Skip to Content
800-533-8762
  • Careers
  • Newsroom
  • Health Care Professionals
  • About Us
  • Contact Us
UPMC
  • Find a Doctor
  • Services
    • Frequently Searched Services
    • Frequently Searched Services
      Allergy & Immunology Behavioral & Mental Health Cancer Ear, Nose & Throat Endocrinology Gastroenterology Heart & Vascular Imaging Neurosciences Orthopaedics
      Physical Rehabilitation Plastic & Reconstructive Surgery Primary Care Senior Services Sports Medicine Telemedicine Transplant Surgery Walk-In Care Weight Management Women’s Health
      See all Services
    • Services by Region
    • Find a UPMC health care facility close to you quickly by browsing by region.
      UPMC in Western Pa. Western Pa. and New York
      UPMC in Central Pa. Central Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Services
  • Locations
    • Locations by Type
    • Locations by Type
      UPMC hospitals
      Hospitals
      Physical Therapy
      Physical Therapy
      Urgent care
      Walk-In Care
      UPMC Outpatient Centers
      Outpatient Centers
      UPMC Imaging Services
      Imaging
      Community Health Centers
      Community Health Centers
      See All Locations
    • Locations by Region
    • Locations by Region
      UPMC in Southwest Pa. Southwest Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Northwest Pa and Ny. Northwest Pa. & Western N.Y.
      UPMC in West Central Pa. West Central Pa.
      UPMC in Central Pa. Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Locations
  • Patients & Visitors
    • Patient & Visitor Resources
    • Patient & Visitor Resources
      Patients and Visitors Resources Pay a Bill Classes & Events Medical Records Health Library Patient Information
      Patient Portals Privacy Information Shared Decision Making Traveling Patients Visitor Information
      Man uses mobile phone
      Pay a Bill
      Nurse reviews medical chart
      Request Medical Records
  • Patient Portals
  • Find Covid-19 updates
  • Schedule an appointment
  • Request medical records
  • Pay a bill
  • Learn about financial assistance
  • Find classes & events
  • Send a patient an eCard
  • Make a donation
  • Volunteer
  • Read HealthBeat blog
  • Explore UPMC Careers
Skip to Content
UPMC
  • Patient Portals
  • For Patients & Visitors
    • Find a Doctor
    • Locations
    • Patient & Visitor Resources
    • Pay a Bill
    • Services
    • More
      • Medical Records
      • Financial Assistance
      • Classes & Events
      • HealthBeat Blog
      • Health Library
  • About UPMC
    • Why UPMC
    • Facts & Stats
    • Supply Chain Management
    • Community Commitment
    • More
      • Financials
      • Support UPMC
      • UPMC Apps
      • UPMC Enterprises
      • UPMC International
  • For Health Care Professionals
    • Physician Information
    • Resources
    • Education & Training
    • Departments
    • Credentialing
  • Careers
  • Contact Us
  • Newsroom
  • UPMC >
  • Media Relations >
  • News Releases >
  • 051722 Flynn
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS

Pitt Researchers Uncover Dynamics of Adaptive Immunity in Tuberculosis

For Journalists

Anastasia (Ana) Gorelova
Senior Manager, Science Writing
412-647-9966
gorelovaa@upmc.edu

Allison Hydzik
Director, Science and Research
412-647-9975
hydzikam@upmc.edu

Want to Make an Appointment or Need Patient Information?
Contact UPMC at

1-800-533-8762.

Go to Find a Doctor to search for a UPMC doctor.

2021 PITT HS horizon

5/17/2022

PITTSBURGH – Unlike other infectious diseases that affect the lungs, the immune response to fight tuberculosis (TB) infections develops at least twice as slowly. Until recently, the dynamic interplay between bacteria and the host’s immune system remained unclear, hampering the development of effective therapies against the disease, which kills more people worldwide than HIV/AIDS and is second only to COVID-19.

 

In a paper published in Cell Reports today, University of Pittsburgh School of Medicine immunologists discovered that adaptive immune response against Mycobacterium tuberculosis – pathogenic bacteria that cause TB -- matures over time. The first subset of infection-fighting T lymphocytes does not become fully active until three months after the infection, and the emergence of a second subset of T cells at five months post-infection can contribute to bacterial clearance and recovery.

 

Such delayed adaptive immune response partially explains why TB infections easily take hold in the host’s lungs and suggests that vaccination strategies against TB should be adjusted to prime T cell responses and kick them into gear at the early stages of infection, ensuring that pathogenic bacteria can be eliminated quickly.

 

Flynn_0012crop“Lung TB infections can start with a single bacterium that divides into hundreds of thousands of bacteria over the course of four to six weeks. Not a lot of bacterial killing happens between then and 10 weeks post-infection,” said senior author JoAnne Flynn, Ph.D., distinguished professor of microbiology and molecular genetics. “In our study, we wanted to find out what changes in the lung immune environment over time that allows it to eventually bring TB infection under control.” 

 

While TB is relatively uncommon in the U.S., it remains a major concern in many countries around the world, disproportionately affecting people in developing countries.

 

TB is a severe respiratory disease caused by bacteria that slowly propagate and expand upon entering the lungs through the airways, causing lung scarring and inflammation, severe cough and chest pain.

 

To wall off the growing bacteria, the body responds by creating cellular barriers called granulomas, organized spheres of cell clusters made up of immune cells that are a tell-tale sign of TB. 

 

And though most people without underlying health conditions can control TB infections and remain asymptomatic without medical assistance, those with weakened immune systems, such as people with HIV/AIDS or those sick with COVID-19, are at high risk of developing complications and succumbing to the disease.

 

The only widely used vaccine against TB, called the bacille Calmette-Guérin (BCG) vaccine, is administered to newborns within the first few hours of life. However, the BCG vaccine is limited in its effectiveness and does not prevent infections in the lungs.

 

Flynn’s previous work showed that administering the BCG vaccine intravenously, as opposed to traditional injection under the skin, offers nearly complete protection against TB infections in monkeys. The new study in Cell Reports provides insights into how this vaccine strategy might be working by speeding up the T cell responses in the lungs so they can quickly shut down infection. 

 

By detecting TB granulomas in macaque monkeys’ lungs using a state-of-the-art imaging technique that allows them to scan lungs of live animals in real time and track development of granulomas as the infection progresses, the researchers were able to isolate granulomas at different times post-infection. 

 

After carefully excising the granulomas and quantifying their cellular composition, researchers found that key players in adaptive immunity, CD8+ T cells, become activated by three months after infection and are joined by CD4+ T cells that further support infection clearance at five months post-infection.

NicoleGrant

 

The emergence of these T cells is inversely correlated with the number of granuloma-contained live bacteria, suggesting that these cells play critical roles in TB control.

 

“Our work highlighted the timing of evolving adaptive immune response and bacterial clearance in TB,” said first author Nicole Grant, Ph.D., postdoctoral fellow at Pitt.

 

“Harnessing that knowledge to increase the number of functional T cells in the early days of infection and getting them to respond and contain bacterial growth quicker is key to creating a therapy that can shut down the infection at its onset.” 

 

Additional authors of the paper include Pauline Maiello M.S., Edwin Klein, D.V.M., Philana Ling Lin, M.D., M.Sc., H. Jacob Borish, Ph.D., Jaime Tomko, L. James Frye, Alexander White, Ph.D., and Joshua Mattila, Ph.D., all at Pitt; and Denise Kirschner, Ph.D., of the University of Michigan.

 

This study was funded by the National Institutes of Health (grants NIH 5T32AI1065380-13 and NIH AI123093).


Top Photo:

PHOTO DETAILS: (click images for high-res versions)
CREDIT: Joshua Franzos
CAPTION: JoAnne Flynn, Ph.D

 

Bottom Photo:

PHOTO DETAILS: (click images for high-res versions)
CREDIT: Nicole Grant
CAPTION: Nicole Grant, Ph.D

UPMC
200 Lothrop Street Pittsburgh, PA 15213

412-647-8762 800-533-8762

Patients And Visitors
  • Find a Doctor
  • Locations
  • Pay a Bill
  • Patient & Visitor Resources
  • Disabilities Resource Center
  • Services
  • Medical Records
  • No Surprises Act
  • Price Transparency
  • Financial Assistance
  • Classes & Events
  • Health Library
Health Care Professionals
  • Physician Information
  • Resources
  • Education & Training
  • Departments
  • Credentialing
Newsroom
  • Newsroom Home
  • Inside Life Changing Medicine Blog
  • News Releases
About
  • Why UPMC
  • Facts & Stats
  • Supply Chain Management
  • Community Commitment
  • Financials
  • Supporting UPMC
  • HealthBeat Blog
  • UPMC Apps
  • UPMC Enterprises
  • UPMC Health Plan
  • UPMC International
  • Nondiscrimination Policy
Life changing is...
Follow UPMC
  • Contact Us
  • Website/Email Terms of Use
  • Medical Advice Disclaimer
  • Privacy Information
  • Active Privacy Alerts
  • Sitemap
© 2025 UPMC I Affiliated with the University of Pittsburgh Schools of the Health Sciences Supplemental content provided by Healthwise, Incorporated. To learn more, visit healthwise.org
Find Care
Providers
Video Visit
Portal Login

Chat Keywords List

  • cancel or exit: Stops your conversation
  • start over: Restarts your current scenario
  • help: Shows what this bot can do
  • terms: Shows terms of use and privacy statement
  • feedback: Give us feedback
Continue
Chat with UPMC
RESTART
MENU
CLOSE