Bacterial pathogenesis II Flashcards
What are the 6 main types of host damaging systems as a result of bacterial infection?
- Acute inflammatory changes
- Damage by bacterial enzymes
- Exotoxins
- Endotoxin and other causes of sepsis
- Superantigen mediated eg toxic shock syndrome
- Immunopathology
What are the symptoms of an infection that causes inflammatory changes?
Local symptoms = redness, swelling, heat, loss of function and pain. Also pus from pyogenic infection
Systemic symptoms = fever, rigor, chills, tachycardia and tachypnoea
What is it that causes these inflammatory changes?
- Local symptoms caused by increased blood flow, permeability, and stickiness of vascular endothelium. All help migration of phagocytes to site of infection
- Triggered by release of toxins and enzymes released from bacteria and amplified by release of histamine, PGs, LTs etc from host cells
- Results in accumulation of pus - phagocytes, mainly neutrophils, and some monocytes, complement and other factors, as well as exudate = pyogenic infection
Give examples of some pyogenic organisms?
- Staphylococci, streptococci and meningococci
What damage can different bacterial enzymes cause?
Hyaluronidase
- From streptococci eg strep pyogenes
- Breaks down hyaluronic acid, disrupting tissue, allowing bacteria and inflammatory exudate to travel deeper and further
Alpha-lecithinase
- From Clostridium perfringens
- Splits lecithin (found on cell surfaces) causing major tissue damage
Other enzymes eg protease, lipase, amylase and nuclease
What damage does bacterial endotoxin cause?
- Secreted by bacterium
- Enzymatic lysis
- Pore formation
- Inhibition of protein synthesis
- Hyperactivation
- Effects on nerve-muscle transmission
What is endotoxin?
- An integral part of the bacterial wall of G-ve bacteria
- Usually released when bacterial cell is damage
- AKA Lipopolysaccharide and lipid A
Give some examples of endotoxin mediated disease
- N.meningitidis
- E coli
- Klebsiella pneumoniae
- Pseudomonas aeruginosa
What are the actions of endotoxin?
- Activates complement - reducing amount available to fight infection
- Polyclonal expansion of B cells
- Activation of macrophages/monocytes
- These release IL-1,6,8, platelet activating factor and TNF, and stimulate PG and LT production
- These act at various sites such as endothelium, liver and clotting cascade
- Causes increased vascular permeability, hypotension, leading to shock, fever, disseminated intravascular coagulation and eventually multi organ failure
What is toxic shock syndrome?
- Caused by toxins released from certain strains of staph aureus (TSST) and strep pyogenes (SPE) - these act as superantigens
- Causes massive activation of immune response and leads to multisystem disease
How do superantigens work?
- Can act simultaneously with MHC class II ags on APCs and Vbeta regions on T-cells causing mass stimulation
- Dont need the specific ag
- Activates macrophage/ monocytes to elicit IL-1,6, TNF-a and IFN-y
- Causes hyperactivation, triggering complement, clotting cascades etc
How does strep pyogenes cause glomerulonephritis?
- Type III hypersensitivity reaction
- Host produces Abs against streptococcal ags
- Abs bind to ags and form immune complexes, which can be deposited in the kidneys, causing glomerular nephritis
What is molecular mimicry?
- Abs are produced against a specific Ag on a pathogen, however this has a similar structre to host
ags - causes cross-reactivity - Happens in myocardium (M-protein of streptococcus pyogenes and cardiac muscle) causing rheumatic heart disease
- Also occurs in synovium (causes arthritis) and brain (cross-react with caudate and subthalamic nuclei leading to involuntary movement)
What cellular immune responses can occur from bacterial infection?
Type IV reactions
- Th cells react to specific antigens, releasing cytokines to activate macrophages, which may cause tissue damage
Granuloma formation
