Neutrophils in health and disease

Question 1

What are the two fathers of immunology?

Answer 1

Metchnikoff

Ehrlich

Question 2

What aspect of immunology was Metchnikoff interested in?

Answer 2

Cells

Question 3

What aspect of immunology was Ehrlich interested in?

Answer 3

Soluble factors

Question 4

What is phagocytosis?

Answer 4

The process by which a cell binds to the molecule it wants to engulf on the cell surface

Draws the molecule inwards whilst engulfind around it

Question 5

Describe the steps of phagocytosis

Answer 5

1. The microbe and phagocyte come into contact with each other
2. The microbe binds to the phagocytic receptor
3. The phagocyte membrane starts to zip up around the microbe
4. The surrounded microbe becomes completely enclosed in a bubble-like structure called the phagosome within the cytoplasm
5. The phagosome fuses with a lysosome, becoming a phagolysosome
6. Degradation of microbe by lysosomal enzymes, including ROS and NO
7. Once the contents have been neutralized the phagolysosome forms a residual body that contains the waste products left over

Question 6

What chemicals in the phagolysosome help destroy the cell?

Answer 6

Oxygen radicals

Nitric oxide

Antimicrobial proteins

Antimicrobial peptides

Binding proteins

Question 7

Are macrophages or neutrophils more efficient at phagocytosis?

Answer 7

Neutrophils

Question 8

How do neutrophils phagocytose bacteria?

Answer 8

Become polarised

Hunt the bacteria that try to escape

Question 9

Which part of the immunity do neutrophils belong to?

Answer 9

Innate immunity

Question 10

What is the defining feature of neutrophils?

Answer 10

Lobed nuclei

Question 11

What proportion of the white blood cell population are composed of neutrophils?

Answer 11

60%

Question 12

Are neutrophils smaller or larger that macrophages?

Answer 12

Smaller

Question 13

What causes granulomatous disease?

Answer 13

Dysfunction of neutrophils

Question 14

What condition arises following the dysfunction of neutrophils?

Answer 14

Chronic granulomatous disease

Question 15

Why does chronic granulomatous disease appear?

Answer 15

Skin lesions develop s a result of poor bacterial clearance

Patient becomes susceptible to pneumonia and bacteria

Question 16

How are neutrophils defective in chronic granulomatous disease?

Answer 16

Defect in the NADPH oxidase system

Causes the neutrophils to become unable to make superoxides

Question 17

What other conditions are caused by neutrophil deficiencies?

Answer 17

Cyclic neutropenia

Severe congenital neutropenia

Kostmann syndrome

MPO deficiency

Lymphocyte adhesion deficiency

Question 18

What do neutrophils require in order to migrate to sites of inflammation?

Answer 18

Chemokines

CXCL8
IL-8
IL-1b

Question 19

What steps allow neutrophils to moe from the blood into tissues?

Answer 19

Rolling

Adhesion

Tight binding

Diapedesis

Migration

Question 20

What are the 3 ways by which neutrophils kill pathogens?

Answer 20

Phagocytosis

Degranulation

NETs

Question 21

What are the 3 main destructive molecules that allow neutrophils to kill pathogens?

Answer 21

ROS

NO

Hydrochlorus acid

Question 22

How are ROS made?

Answer 22

Reduction of oxygen

Question 23

How is NO made?

Answer 23

Derived from arginine

Question 24

How is hydrochlorus acid made?

Answer 24

Reduction of water to make superoxide

Combines with hydrogen and chloride ions to make acid

Question 25

What important protein is involved in the ROS killing mechanism?

Answer 25

Phagocyte oxidase

Question 26

What important proteins is involved in the NO killing mechanism?

Answer 26

iNOS

Question 27

What important protein is involved in the Hydrochlorus acid killing mechanism?

Answer 27

NADPH oxidase complex Protein channel MPO

Question 28

How does neutrophil degranulation kill bacteria?

Answer 28

Granules contain a lot of important enzymes responsible for direct and indirect microbe killing Causes a destruction of microbes whilst stimulating the migration of immune cells by the release of pro-inflammatory molecules

Question 29

What important enzymes are involved in neutrophil degranulation killing mechanisms?

Answer 29

MMPs MPO Lactoferrin Lysozyme Cathepsin HOCl H2O2

Question 30

How do neutrophils form NETs in order to kill bacteria?

Answer 30

Undergo a process of NETosis Characterised by chromatin decodensation and nuclear membrane disintegration These NETs are released into the extracellular space to trap microbes

Question 31

What are the negative effects of NET formation by neutrophils?

Answer 31

Thrombosis Sepsis SLE

Question 32

Why is mucus green?

Answer 32

The myeloperoxidase in neutrophils

Question 33

What is ARDS?

Answer 33

Acute respiratory distress syndrome Condition affecting the alveoli of the lungs

Question 34

What is the cause of ARDS?

Answer 34

Direct and indirect insults to the lungs

Question 35

What is the prevalence of ARDS?

Answer 35

220 000 cases in the USA 33 000 cases in the UK

Question 36

What is the mortality of people suffering with ARDS?

Answer 36

25-40%

Question 37

What is the therapy of ARDS?

Answer 37

Supportive ventilator therapy

Question 38

What leads to ARDS?

Answer 38

Disruption of the endothelium Leads to activation of neutrophils Neutrophils release chemokines, which favours leukocyte migration, and protease, inducing epithelial injury and bacterial killing Edema develops as a result

Question 39

What is characteristic in blood tests of ARDS patients?

Answer 39

Complete infiltration by neutrophils

Question 40

How do neutrophils cause epithelial and endothelial damage?

Answer 40

By the same mechanism they use to kill microbes ``` ROS Proteases Cytokines MMPs NETs ```

Question 41

What are therapeutic agents in ARDS?

Answer 41

Blocking chemokines Leads to a reduction in neutrophil accumulation and a subsequent reduction in inflammation