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Lecture notes Infectious Diseases
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Infectious Diseases Vrije Universiteit Amsterdam
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Lecture 0 – Infectious disease recapClasses 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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