The external barriers of innate immunity

In this article, I briefly explain the external barriers of innate immunity.

Innate immunity

Our immune response includes two interconnected systems that act collaboratively to protect our body from foreign invaders. Innate immunity and adaptive immunity differ from each other in providing immunity.

Innate immunity provides the first line of defense against pathogens and acts agile in contrast to adaptive immunity. It entails anatomical barriers and cellular innate response receptors to combat infections. The complement proteins, which bind common pathogen-associated structures and initiate a cascade of annihilation events, are included under innate immunity.

Physical and chemical barriers to innate immunity

The external barriers are the basic component of innate immunity, which include the epithelial layers giving protection against pathogens, mostly in terms of secretions. Skin and other epithelial layers protect the internal body from infection.

The mucosal epithelial layers lining the respiratory, gastrointestinal, and urogenital tracts, along with the ducts of salivary, lacrimal, and mammary glands, act as barriers to unsheathing the body from pathogens.

These barriers add mechanical and physical processes that assist the body to shed pathogens. The body is also able to produce active chemical defenses that induce antimicrobial activity.

How a pathogen is restricted from gaining entry into our body

Our skin gives protection to us as it is the outermost physical barrier and consists of a thin outer layer, the epidermis, and a thicker layer, the dermis. The outer layer of the epidermis consists of layers of tightly packed epithelial cells and a thicker layer called the dermis, made up of connective tissues.

The outer layer of the epidermis consists mainly of dead cells filled with the protein keratin. The dermis contains blood vessels, sweat glands, sebaceous glands, and hair follicles with antigen-presenting cells like dendritic cells and macrophages and granulocytes like mast cells.

Secretions preventing pathogens

In the secretory tissues like respiratory, gastrointestinal, urogenital, and the ducts of the salivary, lacrimal, and urogenital tracts, the epithelial surfaces are lined by tightly attached epithelial barrier cells, which help in preventing the entry of pathogens into the body.

Secretions, consisting of antimicrobial and antiviral substances from these secretory tissues like mucus, urine, saliva, milk, and tears, cleanse the potential invaders out of the body.

Mucus and saliva-preventing pathogens

Mucosal epithelial layers consist of specialized cells secreting the viscous fluid known as mucus, which traps pathogens, whereas the glycoproteins present in mucus, known as mucins, prevent the attachment of pathogens to the epithelial cells.

The lower respiratory tract contains some hair-like projections of the cell membrane known as cilia enveloping the epithelial cells. From the respiratory tract, mucus-entrapped microorganisms are driven by the synchronous movement of cilia.

Through coughing, excess mucus with trapped microbes can be extruded. Whereas from the urinary tract, many bacteria are swept out with the flow of urine.

Microorganisms entering through food items into our body face defenses starting from saliva, consisting of antimicrobial compounds, in the mouth epithelia and in the stomach where acid with digestive enzymes secretion takes place.

Through vomiting and diarrhea, pathogens exit from the stomach and intestine, which helps in subsiding the infection in the gastrointestinal tract.

Vaginal secretions include the mucus and acidic pH giving protection against bacterial and fungal microbes. Mucosal epithelial layers in the intestine and reproductive tract possess beneficial commensal microbes that restrict infection by harmful microorganisms.

However, some microbes have evolved in many ways to escape from this defense system of epithelial barriers. The influenza virus firmly attaches itself to the cells in the mucous membranes of the respiratory tract through its surface molecule. It thus can not be swept away by the ciliated epithelial cells.

The disease gonorrhea is caused by the bacterium Neisseria gonorrhoeae, which with the help of its fimbriae, or pili (hair-like protrusions), attaches itself to the mucous membrane of the urogenital tract.

Epithelial cells secrete antimicrobial proteins and peptides rendering protection against pathogens

Epithelial cells, including the skin, generate a broad range of antimicrobial proteins and peptides. Antimicrobial proteins, which include mainly enzymes and binding proteins, kill pathogens and constrain their growth too.

Knowing some antimicrobial proteins


Lactoferrin is an enzyme present in milk, intestinal mucus, respiratory tract, and urogenital tract that limits the growth of fungi and bacteria by binding and sequestering iron.


Lysozyme is an enzyme found in tears, saliva, and fluids of the respiratory tract, which acts by cleaving the glycosidic bonds of peptidoglycan in bacterial cell walls, ultimately leading to lysis.


Psoriasin, a small protein of the S-100 family found in tears, saliva, secretions of the intestine, and respiratory and urogenital tracts, possesses a potent antibacterial activity against E. coli (intestinal bacteria). It kills bacteria by disrupting cell membranes.

Reg III proteins

These proteins found in intestinal epithelia work by binding carbohydrates on bacterial cell walls, thus preventing bacteria from binding with intestinal epithelial cells. Reg III proteins create pores in membranes that kill the cells.

Surfactant proteins

Surfactants are the varieties of lubricating lipids and proteins secreted by the epithelium of the respiratory tract. SP-A and SP-D are the two surfactant proteins present in lungs and are included in the class of microbe binding proteins known as collectins. These two surfactants bind differentially to carbohydrates, lipid, and protein components of microbial surfaces. As a result, surface components are blocked and modified, which helps in preventing infection and promoting phagocytosis.

SP-A binds to the complex polysaccharides covering capsulated bacteria. SP-D protein only binds to the uncoated cell wall polysaccharides of the non-capsulated bacteria.

Knowing some antimicrobial peptides

Antimicrobial peptides are an ancient form of innate immunity that keeps their presence in vertebrates, invertebrates, plants, and in some fungi. They are less than 100 amino acids long and rich in cysteine and cationic in nature. These peptides contain both hydrophilic and hydrophobic regions, thus amphipathic.

These peptides can interact with acidic phospholipids in lipid bilayers of microbes due to their cationic and amphipathic nature and eventually form pores and disrupt the microbial membrane.

After forming pores, they can enter inside microbes and exert their toxic effects. The effects include inhibiting the synthesis of nucleic acids and proteins and activating antimicrobial enzymes causing cell death.

Defensins and Cathelicidin

α and β defensins are one of the important antimicrobial peptides found in humans. These are located in the skin and mucosal epithelia of the mouth, intestine, respiratory tract, and urogenital tract.

These can kill a wide range of bacteria, like S. pneumonia, S. aureus, E. coli, Pseudomonas aeruginosa, and H. influenzae. These can disrupt microbial membranes, add toxic effects intracellularly, and kill cells.

Influenza viruses and some herpes viruses can get attacked by these peptides as they target the lipoprotein envelope of the viruses.

Cathelicidin LL-37 is the only one expressed in humans, located in the mucosal epithelia of the respiratory and urogenital tract. It disrupts bacterial membranes and like defensins, adds intracellular toxic effects, ultimately killing cells.


Histatins are potent antifungal peptides found in human saliva. They enter the cytoplasm of fungal cells by binding to surface components present on the cell membrane. They act by interfering with mitochondrial ATP production and have other harmful effects.

Epithelial layers render strong protection against infection. However, through other accidental openings like wounds, abrasions, and insect bites, pathogens gain entry through the epithelial barrier.

Pathogens entering below the epithelial layers are combated by the innate immune system’s second line of defense. This is through cells’ expressing membrane receptors and activating cellular defense mechanisms against pathogens.


Innate immunity acts as the first line of defense against pathogens. Epithelial layers are the external barriers of innate immunity, giving protection against pathogens mostly in terms of secretions.

In the secretory tissues like respiratory, gastrointestinal, urogenital, and the ducts of the salivary, lacrimal, and urogenital tracts, the epithelial surfaces are lined by tightly attached epithelial barrier cells. This helps in preventing the entry of pathogens into the body.

Skin is the outermost physical barrier that obstructs pathogens from gaining entry inside the body. Epithelial cells, including skin generate a broad range of antimicrobial proteins and peptides, giving protection against pathogens.

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