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Sarah Muncy

A Breakthrough Against Leukemia Using Altered T-Cells - NYTimes.com - 1 views

  • To perform the treatment, doctors remove millions of the patient’s T-cells — a type of white blood cell — and insert new genes that enable the T-cells to kill cancer cells. The technique employs a disabled form of H.I.V. because it is very good at carrying genetic material into T-cells. The new genes program the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia.
  • The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells
  • cytokine-release syndrome, or cytokine storm
  • ...5 more annotations...
  • Dr. June knew that a drug could lower IL-6
  • tocilizumab
  • the altered T-cells persist in the bloodstream
  • The researchers are not entirely sure why the treatment works, or why it sometimes fails.
  • It is not clear whether a patient’s body needs the altered T-cells forever. The cells do have a drawback: they destroy healthy B-cells as well as cancerous ones, leaving patients vulnerable to certain types of infections, so Emma and the other patients need regular treatments with immune globulins to prevent illness.
    • Sarah Muncy
       
      I was wondering when they'd get to the consequences of killing off the B cells- that's huge.
  •  
    That's so funny- I just saw the update email and Dr. Finnerty also saw this topic (a different article) and posted it, too!)
Sarah Muncy

ScienceDirect.com - Vaccine - Hemagglutinin Displayed Baculovirus Protects Against High... - 0 views

    • Sarah Muncy
       
      So, the baculovirus on TOP of having the H5HA on it, can also get the immune system to kick in better?
  • It is remarkable that low doses (103pfu/mouse) of BVs act as an effective adjuvant [41]. Therefore, reducing BV concentration and elongating vaccination intervals may prevent memory responses to BV administration
  • scanning densitometry
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  • Foreign immunogens or peptides can be displayed on the envelope of AcMNPV by fusion with the baculovirus major envelope protein gp64
  • Baculoviruses have strong adjuvant activity to promote humoral and cellular immune responses against coadministered antigens, activate dendritic cells maturation, induce the production of cytokines, chemokines, and type I IFNs
  • There are two influenza vaccine approaches licensed in the US; the inactivated, split vaccine and the live-attenuated virus vaccine. Inactivated vaccines can efficiently induce humoral immune responses but generally only poor cellular immune responses.
  • Therefore, influenza HA can be displayed on the surface of baculovirus
  • virus-like particle (VLP)
  • Even though cellular immune responses cannot confer sterilizing immunity, they are able to reduce the severity of infection and lower morbidity and mortality rates [47], and antigen-specific memory T cells are able to rapidly respond to a secondary virus infection [45]. Furthermore, cellular immune responses to the conserved epitopes contained in vaccines may provide cross-protective immunity against different subtypes of influenza virus infection
  • To confirm that each HA was incorporated on the envelope of baculoviruses, supernatants from infected Sf9 cells were used to perform hemagglutination assay
  • Most BV display strategies rely on gp64 protein which is the major envelope protein of baculovirus.
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    This paper gave me a better understanding of some aspects of my focal paper that were unclear. How to test for HA, and how baculoviruses may be adjuvants in addition to expression vectors.
becky214

Targeting therapeutics to an exposed and conserved binding element of the HIV-1 fusion ... - 10 views

  • We report that the C-terminal region of the HIV-1 gp41 ectodomain (and gp160 precursor molecule) appears to be partially exposed and vulnerable to an antiviral agent before the receptor-mediated conformational changes that initiate membrane fusion.
    • laceemarie
       
      How long is this domain "exposed and vulnerable" before the membranes fuse? Would whatever antiviral treatment that targets this have to be able to hang around, so to speak, for a while in between HIV-host interactions, without being degraded or absorbed or moved to another place in or out of the body?
  • and those that can eliminate infected cells, thereby reducing persistent and latent reservoirs of the virus.
    • apopp10
       
      It would be interesting to see if there will be a drug that can eventually do this that will be low-cost and is manageable in dosage. The problem is how much the virus mutates to evade these drugs and the host immune system. Combination therapy with the RT inhibitor, protease inhibitor, the experimental design listed her and this drug may be effective at treating HIV in the future.
  • These studies do not determine whether 5-Helix interacts with the native conformation of Env or, rather, some misfolded conformation of gp41 and gp160 on the cell surface.
    • Sean Hogan
       
      What would cause the misfolding of Env? Wouldn't it be advantageous to interact with both in order to prevent HIV infection?
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  • Moreover, we demonstrate that this binding is sufficient to concentrate a recombinant toxin to selectively kill HIV-1-infected cells. Our results suggest that the gp41 C-peptide region is a viable target for development of antiviral therapeutics, neutralizing antibodies, and cytotoxic agents directed against infected cells.
    • becky214
       
      How could this help develop antibodies when it is a a toxin that will kill HIV-1-infected cells? 
  • Such a molecule, administered together with agents that induce the expression of dormant integrated provirus (e.g., cytokines or activators of protein kinase C), might help to reduce or possibly eliminate latent reservoirs of HIV-1
    • becky214
       
      I think this is really interesting that it can possibly eliminate HIV that is latent. I have not heard of any anti-viral agents that target latent cells, and this sounds like it could be revolutionary in research on HIV-1.
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    Focus paper for wednesday
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