Bovine tuberculosis

126 F.J. Salguero

macrophages, epithelial cells and MNGCs within
the granulomas at different stages of develop-
ment. In general, the number of CD68+ cells is
quite high in stage I granulomas and decreases
throughout the development of the lesion. In
stage I and II, a high percentage of the cells
within the granulomas are CD68+, whereas in
stages III and IV the CD68+ cells display a rim of
macrophages surrounding the necrotic centres
and a few cells in the outer layers of the granu-
loma (Aranday-Cortés et al., 2013) (Fig. 9.4).
CD3+ T lymphocytes appear to be scattered
within the stage I and II granulomas, while
being distributed in the outer layers of the stage
III and IV granulomas (Fig. 9.5), but not imme-
diately adjacent to the necrotic cores. The immu-
nohistochemical detection of CD4+ and CD8+ T
lymphocytes using formalin-fixed paraffin-
embedded (FFPE) tissues has been very difficult
to standardize. However, it has been possible to
study these two cell populations using zinc
salt fixatives (Hicks et al., 2006; Aranday-Cortés
et al., 2013). Experimental studies have shown
that both CD4+ and CD8+ are present within the
granulomas in a similar way to CD3+ cells, scat-
tered within stage I and II granulomas and
within the outer layers of the granuloma in
stage III and IV (Aranday-Cortés et al., 2013)
(also see Chapter 10).
The role of B lymphocytes in the immune
response of bovine tuberculosis and the distribu-
tion of these cells within the tuberculous

granuloma has been historically unappreciated.

However, it has been shown that B cells can

modulate the host response to M. tuberculosis in

murine models in a variety of ways (Maglione

and Chan, 2009). We have found interspersed B

cells within the stage I and II granulomas in

bovine tuberculosis, but also abundant numbers

of B cells in stage III and IV granulomas, often

producing satellite nests of B cells around the

outside of the fibrous capsule (Aranday-Cortés

et al., 2013) (Fig. 9.6). These structures resem-

ble active follicles found in secondary lymphoid

organs, with B cells at many different stages of

maturation present, and it has been proposed

that these clusters of cells might coordinate the

host local immune responses to control the

growth of mycobacteria in the lung (Ulrichs

et al., 2004) (see Chapter 10).

9.4 Local Immunity Against M. bovis

The initial immunologic events following

pathogenic mycobacteria infection include

cytokine- and chemokine-mediated recruitment

of monocytes, neutrophils and macrophages

(Lawn and Zumla, 2011). Macrophages must

interact with activated T cells to organize the

granuloma and act as a functional unit to con-

trol the infection (Mattila et al., 2013).

The pathogenesis of bovine tuberculosis

can be compared with human tuberculosis, and

Fig. 9.4. CD68+ staining in stage I and II granu-
lomas in the lung of a cow experimentally infected
with M. bovis. Heavy positive staining can be
observed within the cytoplasm of macrophages
and multi-nucleated giant cells. (IHC, 100×)

Fig. 9.5. CD3+ staining in stage IV granulo-

mas in the lung of an infected cow with M. bovis.

Abundant positive T cells can be observed

mostly in the outer layers of the granulomas.

(IHC, 100 ×)