Bacterial Pathogenesis and Immunology II

Question 1

Multiplication

Answer 1

• Binary fission
• Location:
• -Extracellular
• -Intracellular - cytoplasm
• -Intracellular - within a vesicle

Question 2

Parasitophorous vacuole

Answer 2

Coxiella burnetti (causative agent of Q-fever in humans)

• Target cells: monocytes and macrophages (obligate intracellular)
• Lives and replicates in acidic environment of phagolysosomes
• Disseminates throughout the body via monocytes and macrophages
• Excreted in milk, urine, and feces, and found in placental and fetal tissues
• Acquired through inhalation, ingestion, or arthropod bites

Question 3

Cell to cell movement

Answer 3

Listeria monocytogenes

1. Invades phagocytic and non-phagocytic cells
   - Surface proteins (internalins) facilitate adherence to host cell membranes and subsequent uptake
2. Survives and replicates intracellularly
   - Cytolytic toxin (listeroiolysin) destroys the membranes of phagocytic vacuoles, allowing escape into the cytoplasm
3. Transfers from cell-to-cell without exposure to humoral defense mechanisms
   - Hijacks actin filaments of the host cell to induce formation of pseudopod-like projections
4. High level of multiplication leads to destruction of host cell and release of bacteria
   - Spread via lymph and blood free of (extracellular) or within phagocytic cells (intracellular)

Question 4

Type III secretion systems

Answer 4

• Complex protein secretion system employed by many gram-negative pathogenic bacteria
• Transports bacterial effector proteins into eukaryotic host cytoplasm
• Effector proteins modulate (interfere with) the host cellular processes

Question 5

T3SS effectors

Answer 5

Pseudomonas aeruginosa

• One of the leading causes of hospital-acquired pneumonia in human hospitals
• Pneumonia can lead to bacteremia:
• -P. aeruginosa uses T3SS to inject the effector ExoS into pulmonary epithelial cells –> disruption of the pulmonary vascular barrier –> dissemination to the bloodstream
• High correlation between T3SS expression and patient death
• T3SS mutants display attenuated virulence

Question 6

Exotoxin

Answer 6

Pseudomonas aeruginosa

• Exotoxin A –> cytotoxic
• Works by suppressing protein expression in host cell
• -Invasion of tissues
• -Local tissue damage
• -Immune evasion (via killing macrophages)

Question 7

Flagella

Answer 7

• Confer motility
• Found on pathogens (not all flagella are pathogenic)
• Found on probiotic bacteria

Proteus mirabilis - swarming motility

• Observed in culture
• May aid in spread in vivo
• -Bladder infection –> kidney infection

Question 8

Damage

Answer 8

• Direct damage

- Immune-mediated damage

Question 9

Damage - direct

Answer 9

Toxins:

• Endotoxins: remains inside or on the surface of the bacteria; part of the bacterial structure
• -Example: LPS of gram-negative bacteria
• Exotoxins: secreted by the bacteria (into the space around it)
• -Example: Leukotoxin

Question 10

Damage - toxins

Answer 10

• E. coli heat-stable and heat-labile enterotoxins –> act upon intestinal enterocytes by disrupting the electrolyte homeostasis –> fluid loss –> secretory diarrhea
• Phospholipases - a group of ubiquitous and diverse enzymes that hydrolyze phospholipids
• Clostridium perfringens - phospholipase C
• -Acts on cell membranes and vesicle membranes
• -Hemolytic activity
• -Phospholipase C is also the way Pseudomonas aeruginosa breaches the cornea
• Clostridium botulinum - botulinum toxins A-G

Question 11

Botulinum neurotoxins

Answer 11

1. Enter cell by endocytosis
2. Cleave specific sites on SNARE proteins
3. Block acetylcholine release
4. Results in flaccid paralysis

Question 12

Exotoxin - Leukotoxin

Answer 12

• Manheimia haemolytica leukotoxin: an exotoxin that attacks host leukocytes (see lots of tissue damage)
• Ovine pneumonic pasteurellosis
• -Leukotoxin is a major contributor to the pathogenesis of lung injury

Question 13

Damage - immune-mediated, Purpura hemorrhagica

Answer 13

=Aseptic necrotizing vasculitis characterized primarily by edema and petechial or ecchymotic hemorrhage

• Pathogenesis: thought to be vasculitis caused by deposition of immune complexes in blood vessel walls
• Possible association with S. equi ssp. equi (strangles) infection

Question 14

Damage - immune-mediated, Sepsis

Answer 14

=Severe, whole body inflammatory response to bacteria

• Response to bacterial components such as the endotoxin lipopolysaccharide (LPS)
• Causes vascular damage, hypotension, multiple organ damage

Question 15

Damage - immune-mediated, Superantigens

Answer 15

• Non-specific activation of T-cells
• Most powerful T-cell mitogens ever discovered
• Massive, non-specific inflammation:
• -Shock
• -Multiple organ failure
• -Death
• S. aureus
• S. equi ssp. zooepidemicus
• Y. pseudotuberculosis

Question 16

Transmission - exiting the host

Answer 16

• Respiratory droplets
• Feces
• Urine
• Milk
• Reproductive fluid/tissues
• Decomposing host tissues

-Back to the environmental reservoir OR directly to another host

Question 17

Transmission - extremes

Answer 17

• Minimal effect on host - keep host healthy to encourage transmission
• -Sexually transmitted diseases
• -Vector borne diseases
• Major effect on host - make host sick to encourage transmission
• -Increase respiratory spread (coughing and sneezing)
• -Increase fecal spread (diarrhea)
• -Kill the host then sit and wait

Question 18

Minimal effect on host

Answer 18

• Campylobacter fetus ssp. venerealis
• Bovine venereal campylobacteriosis
• Bulls - bacterium lives in preputial crypts
• Sexually transmitted from asymptomatic bulls to cows
• Cows - infertility, abortion

Question 19

Major effect on host

Answer 19

• Bordetella bronchiseptica - kennel cough
• Spread by respiratory droplets
• ETEC (Enterotoxigenic E. coli) - calf scours
• Spread by fecal-oral route
• Bacillus anthracis
• -Increase host exploitation
• -Forms spores in decomposing carcasses while awaiting another host (sit and wait)

Question 20

Spores

Answer 20

• Bacterial spores are highly resistant, dormant structures (no metabolic activity) formed in response to adverse environmental conditions (limited nutrients)
• Bacterial spores are highly resistant to:
• -Heat
• -Dehydration
• -Radiation
• -Chemicals
• Bacillus anthracis (central spores)
• Clostridium tetani (terminal spores, looks like drumstick)

Question 21

Fungal spores v. Bacterial spores

Answer 21

• Fungal spores are about reproduction

- Bacterial spores are about survival

Question 22

Dead end hosts

Answer 22

• Not helpful for the pathogen

- End of transmission

Question 23

Lyme disease

Answer 23

• Borrelia burgdorferi
• Enzootic life-cycle = endemic in animals = constantly present in an animal population
• Dogs and humans are dead end hosts (they cannot transmit it to a new host)

Question 24

Zoonotic bacteria

Answer 24

• Can be transmitted from animals to people
• Do NOT confuse with common source infections
• -This is when both animals and people can be infected with the same organism, but they catch it from the same source, not from each other.
• -The pathogen is not transmitted from animals to people in common source infections

Question 25

Fungi

Answer 25

• Molds = multi-celled hyphae; fuzz on solid media
• -Form in the environment
• Yeasts = single-celled; colonies on solid media
• -Form in host tissues
• Dimorphic = can convert to the other form

Question 26

Immunity to fungal infections

Answer 26

• Innate:
• -Fungal PAMPs bind PRRs on innate cells (macrophages, dendritic cells)
• -Phagocytosis
• Adaptive:
• -Th1 and Th17 pathways provide the best protection against fungal infections –> killing by effector cells (neutrophils, macrophages)
• -Th17 - acute inflammation
• -Th1 - chronic inflammation

Question 27

Immunity to fungal infections

Answer 27

How fungi survive the immune response:

• Escape from phagolysosome
• Too large to be phagocytosed
• -Neutrophils cannot totally ingest some fungal structures due to their large size:
• –Neutrophils release enzymes and oxidants –> damage fungal hyphae –> small fungal fragments –> ingestion by macrophages or NK cells