Page 174 - TBE_Book_V2_2019

Chapter 9: Immunology of TBEV infection

had less expression of perforin, granzyme B, Adaptive immune system and
and Bcl-2, suggesting that the cells have
already responded to target cells. In addition, TBE
CD56 dim NK cells had a decreased responsive- The adaptive immune system recognizes and
ness to target cells ex vivo, but recovered their selectively eliminates specific foreign
functional capacity during the convalescent microorganisms and toxic molecules, i.e.
phase of TBE. In contrast to the decreased antigens. The adaptive immune system
response to target cells, the NK cells could displays characteristic attributes including
respond to cytokine stimulation ex vivo antigen specificity, immunologic memory, self-
throughout the infection. Interestingly, the tolerance and non-self-discrimination. The key
characteristics of NK cell responses in TBE cells of adaptive immunity are the T and B
infection are different from those of other lymphocytes, which express antigen-specific
human viral infections. The release of receptors on their cell surface. Adaptive
cytotoxic granules early in NK cell activation immunity can be divided into humoral and cell
may contribute to the pathogenesis in TBEV-
-mediated.
infection.

Neutrophils Antigen presenting cells and antigen
presentation during TBE
Neutrophils contribute to the inflammatory Dendritic cells (DCs) act as an important
response and have phagocytic activity early bridge between the innate and adaptive
during innate immune responses to viral
immune systems. DCs express many types of
infections. They are attracted to the bite site PRRs, thus enabling DCs to respond to various
during tick feeding experiments and can also 50
8 pathogens by the recognition of PAMPs.
be infected by TBEV. Neutrophils are also Antigen uptake and the engagement of PRRs
present at high levels in human CSF early after induce processes of chemokine receptor
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TBE onset, slowly decreasing over time.
switching, upregulation of co-stimulatory
However, despite decreasing numbers, molecules and cytokine secretion. DCs
neutrophil counts in CSF are higher during the become activated and mature after PRR
convalescent phase in patients with persistent stimulation resulting in their migration from
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neurological symptoms. In TBE patients tissues to lymph nodes where they can initiate
concentrations of chemokines signalling
T cell responses.
through CXCR1 and CXCR2 receptors are
upregulated in the CSF suggesting a potential In order to specifically recognise a given
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mechanism for neutrophil infiltration. antigen, naïve antigen-inexperienced T cells
require antigen presentation in the form of a
In a mouse model using Langat virus, peptide by antigen-presenting cells (APC) via
neutrophils have been suggested to mediate Histocompatibility Complex (MHC) molecules
brain injury. Increased levels of neutrophils in on their surface. APCs include DCs,
the CNS were observed during late infection monocytes/macrophages, Langerhans cells
time points in CCR5 deficient mice, together and B cells. DCs are the most potent antigen-
with high levels of neutrophil attracting presenting cells and are professional inducers
chemokines CXCL1 and CXCL2, higher viral of T cell responses. MHC-peptide complexes
load and increased apoptosis in the brain on DCs bind to the T-cell receptor (TCR)
tissue. Depletion of neutrophils reversed this providing the first signal of activation. The
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phenotype (Figure 3). secondary signal of co-stimulatory molecule

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