozyme
-Produced by neutrophils and stored in granules.
-Found in tears, saliva, and milk catalyzes the breakdown of peptidoglycan in bacterial cell walls
-Also found in GI mucus

Give examples of molecular barriers

Numerous molecule defenses coat physical barrier surfaces.
Includes α-defensin, β-defensin and
antibodies (IgA) c
Can be either always expressed or induced by the presence of pathogens

Define: Defensins

- About 30 Amino acids long (very short),
- Produced by epithelial cells, paneth cells, and neutrophils
- Directs antimicrobial activity
- Produced as an inactive pro-peptide, must be cleaved to be activated
- Can activate leukocytes

Why is it important that defensins are produced as inactive pro-peptides that must be cleaved to be activated?

Defensins are non-specific and have poor recognition, the constant presence of active defensins puts our own cells at risk of damage (cell lysing or genetic damage)

What do defensins activate?

Leukocytes

How do defensins disrupt membranes?

They insert themselves into the lipid bilayer (membrane) and reverse the polarity of lipids to create a pore. Water then floods in and lyses the cell

Define: α-defensins

- Found in most mucosal secretions, produced
- Continuously produced by paneth cells and released into the gut mucosa
- Also produced by neutrophils and stored in granules
- Direct anti-microbial activity

Define: Neutrophils

A type of white blood cell that engulfs invading microbes and contributes to the innate defenses of the body against disease.

Define: β-defensins

- Produced by skin epithelial cells
- Stored in lipid-rich lamellar bodies

Define: Immunoglobulin (Ig)

Antibodies made by B-cells.

- Mucosal epithelium are specialized structures that facilitate the transport of immunoglobulin through cells and into the gut/airway lumen
- Transport is mediated by the poly-Ig receptor (pIgR) which binds to IgM or IgA and facilitates transcytosis of the immunoglobulin.
- On the luminal side of the epithelial cell, the pIgR is cleaved and released into the luminal space

Define: Normal Flora

- Non-pathogenic commensal bacteria that occupy space to prevent pathogens from attaching to cells.
- Stimulates immune response via defensin secretion or IgA production.
- Maintain immune-tolerance (capable of eating without attacking the foreign food pathogens)

How can you differentiate between IgA above and below the epithelial layer? (secreted/non-secreted)

IgA beneath epithelial layer does not have a plgR receptor attached to it (non-secreted)
IgA above epithelial layer does have a plgR receptor attached to it (secreted)

Why is the loss of our epithelium dangerous?

Loss of integrity/damage to these barriers increases risks of infection

How do defensins direct antimicrobial activity?

Disrupting membranes - create pores in membranes and lyse cells
Impairing DNA/RNA synthesis (consuming genetic material)

Define: Lamellar Bodies

Lipid rich molecules that are released through various dermal layers to produce the watertight barrier in our skin

Which is the most secreted antibody in our bodies?

IgA

Define: Lumen

Tubules with contact to outside world, technically "outside" of our bodies but actually within us. Interior of colon, esophagus, etc.

How does a bacterium like C.difficile colonize in our gut?

The use of antibiotics (for any condition) kill off the colonies of normal flora in our colon. This allows C.diff to spread and cause mucosal injury. Neutrophils and RBC then leak into git between injured epithelial cells. Connective tissue degradation leads to colitis and pseudomembrane formation.