Unit 4: immunodeficiency

Question 1

primary immunodeficiency

Answer 1

inherited

Question 2

secondary immunodeficiencies occur:

Answer 2

Question 3

common clinical signs of immunodef

Answer 3

Respiratory disease

Otitis externa

Pyoderma

Vomiting/diarrhea

Ill thrift (smaller than other litter mates)

Question 4

defect in neutrophil result in

Answer 4

extracellular bacteria infection

Question 5

defect in cytotoxic T cells cause

Answer 5

recurrent viral infections

Question 6

defect in macrophage results in

Answer 6

superficial cutaneous infection and systemic pyogenic infections

Question 7

defect in complement leads to issue with

Answer 7

phagocytosis

Question 8

neutrophil function test

Answer 8

Adhesion
Surface CD11b-CD18 integrin expression measured by flow cytometry

**Chemotaxis**
Neutrophil transmigration (polycarbonate membrane) under chemotactic gradient

Phagocytosis: Patient neutrophils: opsonized fluorescent latex spheres or bacteria

Bactericidal activity: Feed neutrophils opsonized bacteria, assess viable bacteria

• Indirectly measure via peroxide-myeloperoxidase-halide reaction or staining for myeloperoxidase activity (oxidation burst- green fluorescence)

Question 9

total hemolytic complement

Answer 9

CH50

how well complement works at lysing cells

Question 10

radial immunodiffusion

Answer 10

used to measure complement

Immunochemical quantitation
 C3 and C4 (+ others)

Question 11

Complement function test

Answer 11

C3 and C4 function
Ability of patient’s serum to lyse Ab-coated ovine RBCs (+ others)

Question 12

serum protein electrophoresis

Answer 12

separate by charge, different peaks are different immunoglobulins

Question 13

normal or abnormal

Answer 13

both are abnormal there are large peak where immunoglobulins are

Question 14

T ways to measure T cell competence

Answer 14

Lymphocyte blastogenesis → put T cells in substance that should make them divide if they don’t something is wrong
 Suspension PBMCs exposed to T cell mitogen
 Poor proliferation consistent with a T cell defect; control concurrent
infection first

Flow cytometry
 Enumerate subtypes of T and B cells
 More common in dx/ lymphoma

Question 15

Ciliary dyskinesia

Answer 15

defect in mucociliary escalator → movement of cilia to get stuff out of lungs

Mucoid nasal discharge

Recurrent bronchopneumonia from young age

Bronchiectasis- bronchi dilated and floppy

Secretory otitis media, male infertility

diagnosis: look at biopsy under electron microscope, and Mucociliary transport visualization: 99mTc macro- aggregated albumin

Question 16

diagnosis of ciliary dyskinesia

Answer 16

look at biopsy under electron microscope

Mucociliary transport visualization: 99mTc macro- aggregated albumin - radio labeled albumin placed in nose and see if cilia can move it

Question 17

Leukocyte adhesion deficiency

Answer 17

aka CLAD or granulocytopathy syndrome

leukocytes can’t leave blood stream cause they can’t bind to ICAMs on vessel wall because they don’t have CD18 part (mutation in B chain) of the integrin

common in Irish setter

symptoms: recurrent bacterial infections, severe leukocytosis, and short life span

Rolling
• Selectins

Tight binding
• Adhesion molecule: ICAM-1 (endothelium)

• Integrin (neutrophil)
• LFA-1, CR3 (CD11a/CD18)

Question 18

what cause LAD in irish setters

Answer 18

CD11a/18 deficiency (mutation in β chain of CD18) aka integrin LFA-1

Neutrophils cannot leave bloodstream

Question 19

symptoms of LAD

Answer 19

symptoms: recurrent bacterial infections (Omphalophlebitis, Lymphadenopathy, Pneumonia, Gingivitis), severe leukocytosis(very high 50-100k), and short life span

Question 20

diagnostic test for LAD

Answer 20

leukocyte adhesion deficiency

Neutrophil Function: CBC: Extreme neutrophilia Neutrophil function: Normal

Flow cytometry, looking for CD18

Question 21

Trapped Neutrophil Syndrome

Answer 21

Mutation in Vesicle Protein Sorting 13B (VPS13B) gene
• Neutrophils stuck in the bone marrow

• Marked neutropenia- very low
• Bone marrow biopsy: show high amounts of neutrophils but none in blood (myeloid hyperplasia)

Common in Border collies- Autosomal recessive • Carrier rate 16% in US; average 13% in 9 countries

symptoms: Chronic extracellular bacterial infections • Small stature • Slender extremities • Mental retardation

Question 22

border collies get

Answer 22

trapped neutrophil syndrome

Autosomal recessive • Carrier rate 16% in US; average 13% in 9 countries

Question 23

test for trapped neutrophil syndrome

Answer 23

DNA test available (Davis)
Analogous to Cohen syndrome in humans

Question 24

symptoms of trapped neutrophil syndrome

Answer 24

Chronic extracellular bacterial infections • Small stature • Slender extremities • Mental retardation

CBC shows low neutropenia, while bone marrow shows high white blood cell count (stimulated to be made but can’t get out)

Question 25

cyclic hematopoiesis

Answer 25

gray collie syndrome

Severe neutropenia every 12-14 days, +/- thrombocytopenia

Perturbed neutrophil elastase trafficking within cell (mutation in adapter
protein AP3B1)
• Shuttles elastase Golgi → lysosome
• Usually do not survive > 3y

Question 26

complement component 3 (C3) deficiency

Answer 26

Brittany Spaniel • Autosomal recessive

symptoms: sepsis, abscesses, meningitis

Question 27

selective IgA deficiency

Answer 27

german sherphed, beagles, shar pea

IgA helps with mucosal sites (GI, respiratory ect.)

Pathogenesis
Beagle – No peripheral IgA+ plasma cells
Others – Defective synthesis, secretion of IgA?

Clinicopathological features
Predisposition to mucocutaneous infections:
 Respiratory tract – B. bronchiseptica, PI virus
 Small intestine – enteropathogenic E. coli
 Skin – deep pyoderma, perianal fistulas
 Auditory canal – otitis externa

Question 28

weimaraner immunodeficiency

Answer 28

gets sick after vaccine

Pathogenesis
Immunoglobulin deficiency, commonly IgG alone or IgA and/or IgM
Exaggerated cellular immune response?
± Neutrophil function defect

Clinicopathological features
Young, related weimaraner dogs (~4 mo.)
May occur within 7 days of vaccination

Chronic, recurrent polysystemic inflammation:
GIT (V/D), joints (HOD), lymph nodes, bone (osteomyelitis),CNS (sterile meningitis), urinary tract (UTI), skin (injection reactions, pyoderma), eye (conjunctivitis), lung (pneumonia)

Favorable prognosis in some dogs; in others, recurrent inflammatory disease

Question 29

chediak higashi syndrome

Answer 29

Blue smoke Persian cats

Neonatal septicemia, viral respiratory infections

Impaired chemotaxis, intracellular killing defect

Abnormal platelet function

Question 30

Hypotrichosis with Thymic Aplasia

Answer 30

Birman kittens

No hair

Failure to thrive, death by a few days of age

Necropsy: lack of thymus, aplastic LN

Mutation in FoxN1 gene
• DNA binding element
necessary for hair growth
and thymic development