Neutrophil arrival and function

Question 1

Name the steps of neutrophil arrival and function

Answer 1

1. Margination
2. rolling
3. Adhesion
4. Transmigration and chemotaxis
5. Phagocytosis
6. Destruction of phagocytosed material
7. Resolution

Question 2

Where does margination occur?

Answer 2

Vasodilation in the post capillary venules

Question 3

What are the names of the speed bumps in the second step?

Answer 3

Rolling step: P selectin

E selectin

Question 4

The selectins of the rolling step are induced by what molecules?

Answer 4

P selectin- Histamine

E selectin : TNF and IL 1

Question 5

Function of TNF and IL 1

Answer 5

Induce production of E selectin

Upregulation of cellular adhesion molecules in the endothelium

Question 6

The E selectin is released from what part of the cell?

Answer 6

The Weibel Palade Bodies

Question 7

In Step 3, what are the cells that bind each other?

Answer 7

Endothelium- cellular adhesion molecules

Neutrophils- Integrins

Question 8

The selectins binds to what molecules on leucocytes?

Answer 8

Sialyl Lewis X

Question 9

The integrins are upregulates by what molecules

Answer 9

C5a

LTB4

Question 10

What is the sickness related with a defect in step 3?

Answer 10

Leukocyte adhesion deficiency

Question 11

What is the Leukocyte adhesion deficiency

Answer 11

Autosomal recessive defect of integrins (CD18 subunit)

Question 12

Clinical features of Leukocyte adhesion deficiency

Answer 12

• Delayed separation of umbilical cord
• Increased circulating neutrophils
• Recurrent bacterial infections that LACK PUS formation

Question 13

The neutrophils are chemotactic to what molecules?

Answer 13

IL 8
LTB4
Bacterial products
C5a

Question 14

Phagocytosis is enhanced by what molecules?

Answer 14

Opsonins ( IgG and C3b)

Question 15

How does phagocytosis occur?

Answer 15

1. Neutrophil recognixes pathogen
2. Pseudopes from leukocytes extend from phagosomes
3. Internalized and merged with lysosomes to form phagolysosomes.

Question 16

What is the sickness related with a defect in step 5?

Answer 16

Chediak- Higashi Syndrome

Question 17

What is the Chediak- Higashi Syndrome?

Answer 17

Autosomal Recessive Protein tracking defect (microtubules)

Characterized by impaired phagolysosome formation

Question 18

Clinical features of Chediak- Higashi Syndrome

Answer 18

• Increase risk of pyogenic infections
• Giant granules leukocytes
• Defective primary hemostasis
• Albanims
• Peripheral neuropathy

Question 19

Mechanism to obtain HOCL?

Answer 19

One pathway :
O2 converted to O2- by NADPH oxidase (oxidative burst)
O2- converted to H2O2 by SOD
H2O2 converted to HOCL’by MPO

Second pathway
Bacterias catalase negative produce H2O2
H2O2 converted to HOCL’by MPO

Question 20

Mechanism by which macrophages call in additional neutrophils to continue acute inflammation?

Answer 20

Via IL-8

Question 21

What are the next steps of acute inflammation mediated by the macrophages?

Answer 21

Resolution and healing
Continued acute inflammation
Abscess
Chronic Inflammation

Question 22

How does the Macrophages continue the acute inflammation?

Answer 22

Via IL 8 to call neutrophils

Question 23

What are the pathways to the destruction of phagocytosed material? Which one is more effective?

Answer 23

O2 dependent killing

O2 independent killing

Question 24

What molecules destroys the phagocytosed material?

Answer 24

HOCl

Question 25

What is the sickness related with a defect in step 5?

Answer 25

Chronic granulomatous disease | MPO deficiency

Question 26

what is the Chronic granulomatous disease

Answer 26

Poor dependet killing due to NADPH oxidase defect ( X linked or A Recessive)

Question 27

Why the catalase positive infection create granulomas?

Answer 27

Because the catalase destroys the H2O2. so there is no way to create HOCl and there can be destruction of the infection.

Question 28

What are the catalase positive organisms

Answer 28

``` S. aureus P. CEPACIA S. marcescens Nocordia Aspergillus ```

Question 29

A patient undergo nitroblue tetrazolium test? It report blue staining what does that mean?

Answer 29

There is NADPH oxidase that conver O2 to O2-

Question 30

Patient comes with oral candida. Denies other symptoms. A nitroblue tetrazolium test is realized, it stains blue? What is the probable diagnosis?

Answer 30

MPO (mieloperoxidase) deficiency Defective conversion of H2O2 to HOCl

Question 31

Macrophages undergo what pathway for killing the phagocytosed material

Answer 31

The O2 independent killing Via enzymes presents in secondary granules (LYSOZOMES and major basic proteins)

Question 32

What is the peak of Macrophages?

Answer 32

2-3 days

Question 33

What are the 3 phases of acute inflammation?

Answer 33

Fluid phase Neutrophil phase Macrophages phase

Question 34

How does the neutrophils die in the resolution step?

Answer 34

By apoptosis

Question 35

what cell mediates the abscess creation?

Answer 35

Macrophages

Question 36

Patients with an 8 weeks of cough with pus, in what phase of inflammation is?

Answer 36

Acute inflammation

Question 37

What are the anti inflammatory molecules macrophages secrete so there can be resolution and healing?

Answer 37

IL 10 and TFG B