Immune responses to IBDV

Apart from its immunosuppressive effects, IBDV infection in chickens activates all branches of the immune system. However, the level of activation varies depending on the virulence of infecting strains, age, immune status and genetic background of affected chickens.

2.3.1. Innate immunity

The influx of macrophages, heterophils and mast cells in the bursa of Fabricius constitutes the early innate immune response to IBDV (KHATRI et al. 2005;

PALMQUIST et al. 2006; RAUTENSCHLEIN et al. 2007; WANG et al. 2008). The influx of these cells may be mediated by chemokines (IL-8, iNOS) (KHATRI et al.

2005; ELDAGHAYES et al. 2006; PALMQUIST et al. 2006; RAUTENSCHLEIN et al.

2007; RAUW et al. 2007; RAUF et al. 2011a). Toll-like receptors (TLRs) such as TLR3 and TLR7 expressed by these inflammatory cells detect IBDV nucleic acids.

Their mRNA expressions have been found upregulated during an acute IBDV infection (RAUF et al. 2011a; GUO et al. 2012). These interactions between IBDV and TLR3 or TLR7 have been shown to activate the interferon (IFN) system and also induced proinflammatory cytokines (IL-6, IL-1β, and IL-18) (RAUF et al. 2011a; GUO et al. 2012). The release of these cytokines was suggested to be tightly regulated by NF-κB, whereby its expression was found to be elevated in the bursa during the early phase of IBDV infection (KHATRI u. SHARMA 2006; GUO et al. 2012). The upregulation of IFN-α/β mRNA expression was reported in lymphoid organs and PBL of chickens experimentally infected with virulent IBDV (KIM et al. 1998; RAUF et al.

2011a; MAHGOUB et al. 2012). The expression levels of these cytokines in the bursa differ in relation to the virulence of infecting strains, genetic background and age of infected chickens (ELDAGHAYES et al. 2006; RAUTENSCHLEIN et al. 2007;

ARICIBASI et al. 2010; RAUF et al. 2011a). IFNs may protect chickens against IBDV infection. This was verified experimentally whereby chickens pretreated with

recombinant chicken IFN-α/β and latter challenged with IBDV had reduced challenge virus replication and pathological lesions in the bursa (CAI et al. 2012).

IBDV infection of chicken embryo fibroblasts (CEFs) resulted in upregulation of IFN-inducible 20-50-oligoadenylate synthetase (OAS), IFN regulatory factors, 6 and IL-8 mRNA expression (LI et al. 2007). The OAS and RNase L pathway interferes with viral infection through the cleavage of viral ssRNA, which is one of the recognized viral suppressor activities of OAS (MALATHI et al. 2007). Recombinant type I IFN pretreated CEFs resisted IBDV replication and resulted in reduced viral titer after infection (O'NEILL et al. 2010; CAI et al. 2012).

Nitric oxide released by macrophages may constitute an early host defence against IBDV and promotes the killing of IBDV-infected and possibly virus-free cells (KHATRI et al. 2005; KHATRI u. SHARMA 2006; PALMQUIST et al. 2006; KHATRI u.

SHARMA 2009a).

2.3.2. Humoral immunity

Significant titers of systemic IBDV specific-Abs have been detected in the convalescent sera of chickens that are naturally or experimentally infected with IBDV (ETERRADOSSI u. SAIF 2008). All classes of Igs can be produced, but the Ab response may not protect chickens from antigenetically different IBDV strains.

Neutralizing Abs are directed against the conformation dependent neutralizing epitopes of VP2 (FAHEY et al. 1991; SNYDER et al. 1992). Abs against VP3 (BECHT et al. 1988; FAHEY et al. 1991) and conformation-independent antigenic domains of VP2 (AZAD et al. 1987) are non-neutralizing. Live and inactivated IBDV vaccines may induce vigorous Ab responses in the first few weeks postvaccination (MAAS et al. 2001; ARICIBASI et al. 2010). Compared to cell culture derived strains, bursal and embryo derived strains induce higher neutralizing Ab titers (RODRIGUEZ-CHAVEZ et al. 2002).

Humoral immunity plays a significant role in protection against IBDV. Maternal antibody (MAB) provides passive protection in the first few weeks after hatch (AL-NATOUR et al. 2004). MAB positive chickens developed significantly less bursal lesions than Ab negative chickens after IBDV challenge supporting the role of passive immunity in protection (HASSAN et al. 2002; ARICIBASI et al. 2010). MAB may interfere with the development of an active immune response after IBDV vaccination (RAUTENSCHLEIN et al. 2005a).

Although Ab mediated immunity is crucial against IBDV, an important role of the cell mediated immunity (CMI) is suggested by several groups (RAUTENSCHLEIN et al.

2002a; YEH et al. 2002).

2.3.3. Cellular immunity

During acute IBD, while bursal follicles are B-cell depleted, T-cells accumulate at the site of virus replication (TANIMURA u. SHARMA 1997; KIM et al. 1998; KIM et al.

2000; SHARMA et al. 2000). A notable influx of CD4+- and CD8+ T-cells was detected as early as 1 dpi and peaked at around 7 dpi (KIM et al. 2000). Although viral Ag was cleared by week 3 pi, T-cell influx and activation continued to week 12 pi. No T-cell depletion was detected from the bursa during IBDV infection. However, IBDV particles were detected in intrabursal T-cells (MAHGOUB et al. 2012).

Infiltrating T-cells in the bursa show markers of activation such as upregulated IL-2, major histocompatibility complex (MHC) class II molecules, and IFN-γ mRNA expression (KIM u. SHARMA 2000; RAUW et al. 2007; RAUF et al. 2011b). T-cells are not only involved in bursal recovery by killing virus infected cells, but also contribute to bursal lesions. T-cell compromised SPF-chickens had the highest viral Ag load and milder inflammatory bursal lesions compared to T-cell intact birds after IBDV infection (RAUTENSCHLEIN et al. 2002a). T-cells infiltrating the bursa after IBDV infection expressed higher levels of the mRNA for cell membrane-disrupting proteins such as perforin (PFN) and granzyme A (Gzm A), and other cytolytic molecules such as the high mobility group proteins. PFN and Gzm mediated

cytotoxic activity may contribute to rapid viral clearance from the bursa (RAUF et al.

2011b). The role of T-cells in IBDV protection was supported in vaccination studies with T-cell or B-cell compromised chickens. Chickens depleted of functional T-cells either by neonatal thymectomy or Cyclosporin A treatment showed insufficient protection against IBDV challenge after immunization with an inactivated IBDV vaccine, whereas chickens with intact T-cells had significantly higher IBDV protection rates (RAUTENSCHLEIN et al. 2002b). Chickens with severely compromised Ab-producing ability following treatment with cyclophosphamide were sufficiently protected against IBDV challenge despite the absence of detectable vaccine-induced Abs. This implies that T-cells may have role in protection (YEH et al. 2002).