ICI 2016_Abstract Book

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International Congress of Immunology 2016 Abstract Book
Oral Abstracts | Monday, 22 August 2016
30 Minute Oral | 08:30 - 10:15
B Cells
Novel aspects of B cell response to vaccination and viral
infection
Batista,F. Gaya, M, Martinez, N.
Ragon Institute
B lymphocytes form an integral part of the immune system
via the production of specific antibodies and by establishing
immunological memory enabling a swift an effective response
to pathogenic assault. To fully understand the processes
whereby this is achieved, it is essential to gain a comprehensive
understanding of the events involved in B cell activation and
antibody production. This is initiated by the encounter with
and acquisition of cognate antigen by the B cell receptor
(BCR); processes occurring primarily in secondary lymph nodes
(SLOs) such as the lymph node (LN) and which are regulated by
complex systems. The functionality of these systems is strictly
dependent on maintaining the architecture of the SLOs. During
this talk I will describe how the LN structure enables the early
encounter of B cells with antigen. Antigenic properties such as
the size and nature of the pathogen affect the specialized lymph
n ode antigen delivery systems that exist in readiness to deliver
pathogen-derived antigen to B cells. This variability in the types
of encounter enables the most appropriate response for that
particular antigen to occur, giving the maximal protection to
the host. Lastly, the consequences of the disruption of the LN
architecture, and the help provided by other cells such as iNKTs,
on the immune response will also be described. Their critical role
in the immune response is evident following infection, which
causes a temporary disruption in the cellular organization of
lymphoid organs and lack of essential cytokines leading to a
reduction in immune responses.
Tolerance & Transplantation
Immunoregulation in Transplantation
Wood, K., Bushell, A., Harden, P., Issa, F., Hester, J.
University of Oxford
Immune regulation is fundamental to any immune response
to ensure that it is appropriate for the perceived threat to the
host. Strategies for the induction of specific unresponsiveness
to donor alloantigens currently under investigation in the clinic
takeadvantageof twoof themajormechanisms for the induction
of tolerance to self antigens – deletion and immunoregulation/
have demonstrated that human regulatory
T cells expanded ex vivo can protect human allografts (skin,
islets and vessels) from rejection. Treg migrate to the allograft
and function in situ. Donor alloantigen reactive Treg are more
effective on a per cell basis than polyclonal Treg. Together
with other leukocyte populations, including regulatory T cells,
B cells and macrophages as well as myeloid derived suppressor
cells and dendritic cells, Treg contribute to the regulation of
immune responses in vivo after organ transplantation. The
identification and characterisation of Treg that can control
immune responsiveness to alloantigens has opened up exciting
opportunities for new therapies in transplantation. Phase1/2a
clinical trials are in progress –
A new approach to GVHD based on biomarkers
Ferrara, J.
Icahn School of Medicine at Mount Sinai
Acute graft versus host disease (GVHD) is the major toxicity
of allogeneic bone marrow transplantation. Recent research
has identified and validated unexpected biomarkers that
predict outcomes. This session will review the use of large and
informative biorepositories to create biomarker signatures that
predict severe GVHD prior to its clinical onset and that can
guide preemptive GVHD therapy. This session will also review
mechanistic studies have illuminated unexpected interactions
between the innate and adaptive immune systems in the GI
tract that have led to both conceptual breakthroughs and the
discovery of novel therapeutic approaches.
Cancer Immunotherapy
Immunotherapy for persisting viral infection and associated
cancer
Frazer, I.1, Mattarollo, S.1,Leggatt, G.1, Wells, J.1, Tuong, K.1, Kuo, P. 1,
Jazayeri, S.1, Lambert, P.2, Chandra, J.1,3
1 The University of Queensland, Australia, 2The University of
Madison, Wisconsin, 3Admedus Immunotherapies
While vaccines have proven effective at preventing virus
infections, immunotherapy for persisting cancer associated
viral infections and their associated cancers has proven less
tractable. Using a model where a viral antigen, the E7 protein
of human papillomavirus (HPV)16, is expressed in grafted
mouse skin, we have determined mechanisms preventing
effective immunotherapy of persisting HPV infection. In this
model, the effector functions of vaccine induced cytotoxic T
cells are locally inhibited by multiple mechanisms initiated by
hyper-proliferative epithelium associated with HPV infection,
and mediated via inflammasome activation, IL-18 and IFNg.
Intra-dermal delivery of an E7 specific polynucleotide vaccine
encoding ubiquitin conjugated viral proteins can overcome
inhibition of effector T cell function in this model. A herpes
virus(HSV) glycoprotein D immunotherapy using the same
strategy has, in clinical trial, induced a cell mediated immune
responses,and is currently under evaluation in persistently HSV-
2 infected subjects.