MCB Lecture 50 Pathogenesis II Flashcards

0
Q

Describe Metabolic Burst

A

This is when there is much oxidation, and oxygen is reduced to produce lots of reactive oxygen species: O2- and H2O2

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1
Q

Describe the steps involved in phagocytosis (6)

A
  1. Chemotaxis
  2. Attachment: Fc + FcR
  3. Metabolic burst: oxidation -> O2-, H2O2
  4. Extension of filopodia
  5. Phagolysosome formation
  6. Destruction
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2
Q

What are the bactericidal mechanisms present in normal phagocytosis? (2)

A
  1. Metabolic burst: super oxide, hydrogen peroxide, NO

2. Lysosomal enzymes and defensins

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3
Q

How may pathogens that have been phagocytosed avoid killing? (4)

A
  1. Prevent phagolysosome formation
  2. Break down phagosome membrane and enter the cytosol
  3. Inhibit metabolic burst
  4. Resist lysosomal enzymes and defensins
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4
Q

What are the three main mechanisms of tissue damage by bacteria?

A
  1. Direct toxicity
  2. Induction of cytokines
  3. Induction of immuno pathology
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5
Q

Describe the features of direct toxicity

A

Molecules are either secreted, or present on the bacterium, that bring about damage, eg. Stop host proteins from working normally

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6
Q
Differentiate between an exo- and endotoxin
Potency
Heat resistance
Neutralisation by antibodies
Toxoids
Mode of action
A

Exo: secreted by the bacterium Endo: present on the surface of bacterium
Exo: very potent Endo: moderately potent
Exo: variable heat resistance Endo: extremely heat resistant
Exo: are neutralised by antibodies Endo: are not neutralised by antibodies, because LPS contains a protein and a lipid part. Lipids may not be target by antibodies, thus LPS is still functional
Exo: toxoids may be produced Endo: no toxoids
Exo: variable modes of damage Endo: non specific modes of damage

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7
Q

What is an important outcome of the fact that exotoxins are trans acting?

A

A person can be infected by the toxin alone, they may never see the bacterium

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8
Q

What are the targets of exotoxin? (3)

Give specific examples of how they damage tissue

A
  1. Cells: Haemolysin, Leukocidins
  2. ECM: hyaluranidase, Collagenase
  3. Host molecules: lipid, fibrin, nucleic acid
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9
Q

How many exotoxin be neutralised?

A

With antibodies

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10
Q

What is an intracellularly acting toxin?

Give a specific example

A

The toxin must enter the cell before it can start causing damage

Eg. Diphtheria toxin

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11
Q

Describe the structure of Diphtheria toxin

A

It is a protein with two parts:
A: active part, enzymatic activity, ADP-ribosyl transferase
B: binding part

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12
Q

What is the function of Diphtheria toxin?

A

Once in the cell, the two subunits dissociate
The A subunit catalyses the addition on ADP-ribose to certain enzymes in the host. In humans, this is EF2 (elongation factor 2).
EF2 is no longer active, and protein synthesis in the host is blocked.

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13
Q

Describe the source of the gene for the diphtheria toxin

A

The gene is from a virus (bacteriophage) that infects the Diphtheria bacterium. The virus gene is then transcribed and diphtheria toxin is produced by the bacterium

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14
Q

What is botulism?

What is it an example of?

A

Botulism is a disease caused by bacterial toxins contaminating food leading to paralysis, and eventually requiring the patient to be put on a respirator when the patient can no longer breathe

It is an example of an exotoxin

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15
Q

Describe how tetanus causes disease

A

Tetanus bacteria produce a (tetanospasmin) neurotoxin that enters the blood when an individual treads on a rusty nail, for example.

The toxin affects skeletal muscle and causes muscle spasms

16
Q

Describe how diphtheria causes disease

A

Diphtheria toxin gets into cells and stops protein synthesis

17
Q

Describe how Staphylcoccus causes toxic shock syndrome

A

The toxin produced by these bacteria is a superantigen, and has reduced specificity for TCRs.
It may bind to and activate up to 20% of T lymphocytes, thus producing a massive immune response, with many cytokines produced
This causes damage in the host

18
Q

Describe broadly how induction of cytokines can cause disease

A

Too many cytokines gives too much of an immune response, and can damage tissues

  1. PAMP binding to PRR (toll like receptors)
  2. Superantigens
19
Q

What does presentation of PAMPs result in?

A

Activation of a toll receptor, signal transduction pathway and gene transcription of inflammatory mediators (cytokines)

20
Q

What are super antigens?

A

These antigens only bind to the beta subunit of the TCR, and lack alpha subunit specificity
Thus, they activate a huge number of T lymphocytes

21
Q

Give a summary of pathogenesis

At each stage, give the host mechanisms to combat these stages

A
  1. Adhesion
  2. Penetration
    - -> physical and chemical barriers
  3. Multiplication
  4. Tissue damage
    - -> inflammatory response, phagocytes, adaptive immune system
22
Q

How do phagocytes bind to bacteria that they are going to phagocytose?

A

Fc of the antibodies that have covered the bacteria

FcR on the phagocyte