BIOL 2401 Unit 7: Mechanisms of Disease & Epidemiology

Normal flora

Flora that normally exists in the body that does not typically cause infection

Transient flora

Flora that comes and goes

Advantages of normal flora

Competitive inhibition, production of beneficial molecules (vitamin K)

Competitive inhibition

Way that normal flora ward off pathogen growth through using up space, nutrients, and producing antimicrobial molecules

What antimicrobial molecules are produced by normal flora?

• Lactic acid → creates acidic environment

• Bacteriocins

Commensalism

One benefits, other is unaffected. E.g. S. epidermidis feeds off skin

Symbiosis

Both benefits. E.g. Lactobacillus creates acidic pH

Parasitism

One benefits, other suffers. E.g. all pathogens

Symptoms

SUBJECTIVE changes experienced by patient (pain)

Signs

OBJECTIVE changes that can be measured by a phycision (blood pressure)

Syndrome

Group of symptoms and signs that can accompany particular conditions

Diagnosis

Identification of a disease/injury based on signs and symptoms

Five stages of disease (IPPPP)

1. Incubation period

2. Prodromal period

3. Period of illness

4. Period of decline

5. Period of convalescence

Incubation period

From initial infection → symptom onset

Prodromal period

When symptoms first appear

Period of illness

When symptoms are apparent, and disease is most severe)

Period of decline

When treatment or the immune system is overcoming the disease, making symptoms subside

Period of convalescence

Symptoms basically disappear FOREVER!

Steps of Koch’s postulates

1. Isolation

2. Grown in culture

3. Causes disease in healthy lab animal

4. Isolation again, must be the same organism

Premise of Koch’s postulates

To establish a causal relationship between a specific microbe and a disease

What is a limitation of Koch’s postulates regarding healthy individuals?

Pathogens can sometimes be found in healthy individuals (e.g., Helicobacter pylori, C. difficile).

How do unique culture requirements serve as a limitation for Koch’s postulates?

Some microbes, like viruses, have unique culture requirements that make them difficult to grow according to the postulates

Streptococcus pyogenes can cause multiple diseases. How does this violate a premise of Koch’s postulates?

When re-infecting an animal, a different disease from the original one may manifest. E.g. sore throat vs skin infection vs scarlet fever

How does the host's immune system impact the application of Koch’s postulates?

Variability in an individual’s immune system strength can lead to formation of different symptoms in different people

Reservoir

A continual source from which disease can perpetuate itself. Includes human, animal, and non-living reservoirs

Contact transmission

Transmission of infection through contact, e.g. physical, fomites, or droplets (<1m)

Vehicle transmission

Transmission of infection through vehicles, e.g. waterborne (cholera), foodborne (tapeworms), airborne (aerosols, MEASLES)

Vector transmission

Transmission through a vector (animal or insect)

Mechanical transmission

Vector transmission where pathogens passively transport through body parts (like insect feet). E.g. Shigella

Biological transmission

Vector transmission where an animal/insect bites, directly passing on the pathogen. E.g. Plasmodium

Communicable disease VS contagious disease

Communicable means from one host to another, contagious means from one person to another

R value

Number that one sick person will infect on average. E.g. measles → 18

Non-communicable disease

Diseases that do not spread from person to person. E.g. acne, tooth decay, tetanus

Sepsis

Inflammatory condition arising from the spread of microbes, toxic

Secondary infection

Infection from an opportunistic pathogen ocurring when a primary infection weakens the host immune system

Acute vs chronic disease

Acute diseases develop rapidly and last a short time, chronic diseases develop slowly but persist for a long time

Latent disease

Mostly inactive disease that actives upon certain condition. E.g. shingles, following chickenpox

Sporadic disease

Random disease occurring in a population. E.g. rabies

Endemic disease

Disease that is constantly present in a population, but at a low level. E.g. common cold

Epidemic disease

Where an abnormally large amount of people in an area acquire a disease suddenly

Morbidity rate

% or # people with disease per 100,000

Morality rate

% or # people who died of a disease per 100,000

Prevalence

Number of people with a disease in a population at a given time

Incidence

Number of people developing a disease at a given time

Examples of mucous membrane portals of entry

Respiratory tract, GI tract (food), Genitourinary tract (STIs)

Examples of skin portals of entry

Hair follicles, sweat ducts, skin surface (fungi)

Parenteral route portals of entry

Only when skin is injured. Microbes are deposited directly into tissue

How does Salmonella “prefer” to enter the body?

It needs to be ingested, and does not cause disease through skin contact

Virulence

The degree of a microbe’s pathogenicity (ability to cause disease)

ID₅₀

Way of expressing virulence. The ID₅₀ indicates an infectious dose of a pathogen

LD₅₀

Indicates the lethal dose of a pathogen

Adhesins

Proteins allowing pathogens to attach to certain receptors on host cells. E.g. on fimbriae, flagella, Gp120 spikes,

Gp120 spikes

Adhesins on viral capsids

Purpose of tapeworm hooks

Allows the tapeworms to adhere to mucosal lining of intestinal wall

Ways microbes can evade phagocytosis

1. Inhibit adherence

2. Escape phagosome

3. Prevent phagosome—lysosome fusion

4. Survive in phagolysosome

Methods of inhibiting adherence

Capsules, M protein in cell wall, biofilms

Which organisms inhibit adherence to evade phagocytosis?

• S. pneumoniae

• Hemophilus influenzae

• S. pyogenes

Escape phagosome

Method of phagocytosis evasion through phospholipases

Prevent phagosome—lysosome fusion

Used by HIV to evade phagocytosis

Survive in phagolysosome

Usage of mycolic acid to evade phagocytosis

Which bacteria uses mycolic acid to evade phagocytosis?

Mycobacterium tuberculosis

Examples of exoenzymes

1. Coagulase

2. Kinase

3. IgA proteases

Coagulase

Exoenzyme that forms blood clots around bacteria for protection

Kinase

Exoenzyme that breaks down blood clots to isolate and help spread infection

IgA proteases

Destroys IgA antibodies on mucous membranes

Antigenic variation

Where pathogens avoid the immune system by changing surface antigens, avoiding adaptive immune responses

How does H. pylori liquefy the stomach’s mucous lining?

Through releasing ureaase, which neutralizes stomach acid and breaks down mucous lining

Invasins

Substances that rearrange host cell structure, forcing the cell to take in the pathogen. E.g. Shigella, Salmonella

How does the “crowding effect” cause damage to the host?

Host cells are crowded out, metabolic by-products damage cells, nutrient competition

Siderophores

Proteins made by bacteria that bind to iron more strongly than hemoglobin. Can lead to anemia

Hemolysins

Toxins produced by bacteria that destroy RBCs, making them release heme

Toxemia

Toxins in the blood

Toxigenicity

Capacity of a microorganism to produce toxins that can damage a host

Exotoxins

Proteins (enzymes) produced INSIDE the bacteria

What type of bacteria mainly produces exotoxins?

Mainly gram-positive bacteria produce exotoxins

Endotoxins

Lipids produced as part of LPS component of the outer membrane

What type of bacteria mainly produces endotoxins?

Gram-negative bacteria mainly produce endotoxins?

Are exotoxins more potent than endotoxins?

Yes, since they require little amounts to be toxic.

How does botulinum toxin work?

Through blocking nerve signals (acetylcholine) that tell muscles to contract, causing paralysis

How does tetanus toxin work?

Through blocking release of inhibitory neutrotransmitters glycine and GABA, leading to muscle spasm

Endotoxin = ?

Lipid A (part of LPS)

When are endotoxins released?

During G- bacterial multiplication and cell lysis

What kind of symptoms do endotoxins lead to?

Nonspecific symptoms, such as chills and fever. E.g. Typhoid fever by Salmonella typhi

Process of endotoxins causing fever and inflammation

Macrophage ingests G- bacteria → bacteria degraded, releases endotoxins, produces IL-1 → IL-1 travels to hypothalamus → induces hypothalamus to produce prostaglandins → fever

Epidemiology

Studies the mechanisms and factors that contribute to the spread of health-related problems, such as disease

Why are epidemiological studies done?

To determine a disease’s cause, and figure out ways to prevent its transmission

The first epidemiological study

• Performed by Dr. John Snow

• Tracked cases of cholera

• Figured out cases were clustered around a contaminated pump, leading to the pump’s removal

Nosocomial epidemiology

An infection from a hospital stay or any other medical facility

Exogenous (nonsocomial epidemiology)

External sources of disease (fomites, people, food)

Endogenous (nonsocomial epidemiology)

Sources of disease transferred between areas within the patient, or from opportunistic pathogens

How can nonsocomial infections be minimized?

Through infection control measures such as washing hands, disinfecting body fluid spills, and wearing PPE

Intracellular A-B exotoxin

Exotoxin with an A (Active) component and B (Binding) component. E.g. tetanus toxin

Membrane-disrupting exotoxin

Exotoxin leading to host cell lysis. E.g. C. difficile toxins

Superantigens

Exotoxin that leads to an extreme immune response, called a cytokine storm. E.g. toxic shock syndrome toxin (S. aureus)