Chapter 13 Microbe-Human Interactions Notes

Commensals vs. pathogens

  • Normal Resident microbiota: microbes that engage in mutual or commensal associations with humans (i.e. commensals)

  • Infection: microbe that has penetrated the host defenses, invaded sterile tissue, and multiplied

  • Disease: damage to host, any deviation from health

  • Pathogen: disease-causing microbe

Initial Colonization of the Newborn

  • Uterus and contents are normally sterile and remain so until just before birth

  • Breaking of fetal membrane exposes the infant; all subsequent handling and feeding continue to introduce what will be normal flora

Major Factors in the Development of an Infection

  • Microbes evade barriers

  • Portal of entry

  • Adhesion: Microbes attach to host cells

  • Invasion: Microbes make pathway into cells

  • Multiplication: Microbes grow and spread

  • Infection of target: Microbes attack specific tissues

  • Microbes damage tissues

  • Microbes leave host

  • Disease

  • Portal of exit

Becoming Established

  • Portals of entry – characteristic route a microbe follows to enter the tissues of the body

  • Exogenous agents originate from source outside the body

  • Endogenous agents already exist on or in the body (normal microbiota)

  • Conjunctiva

  • Respiratory tract

  • Gastrointestinal tract

  • Pregnancy and birth

  • Urogenital tract

  • Skin

Portals of Entry – Skin to Transplacental

  • Skin: nicks, abrasions, punctures, incisions

  • Gastrointestinal tract: food, drink, and other ingested materials

  • Respiratory tract: oral and nasal cavities

  • Urogenital tract: sexual, displaced organisms

  • Transplacental

Pathogens That Infect during Pregnancy

  • STORCH – Syphilis, Toxoplasmosis, Other diseases (hepatitis B, AIDS and chlamydia), Rubella, Cytomegalovirus and Herpes simplex virus

  • Maternal blood pools within intervillous space

  • Umbilical cord, umbilical arteries (fetal blood), umbilical vein

  • Bacterial cells

  • Umbilical cord, Maternal blood vessel, Placenta

  • Placenta

Requirement for an Infectious Dose (ID)

  • Infectious Dose: Minimum number of microbes required for infection to proceed

  • Microbes with small IDs have greater virulence

  • Lack of ID will not result in infection

Attaching to the Host

  • Adhesion – microbes gain a stable foothold at the portal of entry; dependent on binding between specific molecules on host and pathogen

  • Structures involved in adhesion: Fimbriae, Flagella, Glycocalyx, Cilia, Suckers, Hooks, Barbs, Viral spikes

  • Examples of adhesion structures include fimbriae, capsules, and viral spikes that interact with host receptors

Adhesion Properties of Microbes

  • Neisseria gonorrhoeae – Gonorrhea: Fimbriae attach to genital epithelium

  • Escherichia coli – Shigella and Salmonella: Well-developed fimbrial adhesin

  • Vibrio: Glycocalyx anchors microbe to intestinal epithelium

  • Treponema: Tapered hook embeds in host cell

  • Mycoplasma: Specialized tip at ends of bacteria fuses tightly to lung epithelium (lack of cell wall for certain species)

  • Pseudomonas aeruginosa: Specialized adherence mechanisms in respiratory and burn infections

  • Streptococcus mutans, S. sobrinus: Dextran slime layer glues cocci to tooth surface (dental caries)

  • Giardia lamblia (protozoan): Small suction disc on underside attaches to intestinal surface

  • Trypanosoma (protozoan): Flagellum is needed to penetrate and stay alive (African and South American trypanosomiasis)

Virulence Factors

  • Virulence factors: traits used to invade and establish themselves in the host, and determine the degree of tissue damage and disease severity

  • Examples include:

    • Blocking phagocytosis

    • Invasion factors

    • Exoenzymes

    • Toxins

Blocking Phagocytosis

  • Initial defense involves phagocytes that engulf and destroy pathogens

  • Antiphagocytic factors help microbes avoid phagocytosis

  • Leukocidins: toxic to white blood cells, produced by Staphylococcus and Streptococcus

  • Slime layer or capsule: makes phagocytosis difficult

  • Some pathogens survive intracellular phagocytosis (e.g., M. tuberculosis)

  • Visual concept: blocked phagocytic response allows continued growth and tissue damage

Entering Host Tissues – invasion factors

  • Some pathogens produce secretion systems to insert virulence proteins directly into host cells (example: Salmonella)

  • Process: adhesion by fimbriae → release of proteins → disruption of actin and membrane ruffling → cell pulled into vacuole

  • Salmonella multiplies internally and moves out into deeper tissues

  • Microvilli may be affected; secretion system involved in pedestal formation

Exoenzymes – Exoenzymes that facilitate spread

  • Exoenzymes (extracellular enzymes) are secreted outside the cell and dissolve barriers or penetrate between cells

  • Examples include mucinase, keratinase, collagenase, hyaluronidase, coagulase, streptokinase/staphylokinase

Bacterial Toxins: A Potent Source of Cellular Damage

  • Toxigenicity: capacity to produce toxins at the site of multiplication

  • Two main types:

    • Endotoxin: not secreted but released after the cell is damaged; component of lipopolysaccharide (LPS) in gram-negative cell walls (makes it inside of it self) not secreted

    • Exotoxin: toxin molecule secreted by a living bacterial cell into infected tissue; highly specific for a target cell; examples include hemolysins and A-B toxins (these toxins are made by bacteria cells, they exit secreted

Bacterial Toxins: Exotoxins and Endotoxins

  • Exotoxins: target specific organ or cell type (e.g., heart, muscle, blood cells, intestinal tract dysfunctions)

  • Endotoxins: cause systemic effects such as fever, malaise, aches, shock

  • Note on stability: exotoxins are proteins; endotoxins are LPS components and are relatively heat-stable

Comparing Exotoxins & Endotoxins

  • Toxicity: exotoxins toxic in tiny amounts; endotoxins toxic in higher doses

  • Effects on the body: exotoxins act on specific cell types; endotoxins cause systemic effects

  • Chemical composition: exotoxins are small proteins; endotoxins are LPS

  • Heat denaturation: exotoxins can be denatured by heat (often at 60 C); endotoxins are more heat-stable

  • Toxoid formation: exotoxins can often be converted to toxoids to stimulate antitoxins; endotoxins cannot

  • Immune response: exotoxins strongly stimulate antitoxins; endotoxins elicit weaker, broader responses

  • Manner of release: exotoxins secreted by live cells; endotoxins released upon cell lysis

  • Typical sources: exotoxins produced by a few gram-positive and some gram-negative bacteria; endotoxins produced by all gram-negative bacteria

  • Examples: exotoxins include tetanus, diphtheria, cholera, anthrax; endotoxins associated with meningitis, endotoxic shock, salmonellosis

A-B Exotoxins

  • Structure: A active component linked to a B binding component

  • Mechanism: A component inhibits a cellular protein to cause damage; receptor binding by B facilitates entry

  • Typical process: toxin precursor is inactive, binds to receptor via B chain, endocytosis occurs, toxin A is released from the vacuole and then inhibits ribosomes to block protein synthesis, leading to cell death

  • Visual depiction source: example in lecture materials

Concept Check: Capsules and slime layers can help pathogens evade the immune system by___.

  • A. Accelerating replication

  • B. Stimulating paralysis

  • C. Prevent phagocytic activity

  • D. Causing tissue damage

The Process of Infection and Disease

  • Four distinct stages of clinical infections:

    • Incubation period: time from initial contact with the infectious agent to the appearance of first symptoms; agent is multiplying but damage is insufficient to cause symptoms; several hours to several years

    • Prodromal stage: vague feelings of discomfort; nonspecific complaints

    • Period of invasion: multiplies at high levels, becomes well-established; more specific signs and symptoms

    • Convalescent period: as the body responds to infection, symptoms decline

  • Timeline: Height of infection -> initial exposure to microbe -> stages listed above

Patterns of Infection

  • Localized infection: microbes enter the body and remain confined to a specific tissue

  • Systemic infection: infection spreads to several sites and tissue fluids, usually in the bloodstream

  • Focal infection: infectious agent breaks from a local infection and is carried to other tissues

  • Mixed infection: several microbes grow simultaneously at the infection site (polymicrobial)

  • Primary infection: initial infection

  • Secondary infection: infection by a different microbe following the primary one

Acute vs Chronic Infections

  • Acute infection: rapid onset with severe but short-lived effects; example: common cold caused by rhinovirus; symptoms begin 2-3 days after contact; resolves ~10 days without therapy

  • Chronic infections: progress and persist over a long period; may involve periods of infection and latency; example: cold sores caused by herpes simplex virus type 2

Signs and Symptoms of Inflammation

  • Earliest symptoms of disease due to activation of body defenses: fever, pain, soreness, swelling

  • Signs of inflammation: edema (fluid accumulation), granulomas and abscesses (walled-off inflammatory collections)

  • Lymphadenitis: swollen lymph nodes

Signs of Infection in the Blood

  • Changes in circulating white blood cells:

    • Leukocytosis: increase in white blood cells

    • Leukopenia: decrease in white blood cells

  • Septicemia: microorganisms multiplying in the blood and present in large numbers

  • Bacteremia: small numbers of bacteria in the blood, not necessarily multiplying

  • Viremia: small numbers of viruses present, not necessarily multiplying

Infections That Go Unnoticed

  • Asymptomatic (subclinical) infections: infected but no signs of disease

  • Inapparent infection: person does not seek medical attention

Portals of Exit

  • Pathogens depart by a specific avenue and this influences dissemination of infection

  • Routes include:

    • Respiratory: mucus, sputum, nasal drainage, saliva

    • Skin scales from open lesions

    • Fecal exit

    • Urogenital tract

    • Removal of blood

Persistence of Microbes and Pathologic Conditions

  • Apparent recovery does not always mean microbe is removed

  • Latency: pathogen not active or causing disease

  • Chronic carrier: latent infection with shedding of agent

  • Sequelae: long-term or permanent damage to tissues or organs

Sources and Transmission of Microbes

  • Reservoir: primary habitat of pathogen in the natural world

  • Carrier, soil, water, plants, animals

  • Source: individual or object from which infection is acquired

  • Examples: influenza reservoir in birds

Living Reservoirs

  • Carrier: inconspicuously shelters a pathogen and spreads it to others

  • Asymptomatic carrier: shows no symptoms

  • Passive carrier: contaminated healthcare worker transfers pathogens to patients; carries pathogen on skin or a fomite

  • Fomites: inanimate objects that transport pathogens (eg, cords, mops, blankets, clothing, stethoscope)

Living Reservoirs (stages of release)

  • Asymptomatic carrier: shows no symptoms

  • Incubation carriers: spread during incubation period

  • Convalescent carriers: recuperating with no symptoms

  • Chronic carriers: long-term carriers

Concept Check: If a nurse transfers a pathogen between patients without becoming infected herself, the nurse acted as the

  • E. Passive Carrier

Acquisition and Transmission of Infectious Agents

  • Communicable disease: when an infected host can transmit the infectious agent to another host and establish infection in that host

  • Highly communicable diseases (direct contact) are contagious

  • Non-communicable infectious disease does not arise through transmission from host to host

  • Occurs primarily when a compromised person is invaded by own microflora

  • Contact with organisms in natural reservoirs can also lead to transmission

Patterns of Transmission

  • Direct contact: physical contact or fine aerosol droplets

  • Indirect contact: via intermediate conveyor; vehicle inanimate material, food, water, biological products, fomites

  • Airborne: droplet nuclei, aerosols

How Communicable Infectious Diseases are Acquired

  • Direct contact: kissing, sex (epstein barr virus, gonorrhea)

  • Droplets: respiratory infections (colds, chickenpox)

  • Vertical transmission: during pregnancy or birth (HIV, syphilis)

  • Biological vectors: West Nile virus, malaria

  • Vehicles: food, water, biological products (Salmonella, E coli)

  • Fecal-oral contamination can lead to both direct and indirect transmission

  • Droplet nuclei and aerosols can be involved in airborne spread

Nosocomial Infections

  • Diseases acquired or developed during a hospital stay

  • From surgical procedures, equipment, personnel, exposure to drug resistant microorganisms

  • Estimated 2 to 4 million cases per year in the U S with approximately 90 000 deaths

  • Common organisms include Enterobacter spp, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, Coagulase-negative staphylococci, E coli, Candida spp, Acinetobacter spp

  • Distribution by site (examples): 12 % Skin, 8 % Blood, 6 % Urinary tract, 39 % Lower respiratory tract, 18 % Surgical wounds, 17 % Other

Epidemiology: how to describe Frequency of Cases

  • Prevalence: total number of existing cases relative to the population; usually represented as a percentage

  • Incidence: number of new cases over a certain time period relative to the healthy population

  • Mortality rate: total deaths in a population due to a disease

  • Morbidity rate: number of people afflicted with a disease

Epidemiological Data from the CDC

  • Infections with the outbreak strain of Salmonella Typhimurium – data example shows illness onset by date and estimates

  • AIDS cases in the United States and dependent areas by year and geographic distribution

  • TB case rates by age group and sex; race/ethnicity breakdowns

  • Data presented as time series and geographic distribution to monitor trends

Endemic – Sporadic Patterns of Infectious Disease Occurrence

  • Endemic: disease with relatively steady frequency over a long period in a geographic locale

  • Sporadic: occasional cases reported at irregular intervals

Epidemic and Pandemic Patterns

  • Epidemic: prevalence of a disease increasing beyond what is expected

  • Pandemic: epidemic occurring across continents

Koch’s Postulates: Determining the causative agent of a disease

1) Find evidence of a particular microbe in every case of a disease
2) Isolate that microbe from an infected subject and cultivate it artificially in the laboratory
3) Inoculate a susceptible healthy subject with the laboratory isolate and observe the resultant disease
4) Reisolate the agent from this subject

  • Process often depicted as steps from specimen collection to animal inoculation to re-isolation

Understanding Germs and Sickness

  • Friendly Germs (Commensals): Microbes that live with us without causing harm, and sometimes even help us.

  • Infection: When a germ gets into our body, past our defenses, and begins to grow where it shouldn't.

  • Disease: When an infection causes harm to our body and makes us sick.

  • Pathogen: A germ that causes disease.

How Newborns Get Germs

  • Babies are usually germ-free inside the mother until just before birth.

  • As a baby is born and handled, it starts picking up germs from the mother and surroundings. These germs eventually become its natural body inhabitants.

How Infections Develop

  1. Germs sneak past defenses: Microbes find a way to get past our body's protective layers.

  2. Entry Point: They enter through specific paths into the body.

  3. Sticking On: Microbes attach themselves to our cells.

  4. Getting Inside: Microbes find a way to enter our cells.

  5. Multiplying: They grow and spread within the body.

  6. Targeting: Microbes attack specific body parts.

  7. Causing Damage: They harm our tissues.

  8. Leaving the Body: Microbes find a way to exit the host.

  9. Sickness Develops: We get sick.

  10. Exit Point: How germs leave the body.

Ways Germs Enter the Body

  • Entry Points: The typical ways microbes get into our body tissues.

  • Outside Germs (Exogenous): Germs that come from outside our body.

  • Inside Germs (Endogenous): Germs that already live on or in our body (our normal friendly germs) but sometimes cause trouble.

  • Entry points include:

    • Eyes

    • Breathing passages (mouth, nose)

    • Digestive system (food, drink)

    • During pregnancy and birth

    • Urinary and genital areas

    • Skin (cuts, scrapes)

Entry Points: Skin to Pregnancy

  • Skin: Through cuts, scrapes, punctures, or surgical openings.

  • Digestive System: Through contaminated food, drink, or other swallowed items.

  • Respiratory System: Through what we breathe in via mouth and nose.

  • Urinary and Genital System: Through sexual contact or misplaced organisms.

  • Through the Placenta: From a pregnant parent to the baby.

Germs That Infect During Pregnancy (STORCH)

  • STORCH is a group of infections that can pass from a pregnant mother to her baby. These include:

    • Syphilis

    • Toxoplasmosis

    • Other diseases (like Hepatitis B, AIDS, Chlamydia)

    • Rubella

    • Cytomegalovirus

    • Herpes simplex virus

  • The mother's blood collects in a space around the placenta.

  • The umbilical cord connects the baby to the mother, carrying the baby's blood through umbilical arteries and a vein.

  • Bacteria can travel through the umbilical cord, the mother's blood vessels, and the placenta to reach the baby.

  • The placenta is the organ that links the mother's blood supply to the baby's.

How Many Germs It Takes to Get Sick (Infectious Dose - ID)

  • Infectious Dose: The smallest number of germs needed for an infection to start.

  • Germs that need only a few to make you sick are considered more dangerous.

  • If there aren't enough germs, you won't get infected.

Sticking to the Host

  • Adhesion: Germs need to get a firm hold at their entry point. They do this by matching special molecules on themselves with specific molecules on our cells.

  • Germs use various parts to stick:

    • Tiny hairs (Fimbriae, Flagella, Cilia)

    • Sticky coating (Glycocalyx, Capsules)

    • Suckers, Hooks, Barbs

    • Spikes (on viruses)

Examples of Germ Sticking Methods

  • The germ causing Gonorrhea uses tiny hairs (fimbriae) to stick to genital tissues.

  • E. coli, Shigella, and Salmonella use strong tiny hairs to stick.

  • Vibrio uses a sticky layer (glycocalyx) to stick to the gut lining.

  • Treponema uses a pointy hook to dig into our cells.

  • Mycoplasma has a special tip that sticks tightly to lung tissue.

  • Pseudomonas aeruginosa has special ways to stick during lung and burn infections.

  • Streptococcus mutans, S. sobrinus use a sticky slime (dextran) to glue themselves to teeth, causing cavities.

  • Giardia lamblia (a tiny protozoan) uses a small suction cup to stick to the inside of the gut.

  • Trypanosoma (another tiny protozoan) uses a whip-like tail (flagellum) to get inside and survive (causes diseases like sleeping sickness).

Virulence Factors (Germ's Tools for Causing Harm)

  • Virulence factors: These are special features germs use to invade our bodies, settle in, and cause damage, determining how sick we get.

  • Examples include:

    • Ways to avoid being