Term
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Definition
| defects in componnents of NADPH oxidase |
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Term
| What do ulcerations signify? |
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Definition
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Term
| Infections common in neutropenic patients |
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Definition
| extracellular infections= staph., strep. Candida, Crypto, Aspergillus |
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Term
| IL-6 assists in what part of leukopoiesis? |
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Definition
| In the self-renewal and differentiation of SCs |
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Term
| IL-6, IL-3 and GM-CSF assist in what part of blood cell differentiation? |
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Definition
| differentiation of myeloid progenitor cells |
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Term
| G-CSF assists in which part of blood cell differentiation? |
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Definition
| myeloid progenitor cellls into neutrophils |
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Term
| M-CSF assists in which part of blood cell differentiation? |
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Definition
| assists in differention of myeloid progenitor cells into monocytes |
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Term
| G-CSF and M-CSF are produced by which type of cell |
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Definition
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Term
| IL-3 and GM-CSF are produced by what cell type? |
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Definition
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Term
| IL-5 (from TH2 cells) assists in which part of leukopoiesis |
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Definition
| myeloid progenitor cells into eosinophils |
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Term
| IL-11 (from BM stromal cells) assist in which part of leukopoiesis |
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Definition
| myeloid progenitor cells into basophils, platelets and erythrocytes |
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Term
| Decribe the most common causes of neutropenia |
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Definition
decreased production: primary, secondary= cytotoxic drugs, leukemia, tumors
increased destruction: splenomegaly, immune-mediate injury, overwhelming infections |
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Term
| Explain the effet of infection on the production and release of neutrophiles from the bone marrow |
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Definition
| PMNs are activated by IFN-g released from NK and Th1 cells--> PMNs release IL-1 and TNF-a--> stimulate release of inflammatory cytokines stored in bone marrow and produce increased amounts of hematopoietic growth factors--> increased number of bands |
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Term
| Describe the characteristics of neutrophil granules, including the major components found in each type |
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Definition
Primary Granules: larger, also called azurophilic granules; formed in early neutrophil maturation= myeloperoxidase, bacteriocidal factors, acid proteases, and neutral proteases
Secondary Granules: smaller, also called specific granules; formed later in neutrophil maturation |
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Term
| Granule stained in AML detection |
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Definition
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Term
| Explain the burst in oxygen consumption (respiratory burst) and describe the generation fo the reactive oxygen intermediates that kill and degrade infectious agents within phagocytic cells |
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Definition
1. bacteria binds to neutrophil
a. if antibody opsonized- by FcgR1
b. if complement opsonized- by CR-1
2. stimulation of neutrophil causes assembly of NADPH oxidase enzyme on membrane of phagolysosome
3. NADPH converts O2 to superoxide; oxygen is consumed
4. superoxide is converted to peroxide and then hydroxyl radical (killing agent) or in the presence of myeloperoxidase peroxide is converted to HOCl
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Term
| Explain the role of NADPH oxidase in microbial killing |
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Definition
| produces superoxide ---killing is accomplish by ROSs |
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Term
| Which mutations can cause CGD? |
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Definition
gp91phox on X chromosome
and p22, p67, and -47 from autosomal chromosomes join to form NADPH oxidase enzyme |
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Term
| Where does the name CGD come from? |
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Definition
| from macrophage-rich inflammatory reaction at site of infection that occur when initial neutrophil response does not kill bacteria |
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Term
| What is the most common recurrent infection for CGD patients? |
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Definition
| catlase positive bacteria -->staph |
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Term
| Explain the use of the NBT and DHR assays in diagnosis of CGD |
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Definition
NBT is added to neutrophils
LPS is added to stimulate neutrophils
in normal neutrophils respiratory burst reduced NBT dye to a deep purple precipitate
DHR is reduced fluorecent marker for intact respiratory burst--> flow cytometry |
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Term
| Explain how migration is affected in LAD-2 |
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Definition
rolling is mediated by interactions between sialyl-Lewis X-modified glycoproteins on luekocytes and E and P selectins on endothelium
patients with LAD-2 have AR mutation required for sialyl-Lewis X synthesis |
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Term
| Explain how migration is affected in LAD-1 |
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Definition
tight binding is mediated by interactions between B2 integrins on leukocytes like LFA-1 and ICAMs on endothelium
LAD-1 patients have a AR mutation in CD18 gene which encodes the common protein in B integrins
B2 integrins are also expressed on Tcells!!!! |
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Term
| A patients leukocytes cannot tightly bind to endothelial cells, but can roll. Which gene is mutated in this patient? |
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Definition
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Term
| Why are catalase positve bacteria a recurrent infector for patients with NADPH oxidase deficiency or CGD? |
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Definition
superoxide isn't competent enough to kill bacteria
myeloperoxidase def. also |
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Term
| What will be absent in a patients pyogenic ulcer with LAD? |
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Definition
| pus- leukocytes have difficulty migrating to infection sites |
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Term
| What chemokine increases integin-endothelium affinity? |
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Definition
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Term
| Explain the role of inflammatory cytokines in phagocytosis |
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Definition
IL-1 and TNF-a= increased release of phagocytes form BM
increased expression of adhesion molecules on endothelial cells and migration chemokines
IFN-g activates macrophages to produce IL-1 and TNF-a
increases NO production |
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