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

VII. Modulation of the Immune Response
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FIGURE 6-13 Tubes containing a solution of zinc sulfate are incubated
with serum from neonatal foals to evaluate the quantity of passively transferred
maternal IgG. Increased turbulence correlates with more IgG.
or piglet fails to suckle or obtains insufficient antibody, it
will be susceptible to disease during the neonatal period.
It is imperative to determine if sufficient antibody has
been acquired. If this is done before the intestinal epithelium
closes (before 18 hours of age), oral supplementation
can be used. There are several tests to evaluate serum IgG
levels in a semiquantitative but quick way. Several companies
make kits based on ELISA technology, but a simple
method that uses zinc sulfate turbidity is adequate. Serum
of the foal is mixed with a solution of zinc sulfate. This test
relies on binding of the sulfate to the IgG and formation of
a precipitate. The more IgG in the serum, the greater the
opacity of the mixture in the tube. An example is shown
in Figure 6-13 . The SRD is far more accurate, but the zinc
sulfate test provides a rough estimate within less than an
hour, thereby allowing oral supplementation of colostrums
to occur within the window of time that it can be effective.
An example of this method is shown in Figure 6-13 .
D . Hypersensitivity Diseases
The diseases known collectively as hypersensitivities are
grouped into four categories based on the mechanism that
causes the pathology. These are types I to IV (Gell and
Coombs). Type I hypersensitivity is the classic allergy,
characterized by clinical signs ranging from systemic
anaphylactic shock to allergic rhinitis and asthma. The
mechanism involved in the pathogenesis of type I disease
is IgE mediated. IgE antibodies, having a high affinity for
mast cell receptors, bind to these cells and release mediators,
such as histamine, upon contact with antigen/allergen.
Arachidonic acid metabolism is also initiated through
phospholipase activation and leukotriene and prostaglandin
mediator synthesis occurs subsequent to the allergic stimulation.
Laboratory diagnosis of type I hypersensitivity relies
on testing serum for allergen-specific IgE, generally by
ELISA. The availability of anti-IgE reagents for the various
domestic animal species has made this diagnostic tool
available in recent years. In addition, there is a commercially
available service that uses a cloned alpha chain of
the human IgE receptor to detect IgE bound to allergen in
an ELISA format. Traditionally, intradermal skin testing
has been used to determine which allergens are causing the
allergic response. Many veterinary dermatologists use this
method with good success.
Type II hypersensitivity occurs when IgG or IgM antibodies
bind to a cell surface and fix complement. When
the cell is an erythrocyte, the ultimate result is immunemediated
anemia. The Coombs’ test described on page 169
for antibody bound to erythrocyte surfaces is the standard
agglutination-type assay used to detect incomplete antibodies
causing erythrocyte destruction. Erythrocyte destruction
in the affected patient results from either complement-mediated
lysis or removal by fixed phagocytes lining splenic
sinusoids. Other type II hypersensitivities that do not
involve erythrocytes include the skin diseases of the pemphigus
complex and the neuromuscular disease, myasthenia
gravis (both are autoimmune). For laboratory diagnosis of
these diseases, immunofluorescence or immunohistochemistry
is often used to demonstrate the deposition of immunoglobulin
or complement within the lesion of affected skin
(pemphigus) or on cells with acetylcholine receptors within
the neuromuscular junction (myasthenia gravis).
Type III hypersensitivities are caused by immune complex
formation. The antigens involved are soluble. Most
commonly immune complexes form in chronic diseases
in which antigen persists in the circulation despite a vigorous
immune response (e.g., equine infectious anemia)
and in certain autoimmune diseases (e.g., systemic lupus
erythematosus) in which antinuclear antibodies are made
and bind to various nuclear components from cell debris.
In these cases, deposition of immune complexes within
the small blood vessels, such as the kidney glomerulus as
shown in Figure 6-7, is common. Detection of immune
complex deposition by immunofluorescence is diagnostic
for their presence.
Type IV hypersensitivity, unlike the previously discussed
types I to III, is not mediated by antibody but is
caused by development of sensitized T lymphocytes specific
for the antigen. The classic example is the intradermal skin
test for tuberculosis, which shows an erythemic-indurated
lesion at the site of injection of tuberculin after 48 to 72
hours in infected individuals. The ELISA for interferon
gamma can be used to evaluate T cell reactivity to antigens
thought to be responsible for a type IV response.
VII . MODULATION OF THE IMMUNE
RESPONSE
Adjuvants in vaccines have been used for many years to
increase the immune response to vaccine antigen. In recent
years, increased understanding of the immune response has
resulted in the emergence of new modalities for immune
modulation, not only for responses to vaccine antigens but