The respiratory tract antimicrobial defense system is a layered defense mechanism which relies on components of both the innate and

adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

s to protect the lungs and the rest of the

respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...

against inhaled

microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

s. In the first line of defense, inhaled bacteria are trapped by

mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...

and are swept toward the

pharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struc ...

and are swallowed. Bacteria which penetrate the mucous layer are dealt with a second line of defense which includes antimicrobial peptides that are secreted by the surface

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

of the respiratory tract which kill many strains of bacteria. Those bacteria that are resistant to antimicrobial peptides are killed by a variety of reactive oxygen species produced by phagocytes. In a third line of defense and as a last resort, persistent bacterial infections which escape the innate immune system are eliminated by the

Lactoferrin

Lactoferrin (LF) is a multifunctional protein which is an essential part of the respiratory tract antimicrobial defense system. LF proteolysis produces the small peptides

lactoferricin Lactoferricin is an amphipathic, cationic peptide with anti-microbial and anti-cancer properties. It can be generated by the pepsin-mediated digestion of lactoferrin. Lactoferricin is the most studied AMP derived from milk protein. The complete se ...

and kaliocin-1 both with antimicrobial activity.

Reactive oxygen species, oxygenated compounds

Phagocytes possess a superoxide-producing NADPH oxidase enzyme complex. Other cells in the respiratory tract also produce superoxide and hydrogen peroxide through the activity of dual oxidase 2 proteins, also known as Duox2. The superoxide generated by these enzymes complexes dismutates into

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%� ...

which in turn is used by myeloperoxidase to produce bactericidal hypochlorous acid. In addition, the submucosal glands of the respiratory tract secrete myeloperoxidase and

lactoperoxidase Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary and other mucosal glands including the lungs, bronchii and nose that functions as a natural and the first line of defense against bacteria and viruses. Lactoperoxidase is a m ...

(LPO) that catalyzes the oxidation of thiocyanate and detoxify hydrogen peroxide or ROS to the antimicrobial hypothiocyanite. The oxygenated compounds produced by the lactoperoxidase system does not attack DNA and is not mutagenic and is known to be safe. Hypothiocyanite generated through this pathway displays broad spectrum bactericidal activity including potent antibacterial action on '' H. pylori''.

Cystic fibrosis

Thiocyanate secretion in

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

patients is decreased resulting in a reduced production of the antimicrobial hypothiocyanite and consequently contributes to the increased risk of airway infection.

Therapeutic applications

Lactoferrin with hypothiocyanite for the treatment of cystic fibrosis has been granted

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

status by the EMEA and the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

References

{{immune_system Immune system Lung