Normal Microbiota and Pathogenesis

LECTURE 3

• Lecture 5, January 23, 2025
• Lecture focused on host-parasite relationships and host defenses

HOST-PARASITE RELATIONSHIP

• Normal flora: humans have approximately 10¹³ cells and 10¹⁴ bacteria, mostly in the large intestine.
• Viruses, fungi, and protozoa are also present, but in smaller numbers.
• Organisms are located in exposed body parts interacting with the external environment (skin, nose, mouth, intestinal and urogenital tracts).
• Internal organs and tissues are typically sterile.
• Normal flora is acquired rapidly after birth and changes throughout life, reflecting the individual's age, nutrition, and environment.
• Different regions of the skin support different flora (moist areas like armpits have Staphylococcus epidermidis; anaerobic bacteria are found in follicles and glands). Candida species are on the scalp and nail area. The nose and mouth are heavily colonized by bacteria, mostly anaerobes.
• Comon colonizers including streptococci, staphylococci and gram negative cocci. Potential pathogens include Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Neisseria meningitidis and Candida.
• Dental caries is a common infectious disease in developed countries, caused by Streptococcus mutans.
• The pharynx and trachea carry normal flora (including alpha and beta hemolytic streptococci, anaerobes, S. aureus, and Neisseria species), while the lower respiratory tract (below the epiglottis) is relatively sterile.
• The density of microbes in the GI tract increases from the stomach to the large intestine.
• The stomach has a high acidity, which inhibits bacterial growth except for Helicobacter pylori, which causes gastric ulcers.
• The small intestine has a mixed population of organisms, with 10⁴ to 10¹¹ organisms per gram in the large intestine. The majority of organisms in the large bowel are anaerobes.
• Hundreds of fungi and billions of viruses are present in the intestine.
• The urethra is lightly colonized, but the vagina has a more extensive flora of bacteria and fungi.
• During puberty, lactobacillus aerophilus becomes the dominant bacteria that maintains acidity and suppresses other organism growth.
• Age-related changes in the vaginal flora: before puberty, there is S. epidermidis, some streptococci and diphtheroids. After puberty, lactobacilli predominates maintaining acidity preventing excessive growth in others. In menopause, the flora is dominated by the skin flora.
• Additional sites may harbor microbiota, identified through nucleic acid detection and sequencing. These sites include the lungs (lower respiratory tract) and bladder and urine (and amniotic fluid and fetus and brain).

HOST-PARASITE RELATIONSHIP - ADVANTAGES & DISADVANTAGES

• Normal flora are beneficial to the host because they prevent colonization by potential pathogens, produce fatty acids that discourage other species, production of factors that prevent harmful bacteria, and produce vitamin B and K and stimulate the immune system.
• The sheer number of organisms in the large bowel makes it difficult for new organisms to take hold.
• The generally antagonistic effect of "good" microbes against intruder microbes is called microbial antagonism.
• Normal microbiota are stable and unlikely to be displaced by new microbes. This protection is partly due to the restricted number of attachment sites and the chemical and biological environment created is not favorable for many other microbes.
• Germ-free animals tend to live longer, due to the absence of pathogens, though their immune system is less developed.
• Normal flora can spread to other tissues and become a cause for hospital-acquired infections (HAIs).

HOST-PARASITE RELATIONSHIP - SYMBIOTIC ASSOCIATIONS

• Commensalism: one species lives harmlessly in, or on, another species (skin and intestinal flora benefit the host by preventing colonization by pathogenic species).
• Mutualism: both species benefit from the relationship. (Not typically seen in humans).
• Parasitism: one species benefits at the cost of another. (All pathogens are parasites, many living harmlessly with their natural host, becoming pathogenic when the conditions change).

HOST-PARASITE RELATIONSHIP - FACTORS AFFECTING SUSCEPTIBILITY TO INFECTION

• Host factors that weaken defense mechanisms may lead to increased susceptibility:

• Extreme age (premature infants and the very elderly)

• Genetic defects in immunity and those acquired(such as HIV/AIDS and transplant patients).

• Surgery and organ transplants

• Underlying diseases (cancer, liver dysfunction, diabetes, and chronic illnesses).

• Chemotherapy/immunosuppressant drugs

• Physical and mental stress

• Pregnancy

• Other infections (like measles)

• Social and behavioral changes may also affect host-parasite relationships, as seen in increased exposures to exotic organisms during tropical vacations, increased antibiotic use and the emergence antibiotic resistant bacteria, and the use of immunosuppressive therapy leading to increased opportunistic infections.

HOST-PARASITE RELATIONSHIP - BACKGROUND TO INFECTIOUS DISEASES

• Microbes rapidly evolve characteristics or properties to overcome host defenses, often with a rapid replication rate (~ ½ hour).
• The speed of the host's response, which can be mobilized to control infections, plays a critical role in infection control.
• A host-microbe encounter depends on the microbe's virulence, its infectious dose, and its portal of entry (exogenous or endogenous microbiota).

HOST-PARASITE RELATIONSHIP - OBLIGATORY STEPS OF INFECTIOUS MICROORGANISMS

1. Attachment/entry: A microbe gains a foothold on host tissue through specific molecular binding.
2. Spreading in the body: Host's immediate local defenses are evaded by microbes. Microbes use virulence factors to avoid engulfment by phagocytes (e.g., capsule, slime layer, leukocidins).
3. Multiplication: Microbes increase in number, stressing the host, leading to tissue damage.
4. Evasion of host defenses: Microbes evade immune and other host defenses long enough to complete their life cycle in the host.
5. Exit: The microbe leaves the body at a specific site, promoting spread to new hosts. (e.g., shedding through secretion, excretion or sloughing tissue).
6. Cause damage in the host: Damage may be immediate, or result in long-term or permanent damage to tissues or organs. Examples: meningitis (deafness), strep throat (rheumatic heart disease), Lyme disease (arthritis), and polio (paralysis).

HOST-PARASITE RELATIONSHIP - TYPES OF INFECTIONS

• Localized: infection remains confined to a specific tissue (e.g., boils, warts).
• Systemic: infection spreads to several sites and tissues/fluids, often carried by blood, lymph, or cerebrospinal fluids (e.g., mumps, rubella, chicken pox).
• Focal: infection spreads from a local site to other tissues (e.g., tuberculosis).
• Mixed: several agents establish themselves at the infection site (e.g., human bite infections).
• Primary: initial infection (eg, common cold, flu).
• Secondary: infection complications arising from a primary infection (e.g., bacterial otitis media associated with a common cold).
• Acute: rapid onset, severe but short-term. (e.g., flu and common cold)
• Chronic: progressive and sustained over a long period.(e.g., HIV, Hepatitis B , Hepatitis C).

HOST-PARASITE RELATIONSHIP - DEFINITIONS

• Pathogen: Microbe causing a disease
• Pathogenicity: Microbe ability to cause disease
• Infectivity: Ability of a microbe to establish a focal point of infection.
• Infection: Microbe is growing and multiplying in/on the host.
• Disease: deviation from a state of health where a part or all of the body can't function normally due to microbe presence or product.
• Virulence: Degree of intensity of pathogenicity.
• Invasiveness: Microbe ability to spread to adjacent or other tissues.
• Toxigenicity: Microbe ability to produce toxins that damage the host and cause disease.
• Edema: fluid accumulation in affected tissue
• Granulomas and Abscesses: walled-off collection of inflammatory cells and microbes.
• Lymphadenitis: Swollen lymph nodes
• Leukocytosis: increase in white blood cells
• Leukopenia: decrease in white blood cells
• Bacteremia/viremia: presence of bacteria/viruses in the blood
• Septicemia: microbes multiplying in the blood and present in large numbers (leads to shock and death)
• Asymptomatic/subclinical: infections produce no noticeable symptoms

HOST-PARASITE RELATIONSHIP - RESERVOIR, CARRIERS

• Reservoir: primary habitat/origin of a pathogen in nature.
• Carrier: individual unknowingly harboring a pathogen and spreads it to others, it can be long- or short-term, and the carrier may or may not have experienced disease.
• Asymptomatic carrier: infected; without symptoms.
• Incubating carrier: spreading an infection during the incubation period; infected.
• Convalescent carrier: shedding viable microbes after recovery; not symptomatic.
• Chronic carrier: harboring a microbe and shedding after recovery, often due to latency.
• Passive carrier: inadvertently introducing microbes(e.g. contaminated surfaces) to others.

HOST-PARASITE RELATIONSHIP - DEFINITIONS (CONT.)

• Communicable disease: spread form person-to-person
• Contagious disease: highly communicable through direct contact.
• Non-communicable disease: not spread from person-to-person.

HOST-PARASITE RELATIONSHIP – PATTERNS OF TRANSMISSION

• Vertical: transmission from parent to offspring (ovum, sperm, placenta, milk).
• Horizontal: transmission between individuals
  • Direct: physical contact, touching, kissing, sex, droplet contact, intentional or unintentional injection.
  • Indirect: contaminated objects, insects, vectors.
• Vector transmission
  • Mechanical vector: insect carries the microbes to the host on its body parts (flies, mosquitoes)
  • Biological vector: insect injects the microbes into the host (ticks, fleas).

HOST DEFENSES

• The immune system:
  • Innate immunity: rapid, non-specific, short duration, first-line of defense (PMNs, Macrophages, NK cells, and complement).
• Adaptive immunity: highly specific and has memory. (T and B cells).
  • Adaptive immunity: slower, highly specific, long-lasting response, second-line of defense (T helper and cytotoxic T cells, B cells, and plasma B cells).

HOST DEFENSE: IMMUNE DYSFUNCTIONS

• Hypersensitivity reactions (Type 1, 2, 3, 4):
• Type 1: immediate hypersensitivity
• Type 2: cytotoxic
• Type 3: immune complex-mediated
• Type 4: cell-mediated delayed
• Immunodeficiencies:
• Inherited genetic mutations
• Infections (e.g. HIV)
• Due to malignancies or increased infections
• Due to Drugs (such as cytoxic drugs and immunosuppressants).

HOST DEFENSES - REVIEW

• Host-parasite relationships: -Symbiotic relationships -Process for infection & disease
• Immune System: -Innate immunity - PMNS - Macrophages - Complement - Natural Killer Cells -Adaptive Immunity -T cells - Th1 vs Th2 -B cells - Plasma B Cells -Memory B Cells

Explore the human microbiome and its role in health and disease. Test your knowledge of the bacteria present in the gut, vagina, and skin, and how these microorganisms interact with the host. Learn the conditions under which normal flora can become pathogenic.