Innate Defense Mechanisms I

Innate defense mechanisms of the humans against microbes are carried out by different ways

  1. Anatomical barriers,
  2. Physiological barriers,
  3. Inflammatory mechanism,
  4. Phagocytic mechanism,
  5. Enzyme and soluble proteins of the innate immune system.

ANATOMICAL BARRIERS

Skin, cornea and mucus membrane lining the respiratory tract, digestive tract, and genitourinary tracts act as mechanical barriers and prevent the entry of pathogenic microbes into the body.

Skin

  1. Intact skin forms a mechanical barrier that prevents most pathogens from penetrating the body. But injury can cause breaks in the skin, through which microorganisms may enter the body. Epithelial cells of the skin are joined by tight junctions to form an external mechanical barrier that prevents pathogenic microbes from entering the body. However, insects like mosquito, ticks, mites, and fleas can penetrate human skin and introduce pathogens into the body.
  2. Skin secretes antimicrobial chemicals in sebum and sweat. Sebum is an acidic substance secreted by sebaceous glands. Sebum is particularly rich in lactic acids, fatty acids, and lysozyme. The acidic components of sebum make the skin surface to be slightly acidic, which is unfavorable to most microbes. Sweat glands secrete an antimicrobial substance called dermicidin in sweat.
  3. Epithelial cells contain defensins, transferrin, and lactoferrin. In addition to this, epithelial cells of the skin contain potent antimicrobial substances such as defensins, transferrin, lactoferrin, and lysozymes.
  4. Bacteria of normal flora of skin prevents pathogenic microbes form invading the body: The surface of a normal human skin is home to about 1013 microorganisms (predominantly bacterial cells). These microbes are mostly found in moist areas such as armpit and groin. Some of them stay for long periods while others stay just for a short while. They reside on the skin without causing a disease (however, they can cause an infection in an immuno-suppressed individual). They constitute the normal flora of the skin.

The normal flora makes the skin almost inaccessible to invading microbes by

a.) Microbial competition: normal flora use up available nutrients and space, consequently reducing the ability of arriving pathogenic microbes to colonize the skin.

b.) Producing bacteriocins: compounds that kill other bacterial cells

c.) Lowering pH: Bacteria of normal flora release chemical substances that make the pH of the skin surface to be acidic so that other bacteria will be unable to survive.

Normal flora is also found in the mouth, colon, and upper respiratory tract.

Defensins: These are small host defense peptides contained in virtually all epithelial cells. Defensins are potent against all classes of pathogens (bacteria, fungi, and viruses). Defensins bind to cell membrane of pathogenic microbes and cause structural and functional damage to the microbial cell membrane ultimately destroying the cell.

Transferrins: Transferrins impede the survival and of microbes by binding iron, ultimately depriving pathogenic microbes of iron needed for their growth.

Lactoferrins: The word ‘lacto’ means ‘milk’ and ‘ferrin’ means ‘iron binding’. Lactoferrins are antimicrobial proteins mainly found in breast milk and bind iron. However, small amount of it is contained in the secretions of salivary glands, prostate, and tear glands. The ability of transferrin to bind iron is many-fold greater when compared to that of transferrin. Even at normal physiologic levels, lactoferrins inhibit the growth of a wide spectrum of pathogens. Of note, lactoferrins destroy viruses, bacteria, fungi, worms and protozoa by binding iron strongly, depriving the pathogens of essential iron. Lactoferrins also interfere with microbial protein synthesis. However, some bacteria are resistant to transferrin and lactoferrin for the reason that they are less dependent on exogenous iron.

Mucus membrane

The mucus membrane lines the surfaces of the GI tract, airways, genitourinary tract, and eyes. Mucus that line the airways, GI tract, and genitourinary tracts are particularly rich in antimicrobial substances such as lysozyme, lactoferrin, defensins, and immunoglobulin-A (the secretory form) and other antimicrobial substances.

Though mucus membrane acts as one of the physical barriers, many pathogens can penetrate the mucus membrane and enter into our body to cause disease. However, a variety of non-specific defense mechanisms at the mucosal surface tend to prevent pathogens from entering our body. The mucus secretions being viscous in nature entrap the organisms so that the organisms are prevented from contacting the mucus membrane. Consequently, the microbes are unable to penetrate the mucus membrane and enter the host.

Saliva, tears and secretions of the mucus membranes wash away the microorganisms. These secretions also contain some antibacterial and antiviral substances.

In the lower respiratory tract and alimentary tract the mucus membrane is covered with cilia. Cilia are hair-like protrusions of the epithelial cell membranes. The cilia continuously move harmoniously in a manner that propels the mucus-entrapped microorganisms outside the body.

Secretions of innate defense system and their functions

Secretion Function
Saliva Contains antimicrobial enzymes which cause severe damage to bacterial cell wall and membrane. Saliva also contains secretory IgA
Tears Lysozyme in tears causes bacterial cell destruction by destroying the peptidoglycan layer of bacterial cell wall
Hcl in gastric juice Acid denatures proteins on microbes.Interferes with vital functions of cell membrane.
Fatty acids Denatures proteins of cell membrane, almost the same effects as Hcl
Lactoferrins and transferrins Bind to iron and thus deprive bacteria of much needed iron
Trypsin Digests proteins of cell wall and cell membrane
Spermine Spermine is an antimicrobial substance present in seminal fluid. It inhibits the growth of gram-positive bacteria

 

 PHYSIOLOGIC BARRIERS

Body temperature, pH, and soluble factors are the physiologic barriers that contribute to innate defenses of the human body.

 Body temperature: Interestingly enough, chickens have innate defense against anthrax bacteria simply because the high body temperature inhibit the growth of the causative agent, anthrax bacillus.

In humans, fever, a rise in body temperature occurs when pyrogenic bacteria invades the body. Although the value of fever in combating invading bacteria remains unresolved, it is believed that fever is a defense mechanism that incapacitates invading bacteria in the system. However, it is a well established most pathogens are killed or incapacitated by heat.

pH: stomach acidity contributes to innate defense mechanism. Most pathogenic microbes are unable to survive in acidic media. The pH in the stomach is very low (between 1 and 2) due to the hydrochloric acid in gastric secretions. Stomach acid makes the lumen of the stomach a harmful environment to many microbial and non-microbial organisms.

As a matter of fact, stomach acid kills most of the pathogens that are either ingested in food or drank in water. Nevertheless, a bacterium called Helicobacter pylori has adapted to life in human stomach, where it causes stomach ulcers. It is observed that stomachs of newborns are less acidic than those of adults, and this is strongly implicated in the susceptibility of newborns to many microorganisms that cause diarrhea.

INFLAMMATION AND INNATE DEFENSE SYSTEM

Inflammation is a tissue response mechanism which serves to amplify the body’s response to a pathogen. Let’s assume that you have a cut on the skin, and bacteria enter through the cut and cause damage to the infected tissue. Recall, that in immunology, infection is the entry of microbe into the body. The infected tissue is the tissue in which the bacteria have entered. Invading bacteria cause damage to the infected tissue; the tissue damage induces a complex sequence of events collectively called as the inflammatory responses. The essence of pathogen-induced inflammation is destruction of the invading pathogen.

The key processes in inflammation are;

  1. Rapid dilation of blood vessels in and around the infected tissue or injured tissue.
  2. The vasodilation of capillaries and venules of injured tissue and those of surrounding tissues allows more blood to flow to the injured site (and the injured site becomes red because of increased perfusion).
  3. Apart from vasodilation of microvessel of injured tissue, the cells lining the venules retract. Retraction of these cells create gaps in between the cells
  4. The result of these vascular changes is that plasma and white blood cells from blood leak out through these gaps into the infected tissue. The white blood cells, especially the neutrophils engulf the bacteria and kill them by phagocytosis.

In this lecture, we have been able to discuss three of the five mechanisms of innate defense system. In our next lecture, we shall study the phagocytic mechanism of the innate defense.

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