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16 May 2022

Immunopathology of Fabricius bursa focused on Gumboro disease

Content available in: Português (Portuguese (Brazil))The birnavirus that causes Gumboro disease is not the only one that affects the bursa […]

Immunopathology of Fabricius bursa focused on Gumboro disease

The birnavirus that causes Gumboro disease is not the only one that affects the bursa of Fabricius and other lymphoid organs, but it is the most important.

The immune system is strategic. The demand for immune efficiency results from environmental pressure, including biosecurity failure and reduced antibiotic use. This requires effective stimulation of the individual immune response of the animal or the flock while adapting the poultry house to the vaccine strains.

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Let's review the bird's immune system and its biggest threat, namely Gumboro disease, its immunopathology, and the lesions resulting from the vaccine “aggression,” in addition to some points not very considered when the subject is discussed.

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The birnavirus that causes Gumboro's disease is not the only one that affects the bursa of Fabricius and other lymphoid organs. Still, it is the most important, even because of its resistance and ability to contaminate facilities, notably because of the habit of reusing the “litter,” in addition to its infectivity, pathotyping, and mutability (new variants).

MORPHOLOGY / HISTOLOGY

Bplsa de Fabricius GumboroThe cells that make up the bursa of Fabricius are adult or immature B lymphocytes with an IgM receptor and, to a lesser extent, T cells, macrophages, dendritic cells, and the [register] epithelial, connective stroma of the organ and the vascular substrate.

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Lymphoid tissue is distributed throughout the body, such as the nasal cavity, cervical and thoracic esophagus, proventricular, Peyer's patches, cecal tonsils, and rectum, moreover as the thymus, spleen, and liver.

Dendritic cells, B cells, and T cells are always present, and depending on the follicle, B cells, and sometimes T cells predominate. Contact with the antigen regulates the development of these germinal nuclei, notably in the GALT.

The primary organs, such as the bursa of Fabricius and the thymus (B and T cells, respectively), are atrophy within 16 - and 17 or more weeks. The secondary lymphoid tissue takes care of the entire immune reaction.

The intestine is the most extensive lymphoid tissue with thousands of intraepithelial conglomerates and hundreds of Peyer's patches (between 200 and 300) and the cecal tonsils.

 

THE IMMUNOPATHOLOGY

imunopatologia da bolsa de fabricius gumboroThe health of birds depends on these parenchymas. Some agents have tropisms, such as birnavirus, which affects immature and dividing B cells, and gyrovirus, which affects T cells, causing infectious avian anemia. Others, such as the virus that causes Newcastle disease and some bacteria and toxins, could damage the tissue.

In acute GD, in animals between 2 to 6 weeks, there is “bursal” inflammation and severe lymphoid depletion (necrosis). Mortality varies from 20 to 30%, and macroscopically, organ edema occurs, with continuity, lack, and atrophy.

Edema raises her weight to 6 g; lasts for three days, with atrophy after 3-5 days. Interestingly, antibodies are produced from mature, multilocated B cells. These cells are more resistant to the virus than the immature ones.

The a.c. titer reaches 1: 1000. This pathology occurs after a decline in passive antibodies. Histopathology shows medullary depletion of follicles, with lymphoid necrosis, inflammatory edema, and characteristic heterophilic infiltration.

Subsequently, the follicles retract, with hypoplasia and atrophy. It additionally occurs with interfollicular fibroblasts, accompanied by macrophagic infiltration in the central regions. The pseudocyst formation occurs. The lesion regenerates as long as the basement membrane remains intact, which is lined by dendritic cells activating genes responsible for the cloning of B cells.

This phenomenon was well characterized by Ivan., J (2001), using Lewis carbohydrate as a marker, indicating gene conversion. This greatly relativizes bursometry and its interpretation.

The classic form of GD has been replaced by those due to viral variants (vvIBDV). In these, rapid immunosuppression is observed, with high mortality rates, occurring earlier and easily breaking through passive defenses. The characteristic acute bursal injury and the clinical phase may not be noticed. Variants depend on the region, and pathotyping varies.

These variants have led to new vaccines, programs, and monitoring. Mild, intermediate, intermediate plus, and hot strains are linked to the researcher's name who described it, such as Lukert, Winterfield, etc., or alphanumeric indications such as D78, V 877, etc. These denominations are confusing, and a new system to designate these isolates has already been proposed ( Jackwood, DJ; 2018)

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Figure 1. Kinetics of infection (PI) Abdul R (2011)

Bolsa de Fabricius Gumboro

After 5 h PI: Primary viremia and arrival at the bursa, followed by secondary viremia in lymphoid clusters in other organs, in the bursa of Fabricius and the spleen, the virus reaches its maximum concentration.

According to Abdul R (2011), the virus remains in the bursa of Fabricius for 21 days, with a low concentration in other tissues.

The virus remains in the “litter” of the chickens and the dust for 60 and 28 days, respectively, requiring investigation of the survival of vaccine strains, which is important in epidemiological control.

Birnavirus affects B cells with IgM receptors in the dividing phase. T cells are refractory and essential in inflammation and viral control. Thus, due to viral division in the latter, there is inflammation, necrosis/apoptosis, and depletion.

This lesion is also the product of vaccine strains, such as the intermediate plus. The lesions reflect the “take” of the vaccine, which is related to passive antibodies. The active antibody is produced in the germ nuclei.

Bolsa de Fabricius Gumboro

INVOLVEMENT OF CELLS IN THE IMMUNE/INFLAMMATORY AND ADAPTIVE RESPONSE

Macrophages and APCs (Antigen Presenting Cells): Phagocytosis and Antigen Recognition. Contact the infectious or vaccine agent. From them comes a cascade of information. To this end, under the influence of inflammatory, regulatory and other genes, they release cytokines such as IL1 (target Th 2 cells and B cells), IL8 (target T cells and neutrophils), IL12 that targets TH1 lymphocytes and NK cells ( “neutral killers”), IL 18 (target, TH1 lymphocytes), not to mention TNF (tumor necrosis factor).

T lymphocytes, CD4 and CD8, and after activation by macrophages and APCs, CD4 differentiates into “TH2 helpers. The immune response branches are the cellular (TH1) and the humoral (TH2). Ideally, both are encouraged—these T lymphocytes, when activated, elaborate interleukins between inflammatory and non-inflammatory.

TH1 releases IL1, IL3, IL15, and IL17, with several target cells among macrophages and others. TH2 releases interleukins, IL3, IL4, IL5, IL9, IL10, and IL13, basically with the same targets. The trend is always the balance between these interleukins and their functions. For example, non-inflammatory interleukin, such as IL10, counterbalances the effects of the distinctly inflammatory IL12. Usually, in laboratory assessments, using ELISA or molecular biology, IL6, IL18, IL8, IL12, IL1, and IFN gamma are essentially inflammatory. Activated T cells also produce lytic proteins, such as perforins, which participate in the necrosis of infected B cells.

As seen above, b cells are either stimulated by T cells, or they interact directly with the antigen, leading to the formation of antibodies after activation of T lymphocytes in the germinal nuclei, such as those of the spleen. They produce a higher concentration of non-inflammatory interleukins, with IL10 and IL14.

On the other hand, CD8 T lymphocytes are toxigenic for cells that harbor antigens, mainly viral ones, and NK cells (neutral killers), a type of lymphocyte, intervene when other “cleaning” mechanisms fail; they are not able to recognize cells. Infected. These cells also depend on interleukins.

The above is a notion of the response process, and addressing all immune mechanisms is beyond the scope of this review. Nor was it mentioned how macrophages and antigen-presenting cells contact the various pathogens before initiating the “innate/acquired immunity” cascade.

There are dozens of receptors in these cells capable of recognizing antigens (TLRs), and in the case of birnavirus, mainly TLR 3. Some globulin receptors (FCyR) are also crucial in binding with the immune complexes.

The bibliography includes some references that may be useful to those who want to delve deeper.

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THE IMMUNOPATHOLOGY OF VACCINE STRAINS

Maternal antibodies protect for three weeks. IgY originates from contact between birds with the virus in the field or vaccine. The peak of antibodies in active immunity is between 3 to 5 weeks.

The vaccine virus, when inactive, does not multiply in the environment—the same for vectored vaccines.

In addition to breaking the barrier of maternal antibodies, the attenuated virus colonizes the bursa of Fabricius and the environment. The greater the attenuation of the virus, the less it breaks down passive antibodies and the less the ability to multiply. Immune complex vaccines (e.g., the V877 strain) are unconventional. There is a combination between a volume of attenuated virus and the exact volume of the pre-elaborated neutralizing antibody.

This set binds to FcRs globulin receptors, specifically the FCy-CHIR-AB1 receptor, which is arranged in large amounts in neutrophils, lymphocytes, and mainly macrophages and follicular dendritic cells, the germinal nuclei, aided by the C3 complement present in the serum.

ICX resists maternal antibodies. The conjugated antibody prevents the action of the passive antibody for weeks, which allows the decrease in the titer of the passive a.c.

bolsa de fabricius gumboroThus, the immunocomplex vaccine antigen (icosome) is protected. Part of the released vaccine virus multiplies, and the bursal lesions as a result.

However, the production of high-affinity antibodies and the cloning of differentiated T and B cells occurs from the interaction of ICX/follicular dendritic cells in the germinal nuclei, such as the splenic, which precede the lesions in the bursa of Fabricius.

In the author's opinion, bursal lesions only indicate the “take” of the vaccine and are unrelated to antibody production.

 

[caption id="attachment_74260" align="aligncenter" width="477"]Bolsa de Fabricius Gumboro Figure 2. Bursa of vaccinated birds exhibiting follicular hypoplasia and follicular retraction at approximately 14 days post-vaccination[/caption]

 

[caption id="attachment_74261" align="aligncenter" width="745"]bolsa de fabricius gumboro Figure 3. Bursa of vaccinated birds, showing full lymphoid repopulation approximately 28 days later.[/caption]

Potential advantages arising from the use of this technology ( Haddad E.E; 2016):

The longer exposure time of the antigen to the various immune effectors, such as follicular dendritic cells, B cells, and T cells (active and adaptive immunity).

Enhanced protection against passive antibodies.

Immunity results from the stimulation of B cells that predominate in the areas of follicular dendritic cells in the germinal nuclei, followed by their activation by T cells. Mutation and cloning of B cells differentiate them as producers of high-affinity antibodies and for the production of memory cells.

The multiplication of the vaccine virus helps to change the pattern of the viral population in the shed.

The type of immunoglobulin produced with an ICX vaccine tends to have more affinity than that obtained from a free virus.

The author draws attention to the excellence of the vaccine arsenal available in Brazil, the need for effective monitoring of use, and the perfect characterization of the survival of vaccine strains in the environment.

References

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