NON-NEOPLASTIC prt.2_ FUNCTIONAL LEUKOCYTE ALTERATIONS Flashcards
Inherited Abnormalities
- Job’s Syndrome
- Lazy Leukocyte
- Defects in Microbial Activity
- Chronic Granulomatous
Disease - Myeloperoxidase Activity
3 Chediak Higashi Syndrome
Lipidoses
Tay Sach Syndrome
Lipidoses
Tay Sach Syndrome
• Random movement of phagocytes are normal
• Directional motility is IMPAIRED = cells response to chemotactic factor is SLOW
Job’s Syndrome
• MUTATION: STAT3 gene
Job’s Syndrome
• Aka: Autosomal Dominant Hyperimmunoglobulin
Syndrome
- Familial disorder
Job’s Syndrome
• Rare condition
• BOTH RANDOM AND DIRECT MOVEMENT ARE IMPAIRED
• Release of cells from the bone marrow - POOR
Lazy Leukocyte Syndrome
• NEUTROPENIA is consistent finding
• cells fail to respond to inflammatory stimuli but otherwise appear to have a normal paghocytic and bacterial activity
Lazy Leukocyte Syndrome
• CLINICAL FEATURES: Low grade fever and recurrent infections (involving the gums, mouth and ears)
• contain defective actin filaments
Lazy Leukocyte Syndrome
• Group of disorders involving inheritance or either X-linked or autosomal recessive gene that affects neutrophil microbicidal function.
• X-linked = accounts 70% and more severe
Chronic Granulomatous Disease
• SYMPTOMS:
• Recurrent suppurative infection
• Pneumonia
• Osteomyelitis
• Draining adenopathy
• Liver abscesses
• Dermatitis
• Hypergammaglobilinemia
Chronic Granulomatous Disease
• SYMPTOMS:
• Recurrent suppurative infection
• Pneumonia
• Osteomyelitis
• Draining adenopathy
• Liver abscesses
• Dermatitis
• Hypergammaglobilinemia
Chronic Granulomatous Disease
• MAIN PROBLEM:
• Decreased ability of phagocytes to
produce superoxide and reactive oxygen species
Chronic Granulomatous Disease
• PHATOPHYSIOLOGY:
• One or more mutations in genes responsible for proteins that make up a complex known as NADPH OXIDASE
• Can result in the CGD phenotype by making the neutrophil Incapable of generating an oxidative burst
Chronic Granulomatous Disease
Chronic Granulomatous Disease
• NORMAL: reduce the Yellow water soluble Nitroblue Tetrazolium to a dark blue insoluble formazan
• ABNORMAL: It will not reduce the yellow and will RETAIN AS YELLOW
Nitroblue Tetrazolium Reduction Test
Chronic Granulomatous Disease
•
• Labelled with dihydrorhodamine (DHR)
• DHR will fluoresce = reduces
FLOW CYTOMETRY ASSAY
• Seen on patients with acute and chronic leukemia, myelodysplastic syndrome, Hodgkin disease and carcinoma
Myeloperoxidase Deficiency
• MAIN PROBLEM: absence of MPO enzyme from neutrophil and monocytes but no eosinophils
• Bacteria killing is slowed but complete
• COMPENSATION: RESPIRATORY BURST ACTIVITY INCREASED
Myeloperoxidase Deficiency
• Aka: Alius-Grignaschi Anomaly
• Benign inherited disorder that is usually transmitted by autosomal recessive genes
Myeloperoxidase Deficiency
• Inherited, autosomal recessive trait
• MUTATION: CHSQ LYST gene on chromosome 1q42.1-2
• Abnormally large lysosomes = conatian fused dysfunctional granules
Chediak - Higashi Syndrome
Chediak - Higashi Syndrome
• MUTATION:…
• Abnormally large lysosomes = conatian fused dysfunctional granules
CHSQ LYST gene on chromosome 1q42.1-2
Chediak - Higashi Syndrome
CLINICAL MANIFESTATIONS OF CHS:
HYPOPIGMENTATION OR PARTIAL ALBINISM
SEVERED IMMUNODEFICIENCY
NEUROLOGIC ABNORMALITIES
MILD BLEEDING TENDENCIES
• Cause: HEXA gene mutation → Deficient β-hexosaminidase A → Accumulation of GM2 gangliosides.
Tay-Sachs Disease
Tay-Sachs Disease
• Cause:______ gene mutation → Deficient ________→ Accumulation of________.
HEXA
β-hexosaminidase A
GM2 gangliosides
• Findings:
• Progressive neurodegeneration
• Common in Ashkenazi Jews, French-Canadians, Amish, and Cajuns
• Clinical Course: Severe infantile form leads to early childhood death.
Tay-Sachs Disease
