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Flashcards covering Borrelia and Lyme Disease based on the lecture notes. Topics include immune evasion, antigenic variation, laboratory testing, and persistence.
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What is the role of OspC during the initial phase of transmission?
Critical for migration from the midgut to the salivary glands.
What happens to OspA when a tick attaches to a mammalian host and takes a blood meal?
OspA is down-regulated due to the increased temperature.
What is Salp15 and what is its function?
Tick salivary protein that inhibits the proliferation of CD4+ T helper cells and may mask OspC.
What is the significance of increased Salp15 mRNA and protein levels in infected tick salivary glands?
Suggests the tick transcriptome is modulated by spirochete infection, indicating a symbiotic relationship.
How does BBK32 contribute to immune evasion in Borrelia burgdorferi?
Inhibits the classical pathway of complement by binding to the C1 complex.
What is the function of VlsE in Borrelia burgdorferi?
Enables the escape of Borrelia from host-specific humoral immunity through antigenic variation.
What triggers the recombination of vls silent cassettes into vlsE?
Signals triggering this mechanism are not yet well understood, but occurs only in vivo.
What is erythema migrans and what is its significance for Lyme disease diagnosis?
A rash that can be used to diagnose and treat Lyme disease without laboratory testing.
What does sensitivity measure in the context of a diagnostic test?
How often a test correctly generates a positive result for people who have the condition.
What does specificity measure in the context of a diagnostic test?
A test’s ability to correctly generate a negative result for people who don’t have the condition.
Why are bacterial culture and qPCR not highly sensitive for Borrelia detection?
Low bacterial numbers, slow growth, and specialist growth media requirements.
Explain the two-tier system used for blood testing for Lyme disease in the UK.
EIA or ELISA screening test is used first, and if positive or equivocal, the sample is sent for confirmatory immunoblot testing.
What does the C6 Lyme EIA measure?
Antibody reactivity to a synthetic peptide corresponding to the sixth invariable region of VlsE.
What is the basis of the Immunetics® C6 Lyme ELISA™ kit?
A synthetic peptide antigen (C6 peptide) derived from the VlsE protein of B. burgdorferi.
What is the conserved region of VlsE used to create tests for Lyme disease?
The C6 peptide from the 26-mer conserved region (IR 6).
What is Post Treatment Lyme Disease Syndrome (PTLDS)?
A condition where symptoms persist after antibiotic treatment for Lyme disease.
Name a proposed hypothesis to explain Post Treatment Lyme Disease Syndrome (PTLDS).
Cellular damage, host response to bacterial debris, autoimmunity, co-infections, or bacterial persisters.
According to research, what occurs in Borrelia burgdorferi after antibiotic treatment?
Significant changes in gene expression
What was the method used to determine the gene expression profile of B. burgdorferi persisters after antibiotic treatment?
RNA Sequencing (RNA-Seq) analysis.
How does doxycycline affect bacterial protein synthesis?
By binding to the 30S ribosomal subunit and preventing amino-acyl tRNA from binding to the A site.
What is the significance of ClpP protease in doxycycline-tolerant B. burgdorferi persisters?
It is an intracellular protease that degrades misfolded proteins; it was highly upregulated in persisters.
What role do heat shock proteins (HSP) play in B. burgdorferi persisters?
Stabilize proteins to ensure correct folding and help to refold damaged proteins under stress.
How could down-regulation of ribosome proteins contribute to persistence of B. burgdorferi?
May reduce metabolism and the demand for nutrients and energy, allowing cells to transition to persistence.
List factors that can contribute to bacterial clearance of Borrelia burgdorferi without antibiotics.
Phagocytic cells, TLR5 recognizing flagellin, lipoproteins signaling through TLR1/TLR2, and PGLYRP1 interacting with peptidoglycan.
What are some unique characteristics of Borrelia burgdorferi?
Unusual membrane structure, unique peptidoglycan structure, no requirement for Fe, and causes a persistent infection.
What are two methods of laboratory testing for Lyme disease?
ELISA and immunoblot
In what way can Borrelia burgdorferi cross the blood brain barrier (BBB)?
As a means to circumvent the adaptive immune response of the host.
What are the functions of Transient and Dragging interactions?
Mediated by Fn-binding BBK32 and host Fibronectin/GAG interactions
What is Salp15 coated on and where does this occur?
Borrelia ; salivary glands
What is the first stage of blood testing?
Enzyme Immunoassay
Between Early and Late stages, during which stages is IgM produced?
Early Stages
Between Early and Late stages, during which stages is IgG produced?
Late Stages
What are the three Borrelia subspecies encountered in Europe?
B. burgdorferi, B. garinii and B. afzellii
What is the only known function of VlsE?
VlsE represents a highly variable structure enabling the escape of Borrelia from host specific humoral immunity
What causes Lyme neuroborreliosis?
Associated with an inflammation of the central nervous system (CNS)
Name three neurological conditions associated with Lyme neuroborreliosis.
Encephalitis, cranial neuropathy, and meningitis
Name three tissues where antibodies against OspA peptides were found to react.
Human brain, spinal cord and dorsal root ganglia.
What is the alternative name for VlsE?
Vmp-Like sequence, Expressed
What is the implication of Borrelia bacteria located on the outside of cells?
Extracellular
What is the implication of Borrelia bacteria located on the inside of cells?
Intracellular
What are some genes associated with Doxycycline tolerant Bb persisters?
Transporter, Protein secretion, chemotaxis, membrane protein, outer membrane/Lipoprotein, protein degradation, dna repair/protection, protein synthesis/Ribosome, heat shock protein
Does Borrelia burgdorferi production require Fe?
No
What is the meaning of transient in the context of escaping from the blood?
Less than one second
What is the meaning of dragging in the context of escaping from the blood?
2-20 seconds
Why can diagnosis be challenging in the absence of EM?
Borrelia utilizes multiple surface proteins and strategies to evade the host immune response and invade various tissues.
Where does VlsE is coded by the vis locus?
linear plasmid lp28-1