Bacterial Pathogenesis 4

Bacterial Pathogenesis 4

1. Types of damage

   • Direct
     • Metabolic
     • Cytolytic
     • Signalling/apoptosis
     • Extracellular enzymes
       • Digestion for substrates for growth, streptokinase (fibrin) and hyaluronidase for invassion, tooth decay
   • Immunopathology 'HYPERSENSITIVITY"
     • I. Anaphylactic: IgE, mast cells, allergen
     • II. Cytotoxic: Ig binding circulating elements (foreign)
     • III. Immune Complex: deposition in tissues e.g. glomerulonephritis
     • IV. Delayed type (cell-mediated: CD4+, NK, M'phage e.g. TB skin test
     • Autoantibodies (II) e..g lupus, RA
   • Toxins
     • Exotoxins
       • Membrane-damaging
         • Enzymatic (phospholipase C) or pore-forming (Staph a-toxin)
       • Cellular modifying
         • AB toxins, A= active subunit (toxic), B= binding subunit (attachment + entry)
           • Internalised and A expresses activity in cytoplasm
         • E.coli Labile Toxin, pore forming, andenylate cyclase, cAMP, release of ions, diarrhoea. Shiga-like Toxin binds glycolipids, internalised, cleaves a bond of ribosomes preventing protein synthesis; neurotoxic, alters vascular permeability, induces enterocyte fluid loss
         • C. diphtheria toxin, inactivates aa transfer + protein synthesis- death
         • Neurotoxic Clostridium toxins activated by proteolysis, internalised and inactivate release mechanisms by for neurotransmitters
     • Endotoxins
       • LIPOPOLYSACCHARIDE (LPS) of G-ve bacteria, released by bacteriolysis interacts and causes inflammatory mediator release can produce fever, shock, death
     • Superantigens
       • non-specifically activate lyphocytes (Step + Staph) bind MHC class II-> proliferation
     • Aggresins + Modulins: intrinsic/extracellular factors- activate + modify immune response
     • Fungal Exotoxins
       • 2' metabolites: ingested and absorbed-> hepatotoxicity, mucosal haermorrhage, immunosuppression, carconogenesis

2. Possible outcomes

   • Acute
     • Excretion followed by recovery/death, may be eliminated before specific immune response
   • Chronic
     • Excretion- recovery/death
   • Asymptomatic
     • Latency
       • e.g. non-replicative phase, reactivate with predisposing circumstances
     • No clinical signs, may persist after clinical recovery, may be onfined in tissue but be triggered e.g. TB, may excrete pathogens
   • Resolution
     • Complete recovery
     • Recovery with persistent damage
     • Persistance + carriage
     • Death

3. Factors that influence outcome

   • Bacterial
     • Virulence/factors produced
       • Cytotoxins, superantigens, inasions etc
       • Global regulators, mutations in loci
   • Host
     • Genetic e.g. receptor molecule polymorphisms
     • Existing infections (modulate immune system)
     • Diet, general health, stress, age
   • Environmental
     • Weather/climate, crowding, hygiene
     • Local-> systemic
   • Control: management+husbandry, specific antimicrobial chemotherapy, immunotherapy, vaccination, quarantine/culling, control of vectors

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