Dr. Khurshid Tariq
Nature has provided us with a defensive and a resistance mechanism in the form of an immune system, which has evolved to safeguard and protect us from the harmful self and environmental agents. Various organs, tissues, cells and molecules make up the immune system divided into innate and adaptive components. For a layman to understand it, immunology is simply the study of immune system of our body. For an efficient working of the immune system, the clonal selection mechanism provides a framework for self (useful) and non-self (harmful) recognition. The body’s own cells, antigens, molecules and the useful microbiota are treated as self and are immunologically tolerated.
However, intruders (pathogens) are treated as foreign and are dealt with severely through an array of immunological mechanisms of innate and adaptive nature. Overall, our immune system is a very much balanced and a highly regulated system. However, the immune system is not 100% fool proof and effective. Sometimes, there is breakdown in the self –tolerance mechanism and the immune system can function improperly or fails to function at all, resulting in certain debilitating and life threatening diseases (cancer, severe immunodeficiency diseases, autoimmune disorders like multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, allergic disorders and so on) or even sudden death.
The immune system spread to two diversified branches including humoral (antibody dependent) and cell mediated (T-cell dependent) has evolved during the last century as a very significant branch of the medical sciences. Indeed the breakthrough discoveries and understanding immunological mechanisms have changed the outlook of modern medicine. From Edward Jenner’s pioneering work in vaccination of 18th century and 19th century Paul Ehrlich’s discovery of magic bullets (or monoclonal antibodies) of immunology to treat infections and recent breakthrough discoveries in the field of immunotherapy and transplantation immunology, immunology have achieved a fatherly status among all medical sciences.
Cancer is a deadly disease characterized by abnormal and uncontrolled proliferation of body cells. The hallmark of a cancerous cell is its capability to avoid immune destruction. Pertinently our immune cells have the capability to identify and kill the tumorous or cancerous cells; however, they fail to do so when a cancer develops. Therefore, this demands manipulating the functioning of immune system and defeating the cancer through immunotherapy including the use of monoclonal antibodies and cancer vaccines. Immunologists have finally solved this problem as has been deciphered by awarding Nobel Prize in Medicine or Physiology of this year to Immunotherapy.
Interestingly, the discipline of immunology has already won around a dozen Nobel Prizes from 1901 to 2011. In 1901, Emil Adolph Von Behring and Paul Ehrlich shared Nobel Prize for their discovery understanding the basic mechanism of immune system including discovery of Magic Bullets of Immunology. In 2011, the Nobel Prize on dendritic cells (antigen presentation cells) was awarded to Bruce A. Beutler, Jules A. Hoffman and Ralph M. Steinman. This year’s Nobel Prize in physiology or medicine has been awarded to two cancer immunologists, who discovered an entirely new way of how the body’s own immune cells can be manipulated to attack and kill (rather the suppressors of brakes- the check points of the human immune system) cancer cells. These two independently working immunologists have developed ways to convert the two immune component systems into therapies.
The researchers are Professor James Allison of the Monroe Dunaway Anderson Cancer Center (MDCC) of the University of Texas and Professor Tasuku Honjo of the Department of Medical Chemistry of Kyoto University, Japan. Their discovery is seen with a hope to make cancer a history. The most prevalent treatment- the chemotherapy makes the disease more dangerous due to multidimensional negative effects on neighbouring cells and tissues. The two immunologists succeeded in identifying separately the two target checkpoint proteins(CTLA-4 discovered in 1990 by Prof. Allison & PD-1 discovered in 1992 by Prof.Honjo) that help to keep our immune T cells from attacking other cells in the body. The basic mechanism of their action as adopted from the journal-Nature is as: The CTLA-4 checkpoint protein prevents dendritic cells (APC) from priming T cells to recognise tumours inhibitor drug block the checkpoint). The PD-1 checkpoint protein prevent T-cells from attacking cancer cells (the inhibitor drug allows T cells to act).So when these proteins are inhibited, the cells can target cancers. Their discovery has given rise to a new immunotherapy pillar – “the immune check point therapy”.
Immunotherapy has, therefore, emerged as a hottest area in cancer research and treatment. The immune dysfunction and immunodeficiency which are generally the hereditary conditions are the two major problem of our immune system. Therefore, a healthy immune system of our body is fundamental to our overall wellbeing and health. So understanding the basic architect of immune system and immune responses and how to evolve immunotherapy by controlling and modulating them is crucial for treating the deadly diseases like cancer, AIDS and diseases involving transplantation therapies and vaccination.
The author is an Assistant Professor of Zoology at the Islamia College, Srinagar. He can be reached at: drkatariq@gmacom