4.6 - 4.7 How Bacteria Cause Disease Flashcards
What are Koch’s postulates to identify a pathogen?
- The organism must be associated with the disease and its characteristic lesions.
- The organism must be isolated from the diseased host and grown in culture.
- The disease must be reproduced when a pure culture of the organism is introduced into a healthy, susceptible host.
- The same organism must be reisolated from the experimentally infected host.
Added later …. Demonstrate a specific immune response
What are the problems with Koch’s postulates?
- The organism must be regularly associated with the disease and its characteristic lesions.
- The organism must be isolated from the diseased host and grown in culture. cannot grow obligate pathogens in culture
- The disease must be reproduced when a pure culture of the organism is introduced into a healthy, susceptible host.
- The same organism must be reisolated from the experimentally infected host.
What are the molecular Koch’s postualtes?
- The phenotype or property under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species
- Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence
- Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity
What are the five attributes of pathogens?
- Colonisation
- Penetration
- Multiplication
- Tissue damage
- Disease
What are the two types of colonisation seen by pathogens?
What features is bacterial colonisation mediated by?
- Mediated by surface proteins
- Fimbriae/pili: molecular hairs/extrusions which have the capacity to stick to each other or human body cells
- Adhesins - outer membrane proteins
How does this show evidence for fimbriae in virulence?
- K88 is the fimbri and Tox is the toxin
- Without K88 0 got diarrhoea when fimbri was missing
- In absence of virulence factor we see no virulence
How does this show immunity to fimbri?
- When injected with recombinant K88 protein the mother pig will make antibodies and be protected
- Expose to the fimbri will give it active immunity
- The piglet will receive these through the placenta (antibodies) protecting it from infection
What are the two outcomes of bacterial invasion?
What are the strategies of bacteria to overcome phagocytosis?
- Direct evasion of phagocytosis
- Interfering with opsonins, namely
- Antibodies
- Complement
- mannose binding protein/lecitin
How do bacteria evade the complement protein cascade?
- Bacterial surface proteins that bind C4BP or FH leading to degradation of complement components OR sequester/inactive C3
- Secreted bacterial proteins that are proteases that specifically degrade complement proteins
How do bacteria directly evade phagocytosis?
- Gram positive pathogen makes leukocidin proteins, interact with each other and form pore on the surface of host cells
- Pore lead to cell death of phagocyte
What is the evidence for capsule in virulence?
- Virulence of capsulated and unencapsulated bacteria
- Anti-capsular antibodies and immunity:
- Passive immunisation with anti-capsule antibodies
- Active immunisation with purified capsuiles
How does the capsule enhance virulence?
- Resemble host components such as hyularonic acid so the host cannot made antibodies to this
- Mask underlying structures
What does this show?
- Bacteria that doesn’t have capsule will be opsonised by complement
- C3b molecule decorate bacterial surface and facilitate phagocytosis
How do antibodies overcome the capsule?
- Unencapsulated bacteria interact with receptors on phagocytosis
- With a capsule C3b can’t interact so well with the bacteria
- Factor H restrict ability of the host to phagocytose
- Antibodies provide another binding site which helps overcome the capsule for phagocytosis pathway
What are the two types of bacterial toxins?
What are the two ways by which bacterial exotoxins are classified?
What kind of structure to intracellular acting exotoxins have?
Many have a bi-functional (A-B) structure
- A part is the active part, enzymatic activity
- B part encodes for part that binds to the target cell
- Usually encoded as one protein that is cleaved
How does the diptheria toxin cause disease?
- Interacts with receptor on host cell surface
- Gets internalised taken up by the cell
- Separation between A and B subunits
- Target of A subunit is EF2 elongation factor which is important for making proteins
- Adds adp-ribose, post translational modification
- Cell dies cannot make proteins
What are some examples of exotoxin mediated diseases?
How does super antigen cause immune mediated damage?
- Superantigen interacts with MHCII to lead to non specific activation of T cells and their proliferation causing polyclonal expansion
- Massive cytokines release which is super toxic to us
- Activates macrophages and innate cells to also start making inflammatory cytokines
- TMF alpha made locally in low levels normally but with mass T cell activation cause septic shock and organ failure
