Page 860 - Veterinary Immunology, 10th Edition

repeats the cycle. A. marginale is transmitted by ticks, so successful
VetBooks.ir spread depends on maintenance of a high bacteremia.

Some bacteria secrete proteases that can destroy
immunoglobulins or cytokines. For example, proteases specific for

IgA are produced by Neisseria gonorrhoeae, Haemophilus influenzae,
and S. pneumoniae. These organisms can thus prevent opsonization
and Fc receptor–mediated phagocytosis. Mannheimia hemolytica
secretes a protease specific for bovine IgG1. P. aeruginosa secretes a

protease that destroys IL-2. B. abortus produces a B cell mitogen that
stimulates the cells to secrete IL-10. This causes transient
immunosuppression and permits the bacterium to successfully
establish a chronic infection.

Pathogenic mycobacteria have evolved to survive within host
macrophages, and Mycobacterium avium paratuberculosis (MAP), the
cause of Johne's disease, is highly adept at such survival. MAP
interacts with receptors on macrophages to initiate cell signaling

and phagocytosis. Thus MAP crosses the intestinal epithelial barrier
by triggering IL-1β production. This recruits macrophages to the
apical side of the epithelium and facilitates entry into its
macrophage habitat. MAP also traffic easily through M cells where

they can be picked up by dendritic cells or macrophages and
carried to the mesenteric lymph node. Mannosylated
lipoarabinomannan (Man-lam) is a major component of the MAP
cell wall. Man-lam binds to TLR2, triggering transcription of IL-10.

The IL-10 suppresses production of proinflammatory cytokines and
attenuates phagosome acidification and phagolysosome fusion.
Thus Man-lam appears to be largely responsible for suppressing the
inflammatory and antimicrobial responses against MAP. IDO is

also generated in MAP infections and may down-regulate the host's
immune responses. Antigen stimulation of mesenteric lymph node
cells from cows severely infected with MAP reveals upregulation of
not only IL-10 but also IFN-γ, IL-13, IL-17A and TNF-α. This

suggests that cytokine synthesis is severely dysregulated. MAP also
blocks macrophage activation by gamma interferon. Macrophage
activation is required in order to kill the intracellular invader and if
activation does not happen then the bacterium can persist. The
interferon blockage results from inhibition of the JAK-STAT

pathway (Chapter 8). MAP-infected cells cannot phosphorylate key

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