Immunodeficiencies - WikiBlood

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Introduction

Immunodeficiency Diagram - Copyright nabrown RVC

Like any system in the body the immune system can go wrong. Autoimmunity is when the immune system begins to attack itself. Immunodeficiency is when the immune system fails to protect itself from disease.

If the immunodeficient defect is present at birth and is therefore a result of a genetic or developmental abnormality, it is called primary immunodeficiency.

Secondary immunodeficiency, soemtimes called aquired immunodeficiency, is the loss of immune function during life, caused by exposure to harmful agents.

Immunodeficiencies can be treated by the replacement of the defective or missing protein, cells or gene. However, in veterinary medicine, vaccinations and drugs are the most common treatments for immunodeficiency.

Primary Immunodeficiency

Primary immunodeficiencies may affect either the innate immune systemor adaptive immune system
They are categorised by either the type or the developmental stage of the cells involved
Lymphoid cell disorders affect T cells or B cells (or both)
Myeloid cell disorders affect phagocytic function
The severity of the immunodeficiency depends on at which stage in development the problem occurs
- E.g. Defects early on in development will affect the entire immune system
T cell deficiencies can affect both the cell-mediated and humoral response as T cells play a central role in the immune system

Deficiencies of Innate Immunity

Canine Cyclic Haematopoiesis

Also called Grey Collie Syndrome
Autosomal recessive
Insertion mutation in AP3B1 gene
Diluted grey coat colour, stunted growth, poor wound healing
Neutropenia every 2 weeks which lasts 3-4 days due to cyclic production of cells from bone marrow
Recurrent infections, e.g. pyrexia, diarrhoea, gingivitis and arthritis

Canine Leukocyte Adhesion Deficiency (CLAD)

Occurs in Irish Setters
Missence mutation of -Cys-36-Ser- in CD18 molecule
- CD18 is required for neutrophil migration and phagocytosis
Recurrent bacterial infection
Neutrophilia (neutrophils remain in the blood and are unable to fight infection in the tissue)

Bovine Leukocyte Adhesion Deficiency (BLAD)

Occurs in Holstein cattle
Missence mutation of -Asp-128-Gly in CD18 molecule
Recurrent infection, e.g. pneumonia

Deficiencies of Adaptive Immunity

Equine Severe Combined Immune Deficiency (Equine SCID)

Autosomal recessive
Occurs in 2-3% of Arabian foals
Defect in DNA-dependent protein kinase gene
- Gene codes for a DNA repair enzyme involved in V(D)J recombination for antigen receptors of lymphocytes (e.g. Ig and TCR)
No functional B cells or T cells
Foals develop infections (usually aorund 8 weeks of age as maternal antibody in colostrum wanes around this time)
Foals usually die from bronchopneumonia

Canine X-Linked Severe Combined Immune Deficiency (Canine SCID)

Affects Basset Hounds and Corgis
X-linked recessive defect in the gene conding for the IL-2 receptor
- IL-2 receptor is a receptor for the cytokine IL-2 which causes T cells to proliferate
Causes lymphoid hypoplasia, stunted growth and increses the animal's susceptibility to infection
Animal usually dies from pneumonia or sepsis as the level of maternal antibody decreases

Selective IgA deficiency of German Shepherd Dogs

Poorly understood
Linked to other disease syndromes such as deep pyoderma, inflammatory bowel disease, anal furunculosis and disseminated aspergillosis
IgA deficiency so more susceptible to mucosal disease

Immunodeficiency of Weimaraners, Irish Wolfhounds and Miniature Dachshunds

Unknown aetiology
Inherited defects
Low levels of circulating IgM and IgG
Impaired neutrophil function
Causes recurrent pyrexia and infections
- E.g. Rhinitis and bronchopneumonia in Irish Wolfhounds due to low IgA
- E.g. Pneumocytosis in Miniature Dachshunds due to low IgG

Labatory Examples of Severe Combined Deficiency

Severe Combined Immune Deficiency(SCID)
- No functional B cells or T cells

Arthymic nude mice (no thymus)
- No functional T cells
- Cell-mediated immunodeficiency

Knock-out mice
- E.g. Gene coding for CD4, CD8, IL-10 removed

Secondary Immunodeficiency

There are many causes of secondary immunodeficiency
- Most deficiencies are not genetic
- Most are agent-induced, such as from X-ray radiation and immunosuppressive drugs

Viral Causes

Feline Leukaemia Virus (FeLV)

FeLV Electron Micrograph Public Health Image Library Image #5610

Oncogenic retrovirus
Causes neoplasia (lymphoma), myelosuppression (anaemia) and immunosuppression (of T cells)
2 strains:
- FeLV-A
  - Natural strain
- FeLV-B
  - Formed through FeLV-A recombining with endogenous retroviral sequences in the feline genome
  - Increases the risks of lymphoma
- FeLV-C
  - Formed from the spontaneous mutation of FeLV-A
  - Is more myelosuppressive
Virus replicates in the oropharyngeal lymphoid tissue causing a viraemia (virus circulating in the bloodstream) which then spreads to the systemic lymphoid tissue
Shed in saliva
Passed by oronasal route, e.g. mutual grooming
Kittens between 6 weeks and 6 months are most susceptible
60% of cats will become immune to the disease and recover
Cats that are persistantly viraemic will progress to develop FeLV-associated diseases
Some cats will become viraemic again if treated with corticosteroids or stressed if the infection lies dormant in the bone marrow
Diagnosis:
- ELISA
- Rapid-Immuno-Migration
- Western Blot
- Virus Isolation
- Immunofluorescence
- PCR
- Antibiotics for secondary infection
- Anti-retroviral therapy
For vaccinations see here

Feline Immunodeficiency Virus (FIV)

Lentivirus
Subtypes A, B and D
Causes increased suscepitbilty to infections and neoplasia
Specifically destroys CD4+ T cells
Virus is present in saliva, blood and other bodily fluids
Feral and outdoor cats (mostly tom cats) are most at risk
Virus replicates in lymphoid tissue
Can remain asymptomatic
Causes pyrexia and lymphadenopathy
Transmitted by biting
Diagnosis:
- ELISA
- Rapid-Immuno-Migration
- Western Blot
- Virus Isolation
- Immunofluorescence
- PCR
Treatment:
- Antibiotics for secondary infection
- Anti-retroviral therapy
For vaccinations see here

Bovine Immunodeficiency Virus (BIV)

Lentivirus (non-oncogenic)
Causes a persistent viral infection and lymphocytosis
Immunocompromised cattle may develop secondary infections
The tranmission is not well known, but the following possibilities are being researched:
- Through milk
- Through infected semen (e.g.artificial insemination)
- Placental transfer
Diagnosis:
- Western Blot
- PCR