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Comment no. 1:
i) AlCl3 dissociates in water to form Al3+ and 3Cl-. On the other hand, ii) AlCl3 is an Lewis acid, whereby proton exchange reaction will take place as soon as it becomes dissolved. iii) Finally, once dissolved, Al3+ will change its form, and form other Al containing species, soluble or insoluble.
Please kindly address items i), ii), and iii). How these chemical equilibria aspect relate to immunological responses reported herein, by discussing available literature and experiments conducted in your laboratory?
Comment no. 2:
iv) The role of chlorine on immunological responses should be discussed if true. Have authors tested the response of other Al salts? How such response compares with that of AlCl3?
Comment no. 3:
v) Lines 127 and over: Considerations on Al speciation may be achieved by computational modeling or the use of commercial software. At any rate, a detailed description of the statistical methods used should be provided. The discussion should include the population size, number of replicates.
Comment no. 4:
vi) Line 180: Cited is Zhu et al., 2012a with regards to the decreased immune function. Please provide herein a detailed description of what functions of the immune system were reduced. When doing so please provide with a detailed description of the study.
Comment no. 5:
The aforementioned considerations on chemical-biological equilibria are intended for authors to propose plausible mechanisms for the release of norepinephrine (NE) after the addition of AlCl3.
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