Acute phase proteins (APP) were first identified in the early 1900s as early reactants to infectious disease. They are now understood to be an integral part of the acute phase response (APR) which is the cornerstone of innate immunity. APP have been shown to be valuable biomarkers as increases can occur with inflammation, infection, neoplasia, stress, and trauma. All animals--from fish to mammals--have demonstrable APP, but the type of major APP differs by species. While the primary application of these proteins in a clinical setting is prognostication, studies in animals have demonstrated relevance to diagnosis and detection and monitoring for subclinical disease. APP have been well documented in laboratory, companion, and large animals. With the advent of standardized and automated assays, these biomarkers are available for use in all fields of veterinary medicine as well as basic and clinical research.

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Acute phase proteins in animals.

Background 
cological immunology requires techniques to reliably measure immunocompetence in wild vertebrates. The PHA-skin test, involving subcutaneous injection of a mitogen (phytohemagglutinin, PHA) and measurement of subsequent swelling as a surrogate of T-cell mediated immunocompetence, has been the test of choice due to its practicality and ease of use in the field. However, mechanisms involved in local immunological and inflammatory processes provoked by PHA are poorly known, and its use and interpretation as an acquired immune response is currently debated.


Methodology 
Here, we present experimental work using a variety of parrot species, to ascertain whether PHA exposure produces larger secondary than primary responses as expected if the test reflects acquired immunocompetence. Moreover, we simultaneously quantified T-lymphocyte subsets (CD4+, CD5+ and CD8+) and plasma proteins circulating in the bloodstream, potentially involved in the immunological and inflammatory processes, through flow cytometry and electrophoresis.


Principal Findings 
Our results showed stronger responses after a second PHA injection, independent of species, time elapsed and changes in body mass of birds between first and second injections, thus supporting the adaptive nature of this immune response. Furthermore, the concomitant changes in the plasma concentrations of T-lymphocyte subsets and globulins indicate a causal link between the activation of the T-cell mediated immune system and local tissue swelling.


Conclusions/Significance 
These findings justify the widespread use of the PHA-skin test as a reliable evaluator of acquired T-cell mediated immunocompetence in diverse biological disciplines. Further experimental research should be aimed at evaluating the relative role of innate immunocompetence in wild conditions, where the access to dietary proteins varies more than in captivity, and to ascertain how PHA responses relate to particular host-parasite interactions.

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The PHA test reflects acquired T-cell mediated immunocompetence in birds.

The possible role of some acute phase proteins (APPs) and immunoglobulins in both the pathogenesis and diagnosis of feline infectious peritonitis (FIP) has been investigated. Serum protein electrophoresis and the concentration of haptoglobin (Hp), serum amyloid A (SAA), α1-acid glycoprotein (AGP), IgG and IgM were evaluated in cats exposed to feline coronavirus (FCoV) and in cats with FIP. The highest concentration of APPs was detected in affected cats, confirming the role of these proteins in supporting a clinical diagnosis of FIP. Repeated samplings from both FIP affected and FCoV-exposed cats showed that when FIP appeared in the group, all the cats had increased APP levels. This increase persisted only in cats that developed FIP (in spite of a decrease in α2-globulins) but it was only transient in FCoV-exposed cats, in which a long lasting increase in α2-globulins was observed. These results suggest that changes in the electrophoretic motility of APPs or APPs other than Hp, SAA and AGP might be involved in the pathogenesis of FIP or in protecting cats from the disease.

Changes in some acute phase protein and immunoglobulin concentrations in cats affected by feline infectious peritonitis or exposed to feline coronavirus infection.

IFN-gamma is a key cytokine controlling Brucella infection, and the diverse functions of this cytokine are mediated by IFN regulatory factors (IRFs) such as IRF-1, IRF-2, and IFN consensus sequence binding protein (ICSBP). However, the roles of these three IRFs in Brucella infection have not been investigated. The infection of each IRF-deficient mouse strain provides an opportunity to determine not only the significance of each IRF molecule but also the crucial immune components necessary for host defense during in vivo infection, because respective IRF-deficient mouse strains contain unique immunodeficient phenotypes. Brucella abortus S2308-infected IRF-1-/- mice were dead within 2 wk postinfection, while IRF-2-/- mice contained less splenic Brucella CFU than wild-type mice at the early stage of infection. Infected ICSBP-/- mice maintained a plateau of splenic Brucella CFU throughout the infection. Additional infection of IL-12p40-, NO synthase 2-, and gp91(phox)-deficient mice indicates that these immune components are crucial for Brucella immunity and may contribute to the susceptibility of IRF-1-/- and ICSBP-/- mice. Immunologic and histopathological analyses of infected IRF-1-/- mice indicate that the absence of IL-12p40 induction and serious hepatic damage are involved in the death of IRF-1-/- mice. These results indicate that 1) IRF-1 and ICSBP are essential transcriptional factors for IFN-gamma-mediated protection against Brucella; 2) IL-12, reactive nitrogen intermediates, and reactive oxygen intermediates are crucial immune components against Brucella, and their absence may contribute to the susceptibility of IRF-1-/- and ICSBP-/- mice; and 3) hepatic damage caused by Brucella virulence contributes to the death of IRF-1-/- mice.

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Susceptibility of IFN Regulatory Factor-1 and IFN Consensus Sequence Binding Protein-Deficient Mice to Brucellosis

The evaluation of serum proteins and their electrophoretic pattern is a well-established laboratory method in the diagnosis of many diseases in humans, which has replaced the biochemical determination of the concentrations of albumin and the ratio of albumin to globulins. The measurement of serum proteins may be an important diagnostic tool for the detection, diagnosis, and monitoring of various diseases and pathological processes. The results of serum protein electrophoresis can be one of the most useful diagnostic aids in a wide spectrum of diseases, including infectious and inflammatory diseases, renal or gastrointestinal disorders, immunodeficiency states, as well as paraproteinaemias caused by lymphoid or plasma cell neoplasia. Although many studies have been carried out to determine the usefulness of the determination of serum proteins and their electrophoretic pattern in various disease conditions and disorders also in animals, serum protein evaluation is still a relatively little-used diagnostic tool in veterinary medicine. In this article, methods of serum protein determination, their diagnostic utility in animal care practice and their different patterns in dysproteinaemias and paraproteinaemias are reviewed.

/pdf/serum-proteins-and-their-diagnostic-utility-in-veterinary-kcp7h909j9.pdf

Serum proteins and their diagnostic utility in veterinary medicine: a review

Serum Proteins and the Dysproteinemias.

THE mechanism of the thymol flocculation test developed by MacLagan in 19441 has in the past four years been the subject of study by several investigators2–5. In the course of a detailed study of the circulating proteins of a patient suffering from advanced liver disease, whose plasma was known to give a strongly positive thymol reaction (18 units), opportunity was taken to examine the observation that normal human albumin would inhibit the thymol reaction3.

Interrelations of the serum protein in the thymol turbidity test.

Marrack and Orlans1, in a careful study of the behaviour of bovine albumin before and after acetylation, demonstrated that the acetylated product interacted with an antibody globulin prepared against the unmodified bovine albumin.

Immuno-chemical Observations on the Intimate Structure of Human Albumin

The overproduction of immunoglobulins.

The invasion of the biological field by physicists and chemists in the last decades has given us a detailed picture of the anatomy of a number of molecules of biological importance. At the same time it has created a new 'horizon' to the consideration of the 'machinery' of normal and abnormal function. Since this is the business of all pathologists, whether they call themselves morbid anatomists, microbiologists or what you will, no apology is made for devoting this Presidential Address to a discussion of the form of a few of the biologically active peptides and proteins ofknown constitution. The field is now so vast that to attempt a comprehensive survey in one lecture would be futile.

Nicholas H Martin

Papers

Serum Proteins and the Dysproteinemias.

Interrelations of the serum protein in the thymol turbidity test.

Immuno-chemical Observations on the Intimate Structure of Human Albumin

The overproduction of immunoglobulins.

Section of pathology. form and function.