ANNUAL REPORT - Department of Biotechnology

Autonomous Institutions
National Institute of Immunology, New Delhi
The National Institute of Immunology (NII)'s primary
mandate is to understand and exploit the
mechanisms of the immune system using various
tools of modern biology in order to pursue creative
solutions to a broad range of health problems. The
focus of research has been on:
Infection, Immune Mechanisms and
Autoimmunity
Studies on Salmonella - host cell interaction
revealed a regulatory mechanism involving
induction of Toll-like receptor-ligand (flagellin)
synthesis for inflammation and innate immunity
during infection by bacterial pathogen. In a study on
Systemic Lupus Erythematosus (SLE), patients
showed that a human monoclonal antibody,
generated from an SLE patient, recognizes antigens
externalized during the process of apoptosis. It can
also mediate a variety of potential pathogenic effects
including stimulation of the idiotypic network and
increasing the range of molecular targets.
Several Ribozymes (Rzs) and DNA-enzymes (Dzs)
were constructed that were specific for HIV-1 Tat and
Rev genes. Rzs and Dzs cleaved the Tat/Rev RNA
very efficiently, and most of them showed excellent
activity under simulated physiological conditions of
cleavage. In a study related to biology of Tlymphocytes,
a major role for Hsp90 activity in MHC
II-mediated antigen presentation pathways in
addition to MHC class I restricted antigen has been
revealed. Studies have shown that the frequency of
naive T cells capable of responding to a given
antigenic stimulus is marginally lower in aged mice
as compared to young mice as also the activated T
cells are more susceptible to death during the
antigen-mediated proliferation phase. Hence,
immune responses are short-lived in the aged mice
and immune memory is also defective.Effect of IL4-
Chapter : 11
and IL10- deficiency on B cell differentiation in vivo
and in vitro reveals that the that IL4 supports clonal
expansion in vivo and that in its absence, both
plasma cell generation as well as memory cell
generation is compromised. IL10, on the other hand,
appears to dampen clonal expansion in vivo. In its
absence, enhanced primary antibody responses as
well as enhanced memory cell generation are
observed early after immunization.Ligation of the
TNFR molecules CD27 and CD40 on B cells has
been shown to skew B cell differentiation towards the
memory pathway. In a study on vaccine against JEV,
replication defective recombinant adenoviruses
(RAds) have been constructed that synthesized the
pre-membrane and envelope (E) proteins of the
virus. Oral immunization of mice with RAdEs
generated high titres of JEV antibodies and
intramuscular immunization of naïve mice with
RAdEs showed complete protection against a lethal
dose of JEV given intra-cerebrally.
A study has shown that size of the polymer particles
being used as adjuvant can modulate the immune
response. It was noted that Nano-particles promoted
cellular immune response, while micro-particles
were good at eliciting a humoral response. Detaied
antigen processing and presentation by polymeric
particles are under investigation. In a study on
inhibition of beta cell autoimmunity in children
predisposed to get type I diabetes, T-cells involved in
presenting auto-antigen peptides to auto-antigens
were designed to inhibit their presentation and hence
abrogate self-destruction of beta cells.
Structural, Chemical & Systems Biology
Correlations between the promiscuity of the primary
antibody response and conformational flexibility in a
germ line antibody were addressed through
crystallographic analyses revealing a simple
mechanism for expanding the primary antibody
repertoire. New insight into the mechanism of
177 Autonomous Institutions