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York University *
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Medicine
Date
Feb 20, 2024
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docx
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Uploaded by Ubutisi
, I will be comprehensively evaluating the scientific article titled “HIV-Infected Children Have Elevated Levels of PD-1+ Memory CD4 T Cells With Low Proliferative Capacity & High Inflammatory Cytokine Effector Functions” for the partial fulfilment of the MICR 270 course.
To begin, and help you understand the content of this article, we should be familiar with the following information and terminology: which has been covered throughout the course thus far specifically in module 2. Lets now go through the terms in this chart.
The overall objective of the study described in the article is to investigate the
role of PD-1 (Programmed Cell Death Protein 1) in the context of HIV infection, particularly in perinatally infected HIV+ children aged 5–18 years. The study aims to understand the significance of elevated levels of PD-1+ memory CD4 T cells in HIV+ children, how they correlate with HIV disease progression, immune activation, and their impact on the immune system. The
article highlights how even with antiretroviral therapy (ART), viral reservoirs continue to arise and trigger chronic T-cell activation. This leads to the exhaustion of T-cells, which can result in the halt of or inability to kill certain cells. PD-1’s role on CD4 T-cells is studied more in adults. PD-1 has increased rates on HIV-specific CD4 T-cells and corresponds with disease progression. Blockade of PD-1/PD- L1 has also been seen to increase HIV-specific CD4 T-cell proliferation, however, these cells in HIV-infected children are poorly understood, which will be the main study of this article.
The immune system is critical for addressing the scientific question because
the study revolves around the immune response to HIV infection. PD-1 is a protein involved in regulating immune responses. The research examines the prevalence of PD-1 expression on memory CD4 T cells, a subset of T cells critical for immune memory and responses. The study investigates how PD-1 expression affects the proliferative capacity and cytokine production of these immune cells in response to both HIV-specific and nonspecific stimuli. By understanding the role of PD-1 in the immune system of HIV+ children, the study sheds light on the immune mechanisms that may contribute to disease progression, immune exhaustion, and potential immune-based therapeutic interventions. The immune system's functions and dysregulations are central to unraveling the complexities of HIV infection in children, and this study seeks to provide insights into these critical aspects.
Key methods used in the article are Flow cytometry, T-cell proliferation
assays, cytokine production analysis, immune activation markers, and PD-1 blockade. The article uses important tools and techniques in the field of immunology. They use something called flow cytometry to study PD-1 and different types of immune cells. This helps them find and count a specific kind of immune cell called PD-1+ memory CD4 T cells. They also test these cells to see if they can multiply properly, and they discover that PD-1+ CD4 T cells don't multiply well. This is a big deal because it affects how our immune system responds to germs. They also look at the production of certain substances in the body, like IFN-γ and IL-17A, which are linked to immune responses. They find that PD-1+ memory CD4 T cells make more of these substances. They check for signs of immune activation using markers like CD38 and HLA-DR, and these markers connect to PD-1+ CD4 T cells, showing that they play a role in immune problems. Lastly, they investigate what happens when they block PD-1, which could help in treating diseases like HIV. These methods and ideas are vital in the bigger study of immunology because they help us understand how immune cells, signals, and checkpoints affect our body's responses and immune issues in diseases like HIV.
References
Foldi, J., Kozhaya, L., McCarty, B., Mwamzuka, M., Marshed, F., Ilmet, T., Kilberg, M., Kravietz, A., Ahmed, A., Borkowsky, W., Unutmaz, D., & Khaitan, A. (15AD). HIV-Infected Children Have Elevated Levels of PD-1+ Memory CD4 T Cells With Low Proliferative Capacity and High Inflammatory Cytokine Effector Functions. The Journal of Infectious Diseases
.
Künzli, M., & Masopust, D. (2023, May 8). CD4+ T cell memory
. Nature News. https://www.nature.com/articles/s41590-023-01510-4 Mayo Clinic College of Medicine and Science. (n.d.). Medical laboratory science program (Florida and Minnesota) - Health Sciences Education - Mayo Clinic College of Medicine & Science
. https://college.mayo.edu/academics/health-sciences-education/medical-
laboratory-science-program-florida-and-minnesota/ PDB101: Molecule of the month: PD-1 (programmed cell death protein 1)
. RCSB. (n.d.). https://pdb101.rcsb.org/motm/204 Sheth, P. (2023). MICR270: Infection Immunity and Inflammation, Module 2 [Section 1-2]. Faculty of Health Sciences, Queen's University, Kingston, Canada
Immune checkpoint expression on HIV-specific CD4+ T cells and response to their blockade are dependent on lineage and function. (n.d.). https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00007-4/fulltext
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