Lecture Notes 12

Microorganisms, Humans, and Disease

Infection and Disease

• Pathogen: A microorganism or agent (like a virus) capable of causing disease.
• Infection: The successful invasion and growth of pathogens in the body.
• Disease: An abnormal state where the body or a part of it cannot perform its functions properly; occurs when a pathogen overcomes the body's defenses.
• It's possible to have contact with pathogens and even have an infection without developing a disease.
• Host: An organism that shelters and/or supports the growth of pathogens.
• Infectious Disease: Disease caused by infective pathogens (as opposed to degenerative diseases).

Pathology

• Pathology: The study of disease in an individual, dealing with:
  • Etiology: The cause of disease.
  • Pathogenesis: The development of disease over time in an individual.
  • Effects/treatments of disease

The Normal Microbiota

• Microbes that are "supposed" to be there.
• Humans (and other animals) are usually sterile before birth, after which they become colonized both internally and externally.
• Normal Microbiota (Resident Flora): Microbes that establish permanent residence inside or on the body surface without causing disease.
• The resident population of microbial cells outnumbers human cells by a factor of 10!
• The normal microbiota includes bacteria, fungi, and protozoa.
• Examples:
  • Gastrointestinal tract: Escherichia coli
  • Oral cavity (mouth): Various Streptococcus species
  • Skin: Various Staphylococcus species
  • Vaginal area: Lactobacillus, Candida (a yeast)

Symbiotic Relationship (Usually Mutualistic)

• Example - E. coli:
  • E. coli gets a warm environment with free food.
  • Humans get Vitamin K and protection from pathogens.
  • E. coli outcompetes potential pathogens that may enter, known as microbial antagonism.

Other Types of Symbioses

• Commensalism: One benefits, the other is unaffected (e.g., microbes that inhabit the skin and live off dead tissue).
• Parasitism: Refers to the state when a pathogen is involved.
• Opportunistic Pathogens: Pathogens that cause disease under certain circumstances when they normally would not; they cause opportunistic infections.

Classification and Terminology of Infectious Diseases

• Symptoms: Subjective reports by a patient (e.g., "I have a stomach ache").
• Signs: Objectively measurable changes in body function (e.g., a fever).
• Both symptoms and signs are used by a physician to make a diagnosis (identification of the disease).
• Syndrome: A certain group of signs and symptoms that always accompany a certain disease (e.g., AIDS).

Severity and Duration of Disease

• A disease's scope may be:
  • Acute: Develops rapidly, with relatively severe symptoms, and lasts a short time (e.g., the flu).
  • Chronic: Develops slowly, with less severe symptoms, and lasts longer (e.g., tuberculosis).
  • Latent: Causative agent is dormant for some time, and then causes disease (e.g., HIV, Shingles).

Extent of Host Involvement

• A disease may be:
  • Local: Infects and remains confined to a small part of the body (e.g., a wart).
  • Systemic: Spread throughout the body (usually by the circulatory system) (e.g., measles, AIDS).
• An infection is:
  • Primary: The initial cause of disease (e.g., HIV).
  • Secondary: Occurs after the host is weakened by a primary infection (e.g., Pneumocystis pneumonia).
  • Subclinical: Does not cause any signs or symptoms (e.g., HIV in early stages).

Microbial Mechanisms of Pathogenicity

• How pathogens actually make us sick.

How Pathogens Enter the Body

• Portals of Entry: Specific routes by which pathogens enter the body.
• Integumentary System: Protects the body and surrounds it entirely. It is also the site of entrance of the pathogen.
• Mucous Membranes:
  • Respiratory tract: Pathogen is inhaled (most susceptible membrane and common portal of entry).
  • Urogenital tract: Often via sexual intercourse.
  • Gastrointestinal tract: Food, water, contaminated fingers.

The Skin (Cutaneous Membrane)

• Intact skin is usually an effective barrier to the entry of pathogens; sometimes they can colonize sweat ducts or hair follicles.
• Parenteral Route: Pathogen introduced through the skin via injection, insect bite, or wound.

Preferred Portal and Adherence

• Some pathogens will only cause disease if they enter the body through their preferred portal of entry (e.g., certain Streptococci that are inhaled can cause pneumonia but if swallowed have little effect).
• Adherence: Pathogens need to attach to host tissue once entry is gained.
• Often occurs due to specialized fimbriae that recognize certain tissues and/or cells.

How Bacterial Pathogens Penetrate Host Cell Defenses

• Capsules: Contribute to virulence because they can protect against phagocytosis.
• Enzymes: Produced by pathogenic bacteria can help them persist in the body:
  • Leukocidins: Destroy neutrophils and macrophages (phagocytosing cells) - Staph and Strep often make them.
  • Hemolysins: Lyse red blood cells (and sometimes white blood cells).
  • Coagulases: Cause blood to clot, protecting and isolating the bacterium from host defenses - common in Staph.

Pathogens Do Not Need to Penetrate the Integument to Cause Illness

• In most cases, they don’t.
• Examples:
  • “Pharyngitis” (sore throat) may be caused by viruses or bacteria, mainly Streptococcus pyogenes.
  • “Pneumonia” (which is really “bronchiolitis” or “alveolitis”).
• The pathogen has caused the inflammatory response to be activated. This is really what the suffix “-itis” means.

How Bacteria Damage You

• Direct Damage: Host cells can be harmed or destroyed if bacteria are growing and metabolizing in or around them.
  • This is particularly true of intracellular bacteria (i.e., Chlamydia, Mycoplasma) and all viruses.
• Indirect Damage: The immune system is activated by the pathogen’s presence and actually causes damage to your body.
  • Can be caused by specific T-cells that are programmed to destroy infected host cells.
  • Can also be associated with the inflammatory response, which is supposed to help, but sometimes does harm.

Direct Damage by Toxins

• Much direct damage is due to the production of Toxins (poisonous substances).
• Two major groups of toxins: exotoxins and endotoxins.
  • Exotoxins: Produced as by-products of bacterial metabolism and are released into the host.
  • Endotoxins: Part of the cell wall; they are liberated only when the bacteria die and the cell walls are degraded.

Bacterial Toxins

• Exotoxins: Primarily produced inside gram-positive bacteria as by-products of their growth and metabolism. They are then released into the surrounding medium.
• Endotoxins: Part of the outer portion of the cell wall of gram-negative bacteria. They are liberated when the bacteria die and the cell wall breaks apart.

Exotoxins

• Proteins mainly produced by gram-positive cells.
• Affect the host in a specific way:
  • Cytotoxins: Kill host cells or render them inactive (example: Diphtheria toxin inhibits protein synthesis in host cells).
  • Neurotoxins: Interfere with the transmission of nerve impulses (examples: botulinum and tetanus toxins).
  • Enterotoxins: Adversely affect cells lining the gastrointestinal tract (example: Vibrio and Staph toxins).
  • Antibodies produced against these toxins are called antitoxins.

Endotoxins

• Lipopolysaccharides that are part of the cell wall; mainly present in the outer membrane of gram-negative bacteria (LIPID A).
• The death of the bacterial cell liberates the toxin as the outer membrane and cell wall break down.
• The immune system’s actions may cause the cells to die, or antibiotics may be the cause.
• Regardless, when the endotoxins are released, they all generally affect the body in a similar fashion.

Endotoxins Effects

• Cause chills and fever (the pyrogenic response) due to the stimulation of production of interleukin-1 by macrophages. This causes the hypothalamus (which controls body temperature) to reset the body's thermostat.

• Can cause shock (loss of blood pressure), in this case called septic or endotoxic shock, due to systemic inflammation that involves blood vessel dilation. This leads to a drop in blood pressure and can be fatal.

• Effective antibodies are usually not made against endotoxins. They have a certain half life, and will produce minor to major effects (but all generally of the same type).

• Process of fever:

  1. A macrophage ingests a gram-negative bacterium
  2. The bacterium is degraded, releasing endotoxins that induce the macrophage to produce Interleukin-1 (IL-1)
  3. IL-1 is released by the macrophage into the bloodstream, through which it travels to the hypothalamus of the brain
  4. IL-1 induces the hypothalamus to produce prostaglandins, which reset the body's "thermostat" to a higher temperature, producing fever

Viruses

• Since viruses reproduce inside host cells, they can avoid certain aspects of the defense system.
• Viruses cause cytopathic (cell+disease) effects (CPE), which may cause cell death (cytocidal) or damage (noncytocidal).
• Interferons are chemicals produced by host cells to protect against viral infection.

Nosocomial Infections

• Acquired in the hospital or other health care facility.
• On average, 5% of patients acquire them, which translates into roughly 3 million cases/year (and about 1% of these lead to death).
• Opportunistic, drug-resistant gram-negative bacteria are usually the culprits (E. coli, Pseudomonas, Klebsiella account for roughly half, with the remainder largely caused by Staphylococcus and Streptococcus species.)
• They can be introduced through surgical procedures, or because the host is compromised physically or immunologically.

Pathogenesis - The Development of a Disease in an Individual

• The following pattern is observed:
  • Incubation Period: The time interval between the initial infection and the first appearance of signs/symptoms.
  • Prodromal Period: Period of mild signs/symptoms.
  • Period of Illness: The height of the disease, all signs and symptoms apparent.
  • Period of Decline: Signs and symptoms decline.
  • Period of Convalescence: Return to normal; recovery has occurred.

Disease Progression Over Time

• A graph shows how the number of microorganisms increases over time with different periods within:
  • Incubation Period: No signs or symptoms
  • Prodromal Period: Mild signs and symptoms
  • Period of Illness: The height of the disease, where death can occur if immune responses and/or medical treatments fail.
  • Period of Decline: Signs and symptoms decline gradually.
  • Period of Convalescence: Recovery, back to the baseline number of microorganisms.