Mechanisms of Bacterial Pathogenesis

Question 1

What are Koch’s Postulates?

When do Opportunistic pathogens cause infection?

What are Virulence factors? What do they do?

How do Adhesins help the bacteria?

How do Capsules help the bacteria?

What are the Stages of Infection?

Answer 1

• Microbe has to be present in all cases of the infection, be cultured from cases in vitro, can reproduce in the host, and can be isolated from the infected host
• When patient’s immunosuppressed
• Molecules produced by Bacteria that cause the disease e.g. Toxins, Adhesins etc.
  o They promote colonisation (adhesion) and tissue damage, and Evade host defences
• Promote adhesion using pili/fimbriae
• Prevent opsonisation and phagocytosis
• Acquisition → Colonisation (Adherence) → Penetration → Multiply and Spread → Immunoevasion → Damage → Transmission → Resolution

Question 2

BACTERIAL TOXINS:
What are Exotoxins? What are they released from?
→ What are they classified by?

What are Endotoxins? Where are they found?

Types of Exotoxins:
Type 1 - Where do they act?
→ What do they do?
→ How does this relate to E. coli?

Type 2 - Where do they act?
→ What do they do?

Type 3 - Where do they act?
→ What are they classified by?

Answer 2

• Proteins released from Gram+ve and Gram-ve bacteria
  → Their site of action e.g. Cytotoxins, Neurotoxins, Enterotoxin etc.
• Powerful Immunostimulants found in Gram-ve cell wall
• Promote adhesion, survival and spread, Damage host cells, Interfere with cell metabolism, or Affect nerves
• AT cell membranes
  → Binds to receptors to activate signalling proteins and alter cell metabolism
  → E.coli Enterotoxin activates GC to form cGMP = ↑Fluid secretion = Diarrhoea
• ON cell membranes
  → Forms Pores and disrupts enzymes, which disrupts ion transport = Cell lysis
• INTRACELLULAR
  → • Enzymatic action e.g. ADP-Ribosylation, Glucosyl Transferase
  • Molecular target/effect

Question 3

SYMPTOMS OF INFECTION:
What triggers inflammation during infection? What is it amplified by?

How does inflammation result in pus formation?
→ What type of infection is this if pus is formed?

What are some of the systemic symptoms of infection?

Answer 3

• Release of bacterial products e.g. Toxins and Enzymes, and is amplified by the release of products from host cells e.g. Histamine, Prostaglandins, Leukotrienes, Kinins
• Accumulation of phagocytes, complement and exudate at the site of infection
  → Pyogenic infection
• Fever, Rigors, Chills, Tachycardia, Tachypnoea

Question 4

Bacterial Enzymes:
Hyaluronidase - What releases it? What does it do? What’s the result of this?

Bacterial Exotoxins:
What can they cause?
——————

Bacterial Endotoxins:
Where are they found?
→ Only when can they be released?

What do they do to APCs? What does this cause?

Where do these Cytokines (IL, TNF, PAF) then act?

What else is activated?

What’s the overall result of all these actions on the body?
→ What signs are seen?

Answer 4

• Streptococci - Breaks down Hyaluronic acid to Disrupts tissue matrix, allowing for bacteria and inflammatory exudate to enter
• Clostridium perfringens - Breaks down Lecithin, causing Major tissue damage
• Enzymatic lysis, Pore formation, Inhibition of protein synthesis, Hyperactivation, Disrupt nerve-muscle transmission
• Gram-ve cell walls
  → When cell is damaged
• Activate Macrophages to release ILs, TNF, PAF, which also stimulate the production of Prostaglandins and Leukotrienes
• Endothelium, Liver, Clotting cascade
• Complements (via alternative pathway)
• ↑Vascular permeability, Hypotension = Shock, Fever, DIC, Multiple organ failure
  → Purpuric lesions (from DIC) and Gangrene

Question 5

SYSTEMIC INFECTIONS:
What is Bacteraemia?

What is Septicaemia/Sepsis?
→ What is it also known as?
——————

Toxic Shock Syndrome (TSS):
What 2 toxins can it be caused by?
→ What do these toxins act as?

What are these Superantigens able to do?

Answer 5

• Bacteria in blood
• Symptomatic bacteriaemia
  → Systemic Inflammatory Response Syndrome (SIRS)
  ——————
• • S. Aureus (Toxic shock syndrome toxin/TSST)
  • S. Pyogenes (Streptococcal pyrogenic exotoxin/SPE)
  → SUPERANTIGENS
• Act simultaneously on MHC II on APCs and Vβ regions on TCRs
  o Activates Macrophages for ↑ILs, TNF, IF-γ

Question 6

IMMUNOPATHOLOGY:
1. Immune Complex Disease - What type of reaction is this?

2. Molecular Mimicry - What condition does this occur in?
   → What occurs here?

What is found in the Heart of patients with this condition? How do they form?

What is the effect on the Synovium?

3. Cellular Immune Response - What types of reaction is this?

How are T cells involved here?

How does this relate to Tuberculosis?

Answer 6

1. Type III Hypersensitivity

• Antibodies bind to S. pyogenes antigens to form Immune complexes, which deposit into the glomerular capillary walls, causing inflammation

2. Rheumatic Heart Disease/Fever
   → Antibodies cross-react with host antigens in the Myocardium, Synovium, and Brain

• Aschoff’s nodules - Antibodies binding to host antigens also activates Complement and Inflammation = Granuloma formation
• Cross reaction, causing Inflammation = Arthritis
• Cross reaction in Caudate/Subthalamic nuclei, causing involuntary movements = Sydenham’s Chorea (St Vitus’ dance)

• Type IV Hypersensitivity
• T cells release cytokines to activate Macrophages, which produce toxic products that can cause tissue damage
• Granulomas form with Caseous Necrosis