PMI02-2007 Pathogenicity: Colonisation & Evasion of Host Defence

Question 1

What is pathogenicity?

Answer 1

Ability of a microbe to cause a disease

Question 2

What is virulence?

Answer 2

The degree of pathogenicity

Question 3

What is virulent bacteria?

Answer 3

Usually cause disease when they infect

Question 4

What is a virulent factor?

Answer 4

Bacterial/ component only involved in pathogenesis

Question 5

What is the housekeeping gene?

Answer 5

Gene involved in all aspects of a bacterium life

Question 6

What were Koch’s postulates?

Answer 6

The pathogen occurs in every case of the disease and distribution corresponds to that of the lesions observed
Pathogen does not occur in healthy subjects
After isolation and repeated growth in pure culture, pathogen can induce disease in susceptible animals

Question 7

What evidence disproves Koch’s postulates?

Answer 7

HIV and Chylamydia cannot grow in culture
For helicobacter pylori, carriage does not mean disease
For Diphtheria, the disease is throughout the body but bacteria is only carried in the throat
TB is carried asymptomatically

Question 8

What are the molecular Koch’s postulates?

Answer 8

The phenotype should be associated more often with a pathogenic organism than a non-pathogenic organism
Deletion or inactivation of specific virulence genes should result in decreased virulence
Restoration of pathogenicity should accompany replacement of the mutated gene with the normal wild type gene

Question 9

What are collections of virulent genes known as?

Answer 9

pathogenicity islands

Question 10

What are the origins of virulent genes?

Answer 10

Come from plasmids such as adhesion genes, antibiotic-resistance genes
Come from bacteriophages
Come from pathogenicity islands

Question 11

How is bacteria transmitted?

Answer 11

Inhalation
Ingestion
Inoculation

Question 12

How do bacteria adhere?

Answer 12

Flagellum is used for adherence and motility
Pili
Some have specialised surface proteins that are involved in direct attachment and signal

Question 13

How do bacteria interact with cells?

Answer 13

Eukaryotic cells have cell-surface receptors
Bacteria will bind to these receptors through pili/ flagella
This leads to a change in gene expression within the microbe which could result in alternative proteins being produced resulting in more binding
It also results in cell signalling and change in gene expression which could result in antimicrobial peptide production, microbial endocytosis or protein production

Question 14

What is colonisation?

Answer 14

presence of microbes without accompanying disease

Question 15

What is infection?

Answer 15

Presence of microbes resulting in disease

Question 16

Why do microbes prefer colonising us?

Answer 16

We provide a rich ecological niche for the microbes with a good source of nutrients

Question 17

How do pathogens invade cells?

Answer 17

They invade through epithelial cells or through intraepithelial tight junctions
They can spread and establish themselves at systemic sites such as liver or blood (leads to septicaemia)

Question 18

What properties of bacteria aid invasion?

Answer 18

Secreted bacterial enzymes such as collagenase and coagulates
Production of antiphagocytic proteins such as M proteins, Fc binding proteins and leukotoxins
Presence of a capsule

Question 19

What are obligative bacteria?

Answer 19

Bacteria that have to live inside a cell

Question 20

What are the 2 invasion mechanisms?

Answer 20

Phagocytosis
Inducing endocytosis or macropinocytosis
Interactions of invasins with host receptors trigger this uptake
Bacterial proteins are then released into the cell

Question 21

How do bacteria survive the inhospitable conditions?

Answer 21

Modify the phagosomal compartment by reversing the effects of antimicrobial peptides so it can survive
Escape from the phagosome into the cytosol
Ultimately it nullifies the host response

Question 22

What are examples of obligate intracellular pathogens?

Answer 22

Mycobacterium leprae associated with leprosy
Chlamydicae which gives STDs
Rickettsia prowazekii associated with typhus

Question 23

What is the life cycle of chylamydia?

Answer 23

Outside of the cell, chylamydia exists as an elementary body, which is infectious but not metabolically active
It attaches to the cell and gets taken up
Upon being in a phagosome, it shifts from an elemental body to a reticulate body
The RB is not infectious but is metabolically active and can replicate
As it multiplies, the RBs condense back into elemental bodies
Once the cell reaches its capacity its bursts, allowing the cycle to repeat

Question 24

How does rickettsia cause disease?

Answer 24

It replicates in the cytosol of the host cell

Question 25

What is the major difference between chylamydia and rickettsia?

Answer 25

Chylamydia survives within the endosomal compartment

Rickettsia escapes the endosomal compartment and survives within the cytosol

Question 26

What are advantages of intracellular infection for the pathogen?

Answer 26

Pathogen can evade the immune system

It can obtain nutrients from the host cell and is easily carried round the body

Question 27

What are disadvantages of intracellular infection for the pathogen?

Answer 27

They have smaller genome so theres a loss of certain metabolic pathways

Question 28

What is the immune response for acute inflammation?

Answer 28

PRRs recognise the pathogen which leads to cytokine induction
Causes recruitment of neutrophils and macrophages and eventually bacterial opsonisation and killing
Which causes pyogenic (acute) inflammation, which results in large amounts of pus, which consists of neutrophils, dead cells and fluid

Question 29

What is the immune response for chronic inflammation?

Answer 29

Recruitment of T cells and macrophages
A granuloma forms in order to trap the pathogen
They bacteria may not be active but remains dormant

Question 30

What is a cytokine storm?

Answer 30

Over-activation of a healthy immune system, which leads to a massive production of cytokines
Pro and anti-inflammatory cytokines are detected in highly increased levels in serum

Question 31

What are key mediators of cytokine softens?

Answer 31

TNF-a

IL-6

Question 32

What are the main effects of cytokine storms?

Answer 32

organ failure
tissue damage
shock and death
Mainly occurs in sepsis and septic shock

Question 33

What do group A streptococcus infection produce?

Answer 33

Haemolysis

harmful antibody response

Question 34

What do superantigens do?

Answer 34

cause non-specific activation of T cells

Cytokine storm