Microbial Pathogenesis and Mechanisms of Virulence

Question 1

Pathogenicity

Answer 1

An organism’s ability to cause disease

Question 2

Pathogenesis

Answer 2

A process resulting in disease

Question 3

Pathogen

Answer 3

organism that can cause disease

Question 4

Virulence

Answer 4

Degree of damage or disease resulting from infection

Question 5

Infectivity

Answer 5

Likelihood of causing infection and/or disease with exposure to a particular dose

Question 6

Three factors influencing infectious disease outcomes

Answer 6

1. Susceptible host
2. Conducive Environment
3. Pathogen

Question 7

Rhinovirus vs. Influenza vs. Ebola

Answer 7

Rhinovirus: High infectivity, low virulence
Influenza: moderate infectivity, greater virulence
Ebola: high both

Question 8

Spectrum of relationships between microbes and hosts

Answer 8

1. Essential/mutually beneficial
2. Colonization
3. Infection/disease (active vs latent)

Question 9

Acquisition/Transmission of Microbial Agents

Answer 9

Endogenous vs. exogeneous

Question 10

Endogenous transmission

Answer 10

Organism escapes from location where it is part of the normal microbiome

Question 11

Exogenous transmission

Answer 11

1. Person to person (communicable)
2. Animal to person (zoonoses)
3. Insect to person (vector borne)
4. Environmental

Question 12

Routes of transmission

Answer 12

1. Epithelial surfaces

2. Deep tissue penetration

Question 13

Conceptual framework for infectious diseases

Answer 13

1. Encounter
2. Entry
3. Spread
4. Multiplication
5. Damage
6. Outcome

Question 14

Three categories for microbial virulence factors

Answer 14

1. Structures involved in attachment, adherence, and invasion
2. Toxins involved in cell or tissue damage
3. Processes involved in immune avoidance

Question 15

Bacterial pili

Answer 15

Filamentous structures extending from the bacterial surface; Allow adherence to host cells/matrix

Question 16

Type IV pili

Answer 16

Extend, bind, and retract

Promote surface motility, microcolony & biofilm formation,, adherence to host cell, and immune evasion

Question 17

Pili vs Flagella

Answer 17

Both filamentous appendages

Pili shorter, thinner, more numerous; may be polar or peritrichous; primary function attachment (vs. locomotion)

Question 18

Specialized bacterial secretion systems

Answer 18

Gram- bacteria can use type III, IV and V systems to inject substrates (virulence factors: toxins or receptors) into other cells

Question 19

Bacterial nanomachines

Answer 19

T3SS

Question 20

E. coli infection strategy

Answer 20

1. Bundle forming pili: initial attachment
2. T3SS injects Tir protein (bacterial receptor) which binds to Intimin (bacterial adhesion)
3. Hijacks host actin filaments
4. Forms pedestal

Question 21

Viral attachment

Answer 21

Mediated by surface proteins of virion:
Naked viruses = capsid proteins (enters via endocytosis)
Enveloped = glycoprotein spikes (enters via membrane fusion or endocytosis)

Question 22

HIV viral attachment

Answer 22

GP120 (binds to CD4 on T-cell) –> conformational change to allow GP41 binding –> initiates viral envelope fusion

Question 23

Endotoxins

Answer 23

Lipopolysaccharide or Lipooligosaccharide (LPS and LOS)

Integral part of gram - bacterial outer membrane - Lipid A = toxic –> stimulator of innate immune responses

Question 24

How are serotypes defined?

Answer 24

O-antigens

Question 25

Pathogen-Associated Molecular Patterns (PAMPS)

Answer 25

Microbial molecules recognized by Pattern Recognition Receptors of the innate immune system

Question 26

Bacterial PAMPS engage ___ TLRs

Answer 26

extracellular

Question 27

Viral (and bacterial) PAMPS engage ____ TLRs

Answer 27

intracellular

Question 28

Exotoxins

Answer 28

Secreted toxins produced by Gram+ and Gram- bacteria; frequently encoded on plasmids or bacteriophage

Question 29

Toxin classifications

Answer 29

1. Based on structure/function (A+B, Pore-forming, and Superantigen toxins) 2. Based on site of action (enterotoxins, neurotoxins, tissue invasive toxins)

Question 30

A+B toxins

Answer 30

Active + Binding, variations on theme (Cholera toxin A + 5B, Anthrax toxin 2A + B)

Question 31

A+B toxin-mediated diseases

Answer 31

1. Diphtheria 2. Tatanus 3. Pertussis

Question 32

DTaP Toxoid-based vaccines

Answer 32

Inactivated toxins, still immunogenic; vaccination can protect from toxin-mediated diseases

Question 33

Pre-forming toxins

Answer 33

S. aureus; | Secretion, binding, oligomerization, insertion (of pore)

Question 34

Superantigens

Answer 34

Nonspecific, stimulate massive polyclonal expansion of T-cells --> cytokine storm; Staphylococcal and Streptococcal Toxic Shock toxins

Question 35

Immune avoidance by microbial pathogens: structures

Answer 35

1. Bacterial and fungal polysaccharide capsules 2. Antigens that induce blocking antibodies 3. Molecules that inactivate antibodies 4. Molecules that mimic host structure

Question 36

Immune avoidance by microbial pathogens: Processes

Answer 36

1. Antigenic variation 2. Avoiding immune surveillance 3. Suppressing immune responses

Question 37

Polysaccharide capsules

Answer 37

Extracellular, but attached to Gram-positive or Gram-negative bacterial surface Define serotypes of pathogen

Question 38

Polysaccharide capsules avoid... (2)

Answer 38

1. Phagocytosis | 2. Immune recognition (complement and Ab)

Question 39

Common feature of pathogens that can disseminate via bloodstream to CNS

Answer 39

Polysaccharide capsules

Question 40

Neisseria meningitidis immune avoidance

Answer 40

1. Antibodies don't protect and block binding to other targets 2. polysaccharide capsule mimics human antigens 3. Produces IgA protease that cleaves IgA

Question 41

Antigenic variation

Answer 41

During infection, pathogens express different versions of key antigens

Question 42

Avoiding immune surveillance

Answer 42

1. Biofilms 2. Granulomas (wall off bacteria) 3. Latency 4. Expression of few surface proteins

Question 43

Suppressing/subverting immune responses

Answer 43

1. HIV: destroys CD4+ cells --> immunodeficiency 2. M. tuberculousis: prevents fusion of phagosomes & lysosomes in macrophages 3. Staphylococcal Protein A binds IgG by the Fc recion