Term
| What are the 3 major types of granulocytic phagocytic leukocytes that function in the innate immune system? |
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Definition
1) Neutrophils
2) Eosinophils
3) Monocytes/macrophages (liver, spleen, lung) |
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Term
| Describe the basic developmental trajectory of a Myeloid precursor cell. |
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Definition
1) MPC arises from a HSC (other option is LPC) and becomes
- Granulocyte monocyte precursor (GMP)
- Eosinophilic precursor, basophilic precursor
- Megakaryocyte erythroid precursor (MEP)
2a) MEP becomes megakaryocyte (platelets) and erythroid (RBC)
2b) GMP becomes granulocyte or monocyte. |
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Term
| Describe the 6 stages of granulocyte development. |
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Definition
Granulocytes come from granulocyte precursor cells, which come from MPCs.
There are 6 morphological stages and 2 basic maturation "pools," each of which lasts 7 days (Proliferating/mitotic and Maturation/post-mitotic)
Mitotic/Proliferating
1) Myeloblast
- Small cell with arge, round nucleus with nucleoli
- No cytoplasmic granules
2) Pro-myelocyte
- larger cell with similar nuclear features
- primary granules with lysosyzme and defensins
3) Myelocyte
- last myeloid precursor capable of mitosis
- coarse/clumped chromatin with sparse/absent nucleoli
- secondary granules form with lactoferrin (competes with bacteria for iron), B12-binding protein, NADPH oxidase membrane components and B2 integrins.
Maturation/Post-mitotic
4) Metamyelocyte
- Cytoplasm resembles mature neutrophil
- Coarse/clumped chromatin
5) Band forms
- Smaller than metamyelocytes with horseshoe nucleus
6) PMN
- 2-5 segments (excessive segmentation seen in B12 or folate deficiency) |
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Term
| What is "Felty's" Syndrome? |
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Definition
Severe neutropenia (ANC <500) and splenomegaly in patients with longstanding RA
Autoimmune is one cause of neutropinia (drugs, malignancy, infection, ethnicity, nutrition and congenital are others). |
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Term
| How are patients with congenital neutropenia generally treated? |
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Definition
| Severe congenital neutropenia (PMN elastase gene mutations) and Cyclic neutropenia (same gene) response to gCSF |
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Term
| Patient's blood work comes back with ANC of 900. What is on your ddx and how do you proceed? |
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Definition
Since elevated WBC is > 11k/uL, and PMNs are 45-78% of this, neutrophilia is defined as >8.5k/uL.
1) Reactive (secondary)
- infection (can be acute or chronic)
- chronic inflammation (RA, IBD, Granulomatous disease, hepatitis)
- smoking
- stress
- drugs
2) Malignant
- Congenital
- Acquired neoplasm (leukemia, polycythemia vera, thrombocytosis, idiopathic fibrosis) |
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Term
| What are the 3 types of disorders of phagocytic function? |
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Definition
1) Response burst microbiocidal pathway (de novo unstable oxygen intermediates)
- NAPH oxidase mutations (CGD)
- PMN G6P DH deficiency
- Glutathione metabolism disorders
- Myeloperoxidase deficiency
2) Phagocyte adhesion
- Leukocyte adhesion deficiency 1
- Hyperimmunoglobulin E syndrome (HIES)
3) Lysosomal granule structure/function (pre-formed antibiotics and proteases)
- Chediak-Higashi
- Specific Granule Deficiency |
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Term
Infant presents with symptoms of pneumonia and a positive NBT test.
You order a lung biopsy and see evidence of chronic inflammation and granuloma formation.
What is the pathogenesis/treatment of this condition? |
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Definition
Chronic Granulomatous Disease
1) X linked and AR forms with mutations in NADPH oxidase, preventing O2- formation and innate immune PMN defenses
2) Early diagnosis and institution of parenteral antibiotics early in infectious treatments
- prophylactic antibiotics and INF-y
- NO STEROIDS |
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Term
What are the defining features of each of the following disorders of PMN respiratory burst?
1) CGD
2) Neutrophil G-6-P-DH deficiency
3) Disorder of glutathione metabolism
4) MPO deficiency |
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Definition
1) AR and X-linked mutations in NAPDH prevent O2- production and defense
2) Enzyme involved in NADPHD generation (primary substrate of burst)
- usually asymptomatic
3) Reduced form of GSH protects PMNs from H2O2 damage to NADPH oxidase
- Reduction in glutathione synthase (de novo) or glutathione reductase (generates GSH from GSSG) prevents this protection.
- burst is normally sufficient, but patients get intermittent neutropenia and oxidant-induced hemolysis
4) Most common inherited disorder of phagocytes (asymptomatic)
- MPO catalyzes production of hypochlorous acid from H2O2 and chloride (helpful in bacterial killing) |
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Term
| Describe the 2 major disorders of phagocytic adhesion. |
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Definition
Short. LAD1= beta integrin absense/infection with no pus
HIES= too much IgE/staph, dental, skeletal, derm
1) Leukocyte Adhesion Deficiency Type 1 (LAD 1)
- rare AR disorder with mutation of B2 integrin gene
- recurrent, severe bacterial/fungal infections WITHOUT pus accumulation
- diagnose with flow cytometry for CD11b (beta integrin)
** look for high WBC count with severe pyogenic infection and no PMN infiltrate **
2) Hyperimmunoglobulin E Syndrome (HIES)
- Increased IgE levels with recurrent staph infections, chronic dermatitis and skeletal/dental abnormalities
- PMNs have "chemotactic" defect |
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Term
| Discuss the pathogenesis/treatment of the 2 major defects in the structure/functional of lysosomal granules. |
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Definition
1) Chediak-Higashi
- Rare AR
- Giant lysosome granules deficient in cathepsin G and elastase
- with infections, cranial neuropathies (optic) and bleeding
- Eventually produces progressive lymphopholiferative syndrome and pancytopenia
2) Specific Granule Deficiency |
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