Mechanism of Infectious Poultry Diseases in Immunosuppression

Former VC, KVAFSU, Bidar, Former Director IAH&VB Bangalore, Former Prof &Head Dept. of Pathology Veterinary college, UAS, Bangalore.

What is Immunosuppression?

Immunosuppression(IS), is defined as “a state of temporary or permanent dysfunction of the immune response resulting from damage to the immune system and leading to increased susceptibility to disease”, includes suboptimal responses in antibody production, innate and cellular immunities. 

In simple terms Immunosuppression means impairment of the immune system that causes a weaker or even no response to antigens in hosts.

How does IS affect the poultry Industry?

Immunosuppression has great economic importance in the poultry industry, because affected flocks are directly causing mortality and subsequent increased susceptibility to secondary infections, respond poorly to vaccines and do not perform as well as non-affected birds and are silent killers. Subclinical immunosuppression in chickens is an important but often underestimated factor in the subsequent development of clinical disease. Immunosuppression can be caused by pathogens such as chicken infectious anemia virus, infectious bursal disease virus, reovirus, and some retroviruses

What Organs are involved in IS?

Basically, the organs or cells involved and production of Cell mediated Immunity (CMI)in chicken are:

Primary Organs:

• The thymus. -T-Cell system. (Cell mediated Immunity)
• The bursa of Fabricius– (B-Cell system and humoral immunity)
• The bone marrow– Production of precursors of blood cells
• Yolk sac -Maternal Immunity
• The lymphoid cell aggregates, the Harderian gland, along the gut, gut associated lymphoid tissue (GALT)), the esophagus spleen, the caecal tonsils and the Peyer’s patches and the trachea and bronchial associated tissue (BALT),

Fig:1. Immune organs of chicken

What blood components involved in Immunity?

1. Blood cells

Lymphocytes are the main tools of acquired immunity. The T lymphocytes (T-Cells) B lymphocytes(B-Cells) are generally responsible for the production of antibodies, while cytotoxic T lymphocytes actively destroy pathogens. Subtypes of T lymphocytes mediate cell killing.

• Humoral components

Humoral immunity is the aspect of immunity that is mediated by macromolecules including secreted antibodies, complement proteins, and certain antimicrobial peptides located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids.

Chickens have 3 immunoglobulins (Ig) classes: IgA, IgM, and IgY. The chicken IgA and IgM are similar in structure to mammalian IgA and IgM. The humoral response is the adaptive immune system’s primary defence mechanism to eliminate pathogens and their toxins coming from outside the bird’s cells.

Cytokines (lymphokines, interleukins, and chemokines) are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. Cytokines are mainly produced by macrophages and lymphocytes, although they can also be produced by Neutrophils, endothelial and epithelial cells, adipocytes, and connective tissue.  When released, they signal the immune system to do its job. Cytokines affect the growth of all blood cells and other cells that help the body’s immune and inflammation responses.

What are the types of Immunity?

• Innate immunity-: is the first response of the body’s immune system to a harmful foreign substance. When bacteria or viruses, enter the body, certain cells in the immune system can quickly respond and try to destroy them.
• Acquired Immunity: When pathogens are introduced into ther body from a vaccine or a disease, the body learns to target those pathogens in the future by making new antibodies.
• Vaccine Immunity: Vaccine produce immune response, helping the bird to fight off and remember the particular pathogen so it can attack it if the same pathogen ever invades again.

What infectious diseases cause Immunosuppression (IS) in poultry?

Immunosuppression can be caused by pathogens such as:

• Infectious Bursal Disease (IBD)
• Chicken infectious anaemia virus. (CIAV)
• Marek’s disease virus. (MDV)
• Reo virus.
• Reticuloendotheliosis virus. (REV)
• Subgroup J avian leukosis virus (responsible for myeloid leukosis).
• Newcastle disease virus. (NDV)
• Infectious bronchitis virus. (IBV)
• Avian pneumovirus (responsible for swollen head syndrome).
• Mycoplasma Spp. (MG, MS)
• Eimeria Spp.                                                                                                                               
• Such a list is certainly not exhaustive

What is the mechanism of IS in infectious diseases?

The most common Viruses, including Infectious Bursal Disease Virus (IBDV), Chicken Infectious Anemia Virus (CIAV), Marek’s Disease Virus (MDV) and Avian Leukosis Virus (ALV), are the major immunosuppressive inducers. They can cause apoptosis and/or necrosis of lymphoid cells and induce the malfunction of immune response regulation. Among them, ALV is known to initiate diseases correlated with tumor formation and induces severe immunosuppression by increasing host vulnerability to other microbial infections and the risk of failure in subsequent vaccination against other diseases.

The following table:1. provide quick reference about the mechanism pf IS in birds by infectious diseases:

Table:1. Immune target cells by common viral infections

Virus replication in lymphoid cells is the major cause of cell death for IBDV, CIAV, reovirus, MDV and, to some degree, REV. In most of these infections, apoptosis is the cause of cell death, although necrotic lesions have been reported for MDV.

Mechanism of IBD in causation of IS

The main target cells for IBDV replication are the actively dividing B-lymphocytes, causing rapid necrosis and depletion of lymphocytes from the bursal follicles. IBDV specifically destroys plasma cells in the BF leading to an impaired humoral response. The BF is principally involved, but lymphoid tissues of other organs (spleen, caecal tonsil, proventriculus) are also affected and cause immunosuppression.

The immunosuppression seems to be a result of direct effect (lysis) of B cells or their precursors. Other mechanisms of immunosuppression have been suggested, notably the development of suppressor cells.

Chicken Anaemia

CAV is a small single-stranded DNA virus that infects hematopoietic cells in the bone marrow and T cell precursors in the thymus. Chicken anemia virus causes an acute, immunosuppressive disease of young chickens, causing atrophy or hypoplasia of lymphoid organs. CAV expresses three proteins, one of which, VP3, is a 14 kD a non-structural protein known as apoptin in light of its ability to selectively induce apoptosis. Apoptin’s selective killing correlates with its subcellular localization, which is cytoplasmic in non-transformed cells but nuclear in transformed cells.

Marek’s Disease

MDV transforms CD4⁺ T cells and causes deadly lymphomas. In addition, MDV induces immunosuppression early during infection by inducing cell death of the infected lymphocytes, and potentially due to activation of regulatory T (Treg)-cells. Apoptosis is the most likely mechanism responsible for cell death during cytolytic infection in the lymphoid organs ffecting CD4⁺CD8⁺ thymocytes. Furthermore, immunosuppression also occurs during the transformation phase of the disease. Is can be noticed in two phases. Early immunosuppression phase during cytolytic infection and a late immunosuppression phase when the virus is reactivated and tumors develop. One of the key characteristics of early immunosuppression is the destruction of lymphocytes in the lymphoid organs during the first two weeks of infection, causing severe atrophy of the thymus and bursa of Fabricius; this may be permanent or transient depending on the MDV pathotypes. MDV also induces immune suppression through activation of macrophages.

Leukosis 

Avian Leukosis/Sarcoma Viruses (ALSVs) belong to the genus Alpha retrovirus of family Retroviridae. ALSVs that occur in chickens have been divided into 6 envelope subgroups (A–E and J) based on the differences in their viral envelope glycoproteins. ALSV infections usually induce several kinds of neoplasm of infected hosts which lead to severe morbidity and mortality. Most importantly, hosts infected with ALSVs often develop immunosuppression.

Immunosuppression can be induced through diverse mechanisms, including direct toxicity to target cells, fetal infection leading to tolerance, viral proteins acting on infected cells or uninfected bystander cells leading to cell death and aberrant production of cytokines, and suppressor T lymphocytes.

There are two distinct ways to cause immunosuppression in acute transforming process of tumor genesis different from slow transforming ALVs. One is immunosuppression caused directly by tumor related antigens and another is immunosuppression caused by the induction and activation of suppressor T lymphocytes and macrophages. Suppressor cells play their inhibitory effect via an interaction between suppressor cells and effect cells or through inhibiting factors.

Subgroup B and D ALVs are capable of inducing Cytopathic Effects (CPEs) upon infection of cultured avian cells. This is most possibly similar to immunosuppression caused directly by tumor related antigens. Symptoms of the disease induced by viruses of ALV subgroup C are most obvious, and a key feature was a depletion of B lymphocytes in the thymus, bursa and spleen.

Subgroup J ALV mainly attacks myeloid cells, causes a malignant growth, interferes synthesis of functional IL-2, influences mature and differentiation of B and T lymphocytes, and thus induces immunosuppression.

Reticuloendothelial virus (REV)-induced immunosuppression may have important practical consequences because REV infection has often contaminated Marek’s disease vaccines

Avian Reo virus infections

Avian reovirus infections can cause tenosynovitis and other diseases in chickens, or result in a subclinical infection. Although horizontal transmission is the main route for infection, egg transmission may occur infrequently in chickens.Infections with pathogenic, but not non-pathogenic, strains have been associated with depletion of lymphoid cells in the bursa and thymus.In early age group up to 7 days Reovirus infection decrease the responses of peripheral blood monocytes and splenocytes,

New castle disease

Newcastle disease virus (NDV) infects poultry and antagonizes host immunity via several mechanisms. Recently emerged genotype VII NDVs (NDV-GVII) have shifted their tropism from gastrointestinal/respiratory tropism to a lymphotropic virus, invading lymphoid organs including spleen and bursa of Fabricius to cause profound lymphoid depletion. 

The avian influenza virus causes reduced production performance and immunosuppression in chickens.

Coccidiosis

Coccidian species are a subclass of obligate intracellular protozoan parasites belonging to the apicomplexan class, among which two groups, Cryptosporidium baileyi and Eimeria species, have been linked to immuno-suppression, although with limited evidence. Eimeria spp. can cause coccidiosis, a major enteric infectious disease in chickens. Coccidiosis is also a predisposing factor for necrotic enteritis. 

Table 2. Agents causing atrophy of different organs  (useful in diagnosisby posr moreem)

How to recognise immunosuppression?

• Immunosuppression may affect both health and performances.
• Increased mortality, uneven growth, decreased body weight, higher feed conversion, higher medication costs and higher rate of condemnations at slaughter.
• By conducting postmortem and observing the immune organs as per table:2.
• Immunosuppressed birds will typically show long and complicated vaccine reactions, and will be more easily predisposed to respiratory diseases with secondary bacterial infection.
• Increase in cost of medication and efficacy of medicines.
• ‘Unusual’ infections may occur, for example gangrenous dermatitis, E. coli, anaemia, or inclusion body hepatitis.
• Lastly, immunosuppressed birds will show a lower antibody response to vaccines than expected.

How to Prevent immunosuppression?

A continuous control of the immunosuppression causes is of paramount importance to protect the integrity and the function of the immune system. This will, in turn, give better flock health, better performances and a better response to any vaccination or infection.

The following practices to be followed:

1. Check the day old chick quality, with a special focus towards mycoplasma vertically transmitted infection.
2. Revise management practices, starting with biosecurity, good sanitation and litter management. a better production yield should be accompanied in parallel with a continuous upgrading in husbandry practices. For instance, the ammonia control is always a balance between good litter management and proper ventilation.
3. Check the feed composition and quality.
4. Check the water quality and, if necessary, add 2-3ppm active chlorine. Also check if the chlorinated water is actually available in all drinkers.
5. To minimise the spreading risk of any disease to susceptible birds, always travel from youngest to oldest age birds.
6.  Implement a relevant vaccination programme.  This includes to chose the right product strengths, to vaccinate at the right time, to deliver every vaccine using the most appropriate administration route, and to check the actual vaccine solution intake by the birds (by using a dye for instance).
7. Adequate vaccination of the breeder flocks is necessary as well, as Gumboro disease, chicken anaemia and reovirus vaccination in breeders will provide protection to the progeny (‘passive immunity’) for the critical first weeks of age.
8. Identify the causative agent(s) through a sound diagnosis, like Gumboro disease virus, chicken anaemia virus, reovirus, or Marek’s disease virus.
9. The post mortem findings are rarely give indication. In addition to post mortem examination, the diagnosis will usually require histopathology analysis – (sample bursa, spleen, liver, sciatic nerve, thymus, brain) is helpful.
10.  Chicken infectious anaemia virus infection will rather be evaluated using serology.

References

1. Dohms JE, Saif YM. Criteria for evaluating immunosuppression. Avian Dis (1984) 28:305–10. doi: 10.2307/1590336 [PubMed] [CrossRef] [Google Scholar]
2. Charles Li, ^, * Leyi Wang,and Shijun Zheng  (2023)Editorial: Immunosuppressive disease in poultry, Frontiers in Immunology : 10.3389/fimmu.2023.1215513  [Google Scholar]
3. Schat K, Skinner MA. Vian immunosuppressive diseases and immunoevasion. Avian Immunol (second edition) Academic Press (2014), 275–97. doi: 10.1016/B978-0-12-396965-1.00016-9 [CrossRef] [Google Scholar]