Mechanisms of bacterial pathogenesis II

Question 1

What are 5 types/consequences of host damage as a result of bacterial infection?

Answer 1

1) Acute Inflammatory Changes
2) Damage by bacterial enzymes and exotoxins
3) Endotoxin and other causes of sepsis
4) Superantigen mediated e.g. toxic shock syndrome
5) Immunopathology; immune complex disease (type 3 hypersensitivity), molecular mimicry, cellular immune response

Question 2

Describe the acute inflammatory changes as a result of bacterial infection

Answer 2

• Increased BF + permeability to fluid and plasma proteins
• Increased stickiness of vascular endothelium, emigration of phagocytes to site of infection
• Response = triggered by release of toxins/enzymes from bacteria
• Amplified by release of products from host cells (e.g. histamine, pgs, leukotrienes, kinins)

Question 3

What is a pyogenic infection and what are pyogenic organisms?

Answer 3

• Infection that causes a lot of pus (neutrophil pus cells)
• Staphylococci, streptococci, meningococci

Question 4

Describe 2 other bacterial enzymes, other than protease, lipase, amylase, nuclease?

Answer 4

Hyaluronidase:
- breaks down hyaluronic acid and disrupts tissue mosaic allowing bacteria and inflammatory exudate to spread
- Origin = streptococci (strep. pyogenes)

Alpha-lecithinase:
- splits lecithin (on surface of many cells) causing major tissue damage
- Source = clostridium perfeinge

Question 5

Describe what bacterial exotoxins are, its classifications and its functions

Answer 5

• Exotoxins are harmful proteins released by certain gram + and - bacteria
• Classified into cytokines, neurotoxins, enterotoxins
• Enzymatic lysis
• Pore formation
• Inhibition of PS
• Hyperactivation
• Effect on nerve-muscle transmission (muscle weakness)

Question 6

Where are endotoxins found, what are their actions and consequences?

Answer 6

• Found only in gram-negative bacteria (cell wall) and released when bacterial cell is damaged
• Activates macrophages/monocytes to release IL-1,6,8, platelet activating factor and TNF-alpha and stimulate pgs and leukotrienes
• Activates complement (via alt pathway) and clotting cascade and B-cell antibody secretion
• Results in increased vascular permeability, hypotension (shock), fever, DIC, multi organ failure

Question 7

Describe toxic shock syndrome and superantigens

Answer 7

TSS toxins can act as superAgs produced by strains of:
- Staph aureus –> Toxic shock syndrome toxin (TSST)
- Strep pyogenes –> Strep pyrogenic exotoxin (SPE)

Superantigens acts simultaneously with MHC class II antigens on APCs AND bind to the beta subunit of TCR in a less specific way
This activates much larger no. of T cells and macrophage/monocytes to elicit IL-1, IL-6, TNF-alpha and INF-γ -> highly uncontrolled inflammation

Question 8

How can strep pyogenes cause glomerular nephritis and what type of reaction is this?

Answer 8

Type III hypersensitivity reaction

Host produces Abs against Strep pyogenes which bind to antigens to form immune complexes = stimulates complement

Large amount of immune complexes can cause damage to tissue in the kidneys leading to glomerulonephritis

Question 9

What is molecular mimicry?

Answer 9

• Streptococcus pyogenes can also cause throat infection= Abs produced
• In some cases, surface Ags are similar to host cell Ags= Abs react to self= cross reactivity
• Sites of cross reactivity:myocardium, synovium (arthiritis), brain (sydenham’s chorea, St Vitus’s dance)

Proposed cause of autoimmune diseases

Question 10

Explain how molecular mimicry causes rheumatic heart disease and rheumatic fever

Answer 10

• Group A carb of strep is similar to glycoprotein of heart valve
• M protein of streptococcus similar to cardiac muscle

Binding of Abs to host antigen activates complement –> inflammation of heart

Granulomas form in the tissue - Aschoff’s nodules