MCB Lecture 50 Pathogenesis II Flashcards
Describe Metabolic Burst
This is when there is much oxidation, and oxygen is reduced to produce lots of reactive oxygen species: O2- and H2O2
Describe the steps involved in phagocytosis (6)
- Chemotaxis
- Attachment: Fc + FcR
- Metabolic burst: oxidation -> O2-, H2O2
- Extension of filopodia
- Phagolysosome formation
- Destruction
What are the bactericidal mechanisms present in normal phagocytosis? (2)
- Metabolic burst: super oxide, hydrogen peroxide, NO
2. Lysosomal enzymes and defensins
How may pathogens that have been phagocytosed avoid killing? (4)
- Prevent phagolysosome formation
- Break down phagosome membrane and enter the cytosol
- Inhibit metabolic burst
- Resist lysosomal enzymes and defensins
What are the three main mechanisms of tissue damage by bacteria?
- Direct toxicity
- Induction of cytokines
- Induction of immuno pathology
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
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
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
What are the targets of exotoxin? (3)
Give specific examples of how they damage tissue
- Cells: Haemolysin, Leukocidins
- ECM: hyaluranidase, Collagenase
- Host molecules: lipid, fibrin, nucleic acid
How many exotoxin be neutralised?
With antibodies
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
Describe the structure of Diphtheria toxin
It is a protein with two parts:
A: active part, enzymatic activity, ADP-ribosyl transferase
B: binding part
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.
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
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