Bacterial pathology

Question 1

Define Commensal organisms

Answer 1

Commensal organisms colonise surfaces such as the skin and mucosal surfaces within the respiratory tract and GI tract.

They are harmless to the host and in exchange for space/surfaces to colonise and supply of nutrients, they offer protection to the host by outcompeting potential pathogens.

Question 2

Define Opportunistic organisms

Answer 2

Opportunistic organisms colonise body surfaces and sometimes cause disease under certain circumstances such as in immunocompromised patients or elimination of commensal microbiota.

Question 3

Define Pathogenic organisms

Answer 3

Pathogenic organisms primarily cause disease in healthy hosts.

Different pathogenic organisms can cause acute infections, persistent infections or latent infections.

Question 4

List the different portals of entry for microorganisms

Answer 4

• Ingestion
• Inhalation
• Inoculation (Insect bites, needle injury, sexual intercourse, vertical transmission/mother to baby, bodily fluid exposure)

Question 5

Define subclinical infections, giving some examples.

Answer 5

These infections are often asymptomatic in some hosts.

1/3 of all rhinoviruses (common cold) infections are asymptomatic

Many individuals are immune to chicken pox

Colonisation of Group A strep or meningococcus in the throat only give rise to a very minor skin infection

It is important to note that the pathogen may still be highly transmissable even in the absence of clinical symptoms, and disease may develop later on.

Question 6

What occurs in a localised infection and through which mechanisms can these infections cause even more damage?

Answer 6

Local damage to tissues and the infection is self-limiting - does not usually progress.

However, in some cases the local disease can spread and give rise to more severe diseases. This occurs by:

1. Invasion of the blood stream
2. Production of potent toxins
3. Host antibodies causing host tissue damage due to molecular mimicry ability of some pathogens

Question 7

How does Staphylococcus aureus cause local damage?

Answer 7

• Release of alpha, beta, gamma, delta cytotoxins
• Coagulase
• Panton Valentine Leucocidin (PVL) - potent local toxin that can lead to necrosis of lung tissue
• Protein A - binds antibodies with Fab regions facing away from the pathogen’s cell surface
• Enterotoxins A-F (Enterotoxin B/Toxic Shock Syndrome Toxin 1 can cause lethal toxaemia)

Question 8

How does Streptococcus pyogenes (Group A Strep) cause local damage?

Answer 8

• Release of Streptolysins (O/S) - cause local cell damage
• Release of Streptokinase and Hyaluronidase which break down blood clots and the intracellular bridges in tissue - causes cellulitis

Question 9

How does Psudeomonas aeruginosa cause local damage?

Answer 9

• Range of enzymes such as Elastase (protease)
• Release of Endotoxins from the cell wall to enhance severe sepsis via shock and coagulopathy

Question 10

Describe what is meant by the term Superantigen and give some examples of them.

Answer 10

Superantigens are highly potent exotoxins

• TSST-1 and Exofoliative toxin (causes scalded skin snydrome) - released by Staph. aureus
• Pyrogenic exotoxins A & C - released by Streptococcus pyogenes

Question 11

Name 4 Classical toxins

Answer 11

• Tetanus toxin
• Botulinum toxin
• Diphtheria toxin
• Cholera toxin

Question 12

Explain with an example how an organism can cause widespread damage to the host through antibody-mediated mechanisms.

Answer 12

Streptococcus pyogenes (Group A strep) primarily causes inflammation of the upper respiratory tract - Pharyngitis

The host produces antibodies that target the pathogen in the throat.

However, the antibody can cross-react with cardiac antigens - Molecular mimicry

Antibodies now also target the cells that express the cross-reacted cardiac antigens - leads to permanent heart damage, severe illness with fevers and joint pains - Rheumatic Fever

Question 13

Explain in TB and Hepatitis B how an organism can cause widespread damage to the host through cell-mediated mechanisms.

Answer 13

T cell responses in TB can cause lung damage and in Hepatitis B cause liver damage.

Question 14

What are the clinical signs of acute inflammation?

Answer 14

Pain

Redness

Heat

Question 15

What are the clinical signs of chronic inflammation?

Answer 15

Abscesses, tissue necrosis, sinuses and tissue scarring

Question 16

Name 3 pro-inflammatory cytokines and 1 chemokine produced at the onset of an acute infection?

Answer 16

TNF-alpha, IL-1 and IL-6

IL-8 (chemokine)

Question 17

Why do we have fevers during infection?

Answer 17

The release of pro-inflammatory cytokines and chemokines into the blood at the onset of infection, signals to the hypothalamic thermoregulatory centre to produce Prostaglandin E2.

The release of Prostaglandin E2 elevates the ‘thermostat’ set point, resulting in heat conservation and production, which culminates in fever

Question 18

How is the fever response beneficial to the host?

Answer 18

Fever is believed to increase T & B cell activity and IgG synthesis

Question 19

What are the effects of sudden, mass cytokine release into the bloodstream?

Answer 19

Complement activation

Coagulation cascade

Kallikrien system/ Nitric oxide

Blood vessels dilate, causing a drop in blood pressure

Vessels become increasingly leaky which further reduces blood pressure

Oedema, arterial thromboembolism and local haemorraging occur, which lead to shock, reduced organ perfusion, multi-organ failure and death.

Question 20

What can cause cytokine release, high fever and toxic shock?

Answer 20

Superantigens which bind to T cell receptors.