Did you know that female mosquitos are responsible for those itchy red bumps you get in the summertime? If you attended the May ARCS Forward on “He Cells, She Cells, and T Cells: How Sex Affects Immune Response,” you would’ve learned that scientific tidbit from Caroline Duncombe, a 2020-2023 ARCS Seattle Scholar.

Duncombe is a PhD candidate at the University of Washington-Seattle studying the impact of biological sex and sex hormones on the cellular immune response to malaria vaccines. She started her ARCS Forward talk by explaining the three influences on biological sex that affect immunity: sex chromosomes, sex hormones, and environment. “All three factors result in females responding better than males in vaccine immune responses,” she says.

Her goal is to create a malaria vaccine for all populations globally. Africa accounts for 95% of malaria cases, and cases will only rise as factors like climate change, the COVID-19 pandemic, and drug resistance accelerate the disease. Duncombe hopes to accomplish this by creating a liver-stage malaria vaccine to clear all parasitic infections prior to blood-stage infections.

To better understand her work, she explains malaria starts with a female mosquito bite injecting the plasmodium parasite into the skin. From there, it will live in the liver for six days to infect the liver cells and replicate the infected cells. After six days, it will enter the bloodstream, and clinical systems begin. Duncombe hopes to stop its entrance into the bloodstream before clinical symptoms appear by cutting off the disease while it’s still in the liver.

So far, her tests on mice have shown removing testosterone reduces protection against malaria in the liver. When estrogen and progesterone are present in female mice, the challenge against the initiation of malaria in the liver increases. In the end, Duncombe summarizes it as follows: “Sex hormones are dynamic modulators of the immune response.”

ARCS Atlanta Scholar Cameron Mattingly, the second speaker, shares her work on CD8+ T cells in lung tissues and their role in the immune response to respiratory viruses. Mattingly is a fifth-year PhD candidate in the Immunology and Molecular Pathogenesis program at Emory University.

Mattingly works specifically with the influenza vaccine and CD8+ T cell tissues, which protect against respiratory viruses. Currently, the influenza vaccine is only 40% effective because the flu changes each year, the vaccine needs to adapt with it too. However, CD8+ T cell tissues can provide protection against future strains of the flu as these specific cells create memory.

Mattingly explains how CD8+ T cells work, “CD8+ T cells create a memory to fight off the virus for one to two weeks. Then, as the virus declines, CD8+ dies off, but a small CD8+ remains behind to fight the same virus, so there won’t be a lag to treat the infection in the future.”

She goes on to explain that she works with human lung tissues and collaborates with LifeLink of Georgia to get healthy lung transplants to run trials of flu peptides to see if CD8+ T cells respond. Mattingly concludes, “In flu infection, memory CD8+ t cells rapidly respond and produce interferon (a protein produced by cells to help the immune system fight infection and disease)”.

If you’re interested in watching the recording, click here to watch the whole ARCS Forward.