Category:Immunodeficiencies

Immunodeficiencies - Introduction

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

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

Kinetics of FeLV - Copyright Dr Brian Catchpole BVetMed PhD MRCVS

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 persistently 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
Treatment:
- Antibiotics for secondary infection
- Anti-retroviral therapy
For vaccinations see here

Feline Immunodeficiency Virus (FIV)

Lentivirus
Subtypes A, B and D
Causes increased susceptibility 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 transmission 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

Toxic Causes

Poisons

Iatrogenic Causes

Drugs
- Corticosteroids
- Cyclosporin
- Cytotoxic cancer therapy

Other Causes

Malnutrition

Chronic disease

Stress

Senescence

Links

Internal

Viruses - WikiBugs

Innate Immune System - WikiBlood

Adaptive Immune System - WikiBlood

External

Grey Collie Syndrome Information on Canine Cyclic Haematopoeisis (Grey Collie Syndrome) including new research into treating the condition and a clinical example