1 - Immunodeficiencies Flashcards
What is the difference between a primary and secondary immunodeficiency?
Primary have a genetic, heritable basis
How can the humoral immunity be evaluated?
- CBC for lymphocytes
- Serum Ig concentrations
- Vaccination (watch response)
- Phenotyping studies (measure B-cells in blood/lymphoid tissues)
- In vitro B-lymphocyte proliferation test (function)
How can the CMI be evaluated?
- CBC for lymphocytes
- Phenotyping studies (measure T-cells in blood/lymphoid tissues)
- In vitro T-lymphocyte proliferation test
- Intradermal injection of PHA (in vivo test of function)
Which is the dominant immunoglobulin in colostrum?
IgG
When is colostrum produced?
During final weeks of pregnancy
Lasts ~24 hours after birth
How is colostrum absorbed by foals? When is it most efficiently absorbed
Specialized enterocytes bind colostral Ig
Transfer across epithelium to lymphatics and capillaries
Best absorption during first 6 hours
Is FPT a humoral or cell-mediated immunodeficiency?
Humoral
What clinical signs are associated with FPT?
D/t secondary infection (doesn’t always occur)
Umbilical infections
Bronchopneumonia
Enteritis
Bacteremia and septicemia (injected, pale, or muddy mms; tachycardia; hypoperfusion)
DIC (petechiation, hemorrhage, thrombosis)
How is sepsis diagnosed in the foal?
- Maintain high index of suspicion in any sick neonatal foal!
1. Sepsis score sheet (>11)
2. Radial immunodiffusion (RID) to measure IgG - gold standard, but pricey and time-consuming
3. ELISA-based tests - IgG >800 = adequate
- IgG <400 = complete FPT
4. SNAP test - color of blue dot indicates strength of IgG
What are the indirect indicators of passive transfer? Are they used in the foal?
Plasma TP, colostrum-derived serum GGT
Both NOT used in foals
If a foal has IgG levels 400-800 mg/dL and is clinically normal, should it be treated for FPT?
Not necessarily
How should a FPT foal <8-12 hours be treated?
PO 2L high quality colostrum (or 2-3 bottles Seramune)
SG >1.060 (colostrometer) / SG >23% (sugar refractometer)
How should a FPT foal >12-24 hours be treated?
1-2L plasma transfused IV
+/- flunixin pretreatment to reduce risk of adverse rxns
How much colostrum should the foal get?
2L of quality colostrum in first 8 hours
What screening is recommended to prevent FPT?
Screen all foals at 24-36 hours
How is FPT screened for/diagnosed in the bovine?
- Direct - FPT = IgG <1000mg/dL
- Indirect - TP (refractometer) <5.0 g/dL
(ONLY run on healthy calves with good hydration)
How much colostrum should the calf get?
100g IgG within 6 hours of birth (SG >1.050)
Dairy cows - 4L
Beef cows - 2L
What is the etiology of SCID?
Primary immunodeficiency - Arabian
Failure to produce functional B and T lymphocytes
What is the pathogenesis of SCID?
Mutation in DNA-dependent protein kinase
Lymphoid stem cells fail to differentiate
Dysfunctional B and T lymphocytes
Complete deficiency in both CMI and humoral immunity
What clinical signs are associated with SCID?
Affected foals normal for 2-3 months (until maternal Ab wanes)
Susceptible to opportunistic infections
Die within 5 months
How is SCID diagnosed?
Severe and persistent leukopenia
Low to absent levels of autologous Ig
PCR test identifies normal, heterozygous, or homozygous
How is SCID treated?
NO treatment. Grave prognosis
How is SCID prevented?
Avoid breeding carriers to one another
What is the etiology of selective IgM deficiency?
Equine specific
Humoral immunodeficiency characterized by persistently low IgM (other classes normal)
What are the clinical presentations of selective IgM deficiency?
- Young foals (most common)
Recurrent infections, grave prognosis, death within first year
Primary genetic basis suspected (Arabians/Quarters) - Horses up to 1-2 years
Hx of chronic recurrent infections, stunted growth
Death before 2 years - Adults 2-5 years
Associated with lymphosarcoma, recurrent infections are rare
Likely secondary immunodeficiency
How is selective IgM deficiency diagnosed?
Serial measurement of serum Ig - IgM persistently low (all others normal)
Normal lymphocyte counts
How is selective IgM deficiency treated?
Supportive care - abx, plasma transfusions
Poor prognosis
What is the etiology of transient hypogammaglobulinemia?
Humoral immunodeficiency - delayed onset of Ig synthesis (until 3-6 months)
Arabians mostly affected
What are the clinical signs associated with transient hypogammaglobulinemia?
Susceptibility to recurrent infections once maternal Ab wanes
How is transient hypogammaglobulinemia diagnosed?
RID demonstration of low IgG, IgM, IgA after 2 months
B/T lymphocyte counts and CMI responses normal
(Autologous Ig levels eventually normalize)
What are the differential diagnoses for transient hypogammaglobulinemia?
FPT
Primary agammaglobulinemia
How is transient hypogammaglobulinemia treated?
Plasma transfusions and serial Ig testing until autologous Ig production
Management may only be practical in valuable foals
What is the etiology of equine x-linked agammaglobulinemia?
Primary immunodeficiency - absence of B-lymphocytes and immunoglobulins (will never develop)
Affects male foals (x-linked)
How is equine x-linked agammaglobulinemia diagnosed?
Total lymphocyte counts normal, but B-lymphs absent
Serum Ig (all classes) persistently low or absent once maternal Ab wanes
No serological response to vaccination
CMI normal
How is equine x-linked agammaglobulinemia treated?
Supportive tx only
Grave prognosis, death within 2 years
What is the etiology of common variable immunodeficiency (CVI)?
Similar to human CVI - group of primary immunodeficiencies
Progressive B-lymph depletion and hypo/agammaglobulinemia
Affects ADULT horses
What clinical signs are associated with CVI?
Recurrent bacterial infections in adult horses
How is CVI diagnosed?
Serial testing shows declining B-cell numbers and Ig levels (beginning later in life)
No serological response to vaccination
How is CVI treated?
Supportive tx only - grave prognosis
What is the etiology of bovine leukocyte adhesion deficiency (BLAD)?
Inherited autosomal recessive disorder of Holsteins
Causes dysfunction of innate immune system
What is the pathogenesis of BLAD?
Point mutation in the gene encoding CD18 (subunit of beta-2 integrins)
Beta-2 integrins = cell surface proteins important for leukocyte adhesion to capillary endothelium
Neutrophils do not express these adhesion molecules - cannot migrate into tissues
What clinical signs are associated with BLAD?
Infectious disease with delayed healing in young cattle
How is BLAD diagnosed?
Marked mature neutrophilia (>40,000 cells/µL)
Genetic testing available (PCR)
How is BLAD treated?
Supportive only - grave prognosis, death within 1st year
How is BLAD prevented?
Avoid breeding carriers
