Immunodeficiencies

Question 1

create a list of appropriate tests to diagnose a primary immunodeficiency (won’t be asked a lot about these, will get more later on)

Answer 1

test innate components:
1. evaluate structural barriers: diagnostic imaging, biopsy, histopathology
2. evaluate complement function: chemotaxis or opsonization assays (rare to ind a lab that can though)
3. evaluate neutrophil activity: PCR for genetic defects, evaluate migration, phagocytosis, oxidative burst with flow cytometry assays

test adaptive components:
1. assess humoral (B cells):
-quantitative serum concentrations to tell if animal capable of class switching (should have IgG, IgM, AND IgA in serum, but if can’t class switch would only see IgM
-ELISA (enzyme-linked immunoassay) can also help quantify antibody levels
-serum radial immunodiffusion (SRID) also for B cells
2. assess T cells:
-flow cytometry can label CD3, CD4, CD8
-blastogenesis/lymphocyte transformation: isolate peripheral blood mononuclear cells, co-culture with a mitogen, and assess lymphocyte proliferation
-phenotypical analysis for IL-2 receptor via flow cytometry
-quantification of cytokines released by activated cells (ELISA, flow cytometry)

Question 2

describe primary immunodeficiency and secondary immunodeficiency

Answer 2

primary: the result of genetic defects; clinical manifestation may not always occur immediately; breed predispositions!!

secondary: caused by environmental factors, such as lentiviruses and malnutrition

Question 3

describe characteristics of primary immunodeficiencies

Answer 3

1. affect young animals, typically after maternal immunity has waned
2. if see
   -infections caused by “non-pathogenic” microbes,
   -an infection that is inexplicably difficult to treat
   -an infection that is normally mild/self-limiting but is now severe/persistent
   -recurrence of previously sub-clinical infections
   -or multiple infections in one patient, may suspect a primary immunodeficiency

Question 4

if there is an immunodeficiency related to the innate immune system’s phagocytic capabilities or with their complement capabilities, what would that look like?

Answer 4

phagocytic: superficial skin infections, systemic infections with pyogenic organisms (lack of neutrophils)

complement: recurrent infections with pyogenic organism

Question 5

if there is an immunodeficiency related to the adaptive immune system’s B cell/humoral capabilities or with their T cell/cytotoxic capabilities, what would that look like?

Answer 5

B cell/humoral: bacterial infections

T cell/cytotoxic: intracellular organisms: viral, bacterial, and fungal infections OR reactivation of modified live vaccines

Question 6

describe examples of primary immunodeficiency diseases

Answer 6

neutrophils: cyclic hematopoiesis, leukocyte adhesion deficiency, chediak-higashi

complement: factos C3 and H

B cell/humoral
-IgA deficiency
-IgG deficiency
-common variable immunodef
-IgM and IgG deficiency
-abnormal B and T cell development

T cell/cytotoxic: thymic aplasia and hypotrichosis

B and T cells: severe combined immunodeficiency: MOST SEVERE OF ALL PRIMARY!! canine and equine forms, and human, and rodent; X-linked or autosomal recessive disorders; hella susceptible to all infections and untreated patients rarely survive past infancy

Question 7

describe bovine LAD

Answer 7

1. leukocyte adhesion disorder
2. deficiency in functional chemotactic and phagocytic neutrophils
3. autosomal recessive trat traced back to one bull
4. a DNA/PCR test exists now yay!
5. causes omphalitis: superficial pyoderma, pododermatitis, gingivitis, deep wound infections, pneumonia, poor wound healing, cellulitis, poor pus formation, progressive neutrophilia
6. calves are unthrifty and often die at 2-4 months

Question 8

list different causes of secondary immunodeficiencies (9)

Answer 8

1. infectious diseases: FIV, canine distemper, EIA, BVD, infectious myelosuppression (HELLA BAD, caused by a lot of diseases)
2. drugs: corticosteroids, but can be intentional to treat hypersensitivities, etc.
3. radiation/toxins: destroy rapidly dividing cells (includes T and B cells)
4. endocrinopathies: hyperadrenocorticism, hypothyroidism, diabetes mellitus; can all cause recurrent infections
5. stress or excess exercise
6. trauma: patients much more susceptible to infection
7. malnutrition: need enough nutrients to make the good stuff
8. age: young/immature immune system, or immunosenescence: age related decline in immunity
9. cancer: both from the neoplastic cells and also from the drugs we give

Question 9

compare the clinical characteristics of primary versus secondary immunodeficiencies

Answer 9

just know that primary is usually younger and genetic cause and usually rule out secondary causes before search for primary