Team:Goettingen/project overview/therapeutics

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         <div id="goenext"><a href="https://2014.igem.org/Team:Goettingen/project_overview/diganosis"><img src='https://static.igem.org/mediawiki/2014/3/32/Goettingen2014-previous.png' width='40px'></a> 14/15 <a href="https://2014.igem.org/Team:Goettingen/project_overview/project_drylab"><img src='https://static.igem.org/mediawiki/2014/e/ea/Goettingen2014-next.png' width='40px'></a></div><br />
         <div id="goenext"><a href="https://2014.igem.org/Team:Goettingen/project_overview/diganosis"><img src='https://static.igem.org/mediawiki/2014/3/32/Goettingen2014-previous.png' width='40px'></a> 14/15 <a href="https://2014.igem.org/Team:Goettingen/project_overview/project_drylab"><img src='https://static.igem.org/mediawiki/2014/e/ea/Goettingen2014-next.png' width='40px'></a></div><br />
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       <h1 >Further perspectives</h1>
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       <h1 >Further perspectives</h1><br /><br />
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       <h2 id="global_burden">Therapeutics</h2>      <br />     
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       <h2 id="global_burden"><center>Therapeutic Applications</center></h2>      <br />     
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<p>Our peptides can also be attached to an antimycotic or opsonizing moiety and act as a therapeutic tool. Again, if the specificity of the peptides is high enough at the species level, it can help to reduce the toxicity issues related to broad-spectrum antimycotics. Regarding opsonizing moieties (such as immune tags or complement ligands), they may help the weakened immune system to attack the fungal cells. An interesting option to explore would be to attach the constant region of human IgG3 immunoglobulins, which can elicit the response of macrophages and neutophils antibody-dependent cell-mediated cytotoxicity and complement-mediated cytotoxicity.</p><br />
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<center><b>FUNGAL INFECTIONS AND THE KEY BRANCHES OF THE IMMUNE SYSTEM TO DEAL WITH THEM </b><br /><br />
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<p>It's important to mention that because most patients suffering from invasive mycoses are immunocompromised patients, the eventual application of peptides as therapeutic tools has to be concomitant with immunostimulant therapy, involving the use of molecules that can modulate the immune system called cytokines which can be used to selectively stimulate branches of the same.</p><br />
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The peptides we developed have significant applications from a clinical standpoint. It has been observed in that individuals suffering from deficiencies in antibody and complement mediated cytotoxicity are less vulnerable to fungal infections than the ones suffering from phagocytic defects. Moreover studies have shown that Neutrophils are pivotal in fending off fungal infections.  This is further supported by the fact that many cases of fungal infections were following a period of Neutropenia (low neutrophil count in blood). <br /><br />
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Two vital principles can be gathered from the aforementioned information: <br /> <br />
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- Phagocytes (especially neutrophils) play a very important role in the resolution (clearance) of the fungal infection. <br /><br />
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- Antibodies and the complement system are not that effective against fungal pathogens due to the surface of these pathogens being unfriendly to binding.</p><br />
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As such, the modulation of these branches of the immune system should aid in the resolution of the disease.  It's important to mention that since most patients suffering from invasive mycoses are immuno-compromised and there are different types of immunodeficiencies. Depending upon which branch is dysfunctional, an appropriate strategy of immunomodulation can be adopted. <br /><br />
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<b>MODIFICATIONS TO THE PEPTIDE SO THAT IT EMULATES AN ANTI-BODY’S STIMULATORY FUNCTION</b><br /><br />
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The novelty in our peptides is that it CAN bind to the fungal surface and it can be further modified using the Fc region of the IgG1 or IgG3 antibody subtype. This region is important as it is recognized by the effector cells (neutrophils and macrophages) of the immune system and thereafter, leads to the death of the target cell. This way, not only can it bind to fungal pathogens but can also “draw attention” towards itself from the immune system. In addition to this, this constant region can also activate the compliment cascade via the "classical" pathway. Essentially, this set-up functions as a modified antibody with added bonus of greater affinity. <br /><br />
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<b>ENHANCEMENT OF IMMUNE RESPONSE IN IMMUNODEFICIENT INDIVIDUALS</b><br /><br />
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As for the stimulation of the immune system in case of individuals with immunodeficiencies, the use of adjuvants (immune response enhancers) to augment the response is one strategy. In addition to this, natural immuno-modulatory molecules called cytokines (such as Interleukin-1 and Interferon-gamma) to stimulate the appropriate branches of the immune system can be employed as well.  
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Revision as of 11:09, 19 September 2014

Project

14/15

Further perspectives



Therapeutic Applications


FUNGAL INFECTIONS AND THE KEY BRANCHES OF THE IMMUNE SYSTEM TO DEAL WITH THEM

The peptides we developed have significant applications from a clinical standpoint. It has been observed in that individuals suffering from deficiencies in antibody and complement mediated cytotoxicity are less vulnerable to fungal infections than the ones suffering from phagocytic defects. Moreover studies have shown that Neutrophils are pivotal in fending off fungal infections. This is further supported by the fact that many cases of fungal infections were following a period of Neutropenia (low neutrophil count in blood).

Two vital principles can be gathered from the aforementioned information:

- Phagocytes (especially neutrophils) play a very important role in the resolution (clearance) of the fungal infection.

- Antibodies and the complement system are not that effective against fungal pathogens due to the surface of these pathogens being unfriendly to binding.


As such, the modulation of these branches of the immune system should aid in the resolution of the disease. It's important to mention that since most patients suffering from invasive mycoses are immuno-compromised and there are different types of immunodeficiencies. Depending upon which branch is dysfunctional, an appropriate strategy of immunomodulation can be adopted.

MODIFICATIONS TO THE PEPTIDE SO THAT IT EMULATES AN ANTI-BODY’S STIMULATORY FUNCTION

The novelty in our peptides is that it CAN bind to the fungal surface and it can be further modified using the Fc region of the IgG1 or IgG3 antibody subtype. This region is important as it is recognized by the effector cells (neutrophils and macrophages) of the immune system and thereafter, leads to the death of the target cell. This way, not only can it bind to fungal pathogens but can also “draw attention” towards itself from the immune system. In addition to this, this constant region can also activate the compliment cascade via the "classical" pathway. Essentially, this set-up functions as a modified antibody with added bonus of greater affinity.

ENHANCEMENT OF IMMUNE RESPONSE IN IMMUNODEFICIENT INDIVIDUALS

As for the stimulation of the immune system in case of individuals with immunodeficiencies, the use of adjuvants (immune response enhancers) to augment the response is one strategy. In addition to this, natural immuno-modulatory molecules called cytokines (such as Interleukin-1 and Interferon-gamma) to stimulate the appropriate branches of the immune system can be employed as well.




14/15

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