Difference between revisions of "Team:Evry/Project/Mait"

 
Line 37: Line 37:
 
<p>(1) Internalization of Salmonella by an antigen-presenting cell, either through infection or actively by phagocytosis. (2) Lysis of the bacteria, within endocytic compartments, releases 5-A-RU, which is converted to 5-OE-RU or 5-OP-RU and binds to and stabilizes MR1. (3) The stable MR1 translocates to the cell surface, where it is presented along with other co-stimulatory molecules, e.g., CD80 or CD86. (4) Bacterial components trigger pathogen recognition receptors (PRR), such as TLR8. (5) PRR triggering drives cytokine expression, such as IL-12, and the activation of the inflammosome, resulting in the release of active-IL-18. (6) MAIT cells are activated either by TCR recognition of MR1 in combination with co-stimulatory receptors, e.g., CD28, and/or by cytokines, e.g., IL-12 and IL18. (7) Activated MAIT cells express pro-inflammatory cytokines, e.g., IFNγ, TNFα, and IL-17. (8) These cytokines can directly act anti-bacterially, or recruit and stimulate other immune cells, e.g., neutrophils by IL-17. (9) Activation of MAIT cells upregulates perforin and granzyme B expression. (10) Theoretically, the degranulation of cytotoxic granules into infected cells (target cells), via recognition of MR1, could induce cell death and, thus, the potential clearance of infected cells.</p>
 
<p>(1) Internalization of Salmonella by an antigen-presenting cell, either through infection or actively by phagocytosis. (2) Lysis of the bacteria, within endocytic compartments, releases 5-A-RU, which is converted to 5-OE-RU or 5-OP-RU and binds to and stabilizes MR1. (3) The stable MR1 translocates to the cell surface, where it is presented along with other co-stimulatory molecules, e.g., CD80 or CD86. (4) Bacterial components trigger pathogen recognition receptors (PRR), such as TLR8. (5) PRR triggering drives cytokine expression, such as IL-12, and the activation of the inflammosome, resulting in the release of active-IL-18. (6) MAIT cells are activated either by TCR recognition of MR1 in combination with co-stimulatory receptors, e.g., CD28, and/or by cytokines, e.g., IL-12 and IL18. (7) Activated MAIT cells express pro-inflammatory cytokines, e.g., IFNγ, TNFα, and IL-17. (8) These cytokines can directly act anti-bacterially, or recruit and stimulate other immune cells, e.g., neutrophils by IL-17. (9) Activation of MAIT cells upregulates perforin and granzyme B expression. (10) Theoretically, the degranulation of cytotoxic granules into infected cells (target cells), via recognition of MR1, could induce cell death and, thus, the potential clearance of infected cells.</p>
  
 +
<div class="row">
 +
<div class="col-md-4"><img border="0" src="https://static.igem.org/mediawiki/2015/4/4e/Capture_du_2015-09-18_23-37-45.png" alt="" /></div>
 +
<div class="col-md-8">
 
<p class="text-justify">The <strong>recognition mechanism</strong> of bacterial infections by MAIT cells is based on the bacterial specific riboflavin metabolism (vitamin B2) which is absent in humain beings. This cellular process is dependent of the 5-amino-ribityl-uracil (5-A-RU), an unstable precursor of riboflavin, which attracts the Antigen Presenting Cell (APC) and MAIT cells.</p>
 
<p class="text-justify">The <strong>recognition mechanism</strong> of bacterial infections by MAIT cells is based on the bacterial specific riboflavin metabolism (vitamin B2) which is absent in humain beings. This cellular process is dependent of the 5-amino-ribityl-uracil (5-A-RU), an unstable precursor of riboflavin, which attracts the Antigen Presenting Cell (APC) and MAIT cells.</p>
  
 
<p class="text-justify">The Curie Institute developped an <em>E.Coli</em> strain (Delta RibE BW25113), in which the genomic RibE enzyme has been deleted. This enzyme is involved in the riboflavin biosynthesis, and more precisely in the chemical transformation of the 5-A-RU in RL-6,7-diMe. Thus, these strain accumulates the 5-A-RU, involved in the MAIT cells attraction, and become a promisive vaccinal vector.</p>
 
<p class="text-justify">The Curie Institute developped an <em>E.Coli</em> strain (Delta RibE BW25113), in which the genomic RibE enzyme has been deleted. This enzyme is involved in the riboflavin biosynthesis, and more precisely in the chemical transformation of the 5-A-RU in RL-6,7-diMe. Thus, these strain accumulates the 5-A-RU, involved in the MAIT cells attraction, and become a promisive vaccinal vector.</p>
  
<img border="0" src="https://static.igem.org/mediawiki/2015/4/4e/Capture_du_2015-09-18_23-37-45.png" alt="" /></p>  
+
</p>
 +
 
 +
<p class="text-justify">Thus the goal is to express in RiboVax some tumoral antigens specific to each patient, in order to bring them to the CMH-I and CMH-II, and carry out an active and personalized immunotherapy. The following picture explains how in details </p>
 +
</div>
 +
 
 +
 
 +
 
  
Thus the goal is to express in RiboVax some tumoral antigens specific to each patient, in order to bring them to the CMH-I and CMH-II, and carry out an active and personalized immunotherapy. The following picture explains how in details </p>
 
  
 
<img src="https://static.igem.org/mediawiki/2015/e/ef/Fimmu-05-00450-g001.jpg" width="1024"/>
 
<img src="https://static.igem.org/mediawiki/2015/e/ef/Fimmu-05-00450-g001.jpg" width="1024"/>

Latest revision as of 20:54, 18 September 2015

Scroll to top To top