Category:Primary Immunodeficiency

• Primary immunodeficiencies may affect either the innate immune system or the 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

Appearance of a puppy with Grey Collie syndrome - Copyright Michelle Tennis & Peggy Melton

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
• Animals are prone to recurrent infections, mainly from the respiratory and gastrointestinal tract
  • E.g. pyrexia, diarrhoea, gingivitis and arthritis
• Puppies can be distinguished from other litter mates by the diluted grey colouring
• Affected puppies show symptoms such as fever, joint pain and eye, skin and respiratory infections from 8 weeks of age
• Affected animals rarely live beyond 2-3 years with most puppies dying within a few weeks of birth

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 around 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 coding 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 increases 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
• [[Immunoglobulin A|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 [[Immunoglobulin A|IgA]]
  • E.g. Pneumocytosis in Miniature Dachshunds due to low IgG

Laboratory Examples of Severe Combined Deficiency

Athymic Nude Mouse - Armin Kübelbeck 2008

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

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

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