ANATOMICAL BARRIERS, MECHANICAL REMOVAL, BACTERIAL ANTAGONISM BY NORMAL FLORA, AND ANTIGEN-NONSPECIFIC ANTIMICROBIAL MOLECULES PRODUCED BY THE BODY

Innate immunity refers to antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to an antigen. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection.

Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize a few highly conserved structures present in many different microorganisms. The structures recognized are called pathogen-associated molecular patterns and include LPS from the gram-negative cell wall, peptidoglycan, lipotechoic acids from the gram-positive cell wall, the sugar mannose (common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial DNA, N-formylmethionine found in bacterial proteins, double-stranded RNA from viruses, and glucans from fungal cell walls. Most body defense cells have pattern-recognition receptors for these common pathogen-associated molecular patterns  and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 molecular patterns. All of this will be discussed in greater detail in upcoming sections.

The innate immune responses involve:

  • phagocytic cells (neutrophils, monocytes, and macrophages);
     

  • cells that release inflammatory mediators (basophils, mast cells, and eosinophils);
     

  • natural killer cells (NK cells); and
     

  • molecules such as complement proteins, acute phase proteins, and cytokines.

Examples of innate immunity include anatomical barriers, mechanical removal, bacterial antagonism, pattern-recognition receptors, antigen-nonspecific defense chemicals, the complement pathways, phagocytosis, inflammation, and fever. In the next several sections we will look at each of these in greater detail.

We will now take a closer look at anatomical barriers, mechanical removal, intraepithelial T-lymphocytes and B-1 cells, and bacterial antagonism.

 

Anatomical Barriers, Mechanical Removal, Intraepithelial T-lymphocytes and B-1 cells, Bacterial Antagonism by Normal Flora, and Antigen-Nonspecific Antimicrobial Molecules Produced by the Body

1. 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.

A. the skin

The skin, consisting of the epidermis and the dermis, is dry, acidic, and has a temperature lower than 37 degrees Celcius (body temperature). These conditions are not favorable to bacterial growth. Resident normal flora of the skin also inhibit potentially harmful microbes. In addition, the dead, keratinized cells that make up the surface of the skin are continously being sloughed off so that microbes that do colonize these cells are constantly being removed. Hair follicles and sweat glands produce lysozyme and toxic lipids that can kill bacteria. Finally, beneath the skin surface is skin-associated lymphoid tissue (SALT) that contains cells for killing microbes and sampling antigens on the skin to start adaptive immune responses against them.

B. 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 to degrade bacterial peptidoglycan, an antibody called secretory IgA that prevents microbes from attaching to mucosal cells and traps them in the mucous, lactoferrin to bind iron and keep it from from being used by microbes, and lactoperoxidase to generate toxic superoxide radicals that kill microbes. Resident normal flora of the mucosa also inhibit 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 cells for killing microbes and sampling antigens on the mucosa to start adaptive immune responses against them.

C. bony encasements

Bony encasements, such as the skull and the thoracic cage, protect vital organs from injury and entry of microbes.

2. Mechanical removal is the process of physically flushing microbes from the body. Methods include:

A. mucus and cilia

Mucus traps microorganisms and prevents them from reaching and colonizing the mucosal epithelium. Mucus also contains lysozyme to degrade bacterial peptidoglycan, an antibody called secretory IgA that prevents microbes from attaching to mucosal cells and traps them in the mucus, lactoferrin to bind iron and keep it from from being used by microbes, and lactoperoxidase to generate toxic superoxide radicals that kill microbes. Cilia on the surface of the epithelial cells propels mucus and trapped microbes upwards towards the throat where it is swallowed. This is sometimes called the tracheal toilet.

B. the cough and sneeze reflex

Coughing and sneezing removes mucus and trapped microbes.

C. vomiting and diarrhea

These processes remove pathogens and toxins in the gastrointestinal tract.

D. 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.

3. Intraepithelial T-lymphocytes and B-1 cells

a. Intraepithelial T-lymphocytes are found in the epidermis of the skin and the mucosal epithelia. These T-lymphocytes, known as gamma delta T-cells, have a limited diversity of antigen receptors for microbes often encountered on the skin and mucous membranes. As such they function more as effector cells for innate immunity rather than adaptive immunity.

b. B-1 cells are B-lymphocytes with a limited diversity of antigen receptors that initially produce a class of antibody called IgM against common polysaccharide and lipid antigens of microbes. As such they function more as effector cells for innate immunity rather than adaptive immunity. Antibodies produced by B-1 cells are often called natural antibodies.

4. Bacterial Antagonism by Normal Flora

Approximately 100 trillion bacteria and other microorganisms reside in or on the human body. These normal body flora keep potentially harmful opportunistic pathogens in check and also inhibit the colonization of pathogens by:

a. producing metabolic products (fatty acids, bacteriocins, etc.) that inhibit the growth of many pathogens;

B. adhering to target host cells thus covering them and preventing pathogens from colonizing;

C. depleting nutrients essential for the growth of pathogens; and

D. nonspecifically stimulating the immune system.

Destruction of normal bacterial flora by the use of broad spectrum antibiotics may result in superinfections or overgrowth by antibiotic resistant opportunistic normal flora. The yeast Candida, that causes infections such as vaginitis and thrush, and the bacterium Clostridium difficile, that causes potentially severe antibiotic-associated colitis , are opportunistic flora normally held in check by normal flora bacteria. Antibiotic-associated colitis is especially common in older adults. It is thought that C. difficile survives the exposure to the antibiotic by sporulation . After the antibiotic is gone, the endospores germinate and C. difficile overgrows the intestinal tract and secretes toxin A that has a cytotoxic effect on the cells. Fortunately, C. difficile does itself respond to certain antibiotics so antibiotic-associated colitis is treatable.

5. Antigen-Nonspecific Antimicrobial Molecules Produced by the Body

There are many antigen-nonspecific antimicrobial chemicals produced by the host that play roles in innate body defense. Examples include the following.

A. Hydrochloric acid and enzymes found in gastric secretions destroy microbes that are swallowed.

B. Lysozyme , found in in tears, mucous, saliva, plasma, tissue fluid, etc., breaks down peptidoglycan in bacteria causing osmotic lysis.

C. Human beta-defensins are short peptides found in blood plasma and mucous. They forms pores in the cytoplasmic membrane of a variety of bacteria causing leakage of cellular needs.

D. Lactic and fatty acids, found in perspiration and sebaceous secretions , inhibit microbes on the skin.

E. Lactoferrin and transferrin, found in body secretions, plasma, and tissue fluid, trap iron for use by human cells while preventing its use by microorganisms.

F. Cytokines are low molecular weight, soluble proteins that are produced in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune systems. They are produced by virtually all cells involved in innate and adaptive immunity, but especially by T helper (Th) lymphocytes. The activation of cytokine-producing cells triggers them to synthesize and secrete their cytokines. The cytokines, in turn, are then able to bind to specific cytokine receptors on other cells of the immune system and influence their activity in some manner.

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