Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 6 Clinical Veterinary Immunology
test is often supplemented with more specific assays for
evaluation of the presence of autoantibodies in animal
patients. Diagnosis of allergic conditions is now commonplace
because of the development of reagents and assays to
measure IgE in dogs, horses, and cats.
This chapter reviews some basic principles of immunology
and presents current methodologies used in the
clinical immunology laboratory.
II . INNATE IMMUNITY
Entry into the body of a pathogen is the first stimulus for
immunity. Pathogens contain pattern recognition receptors
called pathogen associated molecular patterns (PAM P ),
which are recognized by Toll-like receptors (TLR) on the
surface of host cells. There are at least 10 such receptors,
each recognizing a different motif. For example, TLR 2
recognizes the peptidoglycan of the Gram-positive bacterial
cell wall, TLR 4 recognizes lipopolysaccharide from
the Gram-negative bacterial cell wall, TLR 6 recognizes
flagella protein present on motile bacteria, and TLR 9
recognizes DNA containing cytosine-guanine repeating
motifs (CpG). The binding of these TLRs with their ligands
stimulates production of proinflammatory cytokines that
jumpstart the immune response (Takeda, 2005).
The immune response is generally divided into innate
and acquired responses. This division is based on the need
for the host to have previously been exposed to the antigen/
pathogen in order to rapidly mount a protective response.
Innate immunity does not require previous exposure to a
pathogen for it to be effective. It is thus not an antigenspecific
response. Innate immunity is a broad category
that includes protective barriers such as skin and mucosa.
Reflexes are included, such as the cough coupled with the
anatomical/physiological function of the mucociliary apparatus,
which moves inhaled material out of the respiratory
system. Dogs with inherited ciliary dyskinesis have nonfunctional
cilia and suffer from repeated respiratory infections
because of their inability to remove inhaled particles
(such as bacteria) from the lung.
Phagocytes are important components of innate immunity.
The initial responder to infection is usually the
polymorphonuclear leukocyte or neutrophil. These cells
participate in phagocytosis and killing of bacteria. Dogs
with inherited cyclic neutropenia develop cyclic bouts of
bacterial disease that coincide with the episodes during
which the bone marrow shuts down its production of these
essential phagocytes. Other defects, such as that seen in
calves with bovine leukocyte adhesion deficiency (BLAD),
occur when production is good, but the neutrophils lack the
CD18 part of the adhesion molecule that allows them to
adhere to blood vessel endothelium and then exit into the
tissue by diapedesis. These animals develop even more critical
disease because their defect is not cyclic, but constant.
These calves generally succumb to overwhelming bacterial
disease within the first 6 months of life. These experiments
in nature demonstrate the importance of the innate defense
provided by the neutrophil.
The other population of phagocyte is the macrophage.
This cell plays a role not only as a phagocyte, generally
entering an area of inflammation after the neutrophil,
but also as a vital link to the acquired immune response.
Macrophages function as antigen-presenting cells. As such
they engulf a pathogen, digest it within a vacuole, and then
display peptides generated from the engulfed organism on
their cell surface. This antigen presentation function relies
on the presence of a cell surface molecule called major histocompatibility
complex antigen class II (MHC II). Lymphoid
cells of the CD4 T cell lineage then bind to the peptide
and to the MHC II for initiation of the immune response.
This is a critical step in immune responses. However, there is
another cell type, the dendritic cell, that performs the antigen
presentation function more efficiently than the macrophage.
These cells are pivotal to induction of the acquired immune
response and serve as an effecter for innate immunity.
The need for acquired immunity is demonstrated by
certain bacterial species that are able to live and divide
after being ingested by a macrophage. These organisms,
called facultative intracellular bacteria, are able to
overcome the macrophage and prevent their own digestion
in the phagosome. To overcome the infection, the
macrophages infected with these bacteria require signals
from cytokines that are secreted by T cells stimulated in
an acquired immune response. Infection of cattle with
Mycobacterium bovis subspecies paratuberculosis causes a
chronic wasting disease because of the ability of the bacteria
to overcome the killing function of the macrophages.
The acquired immune response required for killing these
organisms is discussed with cellular immunity.
There is a population of lymphocytes that are neither
T nor B cells; they lack the receptors for antigen recognition.
These cells are natural killer cells (NK cells). The NK
cells have the ability to recognize cells that lack or have
depressed levels of the MHC class I molecule on the cell
surface. Many tumor cells and some viral infected cells fall
into this category. It is an evasion technique employed by
some viruses to down-regulate the expression of the MHC
molecules, which are required for recognition of the effector
cells of the immune system. These NK cells are part
of the innate immune system, because they are available to
act on target cells without prior exposure.
III . ACQUIRED IMMUNITY
Acquired immunity is specific for the stimulatory antigen;
and the acquired response has memory. Thus, once a host has
encountered an antigen and initiated an immune response,
the next time the antigen is encountered by that host, the
response is more rapid and more robust. The antigen can be
from a pathogen (bacteria, virus, parasite, fungal) or it can