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Chapter 2 Innate and Adaptive Immunity: From Cell Defense to Tissue Repair

Section 1: Host Resistance and Innate (Non-specific) Defenses

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Zoë Soon

Section 1: Host Resistance and Innate Defenses

The human body must constantly protect itself against microorganisms capable of harming our cells.  The capacity to prevent microorganisms from causing diseases is termed host resistance, categorized as either non-specific (protecting against many different foreign agents) or specific (targeting only particular antigens).  This chapter focuses on non-specific innate defense, the inflammatory response, fever, and the cellular processes underlying healing.

Pathogenic Microorganisms

Most microorganisms are beneficial – decomposing organic material, forming food-web foundations, and fixing atmospheric gases (e.g., nitrogen N2 and carbon dioxide CO2) into usable forms for plants and other organisms.  Microorganisms also synergistically inhabit the intestines of mammals, including humans, producing vitamins (e.g. Vitamin K and B12) which are required for enzymatic functions.  Humans also benefit from industrial usage of microorganisms which are utilized in waste and sewage treatment, as well as in the fermentation and preparation of many foods and beverages (e.g. cheese, bread, yogurt, beer, wine, sauerkraut).

 

While most microorganisms are beneficial, certain species of each type of microorganism are pathogenic:

  • Pathogenic bacteria:  Unicellular prokaryotes that cause surface infections of eyes or skin, or deeper-tissue infections, often secreting toxins that cause further damage.
  • Pathogenic viruses:  Acellular agents that cause damage by entering human cells and replicating inside of them.
  • Pathogenic fungi:  Unicellular (yeast) or multicellular organisms that are capable of damaging skin (e.g. athlete’s foot), mucous membranes (e.g. oral thrush, vaginal yeast infections) or lungs (e.g. aspergillosis).  Some produce lethal toxins.
  • Helminths (parasitic worms):  Multicellular eukaryotes that can be ingested with contaminated food or water – infesting the intestines, disrupting nutrient absorption and causing cellular damage.  Can also penetrate the skin when wading in contaminated water.  Range in size from microscopic to visible to the naked eye.
  • Pathogenic protozoa:  Unicellular eukaryotes such as Plasmodium falciparum, which is transmitted by mosquito bite and responsible for malaria.

Breaking the Chain of Transmission

Preventing infections involves disrupting pathogen transmission at multiple points:

  • Destroy disease reservoirs:  e.g. eliminate standing water where mosquitos breed (harbouring malarial protozoa or West Nile virus).
  • Proper disposal of garbage and sewage, which can harbour pathogens such as hepatitis viruses and cholera-inducing bacteria.
  • Physical barriers include gloves, masks, lab coats, safety goggles, isolation rooms, and sterile equipment in health care.
  • Condoms:  barrier protection against sexually transmitted infections.
  • Hand washing and thoroughly cooking food to prevent ingestion of pathogens.
  • Wound care:  proper cleaning and suturing to prevent infection.
  • Vaccination, optimal nutrition, and adequate sleep reduce susceptibility to disease.
Pathogens are infectious agents that can be transmitted by multiple routes, including direct contact, indirect contact, droplets, the air, water, food, and vectors (e.g., mosquitoes, ticks). Transmission of pathogens can occur through contact with saliva, mucous, blood, feces, or animals or areas that may be contaminated (e.g., locker room floors, linen, door knobs, soil, and waterways).
Pathogens are infectious agents that can be transmitted by multiple routes, including direct contact, indirect contact, droplets in the air, water, food, and vectors (e.g., mosquitoes, ticks). Transmission of pathogens can occur through contact with bodily secretions (saliva, mucous, blood, feces), or contact with animals or areas that may be contaminated (e.g., locker room floors, linen, door knobs, soil, and waterways).

Innate (Non-Specific) Defenses:  An Overview

The body’s first line of defense – called innate or non-specific defense – provides immediate, broad protection.  Innate reflects that these defenses are present from birth (Latin nati for ‘birth’);  non-specific reflects the wide range of pathogens covered.  Categories include:  physical and mechanical, biochemical, normal flora, phagocytes, complement proteins, interferons, inflammation, and fever.

Physical and Mechanical Innate Defenses

  • Skin:  Multiple tightly-bound, dehydrated, water-tight, keratin-filled epithelial layers resist microbial penetration.  Frequent cell shedding continuously renews this layer.
  • Fingernails and hair:  Modified epithelial cells providing physical protection and warmth.
  • Cilia:  In the respiratory mucosa, cilia sweep mucus containing trapped pathogens toward the glottis for swallowing – a mechanism called the mucociliary escalator.
  • Mucus:  Produced by goblet cells lining the digestive, respiratory, urinary, and reproductive tracts.  Contains sticky mucin proteins that trap debris and microbes.
  • Urine flow:  Flushing action through the urinary tract provides physical protection.
Non-Specific Defense: Physical and Chemical Barriers Against Infection
Physical and Chemical Barriers Against Infection: This is a diagram of the human body annotated with descriptions of the various barriers against infection. These comprise: intact skin and the acid in sweat; coughing and sneezing which expel infectious agents; enzymes in mucus, tears and saliva, in the nose and mouth; the mucus and intact mucous membranes of the respiratory tract; cilia in the respiratory tract, which trap foreign material; acid in the stomach; the mucus and intact mucous membranes of both the gut and the genital tract; competition from commensal bacteria in the gut and genital tract; and, in males, antibacterial proteins in semen.
This scanning electron micrograph shows ciliated and non-ciliated epithelial cells from the human trachea. The mucociliary escalator pushes mucus away from the lungs, along with any debris or microorganisms that may be trapped in the sticky mucus, and the mucus moves up to the esophagus where it can be removed by swallowing.
This scanning electron micrograph shows ciliated and non-ciliated epithelial cells from the human trachea. The mucociliary escalator pushes mucus away from the lungs, along with any debris or microorganisms that may be trapped in the sticky mucus, and the mucus moves up to the esophagus where it can be removed by swallowing.
Goblet cells produce and secrete mucus. The arrows in this micrograph point to the mucus-secreting goblet cells (magnification 1600⨯) in the intestinal epithelium. Mucus consists of 95% water and 5% mix of proteins sugars, and salts. The mucins are sticky glycoproteins. IgA antibodies and enzymes (lysozyme and lactoferrin) help destroy bacteria and viruses.
Goblet cells produce and secrete mucus. The arrows in this micrograph point to the mucus-secreting goblet cells (magnification 1600⨯) in the intestinal epithelium. Mucus consists of 95% water and 5% mix of proteins sugars, and salts. The mucins are sticky glycoproteins. IgA antibodies and enzymes (lysozyme and lactoferrin) help destroy bacteria and viruses.

Biochemical Innate Defenses

Secretions from glands and organs create a chemically hostile environment for pathogens:

Sebum Bactericidal oil secrete by sebaceous glands onto the skin.

Contains lysozymes, IgA antibodies, and defensins (antimicrobial peptides that disrupt bacterial or fungal structure or metabolism)

Sweat Contain water, ions, and waste products that flush microorganisms from skin surfaces and make the environment less hospitable to pathogens.
Tears & meibum Tears contain lysozymes and IgA antibodies.  Meibum adds oils and other protective compound.  Together they protect the eye surface.
Cerumen (ear wax) Produced by modified sweat glands.  Slightly acidic and dry with antifungal and antibacterial properties.  Traps pathogens and resists outer ear infection.
Stomach acid Destroys most ingested microbes; strong biochemical protection within the digestive tract.
Bile Produced by the liver, stored, and secreted by the gallbladder.  Alkaline; contains bile salts that are potent antimicrobial agents.
Vaginal secretions Slightly acidic; contain lactoferrin (sequesters iron, depriving bacteria of a required resource) and lysozyme (cleaves bacterial cell wall components)
Seminal fluid Contains antimicrobial peptides and enzymes including lactoferrin and lysozyme.  Composed of secretions from epididymis, seminal vesicles, and bulbourethral and prostate glands.
Sebum is also a food source for resident microbes that produce oleic acid,
Human skin has three layers, the epidermis, the dermis, and the hypodermis, which provide a thick barrier between microbes outside the body and deeper tissues. Dead skin cells on the surface of the epidermis are continually shed, taking with them microbes on the skin’s surface. Sebaceous glands secrete sebum, a chemical mediator that lubricates and protect the skin from invading microbes. Sebum is also a food source for resident microbes that produce oleic acid, making the skin mildly acid and inhospitable to many pathogenic microbes. Sweat glands secrete dermcidin, which disrupts the membrane integrity of bacteria and fungi.
In the ears, cerumen (earwax) exhibits antimicrobial properties due to the presence of fatty acids, which lower the pH to between 3 and 5.
In the ears, cerumen (earwax) exhibits antimicrobial properties and low pH 3-5.

Innate Defenses:  Normal Microbiota

The human microbiome encompasses all microorganisms on the skin, eyes, hair, nails, nose, mouth, respiratory and digestive tracts, urethra, and vagina.  Microbes in these regions that do not cause disease are called normal flora or normal microbiota.  They vary by individual, body location, climate, and diet.

Normal microbiota are commensals  – co-existing without causing harm, benefiting from dead skin cells and secretions.  The relationship is often mutualistic:  both host and microbe benefit.  Normal microbiota protect against pathogens by both occupying surface area and secreting deterrent biochemicals.  Intestinal microbes additionally help break down indigestible compounds (dietary fiber) and produce beneficial vitamins.

normal flora
Human microbiome refers to the microorganisms (bacteria, fungi, protozoa, archaea, and viruses) that naturally inhabit the human body. These microorganisms have a range of roles throughout the body. For example, gut microbiota is known to assist with digestion, the production of vitamins essential to human health (e.g., vitamins B and K, and also provide protection from pathogenic microorganisms. The composition of the gut microbiota is reflective of environmental exposure, diet, and health.

 

A schematic representation of the human gut microbiota, which contains 100 trillion microorganisms. These microorganisms, such as bacteria, viruses, fungi, and protozoa, are part of the gut microbiota.
A schematic representation of the human gut microbiota, which contains 100 trillion microorganisms. These microorganisms (bacteria, viruses, fungi, and protozoa) are part of the gut microbiota.

 

 

Think About Questions:

Why is inflammation considered a non-specific defense?  What are other non-specific defenses of the human body?

Why does inflammation occur any time that there is an injury or disease?

Did you know that biologists sometimes call the digestive system an external tube that penetrates the body?  Name one feature of the digestive system that prevents ingested microbes from causing an infection. 

Why does taking an antacid put you more at risk for stomach infections?

Imagine you have a papercut – list the innate factors of your body that will help eliminate the bacteria that enter that cut. 

On a neutrophil, define the following: pseudopod, phagosome, lysosome, granule

How does a NK cells kill bacteria?

What is properdin?

What is an interferon?

What is a respiratory burst?

Did you know that some diseases are caused by auto-antibodies?  And some are caused by auto-complement proteins?  https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01524-6/fulltext

 

Inspirational Quote: Healing is an art. It takes time, it takes practice. It takes love. ~ Maza Dohta 

 

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