Page 840 - Veterinary Immunology, 10th Edition

VetBooks.ir Innate Immunity

Antimicrobial immunity consists of an early innate response
followed by a sustained adaptive response. Recognition of invading

bacteria through toll-like receptors (TLRs) and other pattern-
recognition receptors (PRRs) induces cytokine release, complement
activation, inflammation, and phagocytosis. If this is insufficient to
eliminate the invaders, adaptive immune mechanisms take over.
Thus dendritic cells and macrophages ingest invading bacteria and

initiate adaptive immunity by secreting cytokines and triggering
both T and B cell responses. The importance of these innate
defenses is emphasized by the observation that the resistance of

chickens to Salmonella enterica Typhimurium appears to be linked to
allelic variations in TLR4, and the resistance of foals to Rhodococcus
equi is linked to TLR2. TLRs are responsible in large part for the
initial recognition of invading bacteria. Binding of microbial
pathogen-associated molecular patterns (PAMPs) to TLRs triggers a

signal cascade that activates genes encoding proteins that are
critical in host defense.
The production of cytokines by horse neutrophils following

exposure to R. equi provides an example of these responses. Thus
after exposure to R. equi, neutrophils express increased amounts of
interleukin-23 (IL-23). This IL-23 promotes Th17 cell differentiation.
Driven by transforming growth factor-β (TGF-β) and IL-6, the Th17
cells then promote inflammation. Not only do these Th17 cells

produce IL-17 but also IL-6, GM-CSF, G-CSF, chemokines, and
metalloproteases. They thus trigger inflammation and coordinate
early neutrophil recruitment to infection sites. Th17 cells confer

protection against extracellular bacteria and fungi, especially at
epithelial surfaces. Type I interferons are also produced in response
to bacterial PAMPs. IFN-α/β boosts macrophage responses
enhancing their production of IFN-γ, nitric oxide, and TNF-α.
Natural killer (NK) cells play a protective role in some bacterial,

protozoan, and fungal infections. For example, some bacteria may
activate NK cells by upregulating expression of NKG2D ligands on
cells. Activated NK cells produce a large amount of IFN-γ that in

turn activates both macrophages and dendritic cells (Chapter 19).

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