I. THE INNATE IMMUNE SYSTEM
C. IMMEDIATE INNATE IMMUNITY
3. ANATOMICAL BARRIERS, MECHANICAL REMOVAL, BACTERIAL ANTAGONISM BY NORMAL MICROBIOTA
Fundamental Statements for this Learning Object:
1. Anatomical barriers such as the skin, the mucous membranes, and bony encasements are tough, intact barriers that prevent the entry and colonization of many microbes.
2. Mechanical removal is the process of physically flushing microbes from the body. Examples include mucus and cilia (the mucociliary esculator), coughing and sneezing, vomiting and diarrhea, and the flushing action of bodily fluids.
3. The normal microbiota keeps potentially harmful opportunistic pathogens in check and also inhibits the colonization of pathogens by producing metabolic products that inhibit the growth of many pathogens, adhering to target host cells so as to cover them and prevent pathogens from colonizing, depleting nutrients essential for the growth of pathogens, and non-specifically stimulating the immune system.
4. Destruction of normal bacterial microbiota by the use of broad spectrum antibiotics may result in superinfections or overgrowth by antibiotic-resistant opportunistic microbiota such as Candida and Clostridioides difficile.
LEARNING OBJECTIVES FOR THIS SECTION
Innate immunity is an antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any microbe. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection. Innate immunity can be divided into immediate innate immunity and early induced innate immunity. In this section we will learn about immediate innate immunity.
C. Immediate Innate Immunity
Immediate innate immunity begins 0-4 hours after exposure to an infectious agent and involves the action of soluble preformed antimicrobial molecules that circulate in the blood, our found in extracellular tissue fluids, and are secreted by epithelial cells. These include:
These preformed antimicrobial molecules are designed to immediately begin to remove infectious agents as soon as they enter the body.
In addition to preformed antimicrobial molecules, the following also play a role in immediate innate immunity:
In this section we will look at how anatomical barriers, mechanical removal, and bacterial antagonism by normal body microbiota function to prevent infection.
3. Anatomical Barriers, Mechanical Removal, and Bacterial Antagonism by Normal Microbiota
a. Anatomical barriers are tough, intact barriers that prevent the entry and colonization of many microbes. Examples include the skin, the mucous membranes, and bony encasements.
1. The skin
The skin, consisting of the epidermis (def) and the dermis (def), is dry, acidic, and has a temperature lower than 37 degrees Celsius (body temperature). These conditions are not favorable to bacterial growth. Resident normal microbiota of the skin also inhibits potentially harmful microbes. In addition, the dead, keratinized cells that make up the surface of the skin are continuously being sloughed off so that microbes that do colonize these cells are constantly being removed. Hair follicles and sweat glands produce lysozyme (def) and toxic lipids that can kill bacteria. Epithelial cells also produce defensins (def) and cathelicidins (def) to kill microbes. Beneath the epidermis of the skin are Langerhans' cells - immature dendritic cells (def) - that phagocytose and kill microbes, carry them to nearby lymph nodes, and present antigens of these microbes to T-lymphocytes to begin adaptive immune responses against them. Finally, intraepithelial T-lymphocytes (def) and B-1 lymphocytes (def) are associated with the epidermis and the mucosal epithelium. These cells recognize microbes common to the epidermis and mucous membranes and start immediate adaptive immune responses against these commonly encountered microbes.
2. The mucous membranes
Mucous membranes line body cavities that open to the exterior, such as the respiratory tract, the gastrointestinal tract, and the genitourinary tract. Mucous membranes are composed of an epithelial layer that secretes mucus, and a connective tissue layer. The mucus is a physical barrier that traps microbes. Mucus also contains lysozyme (def) to degrade bacterial peptidoglycan, an antibody called secretory IgA (def) that prevents microbes from attaching to mucosal cells and traps them in the mucous, lactoferrin (def) to bind iron and keep it from from being used by microbes, and lactoperoxidase (def) to generate toxic superoxide radicals that kill microbes. Resident normal microbiota of the mucosa also inhibits potentially harmful microbes. In addition, the mucous membrane, like the skin, is constantly sloughing cells to remove microbes that have attached to the mucous membranes. Beneath the mucosal membrane is mucosa-associated lymphoid tissue (MALT) that contains Langerhans' cells - immature dendritic cells (def) - that phagocytose and kill microbes, carry them to nearby lymph nodes, and present antigens of these microbes to T-lymphocytes to begin adaptive immune responses against them. Intraepithelial T-lymphocytes (def) and B-1 lymphocytes (def) are associated with the epidermis and the mucosal epithelium. These cells recognize microbes common to the epidermis and mucous membranes and start immediate adaptive immune responses against these commonly encountered microbes.
3. Bony encasements
Bony encasements, such as the skull and the thoracic cage, protect vital organs from injury and entry of microbes.
b. Mechanical removal is the process of physically flushing microbes from the body. Methods include:
1. Mucus and cilia
Mucus traps microorganisms and prevents them from reaching and colonizing the mucosal epithelium. Mucus also contains lysozyme (def) to degrade bacterial peptidoglycan, an antibody called secretory IgA (def) that prevents microbes from attaching to mucosal cells and traps them in the mucus, lactoferrin (def) to bind iron and keep it from from being used by microbes, and lactoperoxidase (def) to generate toxic superoxide radicals that kill microbes. Cilia on the surface of the upper respiratory tract epithelial cells constantly propels mucus, dust, and trapped microbes upwards towards the throat. This is often referred to as the mucociliary escalator. Once at the throat, the mucus is swallowed and the trapped microbes are killed in the stomach. This is sometimes called the tracheal toilet.
2. The cough and sneeze reflex
Coughing and sneezing removes mucus and trapped microbes.
3. Vomiting and diarrhea
These processes remove pathogens and toxins in the gastrointestinal tract.
4.The physical flushing action of body fluids
Fluids such as urine, tears, saliva, perspiration, and blood from injured blood vessels also flush microbes from the body.
c. Bacterial Antagonism (def) by Normal Microbiota (def)
Approximately 100 trillion bacteria and other microorganisms reside in or on the human body. The normal body microbiota keeps potentially harmful opportunistic pathogens (def) in check and also inhibits the colonization of pathogens by:
1. Producing metabolic products (fatty acids, bacteriocins, etc.) that inhibit the growth of many pathogens;
2. Adhering to target host cells so as to cover them and preventing pathogens from colonizing;
3. Depleting nutrients essential for the growth of pathogens; and
4. Non-specifically stimulating the immune system.
Destruction of normal bacterial microbiota by the use of broad spectrum antibiotics may result in superinfections (def) or overgrowth by antibiotic-resistant opportunistic microbiota. For example, the yeast Candida, that causes infections such as vaginitis and thrush, and the bacterium Clostridioides difficile, that causes potentially severe antibiotic-associated colitis (def), are opportunistic microorganisms normally held in check by the normal microbiota.
In the case of Candida infections, the Candida resists the antibacterial antibiotics because being a yeast, it is eukaryotic, not prokaryotic like the bacteria. Once the bacteria are eliminated by the antibiotics, the Candida has no competition and can overgrow the area.
Clostridioides difficile is an opportunistic Gram-positive, endospore-producing bacillus transmitted by the fecal-oral route that causes severe antibiotic-associated colitis. C. difficile is a common healthcare-associated infection (HAIs) and is the most frequent cause of health-care-associated diarrhea. C. difficile infection often recurs and can progress to sepsis and death. CDC has estimated that there are about 500,000 C. difficile infections (CDI) in health-care associated patients each year and is linked to 15,000 American deaths each year.
Antibiotic-associated colitis is especially common in older adults. It is thought that C. difficile survives the exposure to the antibiotic by sporulation (def). After the antibiotic is no longer in the body, the endospores germinate and C. difficile overgrows the intestinal tract and secretes toxin A and toxin B that have a cytotoxic effect (def) on the epithelial cells of the colon. C. difficile has become increasingly resistant to antibiotics in recent years making treatment often difficult. There has been a great deal of success in treating the infection with fecal transplants, still primarily an experimental procedure.The most successful technique in restricting C. difficile infections has been the restriction of the use of antimicrobial agents.
Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
serif">Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.
Last updated: Feb., 2020
Please send comments and inquiries to Dr.
Gary Kaiser