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Molecular Basis of Disease > Neutrophils in health and disease > Flashcards

Neutrophils in health and disease Flashcards

1
Q

What are the two fathers of immunology?

A

Metchnikoff

Ehrlich

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2
Q

What aspect of immunology was Metchnikoff interested in?

A

Cells

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3
Q

What aspect of immunology was Ehrlich interested in?

A

Soluble factors

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4
Q

What is phagocytosis?

A

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

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5
Q

Describe the steps of phagocytosis

A
  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
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6
Q

What chemicals in the phagolysosome help destroy the cell?

A

Oxygen radicals

Nitric oxide

Antimicrobial proteins

Antimicrobial peptides

Binding proteins

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7
Q

Are macrophages or neutrophils more efficient at phagocytosis?

A

Neutrophils

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8
Q

How do neutrophils phagocytose bacteria?

A

Become polarised

Hunt the bacteria that try to escape

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9
Q

Which part of the immunity do neutrophils belong to?

A

Innate immunity

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10
Q

What is the defining feature of neutrophils?

A

Lobed nuclei

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11
Q

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

A

60%

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12
Q

Are neutrophils smaller or larger that macrophages?

A

Smaller

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13
Q

What causes granulomatous disease?

A

Dysfunction of neutrophils

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14
Q

What condition arises following the dysfunction of neutrophils?

A

Chronic granulomatous disease

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15
Q

Why does chronic granulomatous disease appear?

A

Skin lesions develop s a result of poor bacterial clearance

Patient becomes susceptible to pneumonia and bacteria

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16
Q

How are neutrophils defective in chronic granulomatous disease?

A

Defect in the NADPH oxidase system

Causes the neutrophils to become unable to make superoxides

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17
Q

What other conditions are caused by neutrophil deficiencies?

A

Cyclic neutropenia

Severe congenital neutropenia

Kostmann syndrome

MPO deficiency

Lymphocyte adhesion deficiency

18
Q

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

A

Chemokines

CXCL8
IL-8
IL-1b

19
Q

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

A

Rolling

Adhesion

Tight binding

Diapedesis

Migration

20
Q

What are the 3 ways by which neutrophils kill pathogens?

A

Phagocytosis

Degranulation

NETs

21
Q

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

A

ROS

NO

Hydrochlorus acid

22
Q

How are ROS made?

A

Reduction of oxygen

23
Q

How is NO made?

A

Derived from arginine

24
Q

How is hydrochlorus acid made?

A

Reduction of water to make superoxide

Combines with hydrogen and chloride ions to make acid

25
Q

What important protein is involved in the ROS killing mechanism?

A

Phagocyte oxidase

26
Q

What important proteins is involved in the NO killing mechanism?

A

iNOS

27
Q

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

A

NADPH oxidase complex

Protein channel

MPO

28
Q

How does neutrophil degranulation kill bacteria?

A

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

29
Q

What important enzymes are involved in neutrophil degranulation killing mechanisms?

A

MMPs

MPO

Lactoferrin

Lysozyme

Cathepsin

HOCl

H2O2

30
Q

How do neutrophils form NETs in order to kill bacteria?

A

Undergo a process of NETosis

Characterised by chromatin decodensation and nuclear membrane disintegration

These NETs are released into the extracellular space to trap microbes

31
Q

What are the negative effects of NET formation by neutrophils?

A

Thrombosis

Sepsis

SLE

32
Q

Why is mucus green?

A

The myeloperoxidase in neutrophils

33
Q

What is ARDS?

A

Acute respiratory distress syndrome

Condition affecting the alveoli of the lungs

34
Q

What is the cause of ARDS?

A

Direct and indirect insults to the lungs

35
Q

What is the prevalence of ARDS?

A

220 000 cases in the USA

33 000 cases in the UK

36
Q

What is the mortality of people suffering with ARDS?

A

25-40%

37
Q

What is the therapy of ARDS?

A

Supportive ventilator therapy

38
Q

What leads to ARDS?

A

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

39
Q

What is characteristic in blood tests of ARDS patients?

A

Complete infiltration by neutrophils

40
Q

How do neutrophils cause epithelial and endothelial damage?

A

By the same mechanism they use to kill microbes

ROS
Proteases 
Cytokines
MMPs
NETs
41
Q

What are therapeutic agents in ARDS?

A

Blocking chemokines

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

Molecular Basis of Disease (28 decks)

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