Basic Caprine Immunology

The purpose of this section is to highlight information spe­cific to the caprine immune system. A broader view of vet­erinary immunology is available from textbooks on the

Table 7.3 Coagulation parameters reported from normal goats.

subject (Tizard 2017). Specific information on the caprine immune system remains sparse compared to other domes­tic animal species. This relative paucity of information has not escaped the attention of researchers and clinicians. The need for the development of goat-specific immunologic reagents to better study and understand caprine immunol­ogy, particularly in the context of developing new and effective vaccines, has been clearly stated (Hope et al. 2012).

The information on the goat immune response that is available often derives from studies of specific diseases, most notably caprine arthritis encephalitis (CAE), which emerged as an animal model for study of acquired immu­nodeficiency syndrome (AIDS) in humans because of the relatedness of the CAE and human immunodeficiency (HIV) lentiviruses (Cheevers et al. 1997; Sharmila et al. 2002; Fluri et al. 2006; Bouzar et al. 2007). Additional information has also emerged from studies on paratuber­culosis (Storset et al. 2000, 2001) and other diseases.

There are no reported inherited immunodeficiencies in goats. Acquired immune-mediated diseases are uncom­mon and those that occur, such as the pemphigus complex, are discussed in the chapters relating to the organ system most affected. The most important immunologic disease of goats is that shared with other ruminant species, namely failure of transfer of immunoglobulins to the newborn via the dam's colostrum. Failure of transfer of passive immu­nity (FTPI) is discussed in detail later in this chapter.

Immunoglobulins

The structure and function of ruminant immunoglobulins have been reviewed and the categories and distribution of caprine immunoglobulins fit the general ruminant pattern (Butler 1986). The major classes of immunoglobulin iden­tified in the goat are IgG, IgA, and IgM. As in cattle and sheep, there are two distinct IgG subclasses, IgG₁ and IgG₂ (Gray et al. 1969). The major immunoglobulin in goat colostrum is IgG₁, and it is transported preferentially over IgG₂ into the mammary gland from serum (Micusan and Borduas 1976).

Very little is recorded about caprine IgM, possibly because little difference has been observed in the structure and function of IgM between ruminant species (Aalund 1972; Butler 1986). Caprine IgA has been isolated from serum, colostrum, milk, saliva, and urine. A distinct secretory component occurs in secretions, either in the free state or associated with IgA. The small amount of IgA found in serum is rarely associated with secretory component (Pahud and Mach 1970). IgA is considered the primary immunoglobulin of mucosal surfaces. In all the ruminants, including goats, immunoglobulins with biologic activities typical of IgE have been identified. IgE has become recognized as a useful marker for the devel­opment of parasite resistance in ruminant animals, and efforts are underway to develop tests for the measure­ment of IgE to detect resistance. Partial DNA sequencing of caprine IgE has been reported as part of this overall effort (Griot-Wenk et al. 2000). Concentrations of caprine immunoglobulins in serum and various secretions are presented in Table 7.4.

Other Serum Proteins

The range of mean total serum protein concentrations reported in goats is from 6.75 to 7.53 g/dL, with concentra­tions in individual goats ranging from 5.9 to 8.3 g/dL (Fletcher et al. 1964; Melby and Altman 1976; Mitruka and Rawnsley 1981). Concentrations for various serum proteins reported in goats are summarized in Table 7.5.

The normal range of plasma fibrinogen levels in goats, 0.1-0.4 g/dL, is less than that of cows. Hyperfibrinogenemia frequently occurs in conjunction with neutrophilia in inflammatory responses.

Reports of complement component concentrations in goats are limited. However, one study demonstrates hemo­lytic, conglutinating, and bactericidal complement activity, and indicates that complement activity is significantly less in kids younger than 6 months of age than in adults (Bhatnagar et al. 1988). This age differential regarding complement activity in goats was also reported in a more recent study (Semerdjiev et al. 2008). Diet in kids may have an effect as well. In one study, kids fed goat milk daily had complement activity in serum measured through 60 days of age, compared to no measurable activity in kids fed a commercial milk replacer through the same period (Castro et al. 2008).

Cell-Mediated Immune System

The induction of the host immune response begins at mucosal surfaces, where immune cells in mucosa- associated lymphoid tissue (MALT) come into contact with and process antigens for subsequent transport to regional lymph nodes. The structure, function, and distribution of

Table 7.4 Concentrations of immunoglobulin types in various body fluids of normal goats.

IgA, immunoglobin A; IgG, immunoglobin G; nm, not measurable; SD, standard deviation; t, trace. ^a Standard deviations.

^b Ranges.

^c Not reported whether standard error or standard deviation.

^d Standard errors.

Table 7.5 Reported concentrations of serum proteins from normal goats.

the caprine MALT system have been reviewed (Liebler- Tenorio and Pabst 2006).

Distinct populations of B and T lymphocytes have been identified in goats (Sulochana et al. 1982) and subpopula­tions of T lymphocytes also have been identified on the basis of reactivity and non-reactivity to peanut agglutinin (PNA) (Banks and Greenlee 1982). The percentages of B cells and PNA-positive T cells among peripheral blood lym­phocytes have been reported, respectively, as 14 and 69% (Banks and Greenlee 1982; Hedden et al. 1986). Distinct subsets of T lymphocytes in goats also have been character­ized using orthologous monoclonal antibodies specific for bovine lymphocyte antigens, including CD2, CD4, CD8, and gamma delta (γδ) T cells, all of which were present in varying percentages in peripheral blood, lymph nodes, spleen, and ileal Peyer's patches (Navarro et al. 1996; Caro et al. 1998). In contrast to humans, but similar to other ruminants, goats have high percentages of T cells with γδ receptors compared to alpha beta (αβ) receptors. These γδ T cells, which are more common in younger goats than adults, are non-conventional T cells that appear to bridge the innate and adapted immune responses (Guerra- Maupome et al. 2019). CD2, CD4, CD8, and γδ T cells are also present in the caprine mammary gland (Ismail et al. 1996).

There are several reports on optimization, kinetics, and application of the in vitro lymphocyte transformation or blas- togenesis assay for the measurement of lymphocyte responses using standard mitogens (Staples et al. 1981; Greenlee and Banks 1985), specific antigens such as CAE virus (DeMartini et al. 1983), steroids (Staples et al. 1983), and allogeneic lym­phocytes (van Dam et al. 1978).

Normal caprine neutrophil function has been evaluated in female goats using a variety of indices, including migra­tion, chemotaxis, bacterial ingestion, cytochrome C reduc­tion, and antibody-dependent cell-mediated cytotoxicity (Maddux and Keeton 1987a). The effect of dexamethasone and levamisole on neutrophil functions has also been reported (Maddux and Keeton 1987b). Selenium deficiency in goats has been shown to have adverse effects on caprine neutrophil function (Aziz et al. 1984). There is very little information on the characterization and function of caprine macrophages and non-neutrophil leukocytes.

Cytokines

Cytokines are small glycoproteins, important in cell signal­ing, that play a central role as immune mediators during host responses against pathogens. Though knowledge on goat cytokines is far from comprehensive, some informa­tion is available in various research reports.

Interleukin 1 (IL-1, endogenous pyrogen) occurs in the plasma of goats during bacterial-induced febrile episodes (Verheijden et al. 1983). Other studies have demonstrated the existence and activity of neutrophil chemotactic factor, leukocyte migration inhibition factor, and interleukin 2 (IL-2) in goats (Aziz and Klesius 1985, 1986). Caprine mac­rophages stimulated in vitro with lipopolysaccharide expressed tumor necrosis factor (TNF) and interleukin 6 (IL-6) (Adeyemo et al. 1997). Interleukin 8 (IL-8) and mono­cyte chemoattractant protein 1 (MCP-1) were expressed by CAE-infected caprine macrophages in vitro (Lechner et al. 1997) and interleukin 16 (IL-16) was expressed at higher levels from peripheral blood mononuclear cells and synovial membrane cells of goats infected with CAE than from cells from control goats (Sharmila et al. 2002). Goats with caseous lymphadenitis produced greater interferon gamma (IFN-γ) responses than uninfected goats when cells in whole blood were stimulated in vitro with either Corynebacterium pseudotuberculosis-secreted antigen alone or with pokeweed mitogen (Meyer et al. 2005). A recent study demonstrated that Haemonchus contortus produces an excretion and secretion product, HcTTR, that blocked the IL4-induced proliferation of peripheral blood mononuclear cells in goats, suggesting a mechanism by which the parasite can evade the host immune response (Tian et al. 2019).

A constraint on better understanding of caprine cytokines is the lack of specific antibodies that allow for their detection through enzyme-linked immunosorbent assay (ELISA), flow cytometry, or immunohistochemistry, leaving molecular detection through polymerase chain reaction (PCR) as the main tool for investigation. Using PCR, a number of caprine cytokines and chemokines have been detected, including IL-1α, IL-1β, IL-4, IL-10, IL-18, CXCL8, IP-10, TNF-α, and IFN-γ (Hope et al. 2012).

Major Histocompatibility Complex

The major histocompatibility complex (MHC) is a large locus on the DNA of vertebrate animals that contains a set of closely linked, polymorphic genes coding for cell surface proteins that are essential for the adaptive immune system. The gene composition within the MHC region in goats is located on chromosome 23, with a gene arrangement simi­lar to that of sheep and with MHC class I and MHC class II genes present (Dong et al. 2013).

The MHC of goats was previously known as the goat lymphocyte antigen (GLA) system, but is now referred to as the caprine lymphocyte antigen (CLA) system. An effort is progressing to elucidate the histocompatibility complex allele sequences from the domestic goat and apply a stand­ardized, official nomenclature in the framework of the Immuno Polymorphism Database (IPD-MHC) (Ballingall and Todd 2019). The system of nomenclature for the goat alleles identified is based on the goat's Latin name, Capra hircus, e.g. Cαhi-N*01701.

Toll-Like Receptors

Toll-like receptors (TLR) are transmembrane proteins that recognize pathogen-associated molecular patterns from a variety of microbial pathogens. TLR were identified in the 1990s as important elements of the innate immune system, involved in two cell signaling pathways that are essential for the initiation of T cell-mediated immunity. Thirteen differ­ent genes have been identified across various mammalian species that are responsible for the expression of TLR. Full sequencing of TLR genes 1-10 has been accomplished in the goat and it is expected that this knowledge will contrib­ute to better understanding of disease resistance and sus­ceptibility in the caprine species (Raja et al. 2011).