[The role of Toll-like receptors (TLR) in innate and adaptive immune responses and their function in immune response regulation].
The innate immune response is a universal mechanism of host defense against infection. It functions on the basis of special receptors called PRRs (pattern-recognition receptors) which recognize conserved microbial structures called PAMPs (pathogen-associated molecular patterns). Due to PRRs, the human organism is able to discriminate between self and non-self antigens. Toll-like receptors (TLRs) are a group of PRRs that play a crucial role in "danger" recognition and the induction of immune response. Cells of the immune system (macrophages, dendritic cells, mast cells, eosinophils, neutrophils, B lymphocytes), epithelial cells, endothelium, cardio-myocytes and adipocytes all recognize pathogens via TLRs. TLR stimulation via microbial products activates the innate immune response. This results in an upregulated synthesis of anti-bacterial substances and pro-inflammatory cytokines as well as the activation of dendritic cell maturation (increased expression of co-stimulatory molecules and MHC antigens), thereby becoming more effective in antigen presentation. In some cases, the innate immune response is not able to eliminate infection and requires the induction of the adaptive immune response. When activated via TLRs, antigen-presenting cells (APCs) release elevated levels of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6, IL-8, and IL-12), chemokines, and nitric oxide (NO) and show increased expression of co-stimulatory molecules (CD40, CD80, CD86). All these changes in APC function allow the induction of the adaptive immune response, where both T and B lymphocytes play a crucial role. TLRs also play a role in the regulation of immune response via direct or indirect influence on the function of CD4+ CD25+ T regulatory cells (Tregs), which results in their induction and subsequent suppression of the immune response or a reversal of suppression (contrasuppression).
Majewska
Monika
M
Zakład Biologii Rozwoju Człowieka Collegium Medicum Uniwersytetu Jagiellońskiego w Krakowie.
Szczepanik
Marian
M
D000222:Adaptation, Physiological; D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007239:Infections / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
D016207:Cytokines; D051193:Toll-Like Receptors