Mechanisms of Microbial Pathogenesis Flashcards
Which are the endosomal located TLR?
TLR 3, 7, 8, 9
What does the PAMPs interact with initially on TLR?
PAMP interacts with the LRR (leucine-rich repeat regions) which will relay to the TIR domain to relay intracellular signaling.
Viruses will typically activate which TLR?
- TLR 2, 4
- TLR 9
- TLR 3
- TLR 7,8
Gram positive bacteria will activate which TLR?
- DNA: TLR9
- Lipopolysaccharides: TLR2
- PG: TLR2
- LTA: TLR 2
Gram-negative bacteria activate which TLR?
- DNA: TLR 9
- Porins: TLR2
- PG: TLR2
- LPS: TLR4
- Flagellin: TLR5
Zymosan on fungi activate which receptors?
TLR 2
Mannan on fungi activate which receptors?
TLR 2,4
Beta-glycan on fungi activate which receptors?
TLR 2
Activation of the TLR leads to stimulation of what downstream products via which corresponding pathways?
- TRIF pathway: to increase production of IFN and IFN inducible genes
- MyD88 pathway: increases the production of inflammatory cytokines.
What are the 3 broad overview stages of Innate Immune system activation?
- Bacteria trigger macrophage to release cytokines/chemokines to direct inflammation.
- Vasodilation, permeability, and leukocytes/macrophages diapedesis.
- Inflammatory cells reach site and cause pain, temperature
What is the role of Commensal bacteria?
- Commensal bacteria are introduced via vaginal birth passage.
- Microbes still contain PAMPs but the host allows a certain level to maintain life.
- This leads to colonization across the body.
What regulates the commensal bacteria from overgrowth?
- Paneth cells detect the commensal bacteria.
- Leads to activation of the MyD88 pathway, increasing components to remove the commensals and preventing them from overgrowing.
- Lack of Paneth cells or MyD88 mutation
What is unique about opportunistic infections/pathogens?
- These pathogens are most prevalent in immunocompromised individuals.
- allows overgrowth and rapid replication.
- thought to be facultative and obligate pathogens.
What are a few pathogens with opportunistic infectious activity?
- Herpes
- Bacterial pneumonia
- Tuberculosis
- Oral candidiasis
- penumocystis pneumonia
- cryptococcal meningitis.
Bacterial pathogens associated with persistent infections.
- Mycobacterium tuberculosis
- Treponema pallidum
- Borrelia burgdorferi
- E. coli
- Enterococcus
- Chlamydia
- Mycoplasma
- Psuedomonas aeruginosa
- Helicobacter pylori
- Staphylococcus, streptococcus, Brucells abortus
What is the pathology of latent/chronic infections?
- Pathogen infects, and lays dormant within macrophages. Stress leads to increased inhibition of MHC II and allows re-emgergence.
- downregulation of CIITA. transcription factor promoting MHCII expression.
- allows the macrophage(infected) to avoid detention via Th4+ cells.
What is the role of virulence factors?
- Help bacteria to invade the host.
- Help bacteria to casue disease.
- Help bacteria to evasde the host defenses.
What is a list of common virulence factors?
- Adherence factor
- Invasion factor
- Capsule
- Endotoxin
- Exotoxin
- Siderophores.
Adherence factor
Use of pili (fimbriae) to adhere to mucosal sites. Commonly found in GI bugs to assist against peristaltic motion.
Invasion factors.
- virulence factor
- Membrane components taht allow bacterium to invade the host cells based on plasmids, or based on chromosomes.
Endotoxins
- Virulence factor common to Gram(-) bacteria.
- Fever, blood pressure changes, inflammation, shock, toxic shock syndrome.
- Lipopolysaccharide (lipid) based toxin.
Capsules
- Membrane protecting from phagocytosis/opsonization.
- More difficult to detect and more likely to produce sepsis.
- Common recurrent infections with splenectomy.
Exotoxins
- Protein based virulence factor of Gram (-)/(+) bacteria.
- The most toxic type of poison of unit per weight.
- clostridium, corynebacterium.
- Induce more local and non-systemic effects.
Siderophores
- Competitive-Iron binding factors.
- can compete for the host with hemoglobin, transferrin, lactoferrin availability.