Page 175 - TBE_Book_V2_2019

Chapter 9: Immunology of TBEV infection

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engagement is required for full activation of T detected. However, anti-TBEV IgM- and IgG-
cells. The CD28 is a major co-stimulatory antibodies appear in serum during the second
2
molecule on T cells, and it facilitates T cell phase of the disease. During the second
activation upon binding to CD80 and CD86 on phase of TBE, virus is rarely present in human
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DCs. DCs are also producers of type I IFN that serum, therefore detection of viral RNA using
have multiple functions in adaptive immunity, PCR is not optimal for TBE diagnosis. For this
such as T cell proliferation, CD8 T cell reason, diagnosis of TBE is primarily based on
activation, B cell isotype switching and differ- serology, i.e. presence of TBEV-specific IgM
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entiation into plasma cells. and IgG- antibodies in serum and CSF of
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patients.
Many flaviviruses, including Langat virus, can
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infect DCs in vitro. Infection of DCs results in A number of studies have attempted to
impaired DC maturation and subsequently correlate humoral responses to TBE infection
decreased T cell priming/proliferation. with clinical outcome. High anti-TBEV IgM
However, when mouse dendritic cells were antibody levels were detected early during
infected with 2 different strains of TBEV, DC TBE, decreasing over time in both serum and
maturation was instead induced, as measured CSF, whereas IgG antibodies were detected
by co-stimulatory molecule and MHC class II later than IgM, peaked in the six-week
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upregulation on the cell surface. Tick-feeding convalescent samples and persisted for more
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experiments on mice also showed that DCs than a year. The persistence of serum and
and monocytes are locally infected by TBEV at CSF antibodies did not correlate to the disease
the bite site, therefore potentially contributing severity, but patients with low levels of IgM
to subsequent viral spread and the initiation antibodies in CSF during the early second
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of the adaptive immune responses. phase of TBE, and patients with low TBEV-
neutralizing antibody levels in serum suffered
from a more severe disease. 55,56 In addition, a
B lymphocytes and antibody
more recent study found a higher concen-
responses during TBE tration of anti-TBEV IgG antibodies in serum of
patients with a milder disease as compared to
B cells carry a large variety of immunoglobulin 57
(Ig) surface receptors that can directly those with a severe TBE. These studies may
support a link between humoral immunity and
recognize antigens and are responsible for
specific antibody production. Naive B cells are TBE clinical outcome.

activated after primary antigen encounter and
initially produce antigen-specific IgM, and Mouse studies provide additional data that
later IgG. Activated B cells later differentiate suggest that B cells contribute to the outcome
of TBEV infection. Increase of CD19 mRNA
into plasma and memory B cells. Plasma cells
are responsible for antibody secretion during levels in brain tissue of infected mice coincides
with high levels of TBEV-neutralizing anti-
the immune response, whereas memory B 58
cells are responsible for the recall responses bodies. These mice are also less susceptible
during repeated infection with the same to TBEV than mice producing low levels of
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pathogen. neutralizing antibodies. However, the mice
more susceptible to TBEV also exhibited
Many viral infections and vaccines give rise to strong cytokine/chemokine mRNA production
long-lasting protective immunity consisting of in the brain, suggesting that other immuno-
pathogen-specific antibodies and memory B pathological mechanisms are involved in the
cells. TBEV infection also elicits an efficient B disease outcome.
cell response. During the first (viremic) phase
of TBE, anti-TBEV antibodies are generally not

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