MAY 02, 2016 4:24 PM PDT

Designing A Faster, Better, Stronger Immune Response

WRITTEN BY: Kara Marker
It is the antibodies that detect pathogens in order to fight infections and prevent disease, but there is an entire team of immune cells that work together to develop the best, most effective antibodies. New research from the La Jolla Institute for Allergy and Immunology exposes a previously unknown relationship between two key players in the creative process that produces antibodies.
 
Follicular helper T cells (Tfh) are rare compared to the amounts of other types of immune cells that are present in the body, but they are uniquely responsible for helping B cells to mature so they can produce antibodies. Moreover, Tfh cells ensure that high-affinity antibodies make up the army of pathogen-detecting cells, and they do so with the help of two molecular players.
 
Differentiation and function of T follicular helper cells
 
Inducible T cell co-stimulator (ICOS) is a key signaling molecule that scientists previously had only a fuzzy understanding of as far as its relationship with Tfh function. The present study uncovers ICOS’ role in Tfh cells’ ability to manipulate antibody specificity, and now scientists believe they could possibly harness ICOS’ power to develop new vaccines and treat autoimmune disorders.
 
ICOS also has a connection to amyotrophic lateral sclerosis (ALS) and childhood herpes simplex virus encephalitis (HSE). ALS, also known as Lou Gehrig’s disease, progressively affects neurons and spinal cord cells, causing their degeneration and subsequent loss of muscle movement. At the latest stages of ALS, affected people can become completely paralyzed.
 
 
HSE is also associated with the central nervous system, with a third of people affected being children and young adults. Despite several medical attempts at antiviral therapy for HSE, this infection is harsh and undiscriminating; it causes fever and “focal neurological signs.”
 
Scientists from this study believe that the relationship between ICOS and these diseases tie back to an interaction between ICOS and an enzyme also involved in antibody maturation, called TANK-binding kinase 1 (TBK1). Any miscommunication involved in the reaction between ICOS and TBK1 is thought to either cause the production of autoantibodies, in the case of ALS, or an excessive immune response, in the case of childhood HSE.
 
Tfh cells, TBK1 and ICOS are all interconnected during a sort of “B cell boot camp,” where the best and brightest B cells are chosen to protect the body by making antibodies. First, ICOS stimulates maturation of Tfh cells, and the mature cells then migrate to the follicles of B cell-dense immune organs like the spleen and lymph nodes. Upon being united with B cells, the Tfh cells activate them, and the activated B cells travel to the germinal center of the follicle and undergo rapid division.
 
In the germinal center, B cells enter into a vital period of selection where the cells with the highest affinity to pathogens are selected to survive and move on. Those B cells deemed worthy of further existence continue to undergo multiple rounds of further selection. Any error during this complex process could lead to the production of antibodies that either do not bind strongly enough to be effective or antibodies that bind too strongly to the body's own cells instead of foreign cells.
 
Scientists from the La Jolla Institute set out to further understand the very specific relationship between ICOS and TBK1, hoping for insight into how to improve antibody affinity maturation or to improve vaccine development. They found that ICOS recruits TBK1 when the time is right, and TBK1 then activates the Tfh genes needed for producing antibodies with high affinity for detecting pathogens. They also identified the specific region in the ICOS genome required for this recruitment, and disruption of this region has huge consequences for antibody production.
 
With all of the information gleaned from the study about antibody production and the interaction between the molecular players involved, scientists from the study are hoping to incorporate their knowledge into vaccine and/or drug targets. For now, they have a lot of clues to work with.
 
Their study was published recently in the journal Nature Immunology.
 
 
Source: La Jolla Institute for Allergy and Immunology, ALS Association, and Seminars in Pediatric Infectious Diseases
 
About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
APR 21, 2020
Cardiology
APR 21, 2020
Why are More Young People Having Heart Attacks?
Fewer and fewer people have heart attacks in the US thanks to improved lifestyle factors, such as a general reduction in ...
APR 26, 2020
Neuroscience
APR 26, 2020
Can you Get PTSD from the COVID-19 Pandemic?
Following a traumatic experience, some experience intense flashbacks, nightmares, irritability, anger and fear. Key symp ...
APR 27, 2020
Cancer
APR 27, 2020
The Tumor Suppressor and its Regulator: An Indirect Oncogene
Oncogenes, mutations in genes that promote cancer growth, have long been easy targets for cancer research due to the dir ...
MAY 02, 2020
Cancer
MAY 02, 2020
Tracking DNA Methylation as a Prognostic Marker
In the modern age of biological research, one of the tools that have become readily available in the ever-increasing dat ...
APR 30, 2020
Drug Discovery & Development
APR 30, 2020
Researchers Use AI to Accelerate COVID-19 Drug Development
Researchers from the National University of Singapore (NUS) have developed an artificial intelligence platform to accele ...
MAY 23, 2020
Cancer
MAY 23, 2020
A New Biomarker to Identify a Triple Negative Breast Cancer Prognosis
Breast cancer, one of the most common cancers in the world, are commonly separated into one of several sub-types. These ...
Loading Comments...