Unit 4: immunodeficiency Flashcards
primary immunodeficiency
inherited
secondary immunodeficiencies occur:
common clinical signs of immunodef
Respiratory disease
Otitis externa
Pyoderma
Vomiting/diarrhea
Ill thrift (smaller than other litter mates)
defect in neutrophil result in
extracellular bacteria infection
defect in cytotoxic T cells cause
recurrent viral infections
defect in macrophage results in
superficial cutaneous infection and systemic pyogenic infections
defect in complement leads to issue with
phagocytosis
neutrophil function test
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)
total hemolytic complement
CH50
how well complement works at lysing cells
radial immunodiffusion
used to measure complement
Immunochemical quantitation
C3 and C4 (+ others)
Complement function test
C3 and C4 function
Ability of patient’s serum to lyse Ab-coated ovine RBCs (+ others)
serum protein electrophoresis
separate by charge, different peaks are different immunoglobulins
normal or abnormal
both are abnormal there are large peak where immunoglobulins are
T ways to measure T cell competence
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
Ciliary dyskinesia
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
diagnosis of ciliary dyskinesia
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
Leukocyte adhesion deficiency
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)
what cause LAD in irish setters
CD11a/18 deficiency (mutation in β chain of CD18) aka integrin LFA-1
Neutrophils cannot leave bloodstream
symptoms of LAD
symptoms: recurrent bacterial infections (Omphalophlebitis, Lymphadenopathy, Pneumonia, Gingivitis), severe leukocytosis(very high 50-100k), and short life span
diagnostic test for LAD
leukocyte adhesion deficiency
Neutrophil Function: CBC: Extreme neutrophilia Neutrophil function: Normal
Flow cytometry, looking for CD18
Trapped Neutrophil Syndrome
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
border collies get
trapped neutrophil syndrome
Autosomal recessive • Carrier rate 16% in US; average 13% in 9 countries
test for trapped neutrophil syndrome
DNA test available (Davis)
Analogous to Cohen syndrome in humans
symptoms of trapped neutrophil syndrome
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)
