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The idea of creating a national institute for research in basic and applied immunology was conceived in the early eighties when immunology was identified as a priority area by the Science & Engineering Research Council (SERC) wing of the Department of Science and Technology (DST). The SERC deliberations noted the overwhelming potential impact of advances in immunology research on human and animal health, and consequently, initiated consultation with Indian Council of Medical Research (ICMR), the Indian Council of Agricultural Research (ICAR) and experts from various agencies and industry to establish the National Institute of Immunology (NII).The Institute was conceived to grow on the aegis of the ICMRWHO Research & Training Centre in Immunology which had been in operation for many years at the All India Institute of Medical Sciences (AIIMS). NII was registered as an autonomous society on 24th June, 1981 under the Societies Registration Act (XXI of 1860). The first Governing Body of the Institute met under the Chairmanship of Prof MGK Menon on 27th July, 1981. Prof GP Talwar was invited to join as Honorary Director on 14th August, 1981. The ICMR-WHO Research & Training Centre was formally merged with NII on 31st March, 1982. NII started functioning in the laboratory space available to Prof GP Talwar at AIIMS, an arrangement that continued in the interim period till the first buildings of NII were constructed in the current location on the land carved out of the Jawaharlal Nehru University (JNU) campus. Prof Talwar formally joined as full time Director of NII on 2nd November, 1983.

The Construction of buildings spread over a 21 acre plot surrounded by rocky terrain with green cover amidst a commanding view of the historical Qutab Minar began on 27th October 1983, when the President of the Society, Prof MGK Menon laid the foundation stone of the first building --- the Scholars Home. The architectural design of the campus was conceptualized to preserve the natural imprints of the terrain (rocky incline) while building laboratories, animal houses, residential apartments, research scholars home, auditorium, canteen and a swimming pool. While a part of the interim activity shifted to the scholars home after it was completed, additional 7000 square feet of space was rented in a newly constructed building in Kailash Colony of South Delhi.

The Institute was formally dedicated to the Nation by Prime Minister Rajiv Gandhi on 6th October, 1986. The inaugural ceremonies were marked by two international symposia on themes relevant to the research programmes of the Institute. Symposia entitled Contraception Research for Today and the Nineties and on Progress in Vaccinology brought together leading workers from all over the world.

By 1990, NII grew into a vibrant research institution. The institute with several active research groups, doctoral students, post-doctoral fellows and supported by state of the art infrastructure became a prime research institution of the country. This period not only saw the evolution of a functional laboratory complex with superlative research facilities but also witnessed the fruition of the expanded research activity in several areas of contemporary biology and biotechnology.