Maturation of innate immunity

Doctoral Dissertation uoadl:2928469 127 Read counter

Unit:
Faculty of Medicine
Library of the School of Health Sciences
Deposit date:
2020-11-17
Year:
2020
Author:
Georgountzou Anastasia
Dissertation committee:
Αλεξάνδρα Σολδάτου, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Τσολιά, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παρασκευή Ξεπαπαδάκη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αθανάσιος Καδίτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αναστασία Γαρούφη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Σπυρίδης, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Βάρτζελης, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Η ωρίμανση της μη ειδικής ανοσίας
Languages:
Greek
Translated title:
Maturation of innate immunity
Summary:
The present study examined parameters related to the maturation of innate (or non-specific) immunity from birth to adulthood in both healthy and atopic individuals.
First, we observed significant decreases with age in the total white blood cell count in healthy and atopic subjects. Decreases with age were also found in the subpopulations of several leukocytes involved in non-specific immunity, such as eosinophils (in healthy and atopics) and monocytes (in atopics only). The most significant changes mainly occured after the 1st year of life. Furthermore, our study revealed increased numbers of eosinophils in atopic-allergic children after the age of 4, which interestingly coincided with the onset of respiratory allergies. In contrast, increased numbers of monocytes were observed in healthy subjects in the age group of 10-18 years.
Regarding TLR-induced responses to microbial (TLR4) and viral (TLR3 & TLR7/8) stimuli, the present study revealed age-related maturation for a multitude of molecules from birth to adulthood. The type of change (increase or decrease) observed in the production of each molecule, as well as the rate/tempo at which these changes occur vary among different TLR pathways and/or different molecules. In specific, in our study age-related increases were found in the production of i) proinflammatory cytokines (TNF-α – TLR3) (IL-1β – TLR3 & TLR7/8) ii) Th1 cytokines (IL-12- TLR7/8) (IFN-γ ‒ TLR3, TLR4 & TLR7/8) iii) chemokines (MIP-1β ‒ TLR3, TLR4 & TLR7/8) (MCP-3, IP-10 ‒ TLR7/8) iv) anti-inflammatory molecules (IL-10 ‒ TLR3, TLR4 & TLR7/8). In contrast, there was a decrease with age in TLR4-induced production of chemokine MDC.
The aforementioned changes from birth to adulthood were mainly observed in healthy subjects, as atopics only presented an increase with age in the production of IL-10 (for all TLR pathways studied) and a decrease in LPS-induced MDC synthesis (TLR4 pathway). Consequently, the defective maturation of these responses in atopic subjects links the allergic phenotype with a generalized deviation from normal innate immune system development and may be an important contributing factor to the increased susceptibility of allergic subjects to viral infections (mainly respiratory), observed in our study.
Main subject category:
Health Sciences
Keywords:
Innate immunity, Immune maturation, Toll-like receptors, Cytokines, Chemokines, Leukocytes, Atopy, Infections
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
398
Number of pages:
198
ΓΕΩΡΓΟΥΝΤΖΟΥ.PhD.pdf (4 MB) Open in new window