Macrophages

Question 1

Macrophages vs Monocytes:

Answer 1

Macrophages:

• Are not found in the blood
• Mono-nuclear phagocytes found in tissue

Monocytes:

• Mono-nuclear cells generated in the bone marrow
• Circulate in the blood

Question 2

Macrophages types:

Answer 2

Tissue macrophages:

• Derived from yolk sac, fetal liver and bone marrow precursor cells
• Seeded in embryonic development and maintained in adult life
• Each tissue can have its own specalised macrophage -type

Monocyte derived macrophages:
- During adult life, monocytes released into circulation can be recruited to tissues for self defense functions or differentiate into tissue macrophages if an empty niche available

Question 3

Regulators of macrophage development:

Answer 3

Transcription Factors:
- Mafb-deficient mice lack tissue macrophages

Cytokines:
- CSF-1-deficient mice have reduced numbers of blood monocytes

Question 4

Macrophage function:

Answer 4

Non-Immune:

• Developmental biology – apoptotic cell clearance
• Homeostasis – uptake of aged red blood cells and iron recycling
• Metabolism – release of adipokines (cytokine subset)
• Haematopoiesis – uptake of red blood cell nuclei, trophic factors
• Neurobiology – cross-talk with neuronal cells

Immune:
- Acute and chronic inflammation
- Self-defense, especially newly-recruited macrophages
Antigen transfer and antigen presentation

Question 5

Monocytes

Answer 5

• For some tissues (eg gut) monocytes important source of macrophage precursors in adults
  Generated in the bone marrow and the circulate in the blood.
• Most monocytes exist in 2 subsets:
  ‘Inflammatory’ –Ly6c^high
  ‘Patrolling’ – Ly6c^low
• Inflammatory: recruited to tissue during inflammation, may transition to patrolling monocytes
• Patrolling: move slowly along blood vessel walls, may remove small debris.
• Inflammatory monocytes rapidly recruited to inflammatory sites
• Patrolling monocytes maintain endothelial cell integrity in blood vessels

-Monocytes can replace damaged, non-self-renewing macrophages in adult life

Question 6

Macrophages are very good at phagocytosis

TRUE OR FALSE

Answer 6

TRUE
Other immune cells (e.g. neutrophils) can also phagocytose
Zipper- or trigger-type phagocytosis

Question 7

BLANK, BLANK, AND BLANK are all receptors on macrophages that stimulate phagocytosis.

Answer 7

Mannose receptor, Dectin-1, and LPS receptor are all receptors on macrophages that stimulate phagocytosis.

Question 8

Very simple phagocytosis by macrophage overview:

Answer 8

Bacteria bound to receptors on macrophage membrane
Engulfment of bacteria by phagosome
Degradation of bacteria

Question 9

Result of phagocytosis of apoptotic cells:

Answer 9

Phagocytosis of apoptotic cells by macrophages is called efferocytosis

Promotes an anti-inflammatory response:
↑ TGF-β and IL-10
↓ TNF-α, ↓IL-8, ↓IL-1β in response to pathogens

This is important in preventing macrophage activation and potential triggering of autoimmune responses

Question 10

Macrophage activation (or polarisation)

Answer 10

Different macrophage phenotypes have been associated with IFNgamma and IL-4 stimulation

M1 “classical” activation: IFNgamma and TLR agonist

M2 ”alternative” activation: IL-4

Question 11

Limitations of the M1/M2 model:

Answer 11

After the idea of M2 was put forward, other stimuli were also found to generate macrophages with a less “inflammatory phenotype”.

This lead to subdivisions of the M2 macrophage state:
M2a: IL-4
M2b: immune complexes + LPS
M2c : IL-10 or TGFbeta

M1/M2 polarization is not irreversible

The number of macrophages activation states in vivo in much larger and depends on the integration of signals at multiple receptors

M1 / M2 may represent two extremes of macrophage phenotype