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Lecture notes Infectious Diseases

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Infectious Diseases Vrije Universiteit Amsterdam

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  • 22 juni 2024
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Lecture 0 – Infectious disease recap

Classes of pathogens:

1. Viruses
2. Bacteria (prokaryotes)
3. Fungi (eukaryotes)
4. Parasites  protozoa (unicellular eukaryotes); worms (multicellular eukaryotes)
5. Prions

By size:

1. Worms (macro)
2. Protozoa (micro)
3. Fungi (micro)
4. Bacteria (micro)
5. Viruses  not an organism bc it needs a host cell for reproduction
6. Prions  not an organism but protein
 Micro = not visible with the naked eye
Organism = able to reproduce by itself


Infection = colonization and growth of a microorganism within a host  does not always cause
disease

Disease = infection + damage to the host, which interferes with normal functions of the host(-cell)

Pathogenicity = the potential or a microorganism to inflict damage on its host (qualitative)  often
referring to genetic components of the pathogen; host-independent

Virulence = the extent of damage that a pathogen can inflict on its host (quantitative)  host-
pathogen interactions; host-dependent



Koch’s postulates:

1. The same pathogen must be present in every case of the disease, but not in healthy
individuals
2. The pathogen must be isolated from the sick host and grown in a pure culture
3. The pure pathogen must cause the same disease when given to uninfected hosts
4. The pathogen must be re-isolated from the newly infected hosts, and shown to be the same
organisms as isolated initially
 Do not apply to all infectious disease:
- Opportunistic pathogens  present in healthy individuals, fails postulate 1
- Viruses  cannot grow by themselves, fails postulate 2
- Bacteria that cannot be grown in the lab  fails postulate 2
- No animal model available  fails postulate 3


Opportunistic pathogens = causes disease in weakened individuals OR when in an unusual location 
often belong to the commensal microflora (ex. E. coli from gut in sterile bladder  UTI)

Primary pathogens = causes disease in healthy individuals

,Virulence factors = molecules of pathogenic microorganisms that contribute to their ability to cause
disease

- Often specific to pathogenic organisms
- Frequently interact with host cells
- Often on the surface / secreted
 Ex.



Intracellular pathogens:

-Viruses
-Bacteria  in phagocytes
1. Block phagosome-lysosome fusion
2. Escape from phagosome
3. Bacteria survives in macrophages / phagocytes
- Nonphagocytic cells  manipulation of cytoskeleton
 Advantages:
- Hide from immune system
- Invasion  penetrate deeper tissue


Extracellular pathogens:

 Confront the immune system:
- Self-protection  capsule, cell wall
- Weapons  enzymes, toxins
- Antigenic variation  change surface structure in time


Acute infection = multiply as fast as possible and spread rapidly  more virulent, a lot of damage

Chronic / persistent infection = stay in the host for a long time; often have one or more acute phases
 less virulent, little damage
 asymptomatic  infect more people
 deal with both innate and adaptive immune system

, Lecture 1 – Bacterial anatomy

Peptidoglycan (firmness)  consists of sugars bound by peptides:

- N-acetyl glucosamine (NAG)
- N-acetyl muramic acid (NAM)
 Protects cells against osmotic changes, environmental stress


Gram-negative outer membrane:

- Consists of lipids and proteins  lipoproteins attach the outer membrane to
peptidoglycan layer
- Lipid bilayer consists of lipopolysaccharides (LPS)  facing the outside
- Serves as barrier against external factor (hydrophobic)
- Contains porins  forms channels in outer membrane; mediates import / export of
molecules

LPS (endotoxin):
- Polysaccharide (O-specific polysaccharide)  variation between AND within species
(immune recognition point  immune evasion); carbohydrate chain; role in
attachment to host cells
- Lipid A  anchor of LPS in outer membrane; defense of the body is directed against
it (endotoxin activity)

Adhesion:
- Capsule (glycocalyx)  polysaccharide; protects against environmental stress; food
source; involved in attachment to host-cells; inhibit phagocytosis; shielding of surface
antigens; variation within species  immune evasion
 Capsule makes a bacteria pathogenic
- Fimbriae / pili  involved in attachment; protrude from cell; mainly on gram-;
composed of pilin protein
 Fimbriae vs. pili  fimbriae for attachment; pili for attachment, mobility (type IV),
transfer genetic material (conjugation pili), biofilm formation, bind and inactivate
antibodies (S pili)

Mobility:
- Flagella  very long; both gram+ and gram-; consists of filament, hook, basal body
(rotates 1500x/s); provide opportunistic infections through rapid change of location;
escape host defense quickly; cause systemic infection (spread) only bacilli
- Axial filaments (spirochetes)  located between cytoplasmic and outer membrane;
gram-; rotates corkscrew  bore through tissue  syphilis, lyme disease



Secretion systems:

I. .
II. .
III. Gram- only; anneal, penetrate, inject
IV.

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