Page 394 - Avian Virology: Current Research and Future Trends

Avian Immune Responses to Virus Infection | 385

specialized functions. In tetrapods including birds, the primary The BF-BL region is the chicken MHC, defined as the genetic
isotype secreted from mucosa to the outside of the body is IgA, locus with the polymorphic classical MHC genes responsible
which provides a first line of defence towards pathogens and is for graft rejection and antigen presentation to T lymphocytes
typically important to achieve sterile immunity. The third special- (Kaufman, 2013). This region is located on a microchromosome
ized isotype in birds is IgY (analogous to the IgGs of mammals), (chromosome 16) and is small and simple, stripped down to a
which provides high affinity binding after B cells undergo a com- few important genes compared with mammals and therefore
plex selection in germinal centres (GC). dubbed the ‘minimal essential MHC’ (Kaufman et al., 1999).
The initiation of the adaptive immunity is controlled and Moreover, despite having genes to express two classical class I
shaped by innate immune responses, particularly through profes- molecules and two classical class II molecules, only one of each is
sional antigen presenting cells (APCs), which include various expressed at a high level throughout the body (Jacob et al., 2000;
kinds of macrophages and DCs that are found in many tissues. Wallny et al., 2006; Shaw et al., 2007). Current thinking is that
Such APCs use PRRs to detect the broad kind of pathogen and CD8 CTLs primarily recognize the class I molecules encoded by
secrete an appropriate cytokine milieu to stimulate particular the BF2 gene (in association with a non-polymorphic molecule,
kinds of T-cells. The APCs also present peptides to T-cells for β -microglobulin), while CD4 cells primarily recognize the class
2
specific responses, being the only cells (along with B cells and II molecules encoded by the BLB2 gene (in association with the
certain specialized epithelial cells in the thymus) to constitutively non-polymorphic BLA molecule) (Fulton et al., 1995; Thacker et
express high levels of class II molecules and to express so-called al., 1995; Parker and Kaufman, 2017; Kim et al., 2018). The BF1
co-stimulatory molecules that are required for stimulating naïve molecule may be primarily a target of NK cells (as is HLA-C in
T-cells to begin the adaptive immune response. In mammals, humans), while the class II molecule determined by BLB1 may
tissue DCs take up antigen and then travel to the spleen and lymph have a specialized function in intestinal epithelial cells (IECs)
nodes to present to T-cells for initiation and are therefore some- (Parker and Kaufman, 2017; Kim et al., 2018). Other genes
times called the gatekeepers of the immune response. However, present in the BF-BL region include those that encode accessory
birds lack draining lymph nodes as constitutive structures, and molecules, for example the transporter associated with antigen
the locations for the initiation of many T-cell responses remain presentation (consisting of TAP1 and TAP2) that pump peptides
unclear. In the intestine, it seems likely that immune responses from the cytoplasm into the lumen of the endoplasmic reticulum
arise in the Peyer’s patches. (ER) for loading onto class I molecules, and the dedicated chap-
erone tapasin that stabilizes class I molecules during optimization
The chicken MHC: a central role in adaptive of the peptide repertoire (Kaufman et al., 1999).
immune responses There is also the Rfp-Y region (also known as MHC-Y) that
In comparison to typical mammals, the chicken MHC determines contains non-classical class I and class II genes (Afanassieff et al.,
resistance and susceptibility to many infectious diseases (Bacon, 1991; Briles et al., 1993; Miller et al., 1994, 1996), and which is
1987; Plachý et al., 1992; Bacon et al., 2000; Kaufman, 2013; Miller separated from the MHC (BF-BL region) by a region of repeats,
and Taylor, 2016). This phenomenon was discovered as strong so that the two regions are not genetically linked. An early study
genetic associations of the B blood group with economically suggested that this region affected responses to MDV infection
important viral diseases (Hansen et al., 1967; Briles et al., 1977; (Wakenell et al, 1996), but subsequent genetic studies found
Plachý, 1984; Calneck, 1985), and it was only later discovered to no evidence for any effect (Vallejo et al, 1997; Bumstead, 1998;
be due to the location of the MHC (later called the BF-BL region) Lakshmanan and Lamont, 1998). A striking observation (which
within this large genetic region (Plachý and Benda, 1981; Briles et may mean much or little) is the presence of many more non-
al., 1983; Taylor, 2004). Such strong associations were first noticed classical class I (YF) genes in the genome sequence of a red jungle
for MDV (an oncogenic herpesvirus) and Rous sarcoma virus fowl than in experimental chicken lines derived from commercial
(RSV, a retrovirus). Similar associations have now been described egg-laying chickens. More research is required to establish a role,
for other viruses, including avian leucosis virus (ALV, a retrovirus), if any, for this region in immune responses to viruses.
IBV (a coronavirus), ILTV (a herpesvirus), and AIV (an ortho-
myxovirus) (Bacon et al., 1981, 2004; Loudovaris et al., 1991a,b; Single dominantly expressed class I molecule
Mays et al., 2005; Boonyanuwat et al, 2006; Banat et al., 2013). can determine the immune response
However, MHC associations have not been reported for infectious The strong genetic associations of the B locus with resistance
with NDV (a paramyxovirus), FPV (a poxvirus) and IBDV (a birna- and susceptibility to viral diseases can be explained, at least in
virus), which may reflect either life histories of the viruses or lack of part, by the expression of a single dominantly expressed class
thorough examination. MHC associations with vaccine responses I molecule whose peptide-binding specificities determine the
to IBV, IBDV, NDV and MDV have been reported (Butter et al., immune response (Kaufman et al., 1995; Wallny et al., 2006;
1991; Bacon and Witter, 1994; Lee et al., 2004; Esmailnejad et al., Kaufman, 2018). An individual chicken will be protected if it
2017). By comparison of chicken lines with different haplotypes expresses a class I molecule that binds an appropriate pathogen
and recombinants, the level of antibodies elicited by a killed IBDV peptide and presents it to CTLs, while an individual will die
vaccine was found to segregate with particular class II (BLB) if the class I molecule has a peptide-binding specificity that
alleles, along with an adjuvant effect by the nearby BG region (Juul- fails to find a protective peptide to present. This stark contrast
Madsen et al., 2006). between life and death reads out as strong genetic associations.