Diseases of Leukocyte Adhesion Flashcards
What is the role of CD18?
Dimerization with the CD11a to make LFA-1 integrin
-role is adhesion of leukocytes to endothelial cells.
What is another term for CD21?
CD21 is CR2
What is another term for CD95?
CD95 is Fas
What cell type represents the greatest fraction of the white blood cell count?
Neutrophils
What is G-CSF and when would it be used?
Stimulates neutrophil production
-used any time there is something cuasing neutropenia like chemotherapy, BM transplant, immunesuppression
What type of bacterial induce a strong neutrophil response?
Pyogenic Bacteria, “pus forming”
-pyrogenic would be fever forming
What is CD62 and what are its three different types?
CD62 are selectins and the first step of the rolling along endothelial cells for neutrophil extravasation
CD62L is on Leukocytes
CD62E is on endothelial cells
CD62P is on platelte cells but also endothelial cells
What does CD62L bind with?
Ligand is GlyCAM-1/CD34 (remember this is on HSC but turns out also on endothelial cells)
What does CD62E bind with?
Ligand with Sialyl-Lewis CD15s
What does CD62P bind with?
Ligans is Sialyl-Lewis
What is the most important componenet for tight adhesion during neutropihl extravasation?
Tight adhesion due to integrins (transmembrane proteins that mediate cell-cell interactions
What is LFA-1, what is it expressed on, and what is its ligand?
What is CR3 and those same questions
LFA-1 is dimer of CD18-CD11a while CR3 is dimer of CD18-CD11b
-both are integrins expressed on leukocytes
LFA ligand CD54 (ICAM-1) and CR3 ligand is CD102 (ICAM-2), these are on the endotheliam
What are neutrophils activated by?
C5a, Leukotrienes, IL-8
What are endothelial cells activated by?
TNF-alpha
What is moleucle is required for adhesion in diapedisis?
Cells pass between endothelial cells and migrate along a chemokine gradient
-this requries adhesion
the adhesion molecule is CD31(PECAM-1) expressed on both endothelial cells and leukocytes, its ligand is itself CD31
During infection how would the distribution of neutorphils in the body change?
There would be less in the BM, more in the tissue, more in the marginating pool, and more in circulation
How can epinephrine change the distribution of neutorpihls in the body?
It would increased the circulating pool only
How would steroids change the neutropihl distrubtion in the body?
Increase both the circulating pool and the marginating pool
-this would be a slight depression in the bone marrow as well
What would you expect to see in the localization of neutrophils in a leukocyte adhesion defect?
Expect to see an increase in the circulating pool and a decrease in the marginating pool
What is the cause of neutropenia resulting from peripheral pooling?
Acute endotoxemia
What are some casues of neutropenia due to decrased production?
Drug-induced (suppressive)
Aplasic anemia
Chediak-Higashi Syndrome
B12 deficiency
folate deficiency
What are some causes of neutropenia by peripheral destruction?
Anti-neutrophil abs, autoimmunity like SLE, RA
What are some causes of neutrophilia?
due to increased production like from Idiopathic, Glucocorticoids, infection (mostly bacterial, fungal)
due to increased marrow release like steroids, infection, inflammation
-or due to decreased marginalization like epinephrine steroids, stress, and LAD-1, LAD-2
What is chronic granulomatous disease?
Loss of a subunit of NADPH oxidase leading to decresed phagocyte function of neutrophils
-X linked recessive is most common
What are the diagnostic signs of Chronic ganulomatous disease?
Abnormal dihydrohdamine test (flow cytometry and would see decreased green fluorescence)
-nitroblue tetrazolium dye reduction test is obsolete
What is Chediak-Higashi Syndrome?
Defect in LYST (lysosomal trafficking regulator gene), and microtubule dysfunction in phagosome-lysosome fusion
- autosomal recessive
- would see recurrent pyogenic infections by staphloccci and streptococci, partial albinism, peripherla neuropathy, progressive neurodegeneration, infilitrative lymphohistiocytosis
- would see gian granules in granulocytes and platelets, pancytopenia, mild coagulation defects
What is LAD-1?
Defect in CD18 leads to impaired diapesis
- seen as recurrent bacterial skin infections, no pus formation, and inflamed umbilical cord
- on CBC you would see neutrophilia
What is cause of LAD-2?
Reduced expression of Sialyl Lewis
-remember these are the endothelial ligands for selectin CD62E and CD62P
What is Omphalitis?
Swelling and erythema of the umbilicus without drainage
-LAD-1
Test results of phagocytosis of fresh serum-opsonized staph are very low but complement is normal, whats going on?
Since complement is normal must be a neutrohil probel like CD3 and CD4 because apparently complement mediated phagocytosis is not working, yet complement is okay. Most likely way to get CD3 and CD4 problem is with CD18 (LAD-1 defect) becuase it is unlikely both CD11b and CD11c are fucked up
What are cotton balls on CXR of 18 yo most likely?
sign of infection and need to do a fine needle biopsy
Tests reveal impaired reduction of dihydrohodamine following C5a, what the dx doc?
This is chronic granulomatous disease due to a defect id NADPH oxidase
