Diseases of Leukocyte Adhesion

Question 1

What is the role of CD18?

Answer 1

Dimerization with the CD11a to make LFA-1 integrin

-role is adhesion of leukocytes to endothelial cells.

Question 2

What is another term for CD21?

Answer 2

CD21 is CR2

Question 3

What is another term for CD95?

Answer 3

CD95 is Fas

Question 4

What cell type represents the greatest fraction of the white blood cell count?

Answer 4

Neutrophils

Question 5

What is G-CSF and when would it be used?

Answer 5

Stimulates neutrophil production

-used any time there is something cuasing neutropenia like chemotherapy, BM transplant, immunesuppression

Question 6

What type of bacterial induce a strong neutrophil response?

Answer 6

Pyogenic Bacteria, “pus forming”

-pyrogenic would be fever forming

Question 7

What is CD62 and what are its three different types?

Answer 7

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

Question 8

What does CD62L bind with?

Answer 8

Ligand is GlyCAM-1/CD34 (remember this is on HSC but turns out also on endothelial cells)

Question 9

What does CD62E bind with?

Answer 9

Ligand with Sialyl-Lewis CD15s

Question 10

What does CD62P bind with?

Answer 10

Ligans is Sialyl-Lewis

Question 11

What is the most important componenet for tight adhesion during neutropihl extravasation?

Answer 11

Tight adhesion due to integrins (transmembrane proteins that mediate cell-cell interactions

Question 12

What is LFA-1, what is it expressed on, and what is its ligand?

What is CR3 and those same questions

Answer 12

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

Question 13

What are neutrophils activated by?

Answer 13

C5a, Leukotrienes, IL-8

Question 14

What are endothelial cells activated by?

Answer 14

TNF-alpha

Question 15

What is moleucle is required for adhesion in diapedisis?

Answer 15

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

Question 16

During infection how would the distribution of neutorphils in the body change?

Answer 16

There would be less in the BM, more in the tissue, more in the marginating pool, and more in circulation

Question 17

How can epinephrine change the distribution of neutorpihls in the body?

Answer 17

It would increased the circulating pool only

Question 18

How would steroids change the neutropihl distrubtion in the body?

Answer 18

Increase both the circulating pool and the marginating pool

-this would be a slight depression in the bone marrow as well

Question 20

What would you expect to see in the localization of neutrophils in a leukocyte adhesion defect?

Answer 20

Expect to see an increase in the circulating pool and a decrease in the marginating pool

Question 21

What is the cause of neutropenia resulting from peripheral pooling?

Answer 21

Acute endotoxemia

Question 22

What are some casues of neutropenia due to decrased production?

Answer 22

Drug-induced (suppressive)

Aplasic anemia

Chediak-Higashi Syndrome

B12 deficiency

folate deficiency

Question 23

What are some causes of neutropenia by peripheral destruction?

Answer 23

Anti-neutrophil abs, autoimmunity like SLE, RA

Question 24

What are some causes of neutrophilia?

Answer 24

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

Question 26

What is chronic granulomatous disease?

Answer 26

Loss of a subunit of NADPH oxidase leading to decresed phagocyte function of neutrophils -X linked recessive is most common

Question 27

What are the diagnostic signs of Chronic ganulomatous disease?

Answer 27

Abnormal dihydrohdamine test (flow cytometry and would see decreased green fluorescence) -nitroblue tetrazolium dye reduction test is obsolete

Question 28

What is Chediak-Higashi Syndrome?

Answer 28

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

Question 29

What is LAD-1?

Answer 29

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

Question 30

What is cause of LAD-2?

Answer 30

Reduced expression of Sialyl Lewis -remember these are the endothelial ligands for selectin CD62E and CD62P

Question 31

What is Omphalitis?

Answer 31

Swelling and erythema of the umbilicus without drainage -LAD-1

Question 32

Test results of phagocytosis of fresh serum-opsonized staph are very low but complement is normal, whats going on?

Answer 32

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

Question 33

What are cotton balls on CXR of 18 yo most likely?

Answer 33

sign of infection and need to do a fine needle biopsy

Question 34

Tests reveal impaired reduction of dihydrohodamine following C5a, what the dx doc?

Answer 34

This is chronic granulomatous disease due to a defect id NADPH oxidase