S1: White Blood Cells and Phagocytosis Flashcards

1
Q

What are granular leucocytes also called?

A

Granulocytes

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2
Q

Describe the nucleus of granulocytes

A

Polymorphonuclear cells

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3
Q

Give examples of granulocytes

A

Neutrophils
Mast cells
Basophils
Eosinophils

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4
Q

What colour does basophils stain in H and E staining?

A

Blue granules

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5
Q

How many basophils are in circulation (rough percentage of WBC)?

A

0.1-0.2 %

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6
Q

What are the main roles of basophils?

A

Hypersensitivity: type I allergy

Degranulation (e.g. Histamine) for inflammation

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7
Q

Where are mast cells located?

A

In tissues close to blood vessels

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8
Q

Where are basophils and eosinophils located?

A

In blood circulation

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9
Q

What do granules in mast cells contain?

A

Inflammatory mediators

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10
Q

What do mast cells release for inflammation?

A

Degranulation(but less than basophils)

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11
Q

What is the main role of mast cells?

A

Hypersensitivity type I allergy

Parasites

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12
Q

What colour does eosinophils stain in H and E staining?

A

Pink granules

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13
Q

How many eosinophils are in circulation (rough percentage of WBC)?

A

4% of all WBC in circulation

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14
Q

What is the role of eosinophils?

A

They have a role in immune responses to parasites and allergies

Release granules content to kill (bigger) target

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15
Q

Give an example of a granule in eosinophils

A

Eosinophils cationic protein

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16
Q

Describe the nucleus of monocytes/macrophages

A

They are non granulated

Mononuclear

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17
Q

What is the main function of dendritic cells?

A

Antigen presenting cells

They capture microbes and are involved in phagocytosis but they then display the microbes antigens to T cells.

This links innnate and adaptive immune system

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18
Q

What is the definition of phagocytosis?

A

Cell eating microorganism/other cells/nutrients

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19
Q

What’s is the role of phagocytosis?

A
  • protection from pathogens
  • disposal of damaged/dying (apoptotic) cells
  • processing and presentation of antigens
  • link innate and adaptive immunity
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20
Q

What are phagocytes?

A

They are specialised cells that identify, ingest and destroy pathogens

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21
Q

Give some examples of phagocytes

A

Neutrophils
Macrophages
Dendritic cells

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22
Q

Describe the nucleus of neutrophils

A

They are polymorphonuclear leukocytes and they have multiple lobes on their nucleus

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23
Q

What is the lifespan of neutrophils in blood and tissue?

A

They have a relatively short lifespan:

  • hours in blood
  • days in tissue
24
Q

Neutrophils are part of the first response to inflammation and are involved in the phagocytosis and killing of microbes

Name some enzymes that they use to do this and what are they contained in?

A

Lysozyme
Collagenase
Elastase

They are contained in granules

25
Q

What is the difference between monocytes and macrophages?

A

Monocytes are in the blood and once they enter tissue they are called macrophages

26
Q

Name the inflammatory factor that macrophages secrete

A

Cytokines

27
Q

Where are dendritic cells found?

A

Skin, mucosa, tissues

28
Q

Name the 4 steps in phagocytosis

A
  1. Phagocyte mobilisation (through chemotaxis)
  2. Recognition and attachment
  3. Engulfment
  4. Digestion and hence pathogen destruction
29
Q

What is phagocyte mobilisation?

A

The movement of cells towards site of infection guided by chemoattractants

30
Q

What releases chemoattractants?

A
  • bacteria (fMLP)
  • inflammatory cells (which release chemokines- IL-8)
  • damaged tissue
31
Q

What is recognition of pathogens and attachment in phagocytosis?

A

Recognition is to ensure phagocytes only react to invading foreign pathogens instead of body’s own tissues.

This uses ‘Pathogen Associated Molecular Patterns’ (PAMPs) on pathogens

To recognise PAMPs, phagocytes have Pattern recognition receptors (PRRs)

Opsonisation helps identify the pathogens for phagocytosis.

Phagocytes have receptors for these opsonins so they can attach

32
Q

What are pathogen associated molecular patterns (PAMPs)?

A

They are present on pathogen and not host cells.

They are invariant structures (shared by an entire class of pathogens).

They are essential of the survival of pathogens but they also prevent pathogens from completely evading phagocytes

33
Q

Give some examples of PAMPs

A

In gram positive bacteria, PAMPs would include lipoteichoic acid (constituent of cell wall and peptidoglycan

In gram negative bacteria, the lipopolysaccharide layer can act as a PAMP and the peptidoglycan

In mycobacteria, the peptidoglycan cell wall also acts as PAMP as well as other structures

34
Q

What is the role of pattern recognition receptors (PRRs) and where are they found?

A

PRRs recognise PAMPs and therefore help detect foreign invaders.

They are present on phagocytes and other cells such as epithelial cells

35
Q

List some types of pattern recognition receptors (PRRs)

A
  • Toll like receptors (TLC) present in plasma membrane
  • C type lectin in receptors (CTLRs)
  • NOD like receptors (NLRs) as free proteins in cytoplasm
  • RIG like helicase receptors (RLRs) which are cytosolic receptors for viral dsRNA (double stranded RNA)
  • scavenger receptors which recognise various bacterial cell wall
36
Q

Toll like receptors (TLRs) play an essential role in innate immunity

Name some PAMPs that human TLRs recognise:

A
  • lipopolysaccharide (gram negative)
  • lipoteichoic Acid (gram positive)
  • bacterial DNA sequence
  • single double stranded viral DNA
  • glucans
37
Q

What do TLRs also do apart from recognise PAMPs?

A

Stimulate production of inflammatory cytokines

38
Q

What is the function of opsonisation?

A

To facilitate phagocytosis with the recognition of microbes

39
Q

What is opsonisation?

A

It is the coating of microbes which targets them for phagocytosis.

The proteins that coat microbes are called opsonins.

This facilitates phagocytosis as phagocytes have receptors for these opsonins which makes phagocytosis quicker and more efficient

40
Q

Give some examples of opsonins

A

Antibodies such as IgG

Proteins of complement system such as C3b, C4b

41
Q

Why is opsonisation important for encapsulated microorganisms?

A

Encapsulated microorganisms can hide from PRRs so they require opsonisation for phagocytes to recognise them

42
Q

What is engulfment?

A

Where the pathogen enters the phagocyte

This is done through phagosome formation and maturation

43
Q

Describe phagosome formation and maturation

A

When the microbe is attached to the phagocyte, the actin skeleton begins to get rearranged which causes and controls membrane remodelling.

Pseudopods form around the sides of the microbe and eventually the microbe is completely surrounded.

It then buds into the cytoplasm in a phagosome.

The phagosome then fused with lysozyme to forms phagolysosome. The pathogen is then destroyed by the lysosomal enzymes.

44
Q

What are the structures formed during membrane remodelling called?

A

Pseudopods

45
Q

What is the vesicles containing microbes in the cytoplasm of a phagocyte called?

A

Phagosome

46
Q

What is a phagolysosome?

A

A phagosome that fuses with a lysozyme

47
Q

Describe oxygen-independent killing of pathogens

A

This utilises enzymes from the lysozyme

  • proteolytic enzymes which degrade microbes
  • lysozyme which breaks down bacterial cell walls
  • lactoferrin which binds iron that bacteria needs
  • defensins which destroy bacterial cell wall
48
Q

Describe oxygen-dependent killing of pathogens

A

This first involves assembly of NADPH oxidase on the phagolysosome.

This generates superoxide anions (an oxidising radical) which break down bacteria in the activated phagocyte

49
Q

How do oxidising radical kill pathogens?

Examples using Equations - *not an LO

A

O2——> O2- (superoxide)

H2O + O2- ————> H2O2 + OH-
(Enzyme dismutase)

Argenine + O2 ————> NO + citruline (NO is radical)
(iNOS - inducible NO synthase)

NO + H2O2 ————-> peroxynitrate radicals

50
Q

List ways microbes evade phagocytosis

A
  • Encapsulation so PRRs may not be able to detect PAMPs beneath it e.g. streptococcus pneumoniae
  • certain microorganisms block engulfment e.g. yersinia
  • block reactive oxidising radicals from destroying them e.g. salmonella is resistant to reactive oxidising species
  • blocks fusion of phagosome and lysozyme so phagolysosome is not formed e.g. mycobacterium
  • produce toxins which damage the membrane of phagocytes ultimately killing them e.g. staphylococcus aureus
51
Q

What is apoptosis?

A

It is programmed cell death.

52
Q

What cells destroy apoptotic cells?

A

Phagocytes quickly and efficiently remove the cells that have been programmed to die

53
Q

Why is apoptosis known as ‘silent’ removal?

A

There is no inflammation

54
Q

Explain apoptosis

A

This is done due to apoptotic cells expressing ‘eat me’ signals on their membrane. These are attracted to molecules on the phagocyte (which recognised that it needs to be eaten so engulfment takes place)

Viable cells express ‘don’t eat me’ signals on their surface which repulses phagocytes

55
Q

What is secreted as a consequence of apoptotic cell removal?

A

‘Pro-healing’ cytokines which reduce inflammation and promote wound healing

56
Q

What maintains self tolerance of the immune system?

A

Phagocytes which present the antigens if dead host cells to the immune system