Salivary Assisted Transmission (SAT) Flashcards
The two main points to consider with saliva in blood-feeding arthropods and humans
Importance of saliva to transmitted diseases
Importance of saliva to blood-feeding arthropods
When a tick is feeding, what does in release into its host? (think diagram from slides)
Na+, Cl- and H2O
What does the tick feed on when attached to its mammalian host?
Blood and lymph
How is saliva extracted from ticks?
dopamine injection
Example pathogens for background on SAT
Lyme disease
Thogoto virus
Louping ill virus
Tick-borne encephalitis virus (TBE)
How does the tick avoid detection while feeding on its mammalian host?
Suppresses interferon alpha or beta (virus killing aspect of pro-inflammatory response)
Thogoto virus in transmitted by …
Rhipicephalus appendiculatus
What is the Lyme disease tick feeding relationship?
When a tick starts feeding, there is an increase in T° and drop in pH signal.
-> outer surface protein A (OspA) stop being produced
-> OspC starts to be produced
-> spirochaete (Lyme disease parasite) leaves gut and travels to salivary gland
(takes 24-48 hr for B. burgdorferi to appear in saliva)
What is the name of the parasite responsible for Lyme disease?
Borrelia burgorferi
Tick transmitting Lyme disease in UK
Ixodes ricinus
What did Zeidner et al., 2002 show with tick saliva and the transmission of Lyme-disease-causing parasites in the Europe and the USA?
Parasite strains specific to particular tick.
SGE from USA tick enhanced Borrelia from USA, but not the European strain.
SGE from European tick enhanced Borrelia from Europe, but not the USA strain
Ixodes scapularis in USA
Borrelia burgdorferi sensu stricto in USA
Ixodes ricinus in Europe
Borrelia lusitanae in Europe
Tick saliva and immunomodulation - what can a small amount of tick saliva (<1 mL) do?
neutrophil function
macrophage activation
secretion of macropahge-associated cytokines, incl. IL-1 and TNF-a
secretion of T-helper cytokines incl. IL-2 and IFN-g
What did Zeidner et al., 1996 do?
Tried to reconstruct the immune response the the pathogen (parasite) B.burgdorferi (Lyme disease), by adding introducing the “missing” (suppressed by the tick saliva components) cytokines to the infected mice. It worked when TNF-a, IFN-g, and IL-2 were all added. Results were short-term, not long-term.
What did Zeidner et al., 1996 show with cytokines, ticks and Lyme disease infection?
Initial infection with Lyme disease is enhanced/largely reliant on components in the tick saliva suppressing the mammalian host immune response.
What did Wikel et al., 1997 show in terms of SAT and initial infection?
immunity to ticks also confers immunity to SAT (Lyme disease)
- neutralizing antibody to SAT factor(s)
What is OspA?
An outer surface protein A from the Lyme disease spirochete, Borrelia burgdorferi.
What is OspC?
An outer surface protein C from the Lyme disease spirochete, Borrelia burgdorferi. OspC is vital for Borrelia adherance and entry into salivary gland of its tick vector.
What is the significance of Salp15 in B. burgdorferi (Lyme disease) infection of mammals by tick vector?
Salp15 inhibits/suppresses CD4+ cell activation (Anguita et al. 2002). Lyme-disease-infected ticks have up-regulated Salp15 production (x16 normal).
Solution for SAT of Lyme disease
Salp15-deficient nymphs (juvenile ticks) - using dsRNAi to “cut out” dsRNA for Salp15 production.
Purpose of factors in saliva (specific)
platelet aggregation inhibitors
coagulation inhibitor
vasoconstriction inhibitors/ vasodilators
down-regulation of inflammatory response
Purpose of components of saliva responsible for platelet aggregation (specific) - classes of platelet aggregation inhibitors
Anti-ADP
Anti-collagen
Anti-fibrinogen
Anti-thrombin
Brief outline of inflammatory response leading to platelet aggregation
ADP produced from "insulted" cells -> thrombin and fibrinogen -> platelet activating factor \+ collagen (from torn tissue) -> more activated platelets & "insulted" cells
Brief outline of inflammatory response leading to coagulation
exposure of blood to subendothelial components -> thromboplastin
-> fX -> fXa
fXa facilitates the activation of thrombin (from prothrombin)
thrombin facilitates the activation of fibrinogen into fibrin (=clot)
Brief outline of inflammatory response leading to vasoconstriction
tighten of smooth muscle lining vasculature due to various factors
Example(s) of anti-ADP
platelet aggregation inhibitors
e.g.) apyrase - plasmodium sporozoites
Example(s) of anti-collagen
platelet aggregation inhibitors
e.g.) moubatin & tick adhesion inhibitor from Ornithodorous moubata
e.g.) pallidipin - triatomine bug (chagas)
cover collagen receptor
Example(s) of anti-fibrinogen
platelet aggregation inhibitors
e.g.) disagregin and variabilin from ticks
e.g.) disintegrin-like factor from deer flies
covering fibrinogen receptor
Example(s) of anti-thrombin
platelet aggregation inhibitors
e.g.) TAP from Ornithodorous moubata
can inhibit fXa or thrombin - serine proteases
Example(s) of anti-inflammatories
PGE2 (prostaglandin)
Histamine-binding protein
Kininase
Platelet Activating Factor - Acetyl Hydrolase (PAF-AH)
What does PGE2 (prostaglandin) do?
stabilizes granules (of activated mast cells and leukocytes) -> prevents release of serotonin, histamine and bradykinin
How do anti-inflammatories stop the anti-inflammatory reponse?
vasodilation
oedema formation
leukocyte accumulation
Where Histamine-binding protein example found?
R. appendiculatus saliva
What does kininase do? & where found?
deactivates bradykinin (proteolytically) - from Ixodes scapularis saliva (deer tick)
What does Platelet Activating Factor - Acetyl Hydrolase (PAF-AH) do? & where found?
turns PAF into lyso-PAF (from tick saliva)
