Bacterail Pathogenesis Flashcards
Virulence Determinants
- Properties that enable an organism to enter, replicate and persist in a host
*expression of capsule, LPS, pili
*elaboration of exotoxins that kill WBC’s, proteases, siderophores
*generation of DNA inversions that lead to antigenic and phase variation
How we determine what properties of an organism are necessary or involved in the disease process
- Molecular Koch’s postulates
*trait should be assoc. more often w/ pathogenic strains of a species than non-pathogenic strains
*inactivation of the gene(s) assoc. w/ trait should decrease or eliminate virulence
*virulence should be restored when mutated gene is replaced w/ wild-type gene
Role of pili in bacterial pathogenesis
- Allows for adhesion
- Adhesin tip on pilus will bind to specific receptors on a host cell
*a lot of times this specificity can dictate where the organism can cause disease and the type of host that it can cause disease in
*Host specific adherence
*Tissue specific adherence
- Important virulence factor for pathogens like E.coli and Neisseria gonorrohoeae
MSCRAMM’s
- A group of molecules that can be found on the surface of gram(+) bacteria that bind to specific structures in our bodies
- A subfamily of surface adhesions that target host extracellular matrix proteins such as fibrinogen, fibronectin, and collagen for adhesion
- Hav
Siderophores
- Compounds produced by bacteria that bind ferric ions for transport into the cell
Endotoxins vs. Exotoxins chart
Lipid A Induction of Cytokine production
- PAMP; recognized by PRR’s
- Express on gram (-)
- Recognized by TLR-4
- Binds to what is referred to as the LPS binding protein and then that binds to CD14 and then that binds to TLR-4
*activation of NF-kB and the activation of genes that encode for TNF-a and IL-1 as well as other cytokines
PAMP’s
- Lipid A
- LPS, lipoteichoic acid, lipoproteins, mycobacterial lipoarabinomannan
- Peptidoglycan, flagella
- DNA (has unmethylated CpG motifs not in mammalian DNA), toxins
- Molecular motifs conserved within a class of microbes that are recognized by PRR’s
Major mediators of septic shock
- TNF-a
- IL-1
- Produced by macrophages when stimulated by endotoxin
Endotoxin characteristics
- Lipid A part of LPS in the outer membrane of Gram (-) bacteria
- Liberated when bacteria lyse and/or released as part of membrane fractions
- PAMP’s; Molecular motifs conserved within a class of microbes that are recognized by PRR’s
- Endotoxin shock is usually assoc. w/ systemic spread of organisms
*local release > containment and removal of infection
*systemic release > hypotension, DIC, systemic shock (septic shock)
Exotoxin characteristics
- Secreted or membrane bound and released upon lysis
- Specifically destroy or inhibit cellular functions or tissue components
- Vary in specificity (neurotoxin, cytotoxin, enterotoxin)
- Many (but not all) possess enzymatic activity
Exotoxins (AB)
- Some the exotoxins have “A” or active units and “B” or binding units; so they are dimeric molecules
- Pore-forming toxins and superantigens
- Diptheria toxin
- Cholera toxin
- C. perfringens
Superantigens
- Powerful polyclonal T cell mitogens
- Stimulates non-specific T cell responses
*~20% of APC’s stimulated vs 1/10^5-1/10^6 (normal clonal response)
- Binds to MHC class II molecule and T cell receptor outside of antigen binding sites
- Leads to improper immune response and a toxic cascade of cytokines
- Can synergize with agents such as Gram(-) endotoxin to release even greater amounts of TNF-alpha and beta
Toxoid
- A chemically modified toxin from a pathogenic microorganism, which is no longer toxic but is still antigenic and can be used as a vaccine.
NOD-1 receptors
- PRR
Endotoxin vs. Exotoxin
- Exotoxins are toxic substances secreted by bacteria and released outside the cell. Whereas Endotoxins are bacterial toxins consisting of lipids that are located within a cell
