Lecture 6.2: Mechanisms of Pathogenicity

Symptoms Caused by Infections (Slide 3)

How do you figure out what you have? (Slide 4)

  • Although medical professionals rely heavily on signs and symptoms to diagnose diseases and prescribe treatment, many diseases can produce similar signs and symptoms.

Getting Infected by Pathogens (Slide 5)

  • Infection

    • successful colonization within a host of a microorganism (bacterium, virus, fungi, etc…)

    • infections can lead to disease: signs and symptoms resulting in a deviation from the normal structure or functioning of the host

    • Pathogens: microorganisms that can cause disease

Signs of a Disease in Humans (Slide 6)

  • Under Normal Conditions

    • body temperature: 37° C [98.6° F]

    • heart rate (normally 60-100 beats per minute)

    • breathing rate (normally 12-18 breaths per minute)

    • blood pressure (normally between 90/60- and 120/80-mmHg)

  • Signs of disease are objective and measurable

Signs of a Disease in Humans (Slide 7)

  • Additional Observable Conditions

    • presence of antibodies in a patient

    • can be observed and measured through blood tests

    • presence of antibodies is not always a sign of an active disease

    • antibodies can remain in the body long after an infection has resolved

Symptoms of A Disease in Humans (Slide 8)

  • Symptoms of disease are more subjective and may not be objectively measured

Method of Disease Transmission - Exposure (Slide 9)

Stage of the infection process (Slide 10)

  • Portal of Entry

    • the way in which a pathogen enters a susceptible host

  • Penetration or evasion of host defenses

    • when the pathogens establish themselves inside the host

  • Damage to host cells

    • cause host cells to be severely hurt or killed

  • Portal of exit

    • where the pathogens exit to infect another host

Periods of Disease (Slide 11)

  • Incubation Period (1st stage of acute disease)

    • pathogen begins multiplying

    • signs and symptoms are not observable

  • Prodromal Period (2nd stage of acute disease)

    • pathogen continues to multiply

    • nonspecific signs and symptoms become observable

  • Period of Illness (3rd stage of acute disease)

    • number of pathogens present is the greatest

    • signs and symptoms of the disease are most severe

  • Period of decline (4th stage of acute disease)

    • the number of pathogens decreases, along with signs and symptoms of the disease

  • Period of Convalescence (5th stage of acute disease)

    • patient returns to normal function

Pathogenicity & Virulence

Pathogenicity & Virulence (Slide 13)

  • Pathogenicity

    • the ability of a microbe to cause disease

  • Virulence

    • the degree to which an organism is pathogenic; severity of disease signs & symptoms

Pathogens cause disease - Koch’s postulates (Slide 14)

Limitations to Koch’s Postulates (Slide 15)

  • Viruses can’t be grown*

  • Assumes that pathogens are only forced in diseased, not healthy, individuals

    • not true for many pathogens

    • example: H. pylori can cause chronic gastritis, but it is also part of the normal microbiota of the stomach in many healthy humans who never develop gastritis

  • Assumes that all healthy test subjects are equally susceptible to disease

    • makeup of resident microbiota can influence an individual’s susceptibility to infections

    • individuals with differences in immune systems

    • two individuals with the same disease may not present with the same signs and symptoms

  • Assumes that all pathogens can be grown in pure laboratory culture

    • viruses are obligate intracellular pathogens that can grow only when inside a host cell

Measuring virulence - how deadly is an infection (Slide 16)

  • The virulence of a pathogen can be quantified using controlled experiments with laboratory animals

  • Two important indicators of virulence

    • median infections dose (ID50): number of pathogen cells or virions required to cause active infection in 50% of inoculated animals

    • median lethal dose (LD50): number of pathogenic cells, virions, or amount of toxin required to kill 50% of infected animals

Primary Pathogens vs. opportunistic pathogens (Slide 17)

  • Primary Pathogens

    • microorganisms that cause disease in the host regardless of the effectiveness of the host’s immune system.

    • Example: enterohemorrhagic E. coli (EHEC), which produces Shigs toxin and inhibits protein synthesis, leading to severe and bloody diarrhea, inflammation, and renal failure

  • Opportunistic Pathogens → only get sick if you have immunocompromised

    • microorganism that can only cause diseases in individuals with compromised host defenses

    • Example: S. epidermis is found in the normal microbiota of the skin, where it is generally avirulent. Inside the body, S. epidermis can cause serious infections such as endocarditis (heart inflammation)

Lecture Question 1: Covid-19 disease (Slide 18)

  • Considering that COVID-19 affects patients with weakened immune systems sometimes more severely, is COVID-19 a primary pathogen or opportunistic pathogen?

    • A. primary pathogen

Virulence Factors

How do pathogens cause damage to host cells? (Slide 20)

  • Virulence Factors

    • molecules that assist the bacterium colonize the host at the cellular level

      • Colonization of a niche in the host

      • Immunoevasion: evasion of the host’s immune response

      • Immunosuppression: inhibition of the host’s immune response

      • Entry into the exit out of cells

      • Obtain nutrition from the host

Virulence Factors - Destructive Enzymes (Slide 21)

  • Destructive Enzymes

    • some virulence factors can affect the host by causing damage to host tissues:

      • Proteases - enzymes that breakdown host proteins

      • DNases - enzymes that breakdown host DNA

      • Hemolysins - can breakdown red blood cells (RBC’s)

Virulence Factors - Introduction to Toxins (Slide 22)

  • Toxins

    • bacterial toxins are virulence factors that manipulate host cell function and takeover control of vital processes (botox!) of living organisms to favor microbial infection

Virulence Factors for survival in the host (Slide 23)

  • bacterial capsule helps protect the cell from being targeted by white blood cells

  • this helps the cells evade the immune system and survive in the hosts

  • behind their capsule, bacterial cells can continue producing toxins or destructive enzymes

How Viruses can evade the host immune system (Slide 24)

  • Antigenic Variation in Viruses

    • changing of surface antigens (carbohydrates or proteins) such that they are no longer recognized by the host’s immune system

    • viruses change shape to avoid antigens