MCB Lecture 50 Pathogenesis II Flashcards Preview

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Flashcards in MCB Lecture 50 Pathogenesis II Deck (23)
0

Describe the steps involved in phagocytosis (6)

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

1

Describe Metabolic Burst

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

2

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

1. Metabolic burst: super oxide, hydrogen peroxide, NO
2. Lysosomal enzymes and defensins

3

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

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

4

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

1. Direct toxicity
2. Induction of cytokines
3. Induction of immuno pathology

5

Describe the features of direct toxicity

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

6

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

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

7

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

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

8

What are the targets of exotoxin? (3)
Give specific examples of how they damage tissue

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

9

How many exotoxin be neutralised?

With antibodies

10

What is an intracellularly acting toxin?
Give a specific example

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

Eg. Diphtheria toxin

11

Describe the structure of Diphtheria toxin

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

12

What is the function of Diphtheria toxin?

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.

13

Describe the source of the gene for the diphtheria toxin

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

14

What is botulism?
What is it an example of?

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

15

Describe how tetanus causes disease

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

Describe how diphtheria causes disease

Diphtheria toxin gets into cells and stops protein synthesis

17

Describe how Staphylcoccus causes toxic shock syndrome

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

Describe broadly how induction of cytokines can cause disease

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

What does presentation of PAMPs result in?

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

20

What are super antigens?

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

Give a summary of pathogenesis
At each stage, give the host mechanisms to combat these stages

1. Adhesion
2. Penetration
--> physical and chemical barriers

3. Multiplication
4. Tissue damage
--> inflammatory response, phagocytes, adaptive immune system

22

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

Fc of the antibodies that have covered the bacteria

FcR on the phagocyte

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