4.6 - 4.7 How Bacteria Cause Disease

Question 1

What are Koch’s postulates to identify a pathogen?

Answer 1

1. The organism must be associated with the disease and its characteristic lesions.
2. The organism must be isolated from the diseased host and grown in culture.
3. The disease must be reproduced when a pure culture of the organism is introduced into a healthy, susceptible host.
4. The same organism must be reisolated from the experimentally infected host.

Added later …. Demonstrate a specific immune response

Question 2

What are the problems with Koch’s postulates?

Answer 2

1. The organism must be regularly associated with the disease and its characteristic lesions.
2. The organism must be isolated from the diseased host and grown in culture. cannot grow obligate pathogens in culture
3. The disease must be reproduced when a pure culture of the organism is introduced into a healthy, susceptible host.
4. The same organism must be reisolated from the experimentally infected host.

Question 3

What are the molecular Koch’s postualtes?

Answer 3

1. The phenotype or property under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species
2. Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence
3. Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity

Question 4

What are the five attributes of pathogens?

Answer 4

1. Colonisation
2. Penetration
3. Multiplication
4. Tissue damage
5. Disease

Question 5

What are the two types of colonisation seen by pathogens?

Answer 5

Question 6

What features is bacterial colonisation mediated by?

Answer 6

• Mediated by surface proteins
• Fimbriae/pili: molecular hairs/extrusions which have the capacity to stick to each other or human body cells
• Adhesins - outer membrane proteins

Question 7

Answer 7

Question 8

Answer 8

Question 9

How does this show evidence for fimbriae in virulence?

Answer 9

• K88 is the fimbri and Tox is the toxin
• Without K88 0 got diarrhoea when fimbri was missing
• In absence of virulence factor we see no virulence

Question 10

How does this show immunity to fimbri?

Answer 10

• When injected with recombinant K88 protein the mother pig will make antibodies and be protected
• Expose to the fimbri will give it active immunity
• The piglet will receive these through the placenta (antibodies) protecting it from infection

Question 11

What are the two outcomes of bacterial invasion?

Answer 11

Question 12

What are the strategies of bacteria to overcome phagocytosis?

Answer 12

• Direct evasion of phagocytosis
• Interfering with opsonins, namely
  
  • Antibodies
  • Complement
  • mannose binding protein/lecitin

Question 13

How do bacteria evade the complement protein cascade?

Answer 13

• Bacterial surface proteins that bind C4BP or FH leading to degradation of complement components OR sequester/inactive C3
• Secreted bacterial proteins that are proteases that specifically degrade complement proteins

Question 14

How do bacteria directly evade phagocytosis?

Answer 14

• Gram positive pathogen makes leukocidin proteins, interact with each other and form pore on the surface of host cells
• Pore lead to cell death of phagocyte

Question 15

What is the evidence for capsule in virulence?

Answer 15

• Virulence of capsulated and unencapsulated bacteria
• Anti-capsular antibodies and immunity:
  
  • Passive immunisation with anti-capsule antibodies
  • Active immunisation with purified capsuiles

Question 16

How does the capsule enhance virulence?

Answer 16

1. Resemble host components such as hyularonic acid so the host cannot made antibodies to this
2. Mask underlying structures

Question 17

What does this show?

Answer 17

• Bacteria that doesn’t have capsule will be opsonised by complement
• C3b molecule decorate bacterial surface and facilitate phagocytosis

Question 18

How do antibodies overcome the capsule?

Answer 18

• Unencapsulated bacteria interact with receptors on phagocytosis
• With a capsule C3b can’t interact so well with the bacteria
• Factor H restrict ability of the host to phagocytose
• Antibodies provide another binding site which helps overcome the capsule for phagocytosis pathway

Question 19

Answer 19

Question 20

What are some strategies used by intracellular pathogens to resist killing by phagocytes?

Answer 20

• Inhibit the respiratory burst
• Prevent phagolysosome formation
• Escape from the phagocytic vacuole
• Resist bactericidal systems

Question 21

How do bacteria overcome adaptive immunity?

Answer 21

• Direct immunosuppression
• Expression of weak antigens
• Antigen modification
• Antigenic diversity

Question 22

What are the stages of infection?

Answer 22

• Colonisation
• Invasion
• Multiplication
• Tissue Damage

Question 23

What are the three means by which there can be tissue damage?

Answer 23

• Direct toxicity – mediated by bacterial toxins
• Induction of cytokines
• Induction of immunopathology
• Last two are immune mediated damage

Question 24

What are the two types of bacterial toxins?

Answer 24

Question 25

What are the two ways by which bacterial exotoxins are classified?

Answer 25

Question 26

What are the targets of extracellular actin exotoxins of bacteria?

Answer 26

Intact host cells * Haemolysin, leucocidins, lecithinase Extracellular matrix * Hyaluronidase, collagenase Other host molecules * Lipids, fibrin, nucleic acids, urea etc

Question 27

What kind of structure to intracellular acting exotoxins have?

Answer 27

Many have a bi-functional (A-B) structure * A part is the active part, enzymatic activity * B part encodes for part that binds to the target cell * Usually encoded as one protein that is cleaved

Question 28

How does the diptheria toxin cause disease?

Answer 28

* Interacts with receptor on host cell surface * Gets internalised taken up by the cell * Separation between A and B subunits * Target of A subunit is EF2 elongation factor which is important for making proteins * Adds adp-ribose, post translational modification * Cell dies cannot make proteins

Question 29

What are some examples of exotoxin mediated diseases?

Answer 29

Question 30

How does super antigen cause immune mediated damage?

Answer 30

* Superantigen interacts with MHCII to lead to non specific activation of T cells and their proliferation causing polyclonal expansion * Massive cytokines release which is super toxic to us * Activates macrophages and innate cells to also start making inflammatory cytokines * TMF alpha made locally in low levels normally but with mass T cell activation cause septic shock and organ failure