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Deciphering the body’s defense plans

The air around us is replete with millions of microorganisms, dust particles and toxins that are constantly bombarding the defenses of our bodies. Fortunately, we are endowed with an amazing immune system that guards us against such attacks. But how is the immune system able to achieve this remarkable feat?

Nestled in the biological sciences building of the lush green IISc campus is a lab that is trying to demystify the functioning of the immune system. Led by Prof. Dipankar Nandi, one of the main research interests of the lab is in understanding the intricacies of immune responses.

When a foreign invader such as a virus, bacterium or even a parasite like the malarial plasmodium infects our cells, the infected cells release certain chemical signals that alert the immune system. As the immune cells take over the fight against the invader, a communication network of chemical signals is set up to co-ordinate the effort. Some of the main chemicals in this web of interconnected messenger system are a family of proteins called cytokines. A key cytokine involved in such immune responses is a molecule called Interferon-gamma (IFNg).

IFNg plays an important role in promoting host resistance to microbial infections. Recently, there have also been studies suggesting the potential role of IFNg in inhibiting the growth of certain types of tumors. While IFNg has been shown to inhibit the growth of fibrosarcomas (cancer of the fibroblasts, which are cells of connective tissue like bones), in melanomas (skin cancers), IFNg actually seems to promote cell proliferation. The reasons for the varying effects of IFNg on different tumors are largely unclear. Dr. Nandi’s lab has made a key contribution in unraveling the molecular differences between IFNg-sensitive and IFNg-resistant mouse tumor types.

In one of their studies, researchers in the lab discovered that mouse tumor cells sensitive to inhibition by IFNg produce high amounts of ROS (Reactive Oxygen Species) and RNS(Reactive Nitrogen Species). Since many studies till date have shown that ROS and RNS regulate cell survival, IFNg could be killing cancer cells through these highly destructive molecules. It is also known that IFNg induces the production of Nitric oxide (NO) in white blood cells. Once produced, NO can combine with superoxide molecules in the cells to form unstable reactive peroxynitrites, that along with ROS and RNS inhibit tumor growth. Ongoing studies in the lab have revealed that tumors resistant to IFNg were unable to enhance NO production in response to this cytokine. A potential application of this finding is that new therapies that combine IFNg with a NO donor could be designed to inhibit the growth of tumors like melanomas, that are inherently resistant to IFNg alone.

Another study led by Prof. Nandi’s graduate student Bhagwat S. Chandrashekar, has shown that IFNg and NO also mediate the action of certain immune cells called macrophages during infection. Macrophages are white blood cells that are constantly patrolling the body for signs of intruders, and are among the first cells to respond to cytokines released by infected cells. They engulf foreign particles and cellular debris released by dying cells in a process called phagocytosis. The present study revealed that IFNg and NO are important for mediating motility, aggregation and phagocytosis in mouse macrophages. Current efforts in the lab are geared towards further exploring the functions of IFNg regulated genes and gaining a deeper understanding of the immune response as arbitrated by this molecule.

The immune system is a complex, intricate and intriguing network of cells and molecules that guards us against a score of invasion attempts by microorganisms. Understanding how it works is the key towards developing novel treatments for many diseases. Prof. Nandi’s lab has made some significant contributions towards that goal. Abishek Tomar, a former summer student in Prof. Nandi’s lab, aptly sums up the overall tempo of the DpN (Dipankar Nandi) lab as Determination, Perseverance and Non-Stop action.

Dipankar Nandi is a Professor in the Department of Biochemistry, Indian Institute of Science, Bangalore. He studies novel microbial genes during stress and infection. He can be contacted at 91-80-22933051.

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